46 results on '"Valeria Tutino"'
Search Results
2. Correlation between antioxidant and anticancer activity and phenolic profile of new Apulian table grape genotypes (V. Vinifera L.)
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Rosa Anna Milella, Mirko De Rosso, Marica Gasparro, Isabella Gigante, Giambattista Debiase, Lucia Rosaria Forleo, Antonio Domenico Marsico, Rocco Perniola, Valeria Tutino, Maria Notarnicola, Riccardo Velasco, and Riccardo Flamini
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Plant Science - Abstract
Grapes represent a significant source of phenolic compounds known for their health-promoting properties, such as antioxidant capacity on normal cells and prooxidant activity on tumor cells. The genotype highly affects the polyphenolic composition in grapes and, consequently, the nutritional quality of berries. This work aimed to characterize the phenolic composition, the antioxidant, and anticancer activity of grape skin extracts (GSEs) of nine new table grape genotypes selected from a breeding program to obtain new cultivars of seedless table grapes, well adapted to the climatic change and with higher nutraceutical properties. The grape polyphenolic profile was characterized by Ultra-High-Performance Liquid Chromatography/Quadrupole-Time of Flight mass spectrometry analysis. GSE antioxidant activity was determined by the ABTS, DPPH, and ORAC assays; GSE cell growth inhibition test was carried out in the Caco2 human cancer cell line. The nine GSEs showed different flavonoid and non-flavonoid profiles, and all possessed antioxidant activity, with the ‘Aika N.’, ‘Turese N.’, and ‘Egnatia N.’ the most active. As anticancer activity against the tested cancer cell line, ‘Daunia N.’ and ‘Apenestae N.’ showed the EC50 after 24 h of 35.60 µg/mL and 150.91 µg/mL, respectively. The relationship between polyphenolic profile and the antioxidant and anticancer activity of GSE was also investigated. Interestingly, among the different classes of polyphenolics, flavan-3-ols e proanthocyanidins showed the highest positive correlation with the anticancer activity of extracts. These findings can be helpful for the preparation of new extracts for the pharmaceutical and nutraceutical industry and geneticists working in vine breeding programs.
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- 2023
3. Evaluation of the Effects of the Tritordeum-Based Diet Compared to the Low-FODMAPs Diet on the Fecal Metabolome of IBS-D Patients: A Preliminary Investigation
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Giusy Rita Caponio, Giuseppe Celano, Francesco Maria Calabrese, Giuseppe Riezzo, Antonella Orlando, Benedetta D’Attoma, Antonia Ignazzi, Mirco Vacca, Annalisa Porrelli, Valeria Tutino, Maria De Angelis, Gianluigi Giannelli, and Francesco Russo
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Irritable Bowel Syndrome ,Diet, Carbohydrate-Restricted ,Nutrition and Dietetics ,Monosaccharides ,Fermentation ,Metabolome ,Humans ,Oligosaccharides ,diet ,functional gastrointestinal disorders ,irritable bowel syndrome ,metabolome ,short-chain fatty acids ,Tritordeum ,volatile organic compounds ,Pilot Projects ,Disaccharides ,Food Science ,Diet - Abstract
Since irritable bowel syndrome (IBS)—a common gastrointestinal (GI) disorder—still lacks effective therapy, a nutritional approach may represent a practical alternative. Different reports demonstrated that a low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) diet (LFD) reduces symptoms in IBS with diarrhea (IBS-D) patients, also inducing beneficial pathophysiological and biochemical modifications. More recently, diets with alternative cereals having a different gluten composition, such as tritordeum, have also been considered (TBD). We investigated the impact of TBD and LFD on the fecal metabolome composition in 38 IBS-D patients randomly allocated to the two diets for 12 weeks. Summarily, at baseline, the profile of fecal volatile organic compounds (VOCs) of IBS-D patients was not significantly different in the two groups. After treatment, significant changes were observed in the two groups regarding the VOCs content since some of them increased in the TBD group (namely, decanoic acid), whereas others (i.e., nonanal and ethanol) increased in the LFD one. Further, at baseline, short-chain fatty acids were positively related to inflammation and showed a significant decreasing trend after both diets compared to baseline values (namely, acetic and propanoic acid). Preliminary results from this pilot study suggest a potential positive intervention of TBD and LFD affecting the fecal metabolome composition in IBS-D patients.
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- 2022
4. Effects of weight change on all causes, digestive system and other causes mortality in Southern Italy: a competing risk approach
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Isabella Franco, Maria Gabriella Caruso, Benedetta D'Attoma, Antonella Bianco, Antonella Mirizzi, Caterina Bonfiglio, Paolo Sorino, Alberto Rubén Osella, Angelo Campanella, Maria Notarnicola, Anna Maria Cisternino, Giovanni Misciagna, and Valeria Tutino
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Adult ,Male ,medicine.medical_specialty ,Longitudinal study ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Body Mass Index ,Weight management ,Epidemiology ,Humans ,Medicine ,Longitudinal Studies ,Prospective Studies ,Mortality ,Prospective cohort study ,Nutrition and Dietetics ,business.industry ,Weight change ,Middle Aged ,Italy ,Relative risk ,Cohort ,Body-Weight Trajectory ,Female ,business ,Digestive System ,Body mass index ,Demography - Abstract
Weight change is associated with all causes of death, cardiovascular, and cancer mortality and a heterogeneous group of other causes of death. We aimed to estimate the effect of weight change on all causes and cause-specific mortality in a cohort with a high prevalence of deaths due to diseases of the digestive system.MethodsIn this prospective cohort study, 2230 subjects aged 30 to 50 years were examined. The study consisted of a 32-year longitudinal study period (January 1985 to December 2017) and mortality follow-up. Outcomes were mortality from all causes and deaths from gastrointestinal disease. Root Mean Squared Error (RMSE) was evaluated to capture individual residual variation in Body Mass Index (BMI) after adjustment for baseline BMI, and the relationship of residual variation with mortality was calculated as cumulative incidence function and cause-specific hazard (CSH) rate.ResultsIn total, 793 participants died during the follow-up, 96 of them due to Digestive system causes. Magnitude of residual variation weight in the last quintile was associated with all-cause mortality (relative risk, 2.00; 95% CI, 1.54-2.59) and Digestive system causes (relative risk, 3.82; 95% CI, 1.86-7.81).ConclusionThe findings suggest an association between weight change and gastrointestinal disease mortality. Epidemiological works studying the correlation between weight change and mortality should consider this aspect.
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- 2021
5. Plasma-Derived Exosomes from NAFLD Patients Modulate the Cannabinoid Receptors’ Expression in Cultured HepaRG Cells
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Valentina De Nunzio, Livianna Carrieri, Maria Principia Scavo, Tamara Lippolis, Miriam Cofano, Giusy Rita Caponio, Valeria Tutino, Federica Rizzi, Nicoletta Depalo, Alberto Ruben Osella, and Maria Notarnicola
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Inorganic Chemistry ,Organic Chemistry ,nonalcoholic fatty liver disease ,exosome ,cannabinoid receptors ,General Medicine ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Catalysis ,Computer Science Applications - Abstract
Exosomes produced by hepatocytes upon lipotoxic insult play a relevant role in pathogenesis of nonalcoholic fatty liver disease (NAFLD), suggesting an inflammatory response by the activation of monocytes and macrophages and accelerating the disease progression. In the pathogenesis of NAFLD and liver fibrosis, the endogenous cannabinoids and their major receptors CB1 and CB2 appear to be highly involved. This study aimed at evaluating the expression of cannabinoids receptors (CB1R and CB2R) in plasma-derived exosomes extracted from patients with NAFLD, as well as investigating the in vitro effects of the circulating exosomes in cultured human HepaRG cells following their introduction into the culture medium. The results demonstrated that plasma-derived exosomes from NAFLD patients are vehicles for the transport of CB1R and are able to modulate CB receptors’ expression in HepaRG cells. In particular, circulating exosomes from NAFLD patients are inflammatory drivers for HepaRG cells, acting through CB1R activation and the downregulation of CB2R. Moreover, CB1R upregulation was associated with increased expression levels of PPAR-γ, a well-known mediator of liver tissue injury. In conclusion, this study provides evidence for CB1R transport by exosomes and suggests that the in vitro effects of circulating exosomes from NAFLD patients are mediated by the expression of cannabinoid receptors.
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- 2023
6. Nutraceuticals: Focus on Anti-Inflammatory, Anti-Cancer, Antioxidant Properties in Gastrointestinal Tract
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Giusy Caponio, Tamara Lippolis, Valeria Tutino, Isabella Gigante, Valentina De Nunzio, Rosa Milella, Marica Gasparro, and Maria Notarnicola
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Physiology ,Clinical Biochemistry ,Cell Biology ,Molecular Biology ,Biochemistry - Abstract
In recent years, nutraceuticals have gained great popularity, owing to their physiological and potential health effects, such as anti-inflammatory, anti-cancer, antioxidant, and prebiotic effects, and their regulation of lipid metabolism. Since the Mediterranean diet is a nutritionally recommended dietary pattern including high-level consumption of nutraceuticals, this review aimed to summarize the main results obtained by our in vitro and in vivo studies on the effects of the major constituents of the Mediterranean diet (i.e., extra virgin olive oil compounds, polyunsaturated fatty acids, and fruit components). Based on experimental studies, the therapeutic purpose of nutraceuticals depends on their bioavailability, solubility, toxicity, and delivery system. This review provides more in-depth knowledge on the effects linked to nutraceuticals administration on human health, focusing the gastrointestinal tract and suggesting specific dietary components for personalized adjuvant therapies.
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- 2022
7. Menopause Does Not Affect Fatty Liver Severity In Women: A Population Study in a Mediterranean Area
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Nicola Veronese, Gioacchino Leandro, Valeria Tutino, Ornella Rotolo, Maria Notarnicola, Marisa Chiloiro, Giovanni Misciagna, Rosa Reddavide, Alberto Rubén Osella, Mario Correale, Iris Zinzi, Vito Guerra, Anna Maria Cisternino, Rosa Inguaggiato, Caterina Bonfiglio, and Maria Gabriella Caruso
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Adult ,medicine.medical_specialty ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,Physiology ,030204 cardiovascular system & hematology ,Affect (psychology) ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Severity of illness ,Epidemiology ,Prevalence ,Humans ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Adiposity ,Aged ,business.industry ,Fatty liver ,Middle Aged ,Prognosis ,medicine.disease ,Postmenopause ,Menopause ,Cross-Sectional Studies ,Italy ,Liver ,Premenopause ,Population study ,Female ,Metabolic syndrome ,business ,Fatty Liver, Alcoholic - Abstract
Background and objective Estrogens could protect the liver from fatty degeneration, but there is little information about whether menopause is associated with the severity of alcoholic (AFL) and non-alcoholic fatty liver (NAFL). Our aim was to evaluate the distribution of fatty liver detected by ultrasound in pre- and post-menopausal women and the factors associated with these conditions. Methods In this cross-sectional study, the years from menopause were investigated through selfreported information. The degree of fatty liver was assessed through a standardized ultrasound examination (scores 0 to 6, higher values reflecting a greater severity). Liver steatosis was classified as NAFL or AFL based on a daily alcohol intake > 20g/d. Results The study included 752 women in menopause and 535 in pre-menopause. The years from menopause were not associated with the severity of liver steatosis in NAFL (p for trend=0.74; Spearman correlation=0.04; 95%CI: -0.09 to 0.17), whereas all the indexes of adiposity and the number of metabolic syndrome factors were associated with a higher liver steatosis score. Taking AFL liver steatosis as the outcome, the years since menopause were not significantly associated with liver steatosis in AFL (p for trend=0.50; Spearman correlation=0.09; 95%CI: -0.17 to 0.34), whilst the association between anthropometric parameters and liver steatosis severity resulted stronger in postmenopausal compared to pre- menopausal women. Conclusion the higher prevalence of fatty liver observed in post-menopausal women is probably not due to menopause per se, but to the adiposity (particularly abdominal) typical of this age and its consequences (such as metabolic syndrome).
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- 2018
8. Impact of Fresh Table Grape Intake on Circulating microRNAs Levels in Healthy Subjects: A Significant Modulation of Gastrointestinal Cancer‐Related Pathways
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Maria Notarnicola, Anna Maria Cisternino, Rosa Anna Milella, Isabella Gigante, Tamara Lippolis, Valentina De Nunzio, Marica Gasparro, Elsa Lanzilotta, Valeria Tutino, Palma Aurelia Iacovazzi, Maria Gabriella Caruso, and Antonio Lippolis
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business.industry ,Dietary intake ,Table grape ,Healthy subjects ,food and beverages ,Physiology ,medicine.disease ,Healthy Volunteers ,law.invention ,MicroRNAs ,Circulating MicroRNA ,Real-time polymerase chain reaction ,Nutrigenomics ,Randomized controlled trial ,law ,Humans ,Medicine ,Vitis ,Gastrointestinal cancer ,business ,Gastrointestinal Neoplasms ,Food Science ,Biotechnology - Abstract
SCOPE The study aims to investigate the effects of fresh table grape consumption in healthy subjects on circulating levels of the most common human microRNAs (miRNAs). The regulatory network governed by these modulated miRNAs is also investigated. METHODS AND RESULTS Autumn Royal table grape, used in this study, is chosen for its high polyphenolic content and antioxidant properties. The study is a randomized controlled trial, in which 40 consecutive subjects are recruited on a voluntary basis and randomly assigned to two groups of the study, the control group, receiving only dietary recommendations and a grape group receiving a daily dose of 5 g of fresh table grape per kg of body weight for 21 days. All analyses are performed at baseline and after 21 days of dietary treatment. Circulating miRNAs levels are detected by Real-Time quantitative PCR (RT-qPCR) followed by bioinformatic functional analysis. The study identifies 20 circulating miRNAs differentially expressed in healthy subjects after grape intake, and in particular, 18 of 20 are down-regulated and 2 are up-regulated. CONCLUSION The dietary intake of table grape affects circulating miRNAs levels in healthy subjects, particularly the miRNAs related to pathways involved in counteracting cancer development, including gastrointestinal cancers.
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- 2021
9. Nonalcoholic Fatty Liver Disease: Focus on New Biomarkers and Lifestyle Interventions
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Maria Grazia Refolo, Maria Gabriella Caruso, Maria Notarnicola, Caterina Bonfiglio, Pasqua Letizia Pesole, Caterina Messa, Valentina De Nunzio, Alberto Rubén Osella, Rosalba D'Alessandro, Tamara Lippolis, Antonella Mirizzi, Isabella Franco, Antonio Lippolis, Valeria Tutino, and Maria Principia Scavo
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0301 basic medicine ,Health Behavior ,physical activity ,Review ,Bioinformatics ,medicine.disease_cause ,lcsh:Chemistry ,Pathogenesis ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,lipid metabolism ,Nonalcoholic fatty liver disease ,lcsh:QH301-705.5 ,Spectroscopy ,Liver injury ,Microbiota ,Disease Management ,General Medicine ,Lipids ,Computer Science Applications ,Cytokines ,030211 gastroenterology & hepatology ,Disease Susceptibility ,exosomes ,Carbohydrate metabolism ,fatty acids ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,NAFLD ,Mediterranean diet ,medicine ,Animals ,Humans ,Epigenetics ,Physical and Theoretical Chemistry ,Exercise ,Life Style ,Molecular Biology ,business.industry ,Organic Chemistry ,cytokeratins ,nutritional and metabolic diseases ,Lipid metabolism ,medicine.disease ,digestive system diseases ,Diet ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Lipidomics ,Hepatocytes ,Metabolic syndrome ,business ,Biomarkers ,Oxidative stress - Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, characterized from pathological changes in lipid and carbohydrate metabolism. Its main characteristics are excessive lipid accumulation and oxidative stress, which create a lipotoxic environment in hepatocytes leading to liver injury. Recently, many studies have focused on the identification of the genetic and epigenetic modifications that also contribute to NAFLD pathogenesis and their prognostic implications. The present review is aimed to discuss on cellular and metabolic alterations associated with NAFLD, which can be helpful to identify new noninvasive biomarkers. The identification of accumulated lipids in the cell membranes, as well as circulating cytokeratins and exosomes, provides new insights in understanding of NAFLD. This review also suggests that lifestyle modifications remain the main prevention and/or treatment for NAFLD.
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- 2021
10. Dietary olive oil induces cannabinoid CB2 receptor expression in adipose tissue of ApcMin/+ transgenic mice
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Maria Gabriella Caruso, Maria Notarnicola, Emilia Guglielmi, Angela Tafaro, Valeria Tutino, and Giusy Bianco
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Research Report ,0301 basic medicine ,medicine.medical_specialty ,food.ingredient ,Cannabinoid receptor ,medicine.medical_treatment ,Medicine (miscellaneous) ,Adipose tissue ,polyunsatured fatty acids ,Inflammation ,030204 cardiovascular system & hematology ,Biology ,Biochemistry ,Soybean oil ,03 medical and health sciences ,0302 clinical medicine ,food ,Internal medicine ,medicine ,Cannabinoid receptor type 2 ,Receptor ,chemistry.chemical_classification ,Nutrition and Dietetics ,cannabinoid receptor ,adipose tissue ,030104 developmental biology ,Endocrinology ,chemistry ,inflammation ,Cannabinoid ,medicine.symptom ,Olive oil ,Food Science ,Polyunsaturated fatty acid - Abstract
BACKGROUND: Cannabinoid- 2 (CB2) receptor is known for its anti-obesity effects silencing the activated immune cells that are key drivers of metabolic syndrome and inflammation. Nutritional interventions in experimental models of carcinogenesis have been demonstrated to modulate tissue inflammation state and proliferation. OBJECTIVE: Aim of this study was to test, in ApcMin/+ mice, whether a diet enriched with olive oil, omega- 3 and omega-6- PUFAs affects the adipose tissue inflammation status. METHODS: Four groups of animal were studied: ST group, receiving a standard diet; OO group, receiving the standard diet in which soybean oil (source of fats) was replaced with olive oil; OM-3 group, receiving the standard diet in which soybean oil was replaced with salmon oil; OM-6 group, receiving the standard diet in which soybean oil was replaced with oenothera oil. Gene and protein expression, in adipose tissue, were evaluated by RT-PCR and Western Blotting, respectively. Enzymatic activities were assayed by fluorescent and radiometric method, where appropriated. RESULTS: The diet enriched with olive oil significantly induced CB2 receptor expression and it was able to control inflammatory and proliferative activity of mice adipose tissue. CONCLUSIONS: The present findings open opportunities for developing novel nutritional strategies considering olive oil a key ingredient of a healthy dietary pattern.
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- 2016
11. Women in LOVe: Lacto-Ovo-Vegetarian Diet Rich in Omega-3 Improves Vasomotor Symptoms in Postmenopausal Women. An Exploratory Randomized Controlled Trial
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Palma Aurelia Iacovazzi, Raffaella Licinio, Nicola Veronese, Rossella Donghia, Sara Giannico, Tiziana Daddabbo, Giampiero De Leonardis, Vito Guerra, Rosa Inguaggiato, Rosa Reddavide, Maria Notarnicola, Iris Zinzi, Anna Maria Cisternino, Nicola Giampaolo, Gioacchino Leandro, Valentina De Nunzio, Valeria Tutino, Fabio Fucilli, Ornella Rotolo, Anna Mastrosimini, Maria Gabriella Caruso, Caterina Mammone Rinaldi, Rotolo, O., Zinzi, I., Veronese, N., Cisternino, A.M., Reddavide, R., Inguaggiato, R., Leandro, G., Notarnicola, M., Tutino, V., De Nunzio, V., De Leonardis, G., Guerra, V., Donghia, R., Fucilli, F., Licinio, R., Mastrosimini, A., Rinaldi, C.C.M., Daddabbo, T., Giampaolo, N., Iacovazzi, P.A., Giannico, S., and Caruso, M.G.
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0301 basic medicine ,medicine.medical_specialty ,Time Factors ,Endocrinology, Diabetes and Metabolism ,Sweating ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Primary outcome ,Randomized controlled trial ,law ,Internal medicine ,Fatty Acids, Omega-6 ,medicine ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,030109 nutrition & dietetics ,Postmenopausal women ,Vasomotor ,business.industry ,Diet, Vegetarian ,Anthropometry ,Middle Aged ,medicine.disease ,Menopause ,Postmenopause ,Vasomotor System ,Treatment Outcome ,Italy ,Hot Flashes ,Observational study ,Female ,Diet, menopause, omega 3, lacto-ovo-vegetarian, RCT, Kupperman index ,business ,Nutritive Value ,Biomarkers ,Olive oil ,Vegetarians - Abstract
Objective:In the postmenopausal period, most women suffer vasomotor symptoms (VMS). It is well-known that VMS can worsen the quality of life. Diet seems to play a relevant role in the development of VMS, but the effect of diet on VMS is mainly limited to observational studies, and analyses of nutritional supplements. The aim of this study was thus to determine the efficacy of a lactoovo- vegetarian (LOVe) diet rich in omega-3 fatty acids vs. a lacto-ovo-vegetarian diet rich in EVO (extra-virgin olive oil) in reducing VMS frequency in postmenopausal women.Methods:A two-arms (lacto-ovo-vegetarian diet with EVO vs. lacto-ovo-vegetarian diet rich in omega-3) randomized-controlled trial with a follow-up period of 16 weeks. We considered as primary outcome the change in the Kupperman index (follow-up vs. baseline evaluation, reported as delta, D) and in its subscales. Secondary outcomes included changes in common anthropometric and biohumoral measurements.Results:Among 54 women randomly assigned to a study group, 40 (mean age 55.1±5.4 years) completed the study and complied with their assigned diet. Women randomized to the omega-3 group (n=18) showed significant improvements, compared to the EVO group (n=22), in Kupperman index (Δ=-11.4±9.8 vs. -5.9±8.2; p=0.045), hot flashes (Δ=-3.3±3.4 vs. -1.3±2.6; p=0.04), and a marginally significant improvement in nervousness (Δ=-1.7±1.7 vs. -0.8±1.5; p=0.07). No significant differences were observed for the secondary outcomes. No relevant side effects were reported.Conclusion:After 16 weeks, a lacto-ovo-vegetarian diet rich in omega-3 reduced VMS frequency in postmenopausal women more than the lacto-ovo-vegetarian diet rich in EVO.
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- 2019
12. Cannabinoid Receptors Overexpression in a Rat Model of Irritable Bowel Syndrome (IBS) after Treatment with a Ketogenic Diet
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Raffaele Armentano, Sergio Coletta, Maria Gabriella Caruso, Valeria Tutino, Maria Notarnicola, Antonella Orlando, Francesco Russo, Alberto Maria Crovace, Isabella Gigante, and Valentina De Nunzio
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0301 basic medicine ,Cannabinoid receptor ,medicine.medical_treatment ,Receptor, Cannabinoid, CB2 ,lcsh:Chemistry ,0302 clinical medicine ,Receptor, Cannabinoid, CB1 ,Cannabinoid receptor type 2 ,Intestinal Mucosa ,Receptors, Cannabinoid ,Receptor ,lcsh:QH301-705.5 ,Spectroscopy ,Irritable bowel syndrome ,biology ,General Medicine ,Endocannabinoid system ,Computer Science Applications ,ketogenic diet ,Diet, Ketogenic ,medicine.medical_specialty ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,cannabinoid receptors ,Internal medicine ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,irritable bowel syndrome ,Cannabinoids ,business.industry ,rat model ,Organic Chemistry ,Glucose transporter ,medicine.disease ,Rats ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,lcsh:Biology (General) ,lcsh:QD1-999 ,biology.protein ,GLUT1 ,business ,030217 neurology & neurosurgery ,Endocannabinoids ,Ketogenic diet - Abstract
The administration of a ketogenic diet (KD) has been considered therapeutic in subjects with irritable bowel syndrome (IBS). This study aimed to investigate the molecular mechanisms by which a low-carbohydrate diet, such as KD, can improve gastrointestinal symptoms and functions in an animal model of IBS by evaluating possible changes in intestinal tissue expression of endocannabinoid receptors. In rats fed a KD, we detected a significant restoration of cell damage to the intestinal crypt base, a histological feature of IBS condition, and upregulation of CB1 and CB2 receptors. The diet also affected glucose metabolism and intestinal membrane permeability, with an overexpression of the glucose transporter GLUT1 and tight junction proteins in treated rats. The present data suggest that CB receptors represent one of the molecular pathways through which the KD works and support possible cannabinoid-mediated protection at the intestinal level in the IBS rats after dietary treatment.
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- 2021
13. Lovastatin, but not orlistat, reduces intestinal polyp volume in an ApcMin/+ mouse model
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Maria Notarnicola, Valeria Tutino, Maria Principia Scavo, Antonio Francavilla, Giusy Bianco, Lorenzo Polimeno, Mario Minoia, Anna Napoli, Maria Gabriella Caruso, Michele Barone, and Angela Tafaro
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Intestinal polyp ,Gene Expression ,Cell Cycle Proteins ,Biology ,Zinc Finger Protein GLI1 ,Lactones ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Fatty Acids, Omega-3 ,medicine ,Animals ,Estrogen Receptor beta ,Hedgehog Proteins ,Lovastatin ,Olive Oil ,Fatty acid synthesis ,Cell Proliferation ,Orlistat ,chemistry.chemical_classification ,Cholesterol ,Estrogen Receptor alpha ,Intestinal Polyps ,Proteins ,RNA-Binding Proteins ,General Medicine ,Disease Models, Animal ,Fatty acid synthase ,030104 developmental biology ,Endocrinology ,Oncology ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,biology.protein ,Fatty Acid Synthases ,medicine.drug ,Polyunsaturated fatty acid - Abstract
The statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and orlistat, an inhibitor of fatty acid synthase (FAS), inhibit tumor cell growth by restricting cholesterol and fatty acid synthesis, respectively. We previously demonstrated that an omega (ω)-3 polyunsaturated fatty acid (PUFA)- or olive oil-enriched diet reduced the polyp number and volume in ApcMin/+ mice. This phenomenon was associated with a significant inhibition of FAS and HMGCoAR, as well as an increase in the estrogen receptor (ER)β/α ratio. Herein, we evaluated the effect of lovastatin and orlistat on polyp development and ER expression in ApcMin/+ mice, in order to confirm previous data obtained with ω‑3-PUFAs and olive oil. As expected, the use of lovastatin and orlistat significantly reduced HMGCoAR and FAS enzymatic activities and gene expression in colonic tissues, but did not affect the number of intestinal polyps, while there was a statistically significant reduction in polyp volume only in the mouse group treated with lovastatin. In the mice receiving orlistat, we observed a significant increase in cell proliferation in the polyp tissue, as well as enhanced expression of ERα. Moreover, the overexpression of ERα was associated with a statistically significant increase in PES1, Shh and Gli1 protein levels, considered ERα-related molecular targets.
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- 2016
14. n-3 polyunsaturated fatty acids reverse the development of polyps in ApcMin/+ transgenic mice
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Maria Notarnicola, Valeria Tutino, Antonio Francavilla, and Maria Gabriella Caruso
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Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Adenomatous Polyposis Coli Protein ,Colonic Polyps ,Estrogen receptor ,Mice, Transgenic ,Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Internal medicine ,Fatty Acids, Omega-3 ,medicine ,Animals ,Estrogen Receptor beta ,Estrogen receptor beta ,Cell Proliferation ,chemistry.chemical_classification ,Cell growth ,General Medicine ,Fatty acid synthase ,Treatment Outcome ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Receptors, LDL ,Oncology ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,LDL receptor ,Cancer research ,biology.protein ,Polyunsaturated fatty acid - Abstract
Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) have been demonstrated to reduce tumor load in Apc(Min/+) mice, supporting a role for n-3 PUFAs in the inhibition of colon carcinogenesis and progression. The aim of the present study was to investigate whether a diet enriched with n-3 PUFAs, known already to have anti-neoplastic efficacy in Apc(Min/+) mice, would reverse the development of intestinal polyps. For this purpose, Apc(Min/+) mice were randomly divided into 3 groups of 5 animal each and fed as follows: control ST1 and ST2 groups, received a purified AIN-93M standard diet for 5 and 10 weeks, respectively; the OM-3R group received a purified AIN-93M standard diet for 5 weeks and a diet supplemented with salmon oil, rich in n-3 PUFAs, for another 5 weeks. After dietary treatment, in intestinal tissue, we evaluated the polyp number and volume, expression levels of cell proliferation- and apoptosis-related proteins, as well as the protein expression of LDL receptor and the levels of fatty acid synthase (FAS) activity. The results showed the ability of a diet enriched with n-3 PUFAs to suppress intestinal polyps in Apc(Min/+) mice, and to significantly reverse polyp development associated with the downregulation of cell proliferation markers and with the induction of estrogen receptor β and LDL receptor, which are negative modulators of cellular proliferation. This noteworthy finding is important for a translational study evaluating the therapeutic role of n-3 PUFAs in the prevention and treatment of subjects with gastrointestinal diseases.
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- 2015
15. Hydroxytyrosol Inhibits Cannabinoid CB1 Receptor Gene Expression in 3T3-L1 Preadipocyte Cell Line
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Valeria Tutino, Maria Notarnicola, Antonella Orlando, and Francesco Paolo Russo
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0301 basic medicine ,medicine.medical_specialty ,Cannabinoid receptor ,Physiology ,Cell growth ,Cellular differentiation ,medicine.medical_treatment ,Clinical Biochemistry ,3T3-L1 ,Cell Biology ,Biology ,Endocannabinoid system ,03 medical and health sciences ,030104 developmental biology ,Endocrinology ,Internal medicine ,Gene expression ,medicine ,lipids (amino acids, peptides, and proteins) ,Cannabinoid ,Receptor - Abstract
The 3T3-L1 preadipocyte cell line is a well characterized cell model for studying the adipocyte status and the molecular mechanisms involved in differentiation of these cells. 3T3-L1 preadipocytes have the ability to synthesize and degrade endocannabinoid anandamide (AEA) and their differentiation into adipocytes increases the expression of cannabinoid (CB1) and PPAR-γ receptors. Clinically, the blocking stimulation of the endocannabinoid pathway has been one of the first approaches proposed to counteract the obesity and obesity-associated diseases (such as diabetes, metabolic syndrome and cancer). In this connection, here we studied in cultured 3T3-L1 pre-adipocytes the effects of n-3-PUFA, α-Linolenic acid (OM-3), n-6-PUFA, Linoleic acid (OM-6), and hydroxytyrosol (HT) on the expression of CB1 receptor gene and the adipogenesis-related genes PPAR-γ, Fatty Acid Synthase (FAS) and Lipoprotein Lipase (LPL). HT was able to inhibit 3T3-L1 cell differentiation by down-regulating cell proliferation and CB1 receptor gene expression. HT exhibited anti-adipogenic effects, whereas OM-3 and OM-6 exerted an inhibitory action on cell proliferation associated with an induction of the preadipocytes differentiation and CB1 receptor gene expression. Moreover, the expression of FAS and LPL genes resulted increased after treatment with both HT and OM-3 and OM-6. The present study points out that the intake of molecules such as HT, contained in extra virgin olive oil, may be considered also in view of antiobesity and antineoplastic properties by acting directly on the adipose tissue and modulating CB1 receptor gene transcription. J. Cell. Physiol. 231: 483-489, 2016. © 2015 Wiley Periodicals, Inc.
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- 2015
16. Colorectal Cancer and Bone Tissue: Fantastic Relations and Where to Find Them
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Isabella Gigante, Valentina De Nunzio, Maria Notarnicola, and Valeria Tutino
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,bone tissue ,colorectal cancer ,Context (language use) ,Review ,Disease ,Bone tissue ,lcsh:RC254-282 ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,growth factors ,medicine ,metastases ,neoplasms ,Future perspective ,business.industry ,Bone markers ,Cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,digestive system diseases ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,business - Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. There is a need for the early diagnosis of CRC for a better prognostic outcome. It is, therefore, crucial to understand the CRC pathogenesis in all its aspects. In many cases, one of the main causes of cancer-related deaths is the presence of metastases. In this context, an often overlooked aspect is the metastatic tropism, since CRC, like other cancers, is more prone to metastasize some organs rather than others. Beyond the liver and lung, and differently from other types of cancers, a not usual site of CRC metastases is the bone. However, it may assume a crucial role in the development and the outcome of the disease. Therefore, this review aims to discuss the complex relations between bone markers and CRC pathogenesis, suggesting the use of these molecules as potential targets for therapeutic purposes. Different osteogenic molecules, some of whom are growth factors and are implicated in the different osteogenic pathways, have been proved to also be involved in CRC progression. Some of them are oncogenes, while others oncosuppressors, and in a future perspective, some of them may represent new potential CRC biomarkers.
- Published
- 2020
17. Improved Symptom Profiles and Minimal Inflammation in IBS-D Patients Undergoing a Long-Term Low-FODMAP Diet: A Lipidomic Perspective
- Author
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Manuela Martulli, Benedetta D'Attoma, Antonella Orlando, Maria Notarnicola, Francesco Russo, Michele Linsalata, Laura Prospero, Valentina De Nunzio, Valeria Tutino, Caterina Clemente, and Giuseppe Riezzo
- Subjects
Male ,Polymers ,Oligosaccharides ,Disaccharides ,Gastroenterology ,Irritable Bowel Syndrome ,Diet, Carbohydrate-Restricted ,chemistry.chemical_compound ,0302 clinical medicine ,Prostaglandin E2 ,Irritable bowel syndrome ,chemistry.chemical_classification ,Arachidonic Acid ,Nutrition and Dietetics ,Monosaccharides ,food and beverages ,Middle Aged ,Eicosapentaenoic acid ,Pathophysiology ,C-Reactive Protein ,Treatment Outcome ,Eicosapentaenoic Acid ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Arachidonic acid ,dietetics ,Inflammation Mediators ,medicine.symptom ,lcsh:Nutrition. Foods and food supply ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,lcsh:TX341-641 ,Inflammation ,Context (language use) ,fatty acids ,Dinoprostone ,Article ,Young Adult ,03 medical and health sciences ,lipidomic analysis ,Internal medicine ,medicine ,Humans ,FODMAPs ,Aged ,symptom assessment ,business.industry ,Erythrocyte Membrane ,Fatty acid ,red blood cell membranes ,medicine.disease ,chemistry ,Cyclooxygenase 2 ,inflammation ,Fermentation ,business ,Food Science - Abstract
Given the link between the minimal inflammation underlying irritable bowel syndrome (IBS) and dietary treatments, considerable attention has focused on diets low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs). In this context, inflammatory patterns and lipidomic investigations may shed light on the pathophysiological mechanisms whereby a low-FODMAP diet (LFD) improves the IBS diarrhoea (IBS-D) variant. Thus, we investigated whether a long-term LFD induced changes in symptom profiles, anthropometric characteristics, inflammatory markers (C-reactive protein, cyclooxygenase-2, and prostaglandin E2) and erythrocyte-membrane fatty acid (FA) composition in IBS-D patients. Twenty IBS-D patients underwent a 90 day personalised LFD programme, and were regularly evaluated at scheduled visits. At the diet&rsquo, s end, both IBS symptoms and anthropometric parameters were significantly improved. A significant decrease in prostaglandin E2 also accompanied these reductions. As for FAs, the putative inflammatory indicators, arachidonic acid (AA) levels and the AA/eicosapentaenoic acid ratio were significantly decreased. In conclusion, IBS-D patients following a controlled long-term LFD experienced improved symptom profiles and decreased inflammatory markers linked to FAs. Lipidomic data may be insightful for unravelling the molecular mechanisms associated with IBS-D pathophysiology.
- Published
- 2020
18. Effects of Some Food Components on Non-Alcoholic Fatty Liver Disease Severity: Results from a Cross-Sectional Study
- Author
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Paolo Sorino, Raffaele Cozzolongo, Isabella Franco, Filippo Procino, Valentina Deflorio, Valeria Tutino, Irene Bruno, Vito Giannuzzi, Maria Notarnicola, Claudia Buongiorno, Valentina De Nunzio, Caterina Bonfiglio, Antonella Mirizzi, Angelo Campanella, Annamaria Pascale, Alberto Rubén Osella, and Carla Maria Leone
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Mediterranean diet ,Cross-sectional study ,Disease ,Overweight ,Diet, Mediterranean ,Logistic regression ,Risk Assessment ,Severity of Illness Index ,Article ,03 medical and health sciences ,0302 clinical medicine ,NAFLD severity ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Internal medicine ,medicine ,Humans ,Randomized Controlled Trials as Topic ,foods groups components ,Nutrition and Dietetics ,business.industry ,Fatty liver ,Food Frequency Questionnaire ,Fabaceae ,Middle Aged ,Protective Factors ,medicine.disease ,Obesity ,Diet ,Cross-Sectional Studies ,030104 developmental biology ,Italy ,Female ,030211 gastroenterology & hepatology ,Diet, Healthy ,medicine.symptom ,business ,Nutritive Value ,Risk Reduction Behavior ,Weight gain ,Food Science - Abstract
Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) observed in Western countries is due to the concurrent epidemics of overweight/obesity and associated metabolic complications, both recognized risk factors. A Western dietary pattern has been associated with weight gain and obesity, and more recently with NAFLD. Methods: This is a baseline cross-sectional analysis of 136 subjects (79 males) enrolled consecutively in the NUTRIATT (NUTRItion and Ac-TiviTy) study. Study subjects had moderate or severe NAFLD diagnosed by using Fibroscan-CAP. Food Frequency Questionnaire was used to obtain information about food intake. Statistical analysis included descriptive statistics and a multivariable logistic regression model. Results: The mean age was 49.58 (±, 10.18) with a mean BMI of 33.41 (±, 4.74). A significant inverse relationship was revealed between winter ice-cream intake and NAFLD severity (O.R. 0.65, 95% C.I. 0.95&ndash, 0.99), chickpeas intake and NAFLD severity (O.R. 0.57, 95% C.I. 0.34&ndash, 0.97), and not industrial aged-cheeses type (O.R. 0.85, 95% C.I. 0.74&ndash, 0.98). A statistically significant positive association also emerged between rabbit meat (O.R. 1.23, 95% C.I. 1.01&ndash, 1.49), industrial type aged cheeses (O.R. 1.17, 95% C.I. 1.01&ndash, 1.35), milk-based desserts (no winter ice cream) (O.R. 1.11, 95% C.I. 1.01&ndash, 1.21), fats (O.R. 1.12, 95% C.I. 1.01&ndash, 1.25), and NAFLD severity. Conclusion: The fresh foods from non-intensive farming and high legume intake that characterize the Mediterranean diet would seem to be beneficial for patients with NAFLD.
- Published
- 2019
19. Cannabinoid Receptor-1 Up-regulation in Azoxymethane (AOM)-treated Mice After Dietary Treatment with Quercetin
- Author
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Valeria Tutino, Rosalba D'Alessandro, Valentina De Nunzio, Maria Gabriella Caruso, Caterina Messa, Maria Notarnicola, Maria Grazia Refolo, Angela Tafaro, Maria Principia Scavo, Isabella Gigante, and Giusy Bianco
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Carcinogenesis ,medicine.medical_treatment ,Flavonoid ,Azoxymethane ,Gene Expression ,Apoptosis ,Pharmacology ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Downregulation and upregulation ,Receptor, Cannabinoid, CB1 ,Gene expression ,medicine ,Animals ,heterocyclic compounds ,STAT3 ,Cell Proliferation ,bcl-2-Associated X Protein ,chemistry.chemical_classification ,Flavonoids ,biology ,Chemistry ,Cell growth ,General Medicine ,Diet ,Up-Regulation ,Mice, Inbred C57BL ,030104 developmental biology ,Oncology ,Proto-Oncogene Proteins c-bcl-2 ,Colonic Neoplasms ,Dietary Supplements ,biology.protein ,Quercetin ,Cannabinoid - Abstract
Background/aim The expression of cannabinoid receptor-1 (CB1-R) seems to be modulated by bioactive natural components such as the flavonoid quercetin. The aim of this study was to determine in an animal model of induced-colon cancer, whether quercetin inhibits colon carcinogenesis through changes in the expression of CB1-R. Materials and methods C57BL/6J male mice were randomly assigned to standard diet or experimental diet supplemented with 0.5% quercetin. Azoxymethane (AOM) (10 mg/kg body weight) or saline solution (PBS) was intraperitoneally injected, once weekly for 6 weeks. Results The diet supplemented with quercetin induced CB1-R gene expression and protein, inhibiting the protein levels of STAT3 and p-STAT3 (both mediators of cell proliferation). Dietary quercetin also caused a significant increase in Bax/Bcl2 ratio protein expression. Conclusion The anti-proliferative and pro-apoptotic effects of quercetin in AOM-treated mice are mediated by induction of the protein and gene expression levels of CB1-R.
- Published
- 2018
20. The Expression of Riboflavin Transporters in Human Colorectal Cancer
- Author
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Marianna Loredana Defrancesco, Dionigi Lorusso, Valeria Tutino, Maria Barile, Didier Paleni, Maria Gabriella Caruso, Valentina De Nunzio, Maria Tolomeo, and Maria Notarnicola
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Riboflavin ,Flavin group ,Adenocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Gene expression ,Humans ,RNA, Messenger ,RNA, Neoplasm ,Intestinal Mucosa ,Epithelial polarity ,Aged ,Chemistry ,Cell Membrane ,Membrane Transport Proteins ,Cell Differentiation ,General Medicine ,Apical membrane ,Middle Aged ,Molecular biology ,Neoplasm Proteins ,Blot ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Enterocytes ,Oncology ,Riboflavin transport ,Cell culture ,030220 oncology & carcinogenesis ,Female ,Colorectal Neoplasms - Abstract
BACKGROUND/AIM Riboflavin transport in enterocytes is mediated by three translocators: RFVT3 located on the apical membrane, and RFVT1 and RFVT2 on the basolateral membrane. The aim of this study was to investigate whether the expression levels of RFVTs are altered in human colorectal cancer (CRC). MATERIALS AND METHODS In human colon adenocarcinoma cell lines (CaCo2, DLD-1, HT-29) and in tissues of patients with CRC, gene and protein expression levels were evaluated by real time-polymerase chain reaction and western blotting. Intracellular flavin content was determined by high-performance liquid chromatography. RESULTS RFVT3 and RFVT2 gene and protein expression levels were higher in DLD-1 and HT-29 compared to Caco2 cells. In HT-29 cells, the RFVT1 protein level was drastically lower. These differences are presumably responsible for the higher total flavin content in DLD-1 and HT-29 cells. In tumor tissues of patients with CRC, RFVT1 content was reduced at both protein and mRNA levels compared to normal mucosa. RFVT3 and RFVT2 gene expression levels were increased, while protein expression was reduced, with a small reduction in riboflavin amount. CONCLUSION This study provides first evidence that transcription/translation of RFVTs are profoundly altered in CRC.
- Published
- 2018
21. Tissue Fatty Acid Profile is Differently Modulated from Olive Oil and Omega-3 Polyunsaturated Fatty Acids in ApcMin/+ Mice
- Author
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Giampiero De Leonardis, Valeria Tutino, Valentina De Nunzio, Maria Gabriella Caruso, and Maria Notarnicola
- Subjects
0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,Adipose tissue ,Mice, Transgenic ,Apcmin mice ,Fatty Acids, Monounsaturated ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Fatty Acids, Omega-3 ,medicine ,Animals ,Immunology and Allergy ,Food science ,Intestinal Mucosa ,Olive Oil ,chemistry.chemical_classification ,Fatty acid metabolism ,medicine.diagnostic_test ,Fatty acid ,Intestines ,Oleic acid ,030104 developmental biology ,Adipose Tissue ,chemistry ,Biochemistry ,Fatty Acids, Unsaturated ,lipids (amino acids, peptides, and proteins) ,Lipid profile ,Olive oil ,Polyunsaturated fatty acid - Abstract
Background Fatty acid profile can be considered an appropriate biomarker for investigating the relations between the patterns of fatty acid metabolism and specific diseases, as cancer, cardiovascular and degenerative diseases. Objective Aim of this study was to test the effects of diets enriched with olive oil and omega-3 Polyunsaturated Fatty Acids (PUFAs) on fatty acid profile in intestinal tissue of ApcMin/+ mice. Method Three groups of animals were considered: control group, receiving a standard diet; olive oilgroup, receiving a standard diet enriched with olive oil; omega-3 group, receiving a standard diet enriched with salmon fish. Tissue fatty acid profile was evaluated by gas chromatography method. Results Olive oil and omega-3 PUFAs in the diet differently affect the tissue fatty acid profile. Compared to control group, the levels of Saturated Fatty Acids (SFAs) were lower in olive oil group, while an increase of SFAs was found in omega-3 group. Monounsaturated Fatty Acids (MUFAs) levels were enhanced after olive oil treatment, and in particular, a significant increase of oleic acid levels was detected; MUFAs levels were instead reduced in omega-3 group in line with the decrease of oleic acid levels. The total PUFAs levels were lower in olive oil respect to control group. Moreover, a significant induction of Saturation Index (SI) levels was observed after omega-3 PUFAs treatment, while its levels were reduced in mice fed with olive oil. Conclusion Our data demonstrated a different effect of olive oil and omega-3 PUFAs on tissue lipid profile in APCMin/+ mice.
- Published
- 2017
22. Anti Proliferative and Pro Apoptotic Effects of Flavonoid Quercetin Are Mediated by CB1 Receptor in Human Colon Cancer Cell Lines
- Author
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Maria Notarnicola, Maurizio Bifulco, Maria Gabriella Caruso, Rosalba D'Alessandro, Valeria Tutino, Natascia Malerba, Caterina Messa, Maria Grazia Refolo, and Chiara Laezza
- Subjects
chemistry.chemical_classification ,Physiology ,Cell growth ,Clinical Biochemistry ,Flavonoid ,food and beverages ,Cell Biology ,Cell cycle ,Pharmacology ,Biology ,chemistry.chemical_compound ,chemistry ,lipids (amino acids, peptides, and proteins) ,heterocyclic compounds ,Signal transduction ,Quercetin ,Receptor ,Protein kinase B ,PI3K/AKT/mTOR pathway - Abstract
Quercetin, the major constituent of flavonoid and widely present in fruits and vegetables, is an attractive compound for cancer prevention due to its beneficial anti proliferative effects, showing a crucial role in the regulation of apoptosis and cell cycle signaling. In vitro studies have demonstrated that quercetin specifically influences colon cancer cell proliferation. Our experiments, using human colon adenocarcinoma cells, confirmed the anti proliferative effect of quercetin and gave intriguing new insight in to the knowledge of the mechanisms involved. We observed a significant increase in the expression of the endocannabinoids receptor (CB1-R) after quercetin treatment. CB1-R can be considered an estrogen responsive receptor and quercetin, having a structure similar to that of the estrogens, can interact with CB1-R leading to the regulation of cell growth. In order to clarify the contribution of the CB1-R to the quercetin action, we investigated some of the principal molecular pathways that are inhibited or activated by this natural compound. In particular we detected the inhibition of the major survival signals like the PI3K/Akt/mTOR and an induction of the pro apoptotic JNK/JUN pathways. Interestingly, the metabolism of β-catenin was modified by flavonoid both directly and through activated CB1-R. In all the experiments done, the quercetin action has proven to be reinforced by anandamide (Met-F-AEA), a CB1-R agonist, and partially counteracted by SR141716, a CB1-R antagonist. These findings open new perspectives for anticancer therapeutic strategies.
- Published
- 2015
23. Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD)
- Author
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Vincenza Intini, Valentina De Nunzio, Caterina Bonfiglio, Daniela Isabel Abbrescia, Alberto Rubén Osella, Isabella Franco, Vito Giannuzzi, Raffaele Cozzolongo, Maria Gabriella Caruso, Valeria Tutino, Giampiero De Leonardis, Antonella Mirizzi, and Maria Notarnicola
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Chromatography, Gas ,Clinical chemistry ,Endocrinology, Diabetes and Metabolism ,Saturation index ,Clinical Biochemistry ,Vaccenic acid ,Biology ,Body Mass Index ,Fatty acids profile ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,NAFLD ,Azotemia ,medicine ,Palmitoleic acid ,Humans ,Insulin ,Triglycerides ,chemistry.chemical_classification ,Research ,Biochemistry (medical) ,Fatty liver ,Cholesterol, HDL ,Erythrocyte Membrane ,Fatty Acids ,Fatty acid ,Middle Aged ,medicine.disease ,Oleic acid ,Red blood cell ,medicine.anatomical_structure ,Lipidomic analysis ,chemistry ,Liver ,030220 oncology & carcinogenesis ,Ferritins ,030211 gastroenterology & hepatology ,Female ,Lipidology - Abstract
Background The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage. Methods This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD. Diagnosis of liver steatosis was performed by using vibration-controlled elastography implemented on FibroScan. Fatty acids, extracted from phospholipids of erythrocyte membranes, were quantified by gas chromatography method. Results The subjects with severe NAFLD showed a significant decrease of the ratio of stearic acid to oleic acid (saturation index, SI) compared to controls, 1.281 ± 0.31 vs 1.5 ± 0.29, respectively. Low levels of SI in red blood cell membranes, inversely associated with degree of liver damage, suggest that an impairment of circulating cell membrane structure can reflect modifications that take place in the liver. Subjects with severe NAFLDalso showed higher levels of elongase 5 enzymatic activity, evaluated as vaccenic acid to palmitoleic acid ratio. Conclusions Starting from these evidences, our findings show the importance of lipidomic approach in the diagnosis and the staging of NAFLD.
- Published
- 2017
24. Tumor-Induced Alterations in Lipid Metabolism
- Author
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Maria Notarnicola, Valeria Tutino, and Maria Gabriella Caruso
- Subjects
Cell ,Lipid Metabolism Disorders ,Biology ,medicine.disease_cause ,Biochemistry ,Dietary Fats, Unsaturated ,Neoplasms ,Drug Discovery ,medicine ,Animals ,Humans ,Plant Oils ,Olive Oil ,Cell Proliferation ,Pharmacology ,Cell growth ,Organic Chemistry ,Lipid metabolism ,Lipid Metabolism ,Cell biology ,Metabolic pathway ,medicine.anatomical_structure ,Lipogenesis ,Cancer cell ,Molecular Medicine ,Mevalonate pathway ,Carcinogenesis - Abstract
Alterations of lipid metabolism have been increasingly recognized as a hallmark of cancer cells. Cancer cells esterify fatty acids predominantly to phospholipids, an essential component of cell membranes. The main pathway along which proliferating cells gain lipids for membrane synthesis is the endogenous mevalonate pathway. Increased synthesis of mevalonate and mevalonate-derived isoprenoids supports increased cell proliferation through activating growth-regulatory proteins and oncoproteins and promoting DNA synthesis. The importance of a better knowledge of metabolic changes in lipogenic enzymes pathways, as well as of the role of each biochemical pathway in carcinogenesis, provides the rationale for in-depth study of the oncogenic signaling important for the initiation and progression of tumors. The dependence of tumor cells on a dysregulated lipid metabolism suggests that the proteins involved in this process may be excellent chemotherapeutic targets for cancer treatment. Here, we confirm the vital link between lipogenesis and cell proliferation, and our recent findings suggest that nutritional intervention is an effective and safe way to reduce cell proliferation in experimental models of carcinogenesis. The olive oil diet significantly reduces the protein activities of lipogenic enzymes associated with cell growth. The use of natural dietary components could potentially assist in the management of subjects with metabolic disorders-related tumors.
- Published
- 2014
25. Dietary ω-3 Polyunsaturated Fatty Acids Inhibit Tumor Growth in Transgenic Apc
- Author
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Maria, Notarnicola, Valeria, Tutino, Valentina, De Nunzio, Francesco, Dituri, Maria Gabriella, Caruso, and Gianluigi, Giannelli
- Subjects
CB1 receptor ,Genes, APC ,food and beverages ,Gene Expression ,Mice, Transgenic ,olive oil ,Animal Feed ,Xenograft Model Antitumor Assays ,Article ,Disease Models, Animal ,Mice ,ω-3 polyunsaturated fatty acids ,Receptor, Cannabinoid, CB1 ,colon cancer ,transgenic ApcMin/+ mice ,Neoplasms ,Fatty Acids, Omega-3 ,Animals ,Humans ,lipids (amino acids, peptides, and proteins) ,Intestinal Mucosa ,Colorectal Neoplasms - Abstract
Mediterranean diet components, such as olive oil and ω-3 polyunsaturated fatty acids (ω-3 PUFAs), can arrest cell growth and promote cell apoptosis. Recently, olive oil has been demonstrated to modulate type-1 cannabinoid (CB1) receptor gene expression in both human colon cancer cells and rat colon. The aim of this study was to investigate a possible link between olive oil and ω-3 PUFAs effects and CB1 receptor expression in both intestinal and adipose tissue of ApcMin/+ mice. To confirm the role for the CB1 receptor as a negative modulator of cell proliferation in human colon cancer, CB1 receptor gene expression was also detected in tumor tissue and in surrounding normal mucosa of patients with colorectal cancer (CRC). Dietary ω-3 PUFAs significantly inhibited intestinal polyp growth in mice, correlating with CB1 receptor gene and protein expression induction. CB1 receptor gene up-regulation was also detected in adipose tissue, suggesting a close communication between cancer cells and the surrounding environment. Tissue CB1 receptor induction was associated with a concurrent inactivation of the Wnt/β-catenin pathway. Moreover, there was a significant reduction in CB1 receptor gene expression levels in cancer tissue compared to normal surrounding mucosa of patients with CRC, confirming that in cancer the “protective” action of the CB1 receptor is lost.
- Published
- 2016
26. Fatty liver and mortality: a cohort population study in South Italy
- Author
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Marisa Chiloiro, Anna Maria Cisternino, Antonio Logroscino, Valeria Tutino, Alberto Rubén Osella, Giovanni Misciagna, Vito Guerra, Rocco Guerra, Ornella Rotolo, Rosa Inguaggiato, Maria Notarnicola, Nicola Veronese, Rossella Donghia, Gioacchino Leandro, Giampiero De Leonardis, Caterina Bonfiglio, Rosa Reddavide, Maria Gabriella Caruso, Caruso, M.G., Veronese, N., Notarnicola, M., Cisternino, A.M., Reddavide, R., Inguaggiato, R., Guerra, V., Donghia, R., Logroscino, A., Rotolo, O., Chiloiro, M., Leandro, G., De Leonardis, G., Tutino, V., Misciagna, G., Bonfiglio, C., Guerra, R., and Osella, A.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Epidemiology ,Population ,hepatobiliary disease ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Cause of Death ,Internal medicine ,Humans ,Medicine ,Prospective Studies ,Risk factor ,education ,general endocrinology ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Research ,Fatty liver ,Hepatobiliary disease ,General Medicine ,Middle Aged ,medicine.disease ,mortality ,Fatty Liver ,Survival Rate ,Italy ,Population Surveillance ,030220 oncology & carcinogenesis ,Cohort ,Population study ,Female ,030211 gastroenterology & hepatology ,Alcoholic fatty liver ,Steatosis ,business - Abstract
ObjectiveAlcoholic fatty liver (AFLD) and non-alcoholic fatty liver (NAFLD) are two common conditions. However, if they can increase the risk of death is poorly explored. We therefore aimed to investigate the potential association between the presence and severity of liver steatosis and mortality in a large sample of older people.DesignProspective.SettingCommunity.ParticipantsWomen and men randomly sampled from the electoral rolls of the population of Castellana Grotte, a town in Southern Italy (Apulia region) between 2005 and 2006. Among 1942 initially contacted, 1708 (=87.9%) participated to the baseline survey (Multicentrica Colelitiasi III (MICOL III)). This specific study included 1445 older participants (mean age=65.2 years, females=44.2%).ExposureNAFLD or AFLD.Primary and secondary outcomesMortality (all-cause and specific-cause).ResultsAfter a median of 12 years, 312 participants (=21.6%) died. After adjusting for nine potential confounders, the presence of steatosis was not associated with any increased risk of death in both NAFLD and AFLD. The severity of liver steatosis was not associated with any increased risk of mortality in NAFLD, while in AFLD, the presence of moderate steatosis significantly increased the risk of overall (HR=2.16; 95% CI 1.19 to 3.91) and cancer-specific (HR=3.54; 95% CI 1.16 to 10.87) death.ConclusionsLiver steatosis is not associated with any increased risk of death in NAFLD, while moderate steatosis could be a risk factor for mortality (particularly due to cancer) in people affected by AFLD.
- Published
- 2019
27. Low Levels of Lipogenic Enzymes in Peritumoral Adipose Tissue of Colorectal Cancer Patients
- Author
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Angelica Miccolis, Maria Notarnicola, Valeria Tutino, Maria Gabriella Caruso, and Dionigi Lorusso
- Subjects
Male ,medicine.medical_specialty ,Adipose tissue macrophages ,Adipose tissue ,Adenocarcinoma ,Intra-Abdominal Fat ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Body Mass Index ,Internal medicine ,Tumor Microenvironment ,medicine ,Humans ,Radiometry ,Aged ,Tumor microenvironment ,Lipoprotein lipase ,biology ,Tissue Extracts ,Catabolism ,Organic Chemistry ,Lipid metabolism ,Cell Biology ,Middle Aged ,Lipid Metabolism ,Fas receptor ,Fatty Acid Synthase, Type I ,Lipoprotein Lipase ,Fatty acid synthase ,Spectrometry, Fluorescence ,Endocrinology ,biology.protein ,Female ,lipids (amino acids, peptides, and proteins) ,Colorectal Neoplasms - Abstract
Lipoprotein lipase (LPL) is the crucial enzyme for intravascular catabolism of triglyceride-rich lipoproteins. Fatty acid synthase (FAS) is a key anabolic enzyme that catalyzes the terminal steps in the novo biosynthesis of 18:2n-6. The involvement of both LPL and FAS in tumor biology has been widely demonstrated in different studies and to verify whether there are regional differences in the expression of these enzymes in visceral adipose tissue from patients with colorectal cancer might be representative of events which sustain tumor growth. The objective of this study was to evaluate LPL and FAS activity and expression of their genes in adipose tissue adjacent to neoplasia and distant from it from patients operated for colorectal cancer. LPL enzymatic activity was evaluated by a fluorescent method and FAS activity by a radiometer assay. Reverse-transcription and real-time PCR were used to detect mRNA levels of two enzymes. Our findings show a significant reduction in both LPL and FAS gene expression and activity levels in adipose tissue adjacent to tumor lesion compared to those detected in paired tissue distant from neoplasia. These results underline the influence of tumor microenvironment on lipid metabolism in adipose tissue, demonstrating a tumor-induced impairment in the formation and lipid storing capacity of adipose tissue in patients with colorectal cancer.
- Published
- 2011
28. Serum Levels of Fatty Acid Synthase in Colorectal Cancer Patients Are Associated with Tumor Stage
- Author
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Maria Notarnicola, Valeria Tutino, Dionigi Lorusso, Vito Guerra, Maria Gabriella Caruso, and Menotti Calvani
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Colorectal cancer ,Enzyme-Linked Immunosorbent Assay ,Endometrium ,Gastroenterology ,Prostate ,Pancreatic cancer ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Stage (cooking) ,Neoplasm Staging ,Lung ,biology ,business.industry ,Stomach ,Middle Aged ,Prognosis ,medicine.disease ,Fatty Acid Synthase, Type I ,Fatty acid synthase ,medicine.anatomical_structure ,biology.protein ,Female ,Neoplasm Grading ,Colorectal Neoplasms ,business - Abstract
Fatty acid synthase is a common phenotype to various human cancers including those of prostate, colon, lung, endometrium, and stomach. Increased fatty acid synthase levels have been detected in serum from patients with breast and pancreatic cancer. In this study, serum levels of fatty acid synthase were measured in colorectal cancer patients at different stages of disease.Consecutive 67 patients with colorectal cancer were enrolled in the study. Serum levels of fatty acid synthase were examined by ELISA test. The Kruskal-Wallis test and the χ (2) method for trend have been used to analyze data.Serum fatty acid synthase levels of patients belonging to three groups of stage disease are statistically different. The patients with stage III and IV have significantly higher serum levels of fatty acid synthase than patients with stage I-II. There is a positive trend in serum fatty acid synthase levels from stage I-II to stage III and IV of disease.Fatty acid synthase levels are associated with the stage of disease in patients with colorectal cancer.
- Published
- 2011
29. Aerobic Physical Activity and a Low Glycemic Diet Reduce the AA/EPA Ratio in Red Blood Cell Membranes of Patients with NAFLD
- Author
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Giampiero De Leonardis, Isabella Franco, Caterina Bonfiglio, Valentina De Nunzio, Maria Gabriella Caruso, Raffaele Cozzolongo, Alberto Rubén Osella, Gianluigi Giannelli, Antonella Mirizzi, Vito Giannuzzi, Maria Notarnicola, and Valeria Tutino
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Time Factors ,Mediterranean diet ,erythrocyte membrane ,physical activity ,lcsh:TX341-641 ,Diet, Mediterranean ,Article ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Aerobic exercise ,Exercise ,chemistry.chemical_classification ,Arachidonic Acid ,030109 nutrition & dietetics ,Nutrition and Dietetics ,business.industry ,Fatty liver ,non-alcoholic fatty liver disease ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Eicosapentaenoic acid ,Low-glycemic diet ,Treatment Outcome ,Endocrinology ,Glycemic index ,Eicosapentaenoic Acid ,Italy ,chemistry ,Glycemic Index ,Female ,lipids (amino acids, peptides, and proteins) ,Steatosis ,business ,Nutritive Value ,Risk Reduction Behavior ,lcsh:Nutrition. Foods and food supply ,Biomarkers ,polyunsaturated fatty acids ,Food Science ,Polyunsaturated fatty acid - Abstract
Omega-6 Polyunsaturated Fatty Acids (PUFAs), through the eicosanoids derived from arachidonic acid (AA), are able to modulate the inflammatory processes, whereas omega-3 PUFAs, such as eicosapentaenoic acid (EPA), exert anti-oxidant and anti-inflammatory effects. An unbalanced AA/EPA ratio in favor of AA leads to the development of different metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the effects of different diets, alone and in combination with two physical activity programs, on the AA/EPA ratio value in erythrocyte membranes of patients with NAFLD. One hundred forty-two subjects with NAFLD were enrolled in the study and randomized into six treatment groups. AA/EPA ratio was significantly reduced after 90 days of treatment with only a program of aerobic activity. However, it appears that the combination of physical activity and a Low Glycemic Index Mediterranean Diet (LGIMD) was more efficacious in reducing AA/EPA levels, at 45 days of treatment, even if this effect was not maintained over time. The combined effect of diet and physical activity reduced the AA/EPA ratio value improving the score of steatosis. Dietary intake of omega-3 PUFAs, in association with a healthy lifestyle, may be used in the prevention protocols for many chronic diseases, including NAFLD.
- Published
- 2018
30. Reduced fructosamine-3-kinase activity and its mRNA in human distal colorectal carcinoma
- Author
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Maria Gabriella Caruso, S. Frisullo, Donato F. Altomare, Vito Guerra, Giovanni Misciagna, Maria Notarnicola, and Valeria Tutino
- Subjects
chemistry.chemical_classification ,Pathology ,medicine.medical_specialty ,Fructoselysine ,Messenger RNA ,biology ,Colorectal cancer ,business.industry ,Endocrinology, Diabetes and Metabolism ,Cancer ,medicine.disease ,Enzyme assay ,Enzyme ,chemistry ,Glycation ,Gene expression ,Genetics ,medicine ,biology.protein ,Cancer research ,business ,Research Paper - Abstract
Fructosamine-3-Kinase (FN3K) is an enzyme phosphorilating fructoselysine (FL) residues on glycated proteins, resulting in the production of protein-bound FL-3-phosphate. The pathological role of the non-enzymatic modification of proteins by reducing sugars has become increasingly evident in various types of disorders, including the cancer. In this study, our aim was to study FN3K enzyme activity, as well as its mRNA in human colorectal cancer (CRC). Thirty consecutive CRC patients undergoing surgery of the colon were enrolled in the study. FN3K enzymatic activity and gene expression were analyzed using a radiometric assay and quantitative RT-PCR, respectively. FN3K is a functionally active enzyme in human colon tissue, without significant differences between normal mucosa and cancer. The mean level of FN3K mRNA was significantly lower in cancer than in the corresponding normal colorectal mucosa The colorectal tumors located on the left side showed lower levels of both enzymatic activity and mRNA FN3K than tumors located in the right side of colon. This paper is the first studying FN3K enzyme activity in human CRC, showing a significant relationship between enzymatic activity, its mRNA and tumor side.
- Published
- 2010
31. Effect of genistein on cholesterol metabolism-related genes in a colon cancer cell line
- Author
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Caterina Messa, Rosemary Rivizzigno, Valeria Tutino, Maria Notarnicola, Antonella Orlando, Benedetta D'Attoma, and Maria Gabriella Caruso
- Subjects
medicine.medical_specialty ,biology ,Endocrinology, Diabetes and Metabolism ,Estrogen receptor ,Genistein ,Reductase ,Isoflavones ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Cell culture ,Internal medicine ,Gene expression ,HMG-CoA reductase ,LDL receptor ,Genetics ,medicine ,Cancer research ,biology.protein ,Research Paper - Abstract
The major soy-derived isoflavones such as genistein has been demonstrated to possess anticarcinogenic activity in animal model systems. The present study was designed to investigate the effects of isoflavone genistein exposure at concentrations ranging from 0.01 to 50 muM on the LDL receptor and HMG-CoA reductase gene expression in the estrogen receptor positive DLD-1 human colon cancer cell line. LDL receptor and HMG-CoA reductase gene expressions were evaluated by reverse transcription followed by real-time PCR. Genistein induced an increase of LDL receptor gene expression and later decrease of HMG-CoA reductase mRNA expression in DLD-1 cells. These findings provide direct evidence on the role of genistein in regulating LDL receptor and HMG-CoA reductase gene expression in colon cancer.
- Published
- 2008
32. Upregulation of β3-Adrenergic Receptor mRNA in Human Colon Cancer: A Preliminary Study
- Author
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Maria Gabriella Caruso, Maria Notarnicola, Antonio Scilimati, Maria Grazia Perrone, and Valeria Tutino
- Subjects
Cancer Research ,β3 adrenergic receptor ,medicine.medical_specialty ,Messenger RNA ,business.industry ,Cell growth ,Colorectal cancer ,Metastasis formation ,fungi ,food and beverages ,Cancer ,macromolecular substances ,General Medicine ,medicine.disease ,Human colon cancer ,Endocrinology ,Oncology ,Downregulation and upregulation ,Internal medicine ,Cancer research ,Medicine ,business - Abstract
Objective: Tumor cell proliferation and migration, as well as metastasis formation, can be affected by several neurotransmitters, which therefore seem to be involved in the most important aspects of the malignant phenotype. In particular, modified β-adrenergic functions seem to be associated with proliferative alterations of numerous cancer cell lines. Pharmacological modulation of β-adrenoceptors (β-ARs) affects tumor cell growth in several experimental systems, and inhibition of metastasis formation by β-AR antagonists in in vivo models has recently been reported. Initial epidemiological studies have provided evidence that β-blockers can reduce cancer incidence, thus suggesting a possible role also in cancer prevention. Methods: Colorectal mucosa and cancer tissue were obtained from 41 patients. Specimens were taken within 1 h after the surgical procedure and stored at –80°C until assayed. The gene expression of β1-, β2- and β3-ARs in cancer tissue and normal surrounding mucosa was measured by real-time PCRs. Results: Comparable levels of β1- and β2-AR mRNA were found to be expressed in normal mucosa and cancer tissues. A significant difference in β3-AR mRNA levels between normal mucosa and cancer tissues was found, with β3-AR mRNA expression being twice as high in cancer tissue than normal mucosa. Conclusion: The results of the present study indicate that β3-AR mRNA is upregulated in human colon cancer, thus suggesting the possible involvement of β3-AR in malignant transformation in the human colon.
- Published
- 2008
33. Contents Vol. 75, 2008
- Author
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G. Viola, Hiroshi Nokihara, rd Seaborn McDonald Wade, Massimo Lopez, Antonio Scilimati, Tomas Martinez, Erica Travaglino, Maria Grazia Perrone, Joseph Levy, Sanyuan Hu, Chiara Benatti, Guo-hua Zeng, Doron Amichay, Fei Yan, Yuichiro Ohe, Thomas L. Borok, F. Fanfani, Mary Helen Hackney, Fairooz F. Kabbinavar, D. Lorusso, Xia Zhao, A. Giordano, Rosangela Invernizzi, Howard Lee, Qifeng Yang, Ami Goradia, Serena Corsetti, Hanshuo Yang, Xue-cheng Bi, Wei-jun Qin, Zeev Barvish, Lijuan Chen, P. Foggi, James Welsh, Yu-xiang Liang, Richard Dodel, Michael Weller, Martin Glas, Marco Danova, Dorothee Wiewrodt, Paul Vos, Donatella Grasso, Ulrich Herrlinger, Vincent Vinh-Hung, Ulf Karlsson, Yuquan Wei, Yong-kang Ye, Ze Zhang, Katja Rasch, A. Fagotti, Francesco Giotta, Hagar Sharabani, Michael Bacher, Alberto Riccardi, Alison W. Loren, Wei-de Zhong, Luca Livraghi, Russell J. Hamilton, Tiantian Wang, Harukaze Yamamoto, Herbert Hurwitz, Birgit Rinn, Kestutis Suziedelis, G. Vizzielli, Luigi Di Lauro, Haidong Gao, M. Manzoni, Gang Zhu, Maria Notarnicola, James Khatcheressian, Feng Li, Qingbo Su, Rong Ma, C. Rossitto, Cornelia Irl, Zhenhua Pan, Michael Danilenko, A. De Gaetano, Alfredo Zurlo, Hideo Kunitoh, Ayelet Shabtay, Pertti Mutanen, Kirsti Husgafvel-Pursiainen, Selina M. Luger, Diana Giannarelli, George P. Studzinski, Noboru Yamamoto, G. Scambia, Qi-shan Dai, Valeria Tutino, Deirdre Cohen, Yoav Sharoni, Fan Yang, Marcella Mottolese, Nam P. Nguyen, Laurie J. Lyckholm, Ikuo Sekine, Jan-Philipp Bach, Claudio Botti, Maria Gabriella Caruso, Bernhard Meyer, Zhi-nan Chen, Nga T. T. Nguyen, Vikram R. Paralkar, Ly M. Nguyen, Zhiyong Qian, Domenico Sergi, Kristina Kurgonaite, Zhao-dong Han, Silvia Ileana Fattoruso, Tomohide Tamura, Hongxin Deng, Patrizia Vici, Michael Kafka, Hui-chan He, Kazuhiko Yamada, Elena Collovà, Milan R. Uskokovic, Zhengyu Li, Sonata Jarmalaite, and Feliksas Jankevičius
- Subjects
Cancer Research ,Oncology ,General Medicine - Published
- 2008
34. Hydroxytyrosol Inhibits Cannabinoid CB1 Receptor Gene Expression in 3T3-L1 Preadipocyte Cell Line
- Author
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Valeria, Tutino, Antonella, Orlando, Francesco, Russo, and Maria, Notarnicola
- Subjects
Stem Cells ,Gene Expression ,alpha-Linolenic Acid ,Phenylethyl Alcohol ,Linoleic Acid ,PPAR gamma ,Lipoprotein Lipase ,Mice ,Receptor, Cannabinoid, CB1 ,3T3-L1 Cells ,Adipocytes ,Animals ,RNA, Messenger ,fas Receptor ,Cell Proliferation - Abstract
The 3T3-L1 preadipocyte cell line is a well characterized cell model for studying the adipocyte status and the molecular mechanisms involved in differentiation of these cells. 3T3-L1 preadipocytes have the ability to synthesize and degrade endocannabinoid anandamide (AEA) and their differentiation into adipocytes increases the expression of cannabinoid (CB1) and PPAR-γ receptors. Clinically, the blocking stimulation of the endocannabinoid pathway has been one of the first approaches proposed to counteract the obesity and obesity-associated diseases (such as diabetes, metabolic syndrome and cancer). In this connection, here we studied in cultured 3T3-L1 pre-adipocytes the effects of n-3-PUFA, α-Linolenic acid (OM-3), n-6-PUFA, Linoleic acid (OM-6), and hydroxytyrosol (HT) on the expression of CB1 receptor gene and the adipogenesis-related genes PPAR-γ, Fatty Acid Synthase (FAS) and Lipoprotein Lipase (LPL). HT was able to inhibit 3T3-L1 cell differentiation by down-regulating cell proliferation and CB1 receptor gene expression. HT exhibited anti-adipogenic effects, whereas OM-3 and OM-6 exerted an inhibitory action on cell proliferation associated with an induction of the preadipocytes differentiation and CB1 receptor gene expression. Moreover, the expression of FAS and LPL genes resulted increased after treatment with both HT and OM-3 and OM-6. The present study points out that the intake of molecules such as HT, contained in extra virgin olive oil, may be considered also in view of antiobesity and antineoplastic properties by acting directly on the adipose tissue and modulating CB1 receptor gene transcription.
- Published
- 2015
35. Inhibitory effect of vitamin K1 on growth and polyamine biosynthesis of human gastric and colon carcinoma cell lines
- Author
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Valeria Tutino, Benedetta D'Attoma, Francesco Russo, Michele Linsalata, Antonella Orlando, and Maria Notarnicola
- Subjects
Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,MAP Kinase Signaling System ,Cell ,Biology ,Stomach Neoplasms ,Internal medicine ,Cell Line, Tumor ,medicine ,Polyamines ,Humans ,Gastrointestinal cancer ,Phosphorylation ,Cell Proliferation ,Cell growth ,Cancer ,Vitamin K 1 ,Cell cycle ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Endocrinology ,medicine.anatomical_structure ,Oncology ,Cancer cell ,Colonic Neoplasms ,Dietary Supplements ,Cancer research ,Neoplastic cell - Abstract
Gastric and colon cancers remain the leading cause of cancer mortality throughout the world. Since the gastrointestinal tract works in a constant link with the external environment, chemoprevention by dietary constituents could represent a possible approach to reduce cancer risk. Dietary vitamin K1 (VK1) has been shown to prevent the growth of many types of cancer cells. However, no data are available on possible different susceptibility to VK1 by gastric or colon neoplastic cell lines. Moreover, the exact mechanism of action of VK1 is still object of investigation, even if it has been reported that VK1 may induce cell cycle arrest and apoptosis. Therefore, molecules affecting cell growth such as the natural polyamines could be of interest in VK1 action. The aim of the present study was to investigate the effects of increasing concentrations of VK1 (from 10 to 200 µM) administered up to 72 h, on the cell proliferation and apoptosis of a gastric (HGC-27) and a colon (SW480) cancer cell line. Additionally, the polyamine biosynthesis and the MAPK pathway were also examined. VK1 treatments caused an inhibition of cell proliferation and an induction of apoptosis in both cell lines, with a concomitant significant decrease of the polyamine biosynthesis, increased phospho-ERK 1/2 expression was also observed. A different proliferative behavior and a different response to VK1 by gastric and colon cancer cells was evident, with colon cells showing a more pronounced susceptibility to VK1 action. VK1 is safe and without known toxicities in adult humans, consequently it could be effective in prevention and treatment of selected gastrointestinal neoplasms. Protocols based on the use of VK1, along with polyamine inhibitors and/or analogues, could represent a suitable alternative option for improving the efficacy of chemoprevention and treatment in future strategies for gastrointestinal cancer management.
- Published
- 2015
36. Erythrocyte membrane fatty acids profile in colorectal cancer patients: a preliminary study
- Author
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Giuseppe, Coviello, Valeria, Tutino, Maria, Notarnicola, and Maria Gabriella, Caruso
- Subjects
Male ,Case-Control Studies ,Erythrocyte Membrane ,Fatty Acids ,Humans ,Female ,Middle Aged ,Neoplasm Grading ,Colorectal Neoplasms ,Aged ,Neoplasm Staging - Abstract
The study of fatty acid composition of the erythrocytes' membrane can be considered an appropriate biomarker for investigating the relations of the pattern of fatty acids metabolism to a specific disease. The aim of the present study was to analyze the fatty acid profile in red blood cell membranes of patients with colorectal cancer (CRC).Thirteen patients with CRC and 13 patients with no malignant disease were enrolled in the study. Fatty acids were extracted from erythrocytes' membranes and quantified by gas chromatography. The data were analyzed using the Mann-Whitney test.Patients with CRC showed significantly lower mean percentage of n-3 polynunsatured fatty acids (n-3 PUFAs) than controls (5.1% vs. 8.0%, respectively). This finding was reflected in the higher ratio n-6-PUFA/n-3-PUFA observed in cancer patients.Lipidomic analysis of erythrocyte membranes confirmed the presence of an altered fatty acid profile in patients with CRC.
- Published
- 2014
37. Olive oil and omega-3 polyunsaturated fatty acids suppress intestinal polyp growth by modulating the apoptotic process in ApcMin/+ mice
- Author
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Maria Gabriella Caruso, Michele Barone, Maria Notarnicola, B. Pesetti, Maria Principia Scavo, Antonio Francavilla, Maria Teresa Viggiani, Valeria Tutino, Lorenzo Polimeno, and Alfredo Di Leo
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Coenzyme A ,Adenomatous Polyposis Coli Protein ,Blotting, Western ,Intestinal polyp ,Estrogen receptor ,Apoptosis ,Reductase ,Biology ,Real-Time Polymerase Chain Reaction ,chemistry.chemical_compound ,Mice ,Intestinal mucosa ,Internal medicine ,Microsomes ,Fatty Acids, Omega-3 ,medicine ,Animals ,Plant Oils ,RNA, Messenger ,fas Receptor ,Intestinal Mucosa ,Olive Oil ,Cell Proliferation ,chemistry.chemical_classification ,Reverse Transcriptase Polymerase Chain Reaction ,Intestinal Polyps ,Lipid metabolism ,General Medicine ,Lipid Metabolism ,Mice, Inbred C57BL ,Fatty acid synthase ,Endocrinology ,chemistry ,Colonic Neoplasms ,biology.protein ,Hydroxymethylglutaryl CoA Reductases ,Polyunsaturated fatty acid - Abstract
The promotion and progression of carcinogenesis are susceptible to nutritional interventions aimed at counteracting cancer development. Lipid metabolism is essential in the onset and progression of tumors and for cancer cell survival. In this study, we tested the effects of diets enriched with natural compounds, such as olive oil and salmon oil, in mice that spontaneously develop intestinal polyps (Apc(Min/+) mice). For this purpose, we evaluated polyp number and volume, intestinal mucosa proliferation/apoptosis, estrogen receptors (ERs) expression, fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase gene expression and enzymatic activity. Compared with the standard diet, the salmon oil-enriched diet, containing a high percentage of omega-3 polyunsaturated fatty acids, and, to a lesser extent, olive oil-enriched diet reduced polyp number and volume through a reduction of proliferation and a marked proapoptotic effect. These biological effects were mediated by an inhibition of fatty acid synthase and HMGCoA reductase gene expression and activity and an increase of ERβ/ERα ratio. Our findings suggest that a proper dietary lifestyle could contribute to primary cancer prevention.
- Published
- 2014
38. Lactobacillus GG restoration of the gliadin induced epithelial barrier disruption: the role of cellular polyamines
- Author
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Francesco Russo, Maria Notarnicola, Michele Linsalata, Valeria Tutino, and Antonella Orlando
- Subjects
Microbiology (medical) ,Lactobacillus rhamnosus GG ,Paracellular permeability ,Tight junction proteins ,Biology ,Intestinal barrier function ,Occludin ,digestive system ,Microbiology ,Cell junction ,Gliadin ,Permeability ,Tight Junctions ,chemistry.chemical_compound ,Polyamines ,Humans ,Celiac disease ,Barrier function ,Tight junction ,Lacticaseibacillus rhamnosus ,Probiotics ,Zonulin ,Epithelial Cells ,Cell biology ,chemistry ,Biochemistry ,Paracellular transport ,biology.protein ,Caco-2 Cells ,Polyamine ,Research Article - Abstract
Background Celiac disease is characterized by enhanced intestinal paracellular permeability due to alterations of function and expression of tight junction (TJ) proteins including ZO-1, Claudin-1 and Occludin. Polyamines are pivotal in the control of intestinal barrier function and are also involved in the regulation of intercellular junction proteins. Different probiotic strains may inhibit gliadin-induced toxic effects and the Lactobacillus rhamnosus GG (L.GG) is effective in the prevention and treatment of gastrointestinal diseases. Aims of the study were to establish in epithelial Caco-2 cells whether i) gliadin affects paracellular permeability and polyamine profile; ii) co-administration of viable L.GG, heat-killed L.GG (L.GG-HK) or its conditioned medium (L.GG-CM) preserves the intestinal epithelial barrier integrity. Additionally, the effects of L.GG on TJ protein expression were tested in presence or absence of polyamines. Results Administration of gliadin (1 mg/ml) to Caco-2 cells for 6 h caused a significant alteration of paracellular permeability as demonstrated by the rapid decrease in transepithelial resistance with a concomitant zonulin release. These events were followed by a significant increase in lactulose paracellular transport and a slight lowering in ZO-1 and Occludin expression without affecting Claudin-1. Besides, the single and total polyamine content increased significantly. The co-administration of viable L.GG (108 CFU/ml), L.GG-HK and L.GG-CM with gliadin significantly restored barrier function as demonstrated by transepithelial resistance, lactulose flux and zonulin release. Viable L.GG and L.GG-HK, but not L.GG-CM, led to a significant reduction in the single and total polyamine levels. Additionally, only the co-administration of viable L.GG with gliadin significantly increased ZO-1, Claudin-1 and Occludin gene expression compared to control cells. When Caco-2 cells treated with viable L.GG and gliadin were deprived in the polyamine content by α-Difluoromethylornithine, the expression of TJ protein mRNAs was not significantly different from that in controls or cells treated with gliadin alone. Conclusions Gliadin modifies the intestinal paracellular permeability and significantly increases the polyamine content in Caco-2 cells. Concomitant administration of L.GG is able to counteract these effects. Interestingly, the presence of cellular polyamines is necessary for this probiotic to exert its capability in restoring paracellular permeability by affecting the expression of different TJ proteins.
- Published
- 2014
39. Antiproliferative, antioxidant and anti-inflammatory effects of hydroxytyrosol on human hepatoma HepG2 and Hep3B cell lines
- Author
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Valeria, Tutino, Maria G, Caruso, Caterina, Messa, Enzo, Perri, and Maria, Notarnicola
- Subjects
Carcinoma, Hepatocellular ,Dose-Response Relationship, Drug ,Cell Line, Tumor ,Liver Neoplasms ,Anti-Inflammatory Agents ,Humans ,Antineoplastic Agents ,Cell Growth Processes ,Hep G2 Cells ,Phenylethyl Alcohol ,Antioxidants - Abstract
Olive oil intake has been shown to induce beneficial effect on health. This study aimed to investigate the effects of olive oil polyphenol hydroxytyrosol (HT) on cell proliferation and its antioxidant and anti-inflammatory capacity in human hepatoma Hep3B and HepG2 cell lines.Cell growth after HT treatment was measured by 3-(4,5 di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Lipogenic enzyme activity was evaluated by radiochemical assay. Cell total antioxidant activity and cell interleukin-6 (IL-6) levels were measured by enyme linked immunosorbent assay (ELISA) methods.HT caused an evident antiproliferative effect mediated by inhibition of lipogenic enzymes. Moreover, HT induced activation of the cell antioxidant system and reduced cellular IL-6 levels.Our findings provide insights into the mechanisms of action of HT in the context of inhibition of cancer cell proliferation and prevention of oxidative stress in human hepatoma cells. Our results also show a down-regulation of lipogenic enzymes involved in cell proliferation.
- Published
- 2012
40. Increased soluble leptin receptor levels are associated with advanced tumor stage in colorectal cancer patients
- Author
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Valeria, Tutino, Maria, Notarnicola, Vito, Guerra, Dionigi, Lorusso, and Maria Gabriella, Caruso
- Subjects
Leptin ,Male ,Logistic Models ,Solubility ,Humans ,Receptors, Leptin ,Female ,Colorectal Neoplasms ,Aged ,Demography ,Neoplasm Staging - Abstract
The leptin receptor is involved in modulating leptin activity, acting as a carrier protein. A link between leptin or leptin receptor and cancer development has been proposed and here, the hypothesis that leptin and its receptor might be implicated in colorectal cancer (CRC) progression and invasion was investigated.A total of 71 consecutive patients with CRC were enrolled in the study. Serum leptin and leptin receptor levels were evaluated by commercial ELISA kits.The multinomial logistic regression model showed a positive association of leptin and leptin receptor with advanced tumor stages, which was significant for the leptin receptor in stage IV of disease.High circulating levels of leptin receptor occur in patients with advanced stage of colon cancer, suggesting a role for leptin in cancer progression and aggressiveness.
- Published
- 2011
41. Effects of anandamide on polyamine levels and cell growth in human colon cancer cells
- Author
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Michele, Linsalata, Maria, Notarnicola, Valeria, Tutino, Maurizio, Bifulco, Antonietta, Santoro, Chiara, Laezza, Caterina, Messa, Antonella, Orlando, and Maria Gabriella, Caruso
- Subjects
Dose-Response Relationship, Drug ,Receptor, Cannabinoid, CB1 ,Polyunsaturated Alkamides ,Biogenic Polyamines ,Colonic Neoplasms ,Gene Expression ,Humans ,Cell Differentiation ,Arachidonic Acids ,Cell Growth Processes ,RNA, Messenger ,HT29 Cells ,Endocannabinoids - Abstract
Anandamide (AEA) is an endogenous agonist for cannabinoid receptor CB1-R and seems to be involved in the control of cancer growth. Polyamines are compounds that play an important role in cell proliferation and differentiation. Our aim was to investigate the effect of AEA on the polyamine levels (putrescine, spermidine and spermine) and cell growth of three human colon cancer cell lines, positive for CB1-R.After AEA treatment of DLD-1, HT-29 and SW620 cells, polyamine analysis was performed by high-performance liquid chromatography (HPLC) and cell growth was measured by 3-(4,5 di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. CB1 gene expression was determined using reverse transcription and polymerase chain reaction (RT-PCR).AEA significantly reduced polyamine levels and cell proliferation dose-dependently when the tested cell lines were exposed for 24 h and 48 h. This inhibitory effect was mediated by CB1-R, since SR 1411716A, a selective CB-1 receptor antagonist, was able to entirely antagonize the effect of AEA. CB1-R mRNA levels were enhanced after AEA treatment in DLD-1 cells, whereas no induction was found in HT-29 and SW620 cells.It appears that mechanisms by which AEA may affect growth of colon cancer cells involve a decrease in cell proliferation rate by reducing the polyamine levels.
- Published
- 2010
42. Low red blood cell levels of deglycating enzymes in colorectal cancer patients
- Author
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Maria Gabriella Caruso, Vito Guerra, Maria Notarnicola, Valeria Tutino, and Giovanni Misciagna
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Erythrocytes ,Brief Article ,Colorectal cancer ,Colon mucosa ,Malignant transformation ,Lactoylglutathione lyase ,Glycation ,medicine ,Humans ,Aged ,chemistry.chemical_classification ,biology ,business.industry ,Gastroenterology ,Lactoylglutathione Lyase ,General Medicine ,Middle Aged ,medicine.disease ,digestive system diseases ,Red blood cell ,Phosphotransferases (Alcohol Group Acceptor) ,medicine.anatomical_structure ,Enzyme ,chemistry ,biology.protein ,Cancer research ,Fructosamine-3-kinase ,Female ,business ,Colorectal Neoplasms - Abstract
To investigate Glyoxalase I and fructosamine-3-kinase (FN3K) activity in red blood cells from patients with colorectal adenomas and cancer.Thirty three consecutive subjects with one or more histologically confirmed colorectal adenomatous polyps, 16 colorectal cancer patients and a group of 11 control subjects with normal colonoscopy were included in the study. Glyoxalase I and FN3K activities were measured in red blood cells using a spectrophotometric and radiometric assay, respectively.A significant reduction in both Glyoxalase I and FN3K activity was detected in patients with tumors compared to patients with adenomas and the controls. Erythrocyte Glyoxalase I activity in colorectal cancer was approximately 6 times lower than that detected in patients with adenoma (0.022 ± 0.01 mmol/min per milliliter vs 0.128 ± 0.19 mmol/min per milliliter of red blood cells, P = 0.003, Tukey's test). FN3K activity in red blood cells from patients with colon cancer was approximately 2 times lower than that detected in adenoma patients (19.55 ± 6.4 pmol/min per milliliter vs 38.6 ± 31.7 pmol/min per milliliter of red blood cells, P = 0.04, Tukey's test).These findings suggest that deglycating enzymes may be involved in the malignant transformation of colon mucosa.
- Published
- 2010
43. Effects of olive oil polyphenols on fatty acid synthase gene expression and activity in human colorectal cancer cells
- Author
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Maria Notarnicola, Maria Gabriella Caruso, Maurizio Bifulco, Vincenzo Memeo, Simona Pisanti, Enzo Perri, Valeria Tutino, Maria Teresa Rotelli, Domenica Bocale, Antonio Gentile, Notarnicola, M, Pisanti, S, Tutino, V, Bocale, D, Rotelli, Mt, Gentile, A, Memeo, V, Bifulco, Maurizio, Perri, E, and Caruso, M. G.
- Subjects
Cell type ,biology ,Cell growth ,Endocrinology, Diabetes and Metabolism ,Cell cycle ,Fas receptor ,Fatty acid synthase ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Apoptosis ,Cell culture ,Genetics ,biology.protein ,Hydroxytyrosol ,Research Paper - Abstract
Oleuropein (OL) and hydroxytyrosol (HT), the main olive oil polyphenols, possess anti-proliferative effects in vitro. Fatty acid synthase, a key anabolic enzyme of biosynthesis of fatty acids, plays an important role in colon carcinoma development. Our aim was to investigate whether gene expression of FAS, as well as its enzymatic activity, is regulated by HT and OL in two human colon cancer cell lines, as HT-29 and SW620. In addition, we investigated the effects of these polyphenols on growth and apoptosis in these cells. FAS gene expression and activity in treated HT-29 and SW620 cells were evaluated by real-time PCR and radiochemical assay, respectively. Cell growth and apoptosis, after polyphenols treatment, were measured by MTT test and flow cytometry, respectively. The inhibition of proliferation, detected after HT treatment, was mediated by an inhibition of FAS expression and its enzymatic activity in SW620 cells, while the anti-proliferative effect in HT-29 cells seems to be independent from FAS. OL exerted an anti-proliferative effect only on SW620 cells with a mechanism which excluded FAS. Olive oil polyphenols used were able to induce apoptosis in both cell lines studied. The increase of apoptosis in these cells was accompanied by the block of cell cycle in the S phase. This study demonstrates that HT and OL may induce anti-proliferative and pro-apoptotic effects only in certain human colorectal cancer cell types. These effects are FAS mediated only in SW620 cells after treatment with HT.
- Published
- 2010
44. Estrogen receptor (ER) and ER-related receptor expression in normal and atrophic human vagina
- Author
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Giuseppe Loverro, Edoardo Dinaro, A. M. Caringella, R Ferreri, Alessandra Giocolano, Valeria Tutino, and Aldo Cavallini
- Subjects
Adult ,medicine.medical_specialty ,medicine.drug_class ,Receptor expression ,Estrogen receptor ,Down-Regulation ,General Biochemistry, Genetics and Molecular Biology ,Estrogen-related receptor alpha ,Internal medicine ,medicine ,Humans ,RNA, Messenger ,Estrogen receptor beta ,Aged ,business.industry ,Estrogen secretion ,Obstetrics and Gynecology ,Middle Aged ,Postmenopause ,medicine.anatomical_structure ,Endocrinology ,Premenopause ,Receptors, Estrogen ,Estrogen ,Case-Control Studies ,Vagina ,Female ,business ,Estrogen receptor alpha - Abstract
Objectives The estrogen level decline in menopausal status is involved in physiological alterations of different human tissues including vaginal mucosa. In this study, we have evaluated the estrogen receptor (ER) and estrogen receptor-related receptor (ERR) expression in tissue samples of posterior vaginal wall obtained from pre- and post-menopausal women. Methods The nuclear receptor expression was determined by quantitative real-time PCR (qPCR). Results The qPCR results showed the presence of the three isoforms of the ERR family (ERRα, ERRβ and ERRγ) that were coexpressed with ERs in all vaginal tissue samples examined. The ERRα and ERRγ mRNA levels decreased from normal vagina of the pre-menopausal women to atrophic vaginal tissue in post-menopausal women. This trend was also observed for the ERβ subtype. Conclusions The ERRs, such as ERs, are present in human vagina at the mRNA level and the cessation of ovarian estrogen secretion, that is the key event during the post-menopause, may be linked to ERβ, ERRα and ERRγ mRNA decline in human vaginal mucosa. These findings may provide a biological rationale for the clinical susceptibility of the post-menopausal vagina to local estrogen treatment.
- Published
- 2007
45. Subject Index Vol. 75, 2008
- Author
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Hagar Sharabani, Ulrich Herrlinger, C. Rossitto, Michael Danilenko, Ayelet Shabtay, George P. Studzinski, Noboru Yamamoto, Deirdre Cohen, Tomas Martinez, Harukaze Yamamoto, Michael Kafka, Birgit Rinn, Yuichiro Ohe, Elena Collovà, Milan R. Uskokovic, Diana Giannarelli, Lijuan Chen, Xia Zhao, Ze Zhang, Sonata Jarmalaite, Chiara Benatti, James Welsh, Michael Bacher, Alfredo Zurlo, Doron Amichay, Dorothee Wiewrodt, Ikuo Sekine, Zhiyong Qian, Selina M. Luger, Domenico Sergi, Thomas L. Borok, Herbert Hurwitz, Jan-Philipp Bach, Mary Helen Hackney, Marcella Mottolese, Nam P. Nguyen, Alberto Riccardi, Alison W. Loren, Fairooz F. Kabbinavar, Fan Yang, A. Giordano, Haidong Gao, Luca Livraghi, Silvia Ileana Fattoruso, Maria Notarnicola, James Khatcheressian, Yong-kang Ye, Kirsti Husgafvel-Pursiainen, Gang Zhu, Zhao-dong Han, Qingbo Su, Rong Ma, Hiroshi Nokihara, Erica Travaglino, Patrizia Vici, Sanyuan Hu, Tomohide Tamura, F. Fanfani, Hongxin Deng, Ly M. Nguyen, Maria Grazia Perrone, D. Lorusso, Joseph Levy, Xue-cheng Bi, Wei-jun Qin, Maria Gabriella Caruso, Kristina Kurgonaite, Rosangela Invernizzi, Marco Danova, Claudio Botti, Feng Li, Laurie J. Lyckholm, Richard Dodel, A. Fagotti, Donatella Grasso, Ulf Karlsson, Yuquan Wei, Paul Vos, Hideo Kunitoh, Tiantian Wang, Martin Glas, Zhenhua Pan, Howard Lee, Zhi-nan Chen, Nga T. T. Nguyen, Bernhard Meyer, Hanshuo Yang, Vikram R. Paralkar, Kestutis Suziedelis, M. Manzoni, Qifeng Yang, A. De Gaetano, G. Vizzielli, Michael Weller, P. Foggi, Katja Rasch, Kazuhiko Yamada, Zeev Barvish, rd Seaborn McDonald Wade, Massimo Lopez, Pertti Mutanen, G. Viola, G. Scambia, Fei Yan, Luigi Di Lauro, Francesco Giotta, Antonio Scilimati, Guo-hua Zeng, Hui-chan He, Cornelia Irl, Vincent Vinh-Hung, Zhengyu Li, Feliksas Jankevičius, Ami Goradia, Serena Corsetti, Yu-xiang Liang, Wei-de Zhong, Russell J. Hamilton, Qi-shan Dai, Valeria Tutino, and Yoav Sharoni
- Subjects
Cancer Research ,Index (economics) ,Oncology ,Statistics ,Subject (documents) ,General Medicine ,Mathematics - Published
- 2008
46. Dietary-suppression of hepatic lipogenic enzyme expression in intact male transgenic mice
- Author
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Angela Tafaro, Mario Minoia, Maria Gabriella Caruso, Antonio Francavilla, Valeria Tutino, Maria Notarnicola, and Giusy Bianco
- Subjects
Male ,medicine.medical_specialty ,Genes, APC ,Cyclin E ,Genotype ,Brief Article ,Down-Regulation ,Mice, Transgenic ,Biology ,Gene Expression Regulation, Enzymologic ,Lactones ,Mice ,Internal medicine ,medicine ,Animals ,Plant Oils ,Lovastatin ,RNA, Messenger ,Enzyme Inhibitors ,Olive Oil ,Cell Proliferation ,Orlistat ,Lipogenesis ,Gastroenterology ,Dietary management ,Geranyltranstransferase ,General Medicine ,Dietary Fats ,Hydroxymethylglutaryl-CoA reductase ,Fatty Acid Synthase, Type I ,Mice, Inbred C57BL ,Fatty acid synthase ,Phenotype ,Endocrinology ,Liver ,biology.protein ,Hepatic stellate cell ,Hydroxymethylglutaryl CoA Reductases ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Biomarkers ,medicine.drug - Abstract
AIM: To study, in intact male transgenic mice, the effects of three diets based on olive oil and olive oil diet supplemented with lovastatin and orlistat on hepatic lipogenic enzymes expression, considered markers of cell proliferation. METHODS: Forty ApcMin/+ mice were randomly divided into 4 groups and fed for 10 wk: olive oil (OO) group, n = 10 animals received a diet with olive oil 12%; olive oil plus lovastatin (LOVA) group, n = 10 animals received the same diet with olive oil supplemented with lovastatin 5 mg/kg; olive oil plus orlistat (OR) group, n = 10 animals fed the diet with olive oil supplemented with orlistat 50 mg/kg and SD group, n = 10 animals fed a standard diet. The activity of lipogenic enzymes and their gene expression were evaluated by radiometric and real-time reverse transcription-polymerase chain reaction assay, respectively. RESULTS: After 10 wk of dietary treatment, the body weight was no different among animal groups (21.3 ± 3.1 g for standard group, 22.1 ± 3.6 g for OO group, 22.0 ± 3.2 g for LOVA group and 20.7 ± 3.4 g for OR group, data expressed as mean ± SD), observing a generalized well-being in all animals. All the dietary managed treated groups presented significantly reduced hepatic levels of fatty acid synthase, farnesyl pyrophosphate synthase and 3-hydroxyl-3-methyl-glutaryl CoA reductase activity and gene expression when compared with the mice fed the standard diet. To evaluate cell proliferation in the liver of treated mice, the levels of cyclin E mRNA have been measured, demonstrating a significant reduction of cyclin E gene expression in all treated groups. Evidence of reduced hepatic cell proliferation was present overall in OO group mice. CONCLUSION: We confirm the role of lipogenic enzymes as markers of cell proliferation, suggesting that appropriate dietary management alone or with drugs can be a feasible approach to counteract hepatic cell proliferation in mice.
- Published
- 2013
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