91 research outputs found
D-Tagatose Feeding Reduces the Risk of Sugar-Induced Exacerbation of Myocardial I/R Injury When Compared to Its Isomer Fructose
No full textIt is known that fructose may contribute to myocardial vulnerability to ischemia/reperfusion (I/R) injury. D-tagatose is a fructose isomer with less caloric value and used as low-calorie sweetener. Here we compared the metabolic impact of fructose or D-tagatose enriched diets on potential exacerbation of myocardial I/R injury. Wistar rats were randomizedly allocated in the experimental groups and fed with one of the following diets: control (CTRL), 30% fructose-enriched (FRU 30%) or 30% D-tagatose-enriched (TAG 30%). After 24 weeks of dietary manipulation, rats underwent myocardial injury caused by 30 min ligature of the left anterior descending (LAD) coronary artery followed by 24 h′ reperfusion. Fructose consumption resulted in body weight increase (49%) as well as altered glucose, insulin and lipid profiles. These effects were associated with increased I/R-induced myocardial damage, oxidative stress (36.5%) and inflammation marker expression. TAG 30%-fed rats showed lower oxidative stress (21%) and inflammation in comparison with FRU-fed rats. Besides, TAG diet significantly reduced plasmatic inflammatory cytokines and GDF8 expression (50%), while increased myocardial endothelial nitric oxide synthase (eNOS) expression (59%). Overall, we demonstrated that D-tagatose represents an interesting sugar alternative when compared to its isomer fructose with reduced deleterious impact not only on the metabolic profile but also on the related heart susceptibility to I/R injury. © Copyright © 2021 Durante, Sgambellone, Lucarini, Failli, Laurino, Collotta, Provensi, Masini and Collino
Advanced glycation end products (AGEs) in metabolic disease: linking diet, inflammation and microbiota
No full textIntroduction: High sugar consumption promotes endogenous formation of advancedglycation end-products (AGEs), a heterogeneous class of molecules originated from nonenzymaticglycation between reducing sugars and free amino groups of proteins, nucleicacids, or lipids. AGEs accumulation in tissues has been linked to aging and diabetescomplications. AGEs might also play an independent role in inflammation and developmentof cardiovascular disease (CVD). Exogenous dietary AGEs, due to excess intake of modernheat-treated foods, might act synergistically with endogenous AGEs, thus contributing toincrease inflammation and CVD. A large amount of ingested AGEs reaches the colon, wherethey might affect gut microbial metabolism, for example, by acting as substrate for colonicbacterial fermentation, driving alterations of microbiota composition and of intestinalpermeability. However in vitro and in vivo studies (animal and human) on the impact of AGEson the gut microbiota are discordant. This study on mice aims to link the modulation of gutmicrobiota by AGEs-enriched diet (AGE-D) with metabolic and inflammatory markers.Materials and methods: C57BL/6 mice were randomly allocated into the following dietaryregimens: Control (n=24) and AGE-D (n=20) for 22 weeks. AGE-D was prepared replacingcasein (200 g/kg diet) by an equal amount of modified casein where 10% of arginine wasglycated with MG-H1 (methylglyoxal 5-hydro-5-methylimidazolone) for a total of 4 μmol ofMG-H1 per g of diet. Faeces were collected using metabolic cages (18 h starving) at week 0,11 and 22 for fecal DNA extraction and 16SrRNA analysis through Illumina MiSeq using V3-V4 targeted primers. After 22 weeks of dietary manipulation, mice were sacrificed, plasmaand organ lipid profiles and serum metabolic and inflammatory profiles were determined.Results and discussion: AGE-D caused a significant reduction in the blood levels of twoimportant components of the incretin system, GIP and GLP-1, when compared to control diet,suggestive of unbalance in the incretin-insulin axis. AGE-D exposure was associated with asignificant increase in systemic concentrations of inflammatory cytokines, e.g. IL-1β and IL-17, and PAI-1, which has been suggested as both reliable marker and critical mediator ofcellular senescence. We will present how AGEs impact on microbiome community structureand correlate changes in gut microbiota with GIP and GLP-1 levels.Conclusions: AGEs, characteristic of modern processed foods, appear to impact on theincretin-insulin axis, a key regulator of metabolic disease risk. Diets rich in AGEs may mediatethese physiological effects at least in part, by reshaping intestinal microbiota structure
Lightweighting in light commercial vehicles: cradle-to-grave life cycle assessment of a safety-relevant component
No full textPurpose Currently, the reduction of weight in automotive is a very important topic in order to lower the air pollution. In this context, the purpose of the present paper was to analyze a real case study through a comparison of the environmental sustainability between a conventional steel crossbeam for light commercial vehicles and an innovative lightweight aluminum one. Methods For both scenarios, a cradle-to-grave life cycle assessment methodology and a sensitivity analysis has been used through the study of the following phases: mineral extraction, component manufacturing, use on vehicle, and end of life. In particular, many primary data and a complete vehicle model simulation with three different European driving cycles have been used in order to reach the highest possible level of accuracy during the analysis. Results and discussion Regarding the manufacturing phase, the aluminum component’s production gave the highest impact because of the high energy required in the mineral reduction. Anyway, this stage of the analysis had a low effect on the entire LCA,becausethebenefitofweightreductionduringvehicleuseshowedastronglyhighercontribution.Theurbandrivingcycle had the most relevant impact, as a consequence of the frequent start and stop operations and the longest time with engine at idle speed, while the extra-urban cycle is the less demanding due to its higher average speed and no start and stop. Conclusions Inconclusion,thepresentresearchdemonstratedtheenvironmentalimportanceofthelightweightforanactualcase study in the commercial vehicles field
The hidden role of NLRP3 inflammasome in obesity-related COVID-19 exacerbations: Lessons for drug repurposing
No full textCOVID-19, the illness caused by SARS-CoV-2, has a wide-ranging clinical spectrum that, in the worst-case scenario, involves a rapid progression to severe acute respiratory syndrome and death. Epidemiological data show that obesity and diabetes are among the main risk factors associated with high morbidity and mortality. The increased susceptibility to SARS-CoV-2 infection documented in obesity-related metabolic derangements argues for initial defects in defence mechanisms, most likely due to an elevated systemic metabolic inflammation (“metaflammation”). The NLRP3 inflammasome is a master regulator of metaflammation and has a pivotal role in the pathophysiology of either obesity or diabetes. Here, we discuss the most recent findings suggesting contribution of NLRP3 inflammasome to the increase in complications in COVID-19 patients with diabesity. We also review current pharmacological strategies for COVID-19, focusing on treatments whose efficacy could be due, at least in part, to interference with the activation of the NLRP3 inflammasome. Linked Articles: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc
Environmental Assessment of Co-location Alternatives for a Microalgae Cultivation Plant: A Case Study in the City of Kingston (Canada)
No full textAbstractIn recent years there has been growing interest in the use of microalgae as a feedstock for biofuels, particularly for biodiesel. The production process of biodiesel from microalgae generally consists of five different phases: cultivation, harvesting, drying, lipid extraction and transesterification. While existing technologies are available to undertake each of these phases, the process would benefit from enhanced sustainability achieved by reducing environmental impact and costs. One process innovation currently under consideration is the use of waste products as inputs to the process, including CO2 captured from industrial flue gas, or nutrients from wastewater. These could be employed in algae cultivation. The co-location of an algae cultivation plant with other industrial facilities, such as a cement plant or a wastewater treatment facility, could result in significantly reduced atmospheric emissions and improve wastewater effluent discharges. A comparative life cycle assessment approach is used to examine two different, realistic alternatives for the co-location of an algae cultivation plant with an existing cement plant or wastewater treatment facility near Kingston, Ontario, Canada. The study seeks to identify a preferred siting option from the perspective of minimizing environmental impacts. The first alternative involves the co-location with the Lafarge Cement plant, on the north shore of Lake Ontario, near Bath Ontario. The second alternative consists in the co-location with the Ravensview wastewater treatment facility east of the city of Kingston on the St. Lawrence River. The algae production plant is based on an open pond technology and is assumed to have a production capacity of about 120 tons of dry microalgal biomass per year
The AGEs inhibitor pyridoxamine prevents kidney injury and dysfunction in mice fed high-fat high-fructose diet
No full textMetabotropic glutamate receptor blockade reduces preservation damage in livers from donors after cardiac death
No full textWe previously demonstrated that the blockade of mGluR5 by 2-methyl-6(phenylethynyl)pyridine (MPEP) reduces both cold and warm ischemia/reperfusion injury. Here we evaluated whether MPEP reduces the hepatic preservation injury in rat livers from cardiac-death-donors (DCDs). Livers from DCD rats were isolated after an in situ warm ischemia (30 min) and preserved for 22 h at 4 °C with UW solution. Next, 10 mg/Kg MPEP or vehicle were administered 30 min before the portal clamping and added to the UW solution (3 μM). LDH released during washout was quantified. Liver samples were collected for iNOS, eNOS, NO, TNF-α, ICAM-1, caspase-3 and caspase-9 protein expression and nuclear factor-erythroid-2-related fac-tor-2 (Nrf2) gene analysis. Lower LDH levels were detected in control grafts versus DCD groups. An increase in eNOS and NO content occurred after MPEP treatment; iNOS and TNF-α content was unchanged. ICAM-1 expression was reduced in the MPEP-treated livers as well as the levels of caspase-3 and caspase-9. Nrf2, oxidative stress-sensitive gene, was recovered to control value by MPEP. These results suggest that MPEP can be used to reclaim DCD livers subjected to an additional period of cold ischemia during hypothermic storage. MPEP protects against apoptosis and increased eNOS, whose overexpression has been previously demonstrated to be protective in hepatic ischemia/reperfusion damage
Cold ischemic injury is reduced by the mGluR5 negative allosteric modulator MPEP in rat livers from cardiac death donors
No full textWDR45 gene and its role in pediatric epilepsies
No full textWD repeat domain 45 (WDR45) gene has been increasingly found in patients with developmental delay (DD) and epilepsy. Previously, WDR45 de novo mutations were reported in sporadic adult and pediatric patients presenting iron accumulation, while heterozygous mutations were associated with β-propeller protein-associated neurodegeneration (BPAN), a subtype of neurodegeneration with brain iron accumulation disorders, characterized by extrapyramidal movement disorders and abnormal accumulation of iron in the basal ganglia. Overall, people harboring WDR45 mutations have moderate to severe DD and different types of seizures. The phenotype of adult patients is characterized by extrapyramidal movement, dystonia, parkinsonism, language impairment, and involvement of the substantia nigra and in the globus pallidus at brain magnetic resonance imaging. Importantly, there are no findings of brain iron accumulation in brain in BPAN patients in the first decade of life, thus suggesting a progressive course of the disease. Comparatively, the main phenotype of pediatric patients is epilepsy with early onset, most of which present infantile spasms and arrest or regression of psychomotor development. The phenotype of patients with WDR45 mutations is variable, being different if caused by somatic mosaicism or germline mutations, and presenting with a different spectrum of manifestations in males and females. The treatment of affected individuals is symptomatic. Regarding the seizures, specific, gene-based approaches with specific antiepileptic drugs are not currently available. The early diagnosis of BPAN could be useful in some aspects, such as providing families a supportive treatment to their affected children
The anti-inflammatory protein Annexin A1 as new pharmacological approach to counteract the deleterious effects of diet-induced metabolic derangements
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