25 results on '"Giorgia Cioccoloni"'
Search Results
2. Ergothioneine supplementation in people with metabolic syndrome (ErgMS): protocol for a randomised, double-blind, placebo-controlled pilot study
- Author
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Xiaoying Tian, Giorgia Cioccoloni, Joanna H. Sier, Khalid M. Naseem, James L. Thorne, and J. Bernadette Moore
- Subjects
Ergothioneine ,Metabolic syndrome ,Supplementation ,Metabolome ,Oxidative stress ,Inflammation ,Medicine (General) ,R5-920 - Abstract
Abstract Background Ergothioneine is a naturally occurring metabolite of histidine found in many foods and in high amounts in mushrooms. In vivo, ergothioneine acts as an antioxidant and is widely distributed in most mammalian tissues. While ergothioneine is sold as a dietary supplement for its antioxidant and anti-inflammatory properties, to date there are no published intervention trials examining its health benefits in humans. The aim of this work was to develop a study protocol for a pilot interventional trial that will establish the primary and secondary outcomes, and the power required, for a definitive randomised controlled trial to test the hypothesis that ergothioneine supplementation is beneficial for people with metabolic syndrome. Methods We have designed the ErgMS study as a single-centre, randomised, double-blind, placebo-controlled, 3-arm parallel, pilot intervention trial, which aims to supplement participants with either placebo, 5 or 30 mg/day ergothioneine for 12 weeks. Measurements of metabolic syndrome risk factors, serum markers of oxidative stress (lipid peroxidation), inflammation, blood platelet function and liver function will take place at baseline, and after 6 weeks and 12 weeks of supplementation. In addition, we will examine if there are any changes in the serum metabolome in response to ergothioneine supplementation. Linear regression and two-way ANOVA will be utilised to analyse the association between ergothioneine and measured variables. Discussion The ErgMS study will be the first study to address the question does ergothioneine supplementation have health benefits for people with metabolic syndrome. Study results will provide preliminary data as to which dose may improve inflammatory markers in adults with metabolic syndrome and will inform dose and primary outcome selection for a definitive randomised controlled trial. Trial registration ISRCTN, ISRCTN25890011 Registered February 10th, 2021
- Published
- 2021
- Full Text
- View/download PDF
3. Influence of FTO rs9939609 and Mediterranean diet on body composition and weight loss: a randomized clinical trial
- Author
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Laura Di Renzo, Giorgia Cioccoloni, Simone Falco, Ludovico Abenavoli, Alessandra Moia, Paola Sinibaldi Salimei, and Antonino De Lorenzo
- Subjects
Nutrigenetics ,FTO ,Mediterranean diet ,Body composition ,Medicine - Abstract
Abstract Background The Mediterranean diet (MeD) plays a key role in the prevention of obesity. Among the genes involved in obesity, the Fat mass and obesity-associated gene (FTO) is one of the most known, but its interaction with MeD remained uncertain so far. Methods We carried out a study on a sample of 188 Italian subjects, analyzing their FTO rs9939609 alleles, and the difference in body composition between the baseline and a 4-weeks nutritional intervention. The sample was divided into two groups: the control group of 49 subjects, and the MeD group of 139 subjects. Results We found significant relations between MeD and both variation of total body fat (ΔTBFat) (p = 0.00) and gynoid body fat (p = 0.04). ∆TBFat (kg) demonstrated to have a significant relation with the interaction diet-gene (p = 0.04), whereas FTO was associated with the variation of total body water (p = 0.02). Conclusions MeD demonstrated to be a good nutritional treatment to reduce the body fat mass, whereas data about FTO remain uncertain. Confirming or rejecting the hypothesis of FTO and its influence on body tissues during nutritional treatments is fundamental to decide whether its effect has to be taken into consideration during both development of dietetic plans and patients monitoring. Trial Registration ClinicalTrials.gov Id: NCT01890070. Registered 01 July 2013, https://clinicaltrials.gov/ct2/show/NCT01890070
- Published
- 2018
- Full Text
- View/download PDF
4. Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?
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Ornella Franzese, Francesco Torino, Elisa Giannetti, Giorgia Cioccoloni, Angelo Aquino, Isabella Faraoni, Maria Pia Fuggetta, Liana De Vecchis, Anna Giuliani, Bernd Kaina, and Enzo Bonmassar
- Subjects
abscopal effect ,xenogenization ,alkylating agents ,dacarbazine ,temozolomide ,immune response ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients’ quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a biological effect of ionizing radiation that occurs outside the irradiated field), the influence of cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by anticancer agents are the main topics of this presentation. It is widely accepted that tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of anticancer agents are able to amplify already expressed tumor-associated antigens (TAA). More importantly, other drugs, especially triazenes, induce the appearance of new tumor neoantigens (TNA), a phenomenon that we termed drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with drug-induced increase in tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and immunotherapies are interacting and cooperate in evoking the abscopal effect, tumor xenogenization and ICD, paving the way for new and possibly successful approaches in cancer therapy.
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- 2021
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- View/download PDF
5. Can psychobiotics intake modulate psychological profile and body composition of women affected by normal weight obese syndrome and obesity? A double blind randomized clinical trial
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Antonino De Lorenzo, Micaela Costacurta, Giuseppe Merra, Paola Gualtieri, Giorgia Cioccoloni, Massimiliano Marchetti, Dimitrios Varvaras, Raffaella Docimo, and Laura Di Renzo
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NWO syndrome ,Probiotic ,Psychobiotic ,Psychological profile ,Body composition ,Medicine - Abstract
Abstract Background Evidence of probiotics effects on gut function, brain activity and emotional behaviour were provided. Probiotics can have dramatic effects on behaviour through the microbiome–gut–brain axis, through vagus nerve. We investigated whether chronic probiotic intake could modulate psychological state, eating behaviour and body composition of normal weight obese (NWO) and preobese–obese (PreOB/OB) compared to normal weight lean women (NWL). Methods 60 women were enrolled. At baseline and after a 3-week probiotic oral suspension (POS) intake, all subjects underwent evaluation of body composition by anthropometry and dual X-ray absorptiometry, and psychological profile assessment by self-report questionnaires (i.e. EDI-2, SCL90R and BUT). Statistical analysis was carried out using paired t test or a non-parametric Wilcoxon test to evaluate differences between baseline and after POS intake, one-way ANOVA to compare all three groups and, where applicable, Chi square or t test were used to assess symptoms. Results Of the 48 women that concluded the study, 24% were NWO, 26% were NWL and 50% were PreOB/OB. Significant differences in body composition were highlighted among groups both at baseline and after a POS (p
- Published
- 2017
- Full Text
- View/download PDF
6. Nuclear Receptors and Lipid Sensing
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James L, Thorne and Giorgia, Cioccoloni
- Subjects
MicroRNAs ,Lipid Bilayers ,Peroxisome Proliferator-Activated Receptors ,Receptors, Cytoplasmic and Nuclear ,Ligands ,Liver X Receptors - Abstract
Fluctuations in concentration of diverse lipid classes occur in response to diet and metabolism. These changes are managed and mediated by a cell network of enzymes, pumps, and carriers under the control of the lipid responsive nuclear receptors. The understanding of how dysregulation of lipid metabolism are causes and indicators of disease beyond the cardiovascular system has developed in the last decade. A particular emphasis on the role of lipids and lipid-sensing nuclear receptors has emerged in the fields of cancer and the immune system's interaction with cancer. The range of known lipid-based ligands has also expanded. Lipids are not just signalling molecules, but also play structural roles in cells and tissues, for example as major constituents of the lipid bilayer - positioning them as integrators and mediators of signaling. This chapter will discuss the major groups of lipid-sensing nuclear receptors focusing on the liver x receptors, farnesoid x receptor, and the peroxisome proliferator-activated receptors. Initially the reader is presented with information on how these receptors behave and function at the molecular biology level, the range of selective modulation of function by endogenous ligands, and examples of how activity is fine-tuned by mechanisms such as miRNA regulation and post-translational modification of the proteins. We then explore the advances in understanding that have positioned these receptors as therapeutic targets in cancer and immuno-oncology. Finally, the chapter explains the gaps in understanding and experimental challenges that should be prioritized in the coming decade.
- Published
- 2022
7. Phytosterols and phytostanols and the hallmarks of cancer in model organisms: A systematic review and meta-analysis
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Giorgia Cioccoloni, Chrysa Soteriou, Alex Websdale, Lewis Wallis, Michael A. Zulyniak, and James L. Thorne
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030309 nutrition & dietetics ,ved/biology.organism_classification_rank.species ,Drug Evaluation, Preclinical ,Biology ,Bioinformatics ,Industrial and Manufacturing Engineering ,03 medical and health sciences ,0404 agricultural biotechnology ,Neoplasms ,medicine ,Animals ,Model organism ,0303 health sciences ,ved/biology ,Phytosterol ,Incidence (epidemiology) ,digestive, oral, and skin physiology ,Phytosterols ,food and beverages ,Cancer ,04 agricultural and veterinary sciences ,General Medicine ,medicine.disease ,040401 food science ,The Hallmarks of Cancer ,Meta-analysis ,Food products ,Molecular mechanism ,Food Science - Abstract
Phytosterols and phytostanols are natural products present in vegetable oils, nuts, and seeds, or added to consumer food products whose intake is inversely associated with incidence and prognosis of several cancers. Randomized cancer prevention trials in humans are unfeasible due to time and cost yet the cellular processes and signaling cascades that underpin anti-cancer effects of these phytochemicals have been explored extensively in vitro and in preclinical in vivo models. Here we have performed an original systematic review, meta-analysis, and qualitative interpretation of literature published up to June 2020. MEDLINE, Scopus, and hand-searching identified 408 unique records that were screened leading to 32 original articles that had investigated the effects of phytosterols or phytostanols on cancer biology in preclinical models. Data was extracted from 22 publications for meta-analysis. Phytosterols were most commonly studied and found to reduce primary and metastatic tumor burden in all cancer sites evaluated. Expression of pAKT, and markers of metastasis (alkaline phosphatase, matrix metalloproteases, epithelial to mesenchymal transcription factors, lung and brain colonization), angiogenesis (vascular endothelial growth factor, CD31), and proliferation (Ki67, proliferating cell nuclear antigen) were consistently reduced by phytosterol treatment in breast and colorectal cancer. Very high dose treatment (equivalent to 0.2–1 g/kg body weight not easily achievable through diet or supplementation in humans) was associated with adverse events including poor gut health and intestinal adenoma development. Phytosterols and phytostanols are already clinically recommended for cardiovascular disease risk reduction, and represent promising anti-cancer agents that could be delivered in clinic and to the general population at low cost, with a well understood safety profile, and now with a robust understanding of mechanism-of-action.
- Published
- 2020
8. Nuclear Receptors and Lipid Sensing
- Author
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James L. Thorne and Giorgia Cioccoloni
- Published
- 2022
9. Pharmacologic and genetic inhibition of cholesterol esterification enzymes reduces tumour burden: A systematic review and meta-analysis of preclinical models
- Author
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Marc Poirot, Ruoying Wu, Thomas A. Hughes, Xinyu Chen, Michael A. Zulyniak, Xinyu Luo, Philip Chalmers, Alex Websdale, Mengfan Xu, Giorgia Cioccoloni, James L. Thorne, Rufaro Mwarzi, Yi Kiew, Hanne Roberg-Larsen, University of Leeds, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oslo (UiO), Poirot, Marc, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Coenzyme A ,[SDV]Life Sciences [q-bio] ,Organic Anion Transporters ,Antineoplastic Agents ,Pharmacology ,Biochemistry ,Metastasis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Lipid droplet ,medicine ,Animals ,Humans ,Urea ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Clinical Trials as Topic ,Esterification ,Chemistry ,Cholesterol ,Anticholesteremic Agents ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,3. Good health ,Tumor Burden ,[SDV] Life Sciences [q-bio] ,Enzyme ,Apoptosis ,030220 oncology & carcinogenesis ,Cholesteryl ester - Abstract
International audience; Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids conjugated to coenzyme A to esterify cholesterol. Cholesterol esterification is tightly regulated and enables formation of lipid droplets that act as storage organelles for lipid soluble vitamins and minerals, and as cholesterol reservoirs. In cancer, this provides rapid access to cholesterol to maintain continual synthesis of the plasma membrane. In this systematic review and meta-analysis, we summarise the current depth of understanding of the role of this metabolic pathway in pan-cancer development. A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library for preclinical studies identified eight studies where cholesteryl ester concentrations were compared between tumour and adjacent-normal tissue, and 24 studies where cholesterol esterification was blocked by pharmacological or genetic approaches. Tumour tissue had a significantly greater concentration of cholesteryl esters than non-tumour tissue (p < 0.0001). Pharmacological or genetic inhibition of SOAT was associated with significantly smaller tumours of all types (p ≤ 0.002). SOAT inhibition increased tumour apoptosis (p = 0.007), CD8 + lymphocyte infiltration and cytotoxicity (p ≤ 0.05), and reduced proliferation (p = 0.0003) and metastasis (p < 0.0001). Significant risk of publication bias was found and may have contributed to a 32% overestimation of the meta-analysed effect size. Avasimibe, the most frequently used SOAT inhibitor, was effective at doses equivalent to those previously reported to be safe and tolerable in humans. This work indicates that SOAT inhibition should be explored in clinical trials as an adjunct to existing anti-neoplastic agents.
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- 2021
10. Pharmacologic and genetic inhibition of cholesterol esterification reduces tumour burden: a pan-cancer systematic review and meta-analysis of preclinical models
- Author
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X. Chen, Thomas A. Hughes, R. Wu, Hanne Roberg-Larsen, Michael A. Zulyniak, Marc Poirot, Giorgia Cioccoloni, Xu M, X. Luo, Alex Websdale, Y. Kiew, R. Mwarazi, James L. Thorne, and P. Chalmers
- Subjects
chemistry.chemical_classification ,Cholesterol ,Coenzyme A ,Cancer ,Pharmacology ,medicine.disease ,Metastasis ,chemistry.chemical_compound ,Enzyme ,chemistry ,Apoptosis ,Lipid droplet ,Cholesteryl ester ,medicine - Abstract
Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids conjugated to coenzyme A to esterify cholesterol. Cholesterol esterification is tightly regulated and enables formation of lipid droplets that act as storage organelles for lipid soluble vitamins and minerals, and as cholesterol reservoirs. In cancer, this provides rapid access to cholesterol to maintain continual synthesis of the plasma membrane. In this systematic review and meta-analysis, we summarise the current depth of understanding of the role of this metabolic pathway in pan-cancer development. A systematic search of PubMed, Scopus, and Web of Science for preclinical studies identified eight studies where cholesteryl ester concentrations were compared between tumour and adjacent-normal tissue, and 24 studies where cholesterol esterification was blocked by pharmacological or genetic approaches. Tumour tissue had a significantly greater concentration of cholesteryl esters than non-tumour tissue (p
- Published
- 2021
11. Ergothioneine supplementation in people with metabolic syndrome (ErgMS): protocol for a randomised, double-blind, placebo-controlled pilot study
- Author
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J. Bernadette Moore, Joanna H. Sier, Khalid M. Naseem, James L. Thorne, Giorgia Cioccoloni, and Xiaoying Tian
- Subjects
medicine.medical_specialty ,Medicine (General) ,Supplementation ,ALT ,Medicine (miscellaneous) ,Placebo ,law.invention ,Double blind ,chemistry.chemical_compound ,Study Protocol ,R5-920 ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Metabolome ,Inflammation ,business.industry ,Ergothioneine ,medicine.disease ,Metabolic syndrome ,chemistry ,Oxidative stress ,Analysis of variance ,Liver function ,business - Abstract
Background Ergothioneine is a naturally occurring metabolite of histidine found in many foods and in high amounts in mushrooms. In vivo, ergothioneine acts as an antioxidant and is widely distributed in most mammalian tissues. While ergothioneine is sold as a dietary supplement for its antioxidant and anti-inflammatory properties, to date there are no published intervention trials examining its health benefits in humans. The aim of this work was to develop a study protocol for a pilot interventional trial that will establish the primary and secondary outcomes, and the power required, for a definitive randomised controlled trial to test the hypothesis that ergothioneine supplementation is beneficial for people with metabolic syndrome. Methods We have designed the ErgMS study as a single-centre, randomised, double-blind, placebo-controlled, 3-arm parallel, pilot intervention trial, which aims to supplement participants with either placebo, 5 or 30 mg/day ergothioneine for 12 weeks. Measurements of metabolic syndrome risk factors, serum markers of oxidative stress (lipid peroxidation), inflammation, blood platelet function and liver function will take place at baseline, and after 6 weeks and 12 weeks of supplementation. In addition, we will examine if there are any changes in the serum metabolome in response to ergothioneine supplementation. Linear regression and two-way ANOVA will be utilised to analyse the association between ergothioneine and measured variables. Discussion The ErgMS study will be the first study to address the question does ergothioneine supplementation have health benefits for people with metabolic syndrome. Study results will provide preliminary data as to which dose may improve inflammatory markers in adults with metabolic syndrome and will inform dose and primary outcome selection for a definitive randomised controlled trial. Trial registration ISRCTN, ISRCTN25890011 Registered February 10th, 2021
- Published
- 2021
12. Cholesterol esterification enzymes promote cancer growth and are potential therapeutic targets for repurposed drugs: a systematic review and meta-analysis of pre-clinical evidence
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Hanne Roberg-Larsen, P. Chalmers, Michael A. Zulyniak, Alex Websdale, Giorgia Cioccoloni, Y. Kiew, R. Mwarazi, X. Luo, James L. Thorne, Thomas A. Hughes, R. Wu, and X. Chen
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chemistry.chemical_classification ,Nutrition and Dietetics ,Cholesterol ,business.industry ,Medicine (miscellaneous) ,Cancer ,medicine.disease ,Bioinformatics ,chemistry.chemical_compound ,Enzyme ,chemistry ,Clinical evidence ,Meta-analysis ,medicine ,business - Published
- 2021
13. Liver x receptor alpha drives chemoresistance in response to side-chain hydroxycholesterols in triple negative breast cancer
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Giorgia Cioccoloni, Alex Websdale, Liqian Ma, Erik R. Nelson, Madeline A. Henn, Priscilia Lianto, Joy J. Chen, Baek Kim, Laura M. Wastall, J. Bernadette Moore, James L. Thorne, Arindam Pramanik, Samantha A Hutchinson, Chrysa Soteriou, Hanne Roberg-Larsen, Ailsa Rose, Bethany Jill Williams, and Thomas A. Hughes
- Subjects
0301 basic medicine ,Benzylamines ,Cancer Research ,Gene Expression ,Triple Negative Breast Neoplasms ,Disease ,Xenobiotic transporter activity ,Biology ,Benzoates ,Article ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Cell Line, Tumor ,Genetics ,medicine ,Animals ,Humans ,Liver X receptor ,Molecular Biology ,Transcription factor ,Triple-negative breast cancer ,Epirubicin ,Liver X Receptors ,Cancer ,Mice, Inbred BALB C ,Cholesterol ,Mammary Neoplasms, Experimental ,Liver X receptor alpha ,medicine.disease ,Hydroxycholesterols ,Mechanisms of disease ,030104 developmental biology ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,Female ,lipids (amino acids, peptides, and proteins) - Abstract
Triple negative breast cancer (TNBC) is challenging to treat successfully because targeted therapies do not exist. Instead, systemic therapy is typically restricted to cytotoxic chemotherapy, which fails more often in patients with elevated circulating cholesterol. Liver x receptors are ligand-dependent transcription factors that are homeostatic regulators of cholesterol, and are linked to regulation of broad-affinity xenobiotic transporter activity in non-tumor tissues. We show that LXR ligands confer chemotherapy resistance in TNBC cell lines and xenografts, and that LXRalpha is necessary and sufficient to mediate this resistance. Furthermore, in TNBC patients who had cancer recurrences, LXRalpha and ligands were independent markers of poor prognosis and correlated with P-glycoprotein expression. However, in patients who survived their disease, LXRalpha signaling and P-glycoprotein were decoupled. These data reveal a novel chemotherapy resistance mechanism in this poor prognosis subtype of breast cancer. We conclude that systemic chemotherapy failure in some TNBC patients is caused by co-opting the LXRalpha:P-glycoprotein axis, a pathway highly targetable by therapies that are already used for prevention and treatment of other diseases.
- Published
- 2021
14. Liver x receptor alpha drives chemoresistance in response to side-chain hydroxycholesterols in triple negative breast cancer
- Author
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Laura M. Wastall, Priscilia Lianto, Thomas A. Hughes, Madeline A. Henn, Erik R. Nelson, Alex Websdale, Samantha A Hutchinson, Giorgia Cioccoloni, Chrysa Soteriou, Joy J. Chen, Hanne Roberg-Larsen, Liqian Ma, Bethany Jill Williams, Ailsa Rose, Baek Kim, James L. Thorne, and J. Bernadette Moore
- Subjects
business.industry ,Cholesterol ,Liver X receptor alpha ,Disease ,Xenobiotic transporter activity ,medicine.disease ,chemistry.chemical_compound ,Breast cancer ,chemistry ,Cancer research ,Medicine ,lipids (amino acids, peptides, and proteins) ,business ,Liver X receptor ,Transcription factor ,Triple-negative breast cancer - Abstract
Triple negative breast cancer (TNBC) is challenging to treat successfully because targeted therapies do not exist. Instead, systemic therapy is typically restricted to cytotoxic chemotherapy, which fails more often in patients with elevated circulating cholesterol. Liver x receptors are ligand-dependent transcription factors that are homeostatic regulators of cholesterol, and are linked to regulation of broad-affinity xenobiotic transporter activity in non-tumor tissues. We show that LXR ligands confer chemotherapy resistance in TNBC cell lines and xenografts, and that LXRalpha is necessary and sufficient to mediate this resistance. Furthermore, in TNBC patients who had cancer recurrences, LXRalpha and ligands were independent markers of poor prognosis and correlated with P-glycoprotein expression. However, in patients who survived their disease, LXRalpha signaling and P-glycoprotein were decoupled. These data reveal a novel chemotherapy resistance mechanism in this poor prognosis subtype of breast cancer. We conclude that systemic chemotherapy failure in some TNBC patients is caused by co-opting the LXRalpha:P-glycoprotein axis, a pathway highly targetable by therapies that are already used for prevention and treatment of other diseases.
- Published
- 2020
15. Phytosterols and phytostanols and the hallmarks of cancer: a meta-analysis of pre-clinical animal models
- Author
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Michael A. Zulyniak, Lewis Wallis, James L. Thorne, Giorgia Cioccoloni, Alex Websdale, and Chrysa Soteriou
- Subjects
Oncology ,medicine.medical_specialty ,education.field_of_study ,Cancer prevention ,Colorectal cancer ,business.industry ,Population ,MEDLINE ,Cancer ,medicine.disease ,Metastasis ,Meta-analysis ,Internal medicine ,medicine ,education ,Adverse effect ,business - Abstract
Background and Purpose Phytosterols and phytostanols are natural products present in vegetable oils, nuts, and seeds, or added to consumer food products and intake is inversely associated with incidence and prognosis of several cancers. Randomised cancer prevention trials in humans are unfeasible due to time and cost yet the cellular processes and signalling cascades that underpin anti-cancer effects of these phytochemicals have been explored extensively in vitro and in preclinical in vivo models. Experimental Approach Here we have performed an original systematic review, meta-analysis, and qualitative interpretation of literature published up to June 2020. MEDLINE, Scopus, and hand-searching identified 408 unique records that were screen leading to 32 original articles that had investigated the effects of phytosterols or phytostanols on cancer biology in preclinical models. Data was extracted from 22 publications for meta-analysis. Key Results Phytosterols were most commonly studied and found to reduce primary and metastatic tumour burden in all cancer sites evaluated. Expression of pAKT, and markers of metastasis, angiogenesis, and proliferation were consistently reduced in breast and colorectal cancer. Very high dose treatment (not easily achievable through diet or supplementation in humans) was associated with adverse events including poor gut health and intestinal adenoma development. Conclusion and Implications Phytosterols and phytostanols are already clinically recommended for cardio-vascular disease risk reduction, and represent promising anti-cancer agents that could be delivered in clinic and to the general population at low cost, with a well understood safety profile, and now with a robust understanding of mechanism-of-action.
- Published
- 2020
16. Alcoholic Beverage and Meal Choices for the Prevention of Noncommunicable Diseases: A Randomized Nutrigenomic Trial
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Antonino De Lorenzo, Paola Sinibaldi Salimei, Giorgia Cioccoloni, Santo Gratteri, Laura Di Renzo, and Ida Ceravolo
- Subjects
Male ,0301 basic medicine ,Aging ,GPX1 ,Antioxidant ,Mediterranean diet ,medicine.medical_treatment ,Wine ,Mediterranean ,030204 cardiovascular system & hematology ,Diet, Mediterranean ,medicine.disease_cause ,Biochemistry ,Antioxidants ,Nutrigenomics ,Glutathione Peroxidase GPX1 ,0302 clinical medicine ,Settore MED/49 - Scienze Tecniche Dietetiche Applicate ,chemistry.chemical_classification ,Meal ,lcsh:Cytology ,Alcoholic Beverages ,Glutathione peroxidase ,General Medicine ,Middle Aged ,Catalase ,Lipoproteins, LDL ,Adolescent ,Adult ,Aged ,Diet, High-Fat ,Ethanol ,Female ,Glutathione Peroxidase ,Humans ,Noncommunicable Diseases ,Oxidative Stress ,Superoxide Dismutase ,Young Adult ,Cell Biology ,Research Article ,medicine.medical_specialty ,Article Subject ,Lipoproteins ,SOD2 ,LDL ,03 medical and health sciences ,Internal medicine ,medicine ,lcsh:QH573-671 ,business.industry ,Diet ,High-Fat ,030104 developmental biology ,Endocrinology ,chemistry ,White Wine ,business ,Oxidative stress - Abstract
Background. Noncommunicable diseases (NCDs) are the first cause of death worldwide. Mediterranean diet may play a crucial role in the prevention of NCDs, and the presence of wine in this diet could play a positive role on health. Methods. 54 healthy volunteers consumed one of the following beverages: red (RW) or white wine (WW), vodka (VDK), and/or Mediterranean meal (MeDM) and high-fat meal (HFM). Results. OxLDL-C changed significantly between baseline versus HFM, MeDM versus HFM, and HFM versus HFM + RW (p<0.05). Significant upregulation of catalase (CAT) was observed only after RW. Conversely, WW, VDK, RW + MeDM, HF + WW, and HF + VDK determined a significant downregulation of CAT gene. Superoxide dismutase 2 (SOD2) gene expression was upregulated in WW, MeDM + VDK, and RW. Contrariwise, HFM + VDK determined a downregulation of its expression. RW, RW + MeDM, and RW + HFM caused the upregulation of glutathione peroxidase-1 (GPX1). Conclusions. Our results suggest that the association of low/moderate intake of alcohol beverages, with nutraceutical-proven effectiveness, and ethanol, in association with a Mediterranean diet, could determine a reduction of atherosclerosis risk onset through a positive modulation of antioxidant gene expression helping in the prevention of inflammatory and oxidative damages.
- Published
- 2018
17. A Hazelnut-Enriched Diet Modulates Oxidative Stress and Inflammation Gene Expression without Weight Gain
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Ludovico Abenavoli, Andrea Cammarano, Santo Gratteri, Giorgia Cioccoloni, Marco Marchetti, Iraj Alipourfard, Vincenzo Aiello, Sergio Bernardini, Laura Di Renzo, and Ida Ceravolo
- Subjects
0301 basic medicine ,Aging ,Antioxidant ,Article Subject ,medicine.medical_treatment ,Gene Expression ,Inflammation ,Pilot Projects ,030204 cardiovascular system & hematology ,Biology ,medicine.disease_cause ,Settore BIO/09 ,Biochemistry ,Calcitriol receptor ,Corylus ,Healthy Volunteers ,Humans ,Middle Aged ,Obesity ,Oxidative Stress ,Prospective Studies ,03 medical and health sciences ,0302 clinical medicine ,Nutraceutical ,medicine ,Food science ,lcsh:QH573-671 ,lcsh:Cytology ,Settore BIO/12 ,Cell Biology ,General Medicine ,medicine.disease ,030104 developmental biology ,Methylenetetrahydrofolate reductase ,biology.protein ,Clinical Study ,medicine.symptom ,Weight gain ,Oxidative stress - Abstract
Introduction. Inflammation is associated with obesity condition and plays a pivotal role in the onset and progression of many chronic diseases. Among several nutraceutical foods, hazelnuts (Corylus avellana L.) are considered an excellent anti-inflammatory and hypolipidemic food being the second richest source of monounsaturated fatty acids among nuts and because they are rich in vitamins, minerals, and phenolic compounds. Materials and Methods. A prospective pilot clinical trial on 24 healthy volunteers who consumed daily, as a snack, 40 g of hazelnuts (261.99 kcal/1096.17 kJ) for six weeks was conducted. Anthropometric measurements, body composition analysis, and nutrigenomic analysis on 12 anti-inflammatory and antioxidant genes were evaluated at baseline (T0) and after hazelnut intervention (T1). Results. No significant changes were detected on body composition analysis after hazelnut consumption. Conversely, significant upregulation was detected for SOD1 (2−ΔΔCt=2.42), CAT (2−ΔΔCt=2.41), MIF (2−ΔΔCt=4.12), PPARγ (2−ΔΔCt=5.89), VDR (2−ΔΔCt=3.61), MTHFR (2−ΔΔCt=2.40), and ACE (2−ΔΔCt=2.16) at the end of the study. Conclusions. According to emerging evidences, hazelnut consumption does not lead to weight gain probably due to the improvement of the body’s antioxidant capacity by the upregulation of genes implied in oxidant reactions and inflammation.
- Published
- 2019
18. Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line
- Author
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Manuela Zonfrillo, Angelo Aquino, Maria Notarnicola, Isabella Faraoni, Simona Caporali, Maria Pia Fuggetta, Ornella Franzese, Maria Gabriella Caruso, Cristina Villivà, Giorgia Cioccoloni, and Enzo Bonmassar
- Subjects
0301 basic medicine ,PD-L1 ,Settore BIO/04 ,Leukemia, T-Cell ,030106 microbiology ,Down-Regulation ,Jurkat cells ,B7-H1 Antigen ,Jurkat Cells ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Pharmacology (medical) ,Enzyme Inhibitors ,Cell Proliferation ,Orlistat ,Pharmacology ,Tumor microenvironment ,biology ,Chemistry ,Cell growth ,leukemia ,Cell cycle ,Tumor Cell Biology ,FASN ,Cell biology ,Fatty Acid Synthase, Type I ,Fatty acid synthase ,Infectious Diseases ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Signal transduction ,medicine.drug - Abstract
Fatty Acid Synthase (FASN) is responsible for the de novo synthesis of fatty acids, which are involved in the preservation of biological membrane structure, energy storage and assembly of factors involved in signal transduction. FASN plays a critical role in supporting tumor cell growth, thus representing a potential target for anti-cancer therapies. Moreover, this enzyme has been recently associated with increased PD-L1 expression, suggesting a role for fatty acids in the impairment of the immune response in the tumor microenvironment. Orlistat, a tetrahydrolipstatin used for the treatment of obesity, has been reported to reduce FASN activity, while inducing a sensible reduction of the growth potential in different cancer models. We have analyzed the effect of orlistat on different features involved in the tumor cell biology of the T-ALL Jurkat cell line. In particular, we have observed that orlistat inhibits Jurkat cell growth and induces a perturbation of cell cycle along with a decline of FASN activity and protein levels. Moreover, the drug produces a remarkable impairment of PD-L1 expression. These findings suggest that orlistat interferes with different mechanisms involved in the control of tumor cell growth and can potentially contribute to decrease the tumor-associated immune-pathogenesis.
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- 2019
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19. Single nucleotide polymorphism A-511 G of IL-1 gene modifies anthropometric and physiological parameters of athletes
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Fabrizio Spataro, Akbar Abbasi, A. Khamoushi, A De Lorenzo, L Di Renzo, Iraj Alipourfard, and Giorgia Cioccoloni
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0301 basic medicine ,medicine.medical_specialty ,Genotyping ,medicine.medical_treatment ,Single-nucleotide polymorphism ,Biology ,Settore MED/49 ,03 medical and health sciences ,0302 clinical medicine ,Anthropometric ,IL-1 ,Physiological parameters ,Internal medicine ,Genetics ,medicine ,SNP ,Allele ,Gene ,Genetics (clinical) ,Athletes ,Leptin ,Wild type ,biology.organism_classification ,030104 developmental biology ,Cytokine ,Endocrinology ,030220 oncology & carcinogenesis - Abstract
Interleukin-1β is one of pro-inflammatory responses and plays an important role in cell proliferation, differentiation, and apoptosis . The gene of this cytokine is highly polymorphic, one of which is located on 5´flanking region at position −511 (rs16944, A-511 G). This allele encodes IL-1β protein with less activity in comparison with wild type. In this research, 40 subjects of professional athletes in futsal and volleyball fields have been studied in their anthropometric and physiological indexes and also IL-1β genetic polymorphisms. Our results show that in subjects carrying IL-1β A (−) SNP or wild type allele, the weight, body fat and some other physiological indexes have been increased. This might have relation with elevated plasma level of leptin which is conducted by IL-1β A (−) allele. These findings suggest a remarkable relation between genetic polymorphisms of IL-1β gene and physical potential of athletes.
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- 2019
20. Influence of FTO rs9939609 and Mediterranean diet on body composition and weight loss: a randomized clinical trial
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Alessandra Moia, Ludovico Abenavoli, Laura Di Renzo, Giorgia Cioccoloni, Antonino De Lorenzo, Simone Falco, and Paola Sinibaldi Salimei
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Male ,Mediterranean diet ,Body water ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Physiology ,lcsh:Medicine ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Diet, Mediterranean ,Polymorphism, Single Nucleotide ,Body composition ,General Biochemistry, Genetics and Molecular Biology ,Nutrigenetics ,Body Mass Index ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Randomized controlled trial ,Weight loss ,law ,Weight Loss ,medicine ,Humans ,Trial registration ,business.industry ,Research ,lcsh:R ,Total body ,General Medicine ,Middle Aged ,medicine.disease ,Obesity ,Italy ,Female ,medicine.symptom ,business ,FTO - Abstract
Background The Mediterranean diet (MeD) plays a key role in the prevention of obesity. Among the genes involved in obesity, the Fat mass and obesity-associated gene (FTO) is one of the most known, but its interaction with MeD remained uncertain so far. Methods We carried out a study on a sample of 188 Italian subjects, analyzing their FTO rs9939609 alleles, and the difference in body composition between the baseline and a 4-weeks nutritional intervention. The sample was divided into two groups: the control group of 49 subjects, and the MeD group of 139 subjects. Results We found significant relations between MeD and both variation of total body fat (ΔTBFat) (p = 0.00) and gynoid body fat (p = 0.04). ∆TBFat (kg) demonstrated to have a significant relation with the interaction diet-gene (p = 0.04), whereas FTO was associated with the variation of total body water (p = 0.02). Conclusions MeD demonstrated to be a good nutritional treatment to reduce the body fat mass, whereas data about FTO remain uncertain. Confirming or rejecting the hypothesis of FTO and its influence on body tissues during nutritional treatments is fundamental to decide whether its effect has to be taken into consideration during both development of dietetic plans and patients monitoring. Trial Registration ClinicalTrials.gov Id: NCT01890070. Registered 01 July 2013, https://clinicaltrials.gov/ct2/show/NCT01890070
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- 2018
21. Influence of fatty acid synthase inhibitor orlistat on the DNA repair enzyme O6-methylguanine-DNA methyltransferase in human normal or malignant cells in vitro
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Laura Bonmassar, Maria Pia Fuggetta, Enzo Bonmassar, Elena Pagani, Giorgia Cioccoloni, Stefania D'Atri, Angelo Aquino, and Simona Caporali
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Cancer Research ,Methyltransferase ,DNA damage ,DNA repair ,human cancer cells ,anti-obesity drugs ,carcinogenesis ,O6-methylguanine-DNA methyltransferase ,temozolomide ,In Vitro Techniques ,Biology ,medicine.disease_cause ,DNA methyltransferase ,Lactones ,Cell Line, Tumor ,Neoplasms ,medicine ,Humans ,Enzyme Inhibitors ,MGMT inhibitors ,DNA Modification Methylases ,neoplasms ,orlistat ,O-6-methylguanine-DNA methyltransferase ,Tumor Suppressor Proteins ,Settore BIO/14 ,Cell cycle ,HCT116 Cells ,Molecular biology ,digestive system diseases ,Dacarbazine ,Orlistat ,DNA Repair Enzymes ,Oncology ,Purines ,Leukocytes, Mononuclear ,Cancer research ,Carcinogenesis ,HT29 Cells ,lomeguatrib ,medicine.drug - Abstract
Tetrahydrolipstatin (orlistat), an inhibitor of lipases and fatty acid synthase, is used orally for long-term treatment of obesity. Although the drug possesses striking antitumor activities in vitro against human cancer cells and in vitro and in vivo against animal tumors, it also induces precancerous lesions in rat colon. Therefore, we tested the in vitro effect of orlistat on the expression of O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that plays an essential role in the control of mutagenesis and carcinogenesis. Western blot analysis demonstrated that 2-day continuous exposure to 40 mu M orlistat did not affect MGMT levels in a human melanoma cell line, but downregulated the repair protein by 30-70% in human peripheral blood mononuclear cells, in two leukemia and two colon cancer cell lines. On the other hand, orlistat did not alter noticeably MGMT mRNA expression. Differently from lomeguatrib (a false substrate, strong inhibitor of MGMT) orlistat did not reduce substantially MGMT function after 2-h exposure of target cells to the agent, suggesting that this drug is not a competitive inhibitor of the repair protein. Combined treatment with orlistat and lomeguatrib showed additive reduction of MGMT levels. More importantly, orlistat-mediated downregulation of MGMT protein expression was markedly amplified when the drug was combined with a DNA methylating agent endowed with carcinogenic properties such as temozolomide. In conclusion, even if orlistat is scarcely absorbed by oral route, it is possible that this drug could reduce local MGMT-mediated protection against DNA damage provoked by DNA methylating compounds on gastrointestinal tract epithelial cells, thus favoring chemical carcinogenesis.
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- 2015
22. Antioxidant Effects of a Hydroxytyrosol-Based Pharmaceutical Formulation on Body Composition, Metabolic State, and Gene Expression: A Randomized Double-Blinded, Placebo-Controlled Crossover Trial
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Renata Costa de Miranda, Domenico Trombetta, Antonino De Lorenzo, Giorgia Cioccoloni, Paola Gualtieri, Carmela Colica, Antonella Smeriglio, Laura Di Renzo, Sergio Bernardini, and Paola Sinibaldi Salimei
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0301 basic medicine ,Male ,Aging ,Antioxidant ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Pharmacology ,medicine.disease_cause ,Biochemistry ,Biochemistry, Aging, Cell Biology ,Antioxidants ,Placebos ,chemistry.chemical_compound ,Eating ,0302 clinical medicine ,Settore MED/49 - Scienze Tecniche Dietetiche Applicate ,Endothelial dysfunction ,Unsaturated ,biology ,lcsh:Cytology ,Chemistry ,Fatty Acids ,General Medicine ,Middle Aged ,Phenylethyl Alcohol ,Malondialdehyde ,Body Composition ,Fatty Acids, Unsaturated ,Female ,Adult ,Article Subject ,Drug Compounding ,Placebo ,Superoxide dismutase ,03 medical and health sciences ,Young Adult ,Double-Blind Method ,medicine ,Humans ,lcsh:QH573-671 ,030109 nutrition & dietetics ,Erythrocyte Membrane ,Cell Biology ,medicine.disease ,Crossover study ,Gene Expression Regulation ,biology.protein ,Clinical Study ,Hydroxytyrosol ,Oxidative stress - Abstract
Hydroxytyrosol (HT) plays a significant role in cardiovascular disease (CVD) protection, and its metabolites are able to protect from the endothelial dysfunction commonly present in atherosclerosis. This randomized double-blinded, placebo-controlled crossover trial determined the effect in healthy volunteers of two gastroresistant capsules containing 15 mg/day of HT, for a 3-week period (HTT). Evaluation of nutritional status, serum metabolites, oxidative stress biomarkers, and gene expression of 9 genes related to oxidative stress, inflammation, and CVDs was performed. Oxidation biomarkers like thiol group (p=0.001), total antioxidant status (TAS) (p=0.001), superoxide dismutase 1 (SOD1) (2−ΔΔCt = 3.7), and plasma concentration of HT (2.83μg·mL−1) were significantly increased, while nitrite (p=0.001), nitrate (p=0.001), and malondialdehyde (MDA) (p=0.02) were drastically reduced after HTT. A significant reduction of body fat mass percentage (p=0.01), suprailiac skinfold (p=0.01), and weight (p=0.04; Δ% = −0.46%) was observed after HTT. This study shows that regular intake of 15 mg/day of HT changed body composition parameters and modulated the antioxidant profile and the expression of inflammation and oxidative stress-related genes. However, it is advisable to personalize HT doses in order to exert its health benefits in CVD prevention and protection of LDL-C particles from oxidative damage. This trial is registered with ClinicalTrials.govNCT01890070.
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- 2017
23. Antioxidant effects of a hydroxytyrosol-based pharmaceutical formulation on body composition, metabolic state, and gene expression: a randomized double-blinded, placebo-controlled crossover trial
- Author
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Trombetta, Domenico, Laura Di Renzo, Smeriglio, Antonella, Sergio, Bernardini, Giorgia, Cioccoloni, Renata, Miranda, Paola, Gualtieri, and Antonino De Lorenzo
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- 2017
24. Can psychobiotics intake modulate psychological profile and body composition of women affected by normal weight obese syndrome and obesity? A double bind randomized clinical trial
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Giuseppe Merra, Giorgia Cioccoloni, M Marchetti, Laura Di Renzo, Paola Gualtieri, Dimitrios Varvaras, Antonino De Lorenzo, Raffaella Docimo, and M Costacurta
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0301 basic medicine ,Oral ,Adult ,Genetics and Molecular Biology (all) ,medicine.medical_specialty ,Psychometrics ,Population ,Psychobiotic ,Administration, Oral ,lcsh:Medicine ,Probiotic ,Gastroenterology ,Biochemistry ,Body composition ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Chi-square test ,Medicine ,Humans ,Obesity ,Settore MED/49 - Scienze Tecniche Dietetiche Applicate ,education ,education.field_of_study ,NWO syndrome ,Psychological profile ,Female ,Probiotics ,Body Composition ,Body Weight ,Biochemistry, Genetics and Molecular Biology (all) ,business.industry ,Research ,lcsh:R ,General Medicine ,Anthropometry ,medicine.disease ,030104 developmental biology ,Endocrinology ,Administration ,Defecation ,Analysis of variance ,business ,030217 neurology & neurosurgery ,Psychopathology - Abstract
Background Evidence of probiotics effects on gut function, brain activity and emotional behaviour were provided. Probiotics can have dramatic effects on behaviour through the microbiome–gut–brain axis, through vagus nerve. We investigated whether chronic probiotic intake could modulate psychological state, eating behaviour and body composition of normal weight obese (NWO) and preobese–obese (PreOB/OB) compared to normal weight lean women (NWL). Methods 60 women were enrolled. At baseline and after a 3-week probiotic oral suspension (POS) intake, all subjects underwent evaluation of body composition by anthropometry and dual X-ray absorptiometry, and psychological profile assessment by self-report questionnaires (i.e. EDI-2, SCL90R and BUT). Statistical analysis was carried out using paired t test or a non-parametric Wilcoxon test to evaluate differences between baseline and after POS intake, one-way ANOVA to compare all three groups and, where applicable, Chi square or t test were used to assess symptoms. Results Of the 48 women that concluded the study, 24% were NWO, 26% were NWL and 50% were PreOB/OB. Significant differences in body composition were highlighted among groups both at baseline and after a POS (p Conclusions A 3-week intake of selected psychobiotics modulated body composition, bacterial contamination, psychopathological scores of NWO and PreOB/OB women. Further research is needed on a larger population and for a longer period of treatment before definitive conclusions can be made. Trial registration ClinicalTrials.gov Id: NCT01890070
- Published
- 2017
25. Cardiovascular diseases prevention through the modulation of antioxidant genes expression and ox-ldl levels by polyphenolic content of alcoholic beverages and meals
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Giorgia Cioccoloni, L Di Renzo, S. Falco, and A De Lorenzo
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,Nutrition and Dietetics ,Antioxidant ,Polyphenol ,business.industry ,medicine.medical_treatment ,medicine ,Pharmacology ,Critical Care and Intensive Care Medicine ,business ,Gene - Published
- 2018
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