Glycolytic phenotype and AMP kinase modify the pathologic response of tumor xenografts to VEGF neutralization.
Abstract VEGF antagonists are now widely used cancer therapeutics, but predictive biomarkers of response or toxicity remain unavailable. In this study, we analyzed the effects of anti-VEGF therapy on tumor metabolism and therapeutic response by using an integrated set of imaging techniques, including bioluminescence metabolic imaging, 18-fluorodeoxyglucose positron emission tomography, and MRI imaging and spectroscopy. Our results revealed that anti-VEGF therapy caused a dramatic depletion of glucose and an exhaustion of ATP levels in tumors, although glucose uptake was maintained. These metabolic changes selectively accompanied the presence of large necrotic areas and partial tumor regress…
Co-production of Hydrogen and Methane From the Organic Fraction of Municipal Solid Waste in a Pilot Scale Dark Fermenter and Methanogenic Biofilm Reactor
The co-production of biohydrogen and methane from the organic fraction of municipal solid waste was investigated using a two-stage AD system, composed of a pilot scale dark fermenter (DF) and a continuous methanogenic biofilm reactor. From the DF process, a biohydrogen yield of 41.7 (± 2.3) ml H2/gVSadded was achieved. The liquid DF effluent (DFE) was rich in short chain volatile fatty acids, i.e., mainly acetic and butyric acid. The DFE was valorized by producing methane in the methanogenic biofilm reactor. Two methanogenic biofilm reactors were used to assess the biotic and abiotic role of the DFE on the performance of the reactors. Regardless of the different DFE feeding (i.e., biotic an…
Pediatric Endoscopic Pilonidal Sinus Treatment (PEPSiT) in Children With Pilonidal Sinus Disease: Tips and Tricks and New Structurated Protocol
Background: The advent of pediatric endoscopic pilonidal sinus treatment (PEPSiT) has dramatically changed the surgical management of pilonidal sinus disease (PSD) in children and adolescents. This study aimed to report the outcome of our new structurated protocol, including PEPSiT, laser epilation, and oxygen-enriched oil-based gel dressing, for treatment of PSD in pediatric patients and describe tips and tricks of the technique. Methods: We retrospectively reviewed the data of 127 pediatric patients, who underwent PEPSiT for PSD in our institutions over a 36-month period. All patients received laser epilation (LE) before and after surgery. Post-operative dressing was performed using silve…
miR-128 Is Implicated in Stress Responses by Targeting MAFG in Skeletal Muscle Cells.
MAFG (v-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) is a bZIP-type transcriptional regulator that belongs to the small MAF (sMAFs) protein family. By interacting with other bZIP transcription factors, sMAFs can form homo- and heterodimers governing either repressive or activating transcriptional functions. As heterodimeric partner of Nrf2, MAFG positively influences the ARE-dependent antioxidant/xenobiotic pathways, at least in condition of a correct MAFG:Nrf2 balance. MicroRNAs (miRs) participate to different regulatory networks being involved as fine-tuning regulators of gene expression. However, the connections between cellular surveillance to stresses mediated by MAFG:…
Vorapaxar in the secondary prevention of atherothrombotic events
BACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients …
A Graphical User Interface as a DSS Tool for GHG Emission Estimation from Water Resource Recovery Facilities
A Grafical User Interface (GUI) for the greenhouse gas (GHG) emissions from WWTPs based on four models aimed at quantifying the gas emissions from the aerated tanks (i.e. CAS and MBR reactor), aerobic digesters, secondary clarifiers and anaerobic digesters have been englobed in a GUI in order to provide a valid decision support system (DSS) to the practitioners. The GUI allows to estimate such emissions for the different WWTP phases considered. The GUI has been developed on MATLAB platform and provides as output the GHG emissions in terms of CO2 and N2O fluxes.
VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells
Abstract Anti-VEGF therapy perturbs tumor metabolism, severely impairing oxygen, glucose, and ATP levels. In this study, we investigated the effects of anti-VEGF therapy in multiple experimental tumor models that differ in their glycolytic phenotypes to gain insights into optimal modulation of the metabolic features of this therapy. Prolonged treatments induced vascular regression and necrosis in tumor xenograft models, with highly glycolytic tumors becoming treatment resistant more rapidly than poorly glycolytic tumors. By PET imaging, prolonged treatments yielded an increase in both hypoxic and proliferative regions of tumors. A selection for highly glycolytic cells was noted and this met…
Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era
Abstract Aims To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P …
Toward a New Plant-Wide Experimental and Modeling Approach for Reduction of Greenhouse Gas Emission from Wastewater Treatment Plants
Mechanisms causing greenhouse gas (GHG) emission in wastewater treatment plants are of great interest among researchers, encouraging the development of new methods for wastewater management. Wastewater treatment plants (WWTPs) emit three major greenhouse gases during the treatment processes: CO2, CH4, and N2O. Additional amounts of CO2 and CH4 are produced during energy consumption, which can be considered an indirect source of GHGs. Recently, several efforts have been undertaken to assess GHGs from WWTPs, with particular attention paid to the N2O assessment due to its high warming potential (300 times stronger than CO2). This study proposes an integrated model platform for WWTP simulation,…
Dewaterability of CAS and MBR Sludge: Effect of Biological Stability and EPS Composition
The dewaterability of sludge from two conventional activated sludge (CAS) and three membrane bioreactor (MBR)-based wastewater treatment plants is investigated prior to and after anaerobic digestion. The concentration and composition of extracellular polymeric substances (EPS) mostly affect the dewaterability of all raw sludge samples. Better sludge dewaterability is observed when the concentration of proteins, carbohydrates, uronic acids, and humic acids is below approximately 400, 250, 200, and 40 mg/L, respectively. In contrast, the specific resistance to filtration (SRF) increases in the sludge samples with a higher EPS concentration. The MBR results in a lower EPS production and a uron…
MiR-133 Modulates the β1Adrenergic Receptor Transduction Cascade.
Rationale : The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, overactivation of the sympathetic nervous system induces the release of catecholamines, which activate β-adrenergic receptors in cardiomyocytes and lead to increased heart rate and cardiac contractility. However, chronic stimulation of β-adrenergic receptors leads to impaired cardiac function, and β-blockers are widely used as therapeutic agents for the treatment of cardiac disease. MicroRNA-133 (miR-133) is highly expressed in the myocardium and is involved in controlling cardiac function through regulation of messenger RNA translation/stability. …
Towards A New Decision Support System for Design, Management and Operation of Wastewater Treatment Plants for the Reduction of Greenhouse Gases Emission
The increasing attention paid to the environment has led to a reduction in the emissions from wastewater treatment plants (WWTPs). Moreover, the increasing interest in the greenhouse gas (GHG) emissions from WWTPs suggests that we reconsider the traditional tools used for designing and managing WWTPs. Indeed, nitrous oxide, carbon dioxide and methane can be emitted from wastewater treatment, significantly contributing to the greenhouse gas (GHG) footprint. The reduction of energy consumption as well as GHG emission are of particular concern for large WWTPs which treat the majority of wastewater in terms of both volume and pollution load. Nowadays, there is an increasing need to develop new …
A novel comprehensive procedure for estimating greenhouse gas emissions from water resource recovery facilities
The emissions of the major greenhouse gases (GHGs), i.e. carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) from water resource recovery facilities (WRRFs) are of increasing concern in the water industry. In order to produce useful and comparable information for monitoring, assessing, and reporting GHG emissions from WRRFs, there is a need for a generally accepted methodology for their quantification. This paper aims at proposing the first protocol for monitoring and accounting for GHG emissions from WRRFs, taking into account both direct and indirect internal emissions and focusing the attention on plant sections known to be primarily responsible for GHG emissions (i.e. oxidation…
Hypoxia inducible factor-1alpha inactivation unveils a link between tumor cell metabolism and hypoxia-induced cell death.
Hypoxia and the acquisition of a glycolytic phenotype are intrinsic features of the tumor microenvironment. The hypoxia inducible factor-1alpha (HIF-1alpha) pathway is activated under hypoxic conditions and orchestrates a complex transcriptional program that enhances cell survival. Although the consequences of HIF-1alpha inactivation in cancer cells have been widely investigated, only a few studies have addressed the role of HIF-1alpha in the survival of cancer cells endowed with different glycolytic capacities. In this study, we investigated this aspect in ovarian cancer cells. Hypoxia-induced toxicity was increased in highly glycolytic cells compared with poorly glycolytic cells; it was a…
Membrane bioreactors sludge: From production to disposal
Abstract This chapter reviews the MBR activated sludge from production to disposal. Starting from sludge characterization, the chapter first presents the features of MBR sludge (morphology and EPS chemical composition), also in terms of differences with the activated sludge from conventional activated sludge plants. Sludge dewaterability is then discussed, focusing on the differences between aerobically and anaerobically digested sludge. An analysis of the costs related to MBR sludge treatment and disposal also is presented in order to provide a framework for a sustainable MBR sludge management.
Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure
AIMS: Recent studies have demonstrated the importance of chromatin remodelling via histone acetylation/deacetylation for the control of cardiac gene expression. Specific histone deacetylases (HDACs) can, in fact, play a positive or negative role in determining cardiac myocyte (CM) size. Here, we report on the effect on hypertrophy development of three inhibitors (HDACi) of class I HDACs. METHODS AND RESULTS: The compounds were first analysed in vitro by scoring hypertrophy, expression of foetal genes, and apoptosis of neonatal rat CMs stimulated with phenylephrine, an alpha1-adrenergic agonist. This initial screening indicated that a truncated derivative of apicidin with class I HDAC specif…
Greenhouse gases from wastewater treatment — A review of modelling tools
Nitrous oxide, carbon dioxide and methane are greenhouse gases (GHG) emitted from wastewater treatment that contribute to its carbon footprint. As a result of the increasing awareness of GHG emissions from wastewater treatment plants (WWTPs), new modelling, design, and operational tools have been developed to address and reduce GHG emissions at the plant-wide scale and beyond. This paper reviews the state-of-the-art and the recently developed tools used to understand and manage GHG emissions from WWTPs, and discusses open problems and research gaps. The literature review reveals that knowledge on the processes related to N2O formation, especially due to autotrophic biomass, is still incompl…
A new plant wide modelling approach for the reduction of greenhouse Gas emission from wastewater treatment plants
Recent studies about greenhouse gas (GHG) emissions show that sewer collection systems and wastewater treatment plants (WWTPs) are anthropogenic GHG potential sources. Therefore, they contribute to the climate change and air pollution. This increasing interest towards climate change has led to the development of new tools for WWTP design and management. This paper presents the first results of a research project aiming at setting-up an innovative mathematical model platform for the design and management of WWTPs. More specifically, the study presents the project’s strategy aimed at setting-up a plant-wide mathematical model which can be used as a tool for reducing/controlling GHG from WWTP.…