The Saccharomyces cerevisiae acetyltransferase Gcn5 exerts antagonistic pleiotropic effects on chronological ageing.

ACKNOWLEDGMENTS We would like to thank Dr Juan Mata for his help with the transcriptome analysis. The Flow cytometry facility of the School of Biological Sciences is thanked for their excellent help in FACS analysis FUNDING The metabolomics study was funded by the MRC Programme in Lipid Profiling and Signalling (MC_UP_A090_1006) to JLG. NZ is grateful to the Wellcome Trust and the University of Cambridge for support and facilities.Peer reviewedPublisher PD

Adhesions due to peritoneal carcinomatosis caused by a renal carcinoma leading to mechanical gastric outlet obstruction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Gastric outlet obstruction is a clinical syndrome caused by a variety of mechanical obstructions. Peptic ulcer disease used to be responsible for most gastric outlet obstruction, but in the last 40 years the prevalence of malignant tumors has risen significantly. Adhesive disease is an infrequent and insidious cause of mechanical gastric outlet obstruction.</p> <p>Case presentation</p> <p>We report the case of a 78-year-old Caucasian man who had a clinical history of a right nephrectomy for malignancy three years earlier and who was admitted for a severe gastric outlet obstruction (score of 1) confirmed both by an upper endoscopy and by a fluoroscopic view after contrast injection. A computed tomography scan and a laparotomy, with omental biopsies, showed a peritoneal carcinomatosis with the development of abdominal adhesions that prompted an abnormal gastric rotation around the perpendicular axis of his antrum with a dislocation in the empty space of his right kidney. Symptoms disappeared after surgical bypass through a gastrojejunostomy.</p> <p>Conclusions</p> <p>Our patient experienced a very rare complication characterized by the development of adhesions due to peritoneal carcinomatosis caused by a renal carcinoma treated with nephrectomy. These adhesions prompted an abnormal dislocation of his antrum, as an internal hernia, in the empty space of his right kidney.</p

Lipid Remodeling in Hepatocyte Proliferation and Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Hepatocytes undergo profound metabolic rewiring when primed to proliferate during compensatory regeneration and in hepatocellular carcinoma (HCC). However, the metabolic control of these processes is not fully understood. In order to capture the metabolic signature of proliferating hepatocytes, we applied state-of-the-art systems biology approaches to models of liver regeneration, pharmacologically and genetically activated cell proliferation, and HCC. APPROACH AND RESULTS: Integrating metabolomics, lipidomics, and transcriptomics, we link changes in the lipidome of proliferating hepatocytes to altered metabolic pathways including lipogenesis, fatty acid desaturation, and generation of phosphatidylcholine (PC). We confirm this altered lipid signature in human HCC and show a positive correlation of monounsaturated PC with hallmarks of cell proliferation and hepatic carcinogenesis. CONCLUSIONS: Overall, we demonstrate that specific lipid metabolic pathways are coherently altered when hepatocytes switch to proliferation. These represent a source of targets for the development of therapeutic strategies and prognostic biomarkers of HCC.J.L.G., Z.H. and M.V. are funded by the Medical Research Council (MRC grant MC UP A90 1006 & MC PC 13030). J.L.G. and Z.H. are supported by the Imperial Biomedical Research Centre, NIHR. M.A., A.V-P., F.O., Q.M.A. and M.V. are members of the EPoS consortium, which is funded by the Horizon 2020 Framework Program of the European Union under Grant Agreement 634413. F.O. is supported by MRC program grants (MR/K0019494/1 and MR/R023026/1). J.L is supported by MRC PhD studentship and a CRUK program grant (C18342/A23390). M.V. and A.V-P. are supported by MRC MDU and MRC DMC (MC UU 12012/2). Q.M.A. received additional research support from The Liver Research Trust and is a Newcastle NIHR Biomedical Research Centre investigator. M.A., M.V., A.V-P. and J.L.G. received research support from the Evelyn Trust and the NIHR Cambridge Biomedical Research Centre (Gastroenterology Theme)

Lipoprotein lipidomics in obesity-associated metabolic and hepatic disorders

Over the last few decades, obesity has reached epidemic proportions. Obesity is strongly associated with insulin resistance (IR), hyperglycaemia, mixed dyslipidaemia, and hypertension. These metabolic risk factors, grouped under the definition of the Metabolic Syndrome (MetS), increase the risk of cardiovascular disease (CVD). Non-alcoholic fatty liver disease (NAFLD) is one of the most common co-morbidities of MetS. NAFLD ranges from simple steatosis to more aggressive forms, with the potential to evolve to hepatocellular carcinoma and CVD. Lipoprotein dysmetabolism is crucial to both MetS and NAFLD and few studies have investigated the circulating lipidome, defined as the complete lipid profile in a specific tissue/biofluid, in these conditions. The work contained in this thesis studied the lipoprotein remodelling occurring in two cohorts; MetS cohort including 11 healthy people and 14 MetS subjects and BioNASH cohort including 20 healthy people and 89 biopsy-proven patients across the entire spectrum of NAFLD. To this end, we employed state-of-the-art analytical techniques (mass spectrometry-based) along with molecular biology assays to study the serum and lipoprotein lipidome of these patients. In the MetS study, we found that the circulating lipidome of MetS was characterised by a phospholipid (PL) dysmetabolism. The latter was driven, at least in part, by a reduced activity of the enzyme lecithin–cholesterol acyltransferase (LCAT). Dysfunctional LCAT could partly mediate the elevated CVD risk in MetS patients. Our study demonstrated, for the first time, the link between reduced LCAT activity and plasma lipidome in MetS. In the BioNASH cohort, we observed a generalised PL and polyunsaturated fatty acids (PUFA) depletion in NAFLD compared to the control group. By using fast protein liquid chromatography, we isolated HDL and VLDL fractions where we performed lipidomic analyses. As opposed to VLDL, the HDL lipidome was characterised by PL and PUFA depletion. These changes have been reported in hepatic lipidomic studies of NAFLD patients, thus suggesting a close link between peripheral tissues and the liver via HDL. These results provide the basis for the study of HDL composition as a novel player in the pathogenesis of NAFLD. In conclusion, these data demonstrate how the study of lipoprotein metabolism in obesity-related metabolic disorders can shed light on novel pathophysiological mechanisms. Further efforts along these lines will clarify the role of LCAT in MetS and CVD alongside establishing the contribution of the HDL lipidome to the liver composition of NAFLD patients

Adipose tissue insulin resistance and lipidome alterations as the characterizing factors of non-alcoholic steatohepatitis

The prevalence of non-alcoholic fatty liver disease (NAFLD) is now 25% in the general population but increases to more than 55% in subjects with obesity and/or type 2 diabetes. Simple steatosis (NAFL) can develop into more severe forms, that is non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma leading to death

Cardiovascular health and cancer risk associated with plant based diets: An umbrella review

Context: Cardiovascular diseases (CVDs) and cancer are the two main leading causes of death and disability worldwide. Suboptimal diet, poor in vegetables, fruits, legumes and whole grain, and rich in processed and red meat, refined grains, and added sugars, is a primary modifiable risk factor. Based on health, economic and ethical concerns, plant-based diets have progressively widespread worldwide. Objective: This umbrella review aims at assessing the impact of animal-free and animal-products-free diets (A/APFDs) on the risk factors associated with the development of cardiometabolic diseases, cancer and their related mortalities. Data sources: PubMed and Scopus were searched for reviews, systematic reviews, and meta-analyses published from 1st January 2000 to 31st June 2023, written in English and involving human subjects of all ages. Primary studies and reviews/meta-analyses based on interventional trials which used A/APFDs as a therapy for people with metabolic diseases were excluded. Data extraction: The umbrella review approach was applied for data extraction and analysis. The revised AMSTAR-R 11-item tool was applied to assess the quality of reviews/meta-analyses. Results: Overall, vegetarian and vegan diets are significantly associated with better lipid profile, glycemic control, body weight/BMI, inflammation, and lower risk of ischemic heart disease and cancer. Vegetarian diet is also associated with lower mortality from CVDs. On the other hand, no difference in the risk of developing gestational diabetes and hypertension were reported in pregnant women following vegetarian diets. Study quality was average. A key limitation is represented by the high heterogeneity of the study population in terms of sample size, demography, geographical origin, dietary patterns, and other lifestyle confounders. Conclusions: Plant-based diets appear beneficial in reducing cardiometabolic risk factors, as well as CVDs, cancer risk and mortality. However, caution should be paid before broadly suggesting the adoption of A/AFPDs since the strength-of-evidence of study results is significantly limited by the large study heterogeneity alongside the potential risks associated with potentially restrictive regimens

Cardiovascular health and cancer risk associated with plant based diets: An umbrella review.

CONTEXT: Cardiovascular diseases (CVDs) and cancer are the two main leading causes of death and disability worldwide. Suboptimal diet, poor in vegetables, fruits, legumes and whole grain, and rich in processed and red meat, refined grains, and added sugars, is a primary modifiable risk factor. Based on health, economic and ethical concerns, plant-based diets have progressively widespread worldwide. OBJECTIVE: This umbrella review aims at assessing the impact of animal-free and animal-products-free diets (A/APFDs) on the risk factors associated with the development of cardiometabolic diseases, cancer and their related mortalities. DATA SOURCES: PubMed and Scopus were searched for reviews, systematic reviews, and meta-analyses published from 1st January 2000 to 31st June 2023, written in English and involving human subjects of all ages. Primary studies and reviews/meta-analyses based on interventional trials which used A/APFDs as a therapy for people with metabolic diseases were excluded. DATA EXTRACTION: The umbrella review approach was applied for data extraction and analysis. The revised AMSTAR-R 11-item tool was applied to assess the quality of reviews/meta-analyses. RESULTS: Overall, vegetarian and vegan diets are significantly associated with better lipid profile, glycemic control, body weight/BMI, inflammation, and lower risk of ischemic heart disease and cancer. Vegetarian diet is also associated with lower mortality from CVDs. On the other hand, no difference in the risk of developing gestational diabetes and hypertension were reported in pregnant women following vegetarian diets. Study quality was average. A key limitation is represented by the high heterogeneity of the study population in terms of sample size, demography, geographical origin, dietary patterns, and other lifestyle confounders. CONCLUSIONS: Plant-based diets appear beneficial in reducing cardiometabolic risk factors, as well as CVDs, cancer risk and mortality. However, caution should be paid before broadly suggesting the adoption of A/AFPDs since the strength-of-evidence of study results is significantly limited by the large study heterogeneity alongside the potential risks associated with potentially restrictive regimens