"ST-elevation myocardial infarction associated with air pollution levels in Mexico City".

Background Coronary heart disease has multiple risk factors, including air pollution. Numerous pathophysiological mechanisms have been identified with increasing levels of air pollution, mainly with ozone (O3), nitrogen dioxide (NO2), sulphur dioxide (SO2), particulate matter (PM10), fine particulate matter (PM2.5) and carbon monoxide (CO). In Mexico, the pollution level is reported using an air quality index called IMECA. Methods All patients with STEMI admitted at Hospital Español were collected between 2012 and 2019 (N = 348). We conducted a retrospective analysis using the air pollution exposure at the time of each event (lag0), the previous 24 h (lag1), 48 h (lag2), 72 h (lag3) and 5-day cumulative lag. The level of air pollution was analyzed independently using IMECA and particle concentrations. The data was divided in two groups: days with one of more STEMI's (MI group) and days free of events (Control group), using ANCOVA to evaluate the difference between means of both groups taking into account confounders. Results: For days with one or more cardiovascular event, a significant increase in SO2 was observed at lag1; similar increase was found in CO, PM2.5, SO2 at lag2. For the 5-day cumulative lag, SO2 and PM2.5 showed a significant increase. No differences were found using the IMECA levels in both groups. Conclusions: The elevated concentrations levels of CO, SO2 and PM2.5 showed significant association with STEMI at different time points before the event. Ozone, PM10 and NO2 showed no difference between groups. IMECA levels showed no association with STEMI in our study.

Re-establishment of the epigenetic state and rescue of kinome deregulation in Ts65Dn mice upon treatment with green tea extract and environmental enrichment.

Down syndrome (DS) is the main genetic cause of intellectual disability due to triplication of human chromosome 21 (HSA21). Although there is no treatment for intellectual disability, environmental enrichment (EE) and the administration of green tea extracts containing epigallocatechin-3-gallate (EGCG) improve cognition in mouse models and individuals with DS. Using proteome, and phosphoproteome analysis in the hippocampi of a DS mouse model (Ts65Dn), we investigated the possible mechanisms underlying the effects of green tea extracts, EE and their combination. Our results revealed disturbances in cognitive-related (synaptic proteins, neuronal projection, neuron development, microtubule), GTPase/kinase activity and chromatin proteins. Green tea extracts, EE, and their combination restored more than 70% of the phosphoprotein deregulation in Ts65Dn, and induced possible compensatory effects. Our downstream analyses indicate that re-establishment of a proper epigenetic state and rescue of the kinome deregulation may contribute to the cognitive rescue induced by green tea extracts.

Efficacy of dietary intervention and physical activity in children and adolescents with nonalcoholic fatty liver disease associated with obesity: A scoping review. / Eficacia de la intervención nutricia y de la actividad física en niños y adolescentes con hígado graso no alcohólico asociado a obesidad: revisión sistemática exploratoria.

AIM: To identify and discuss the efficacy of dietary interventions, antioxidant supplementation, physical activity, and nutritional and psychologic counseling in the treatment of children and adolescents with non alcoholic fatty liver disease associated with obesity. MATERIALS AND METHODS: A scoping review of studies on nutritional and educational interventions and physical activity in pediatric patients with non alcoholic fatty liver disease was conducted. A search for randomized clinical trials or quasi-experimental studies published up to December 2017 was carried out, utilizing seven databases (Medline, EBSCO, OVID, Science Direct, JSTOR, Wiley, and Biblioteca Digital UDG). RESULTS: From a total of 751 articles, 729 were excluded due to the criteria of age, design, language, diagnostic method, and outcome variables. The analysis included 22 articles. The most frequently used intervention variables were diet and physical activity. The interventions had different durations, but most were carried out for one year. Some authors employed ascorbic acid, vitamin E, or omega-3 fatty acid supplementation. There were varying degrees of improvement in the variables analyzed in the majority of the studies, such as a decrease in ALT levels, a reduced frequency of steatosis determined through imaging studies, and a decrease in body mass index. CONCLUSIONS: The dietary interventions, omega-3 fatty acid supplementation, physical activity, and nutritional and psychologic counseling were identified as efficacious measures in the treatment of non alcoholic fatty liver disease associated with obesity in children and adolescents, according to biochemical or imaging study indicators, within the time frame of the intervention.

Chemically synthesized peptide libraries as a new source of BBB shuttles. Use of mass spectrometry for peptide identification.

The blood-brain barrier (BBB) is a biological barrier that protects the brain from neurotoxic agents and regulates the influx and efflux of molecules required for its correct function. This stringent regulation hampers the passage of brain parenchyma-targeting drugs across the BBB. BBB shuttles have been proposed as a way to overcome this hurdle because these peptides can not only cross the BBB but also carry molecules which would otherwise be unable to cross the barrier unaided. Here we developed a new high-throughput screening methodology to identify new peptide BBB shuttles in a broadly unexplored chemical space. By introducing d-amino acids, this approach screens only protease-resistant peptides. This methodology combines combinatorial chemistry for peptide library synthesis, in vitro models mimicking the BBB for library evaluation and state-of-the-art mass spectrometry techniques to identify those peptides able to cross the in vitro assays. BBB shuttle synthesis was performed by the mix-and-split technique to generate a library based on the following: Ac-d-Arg-XXXXX-NH2 , where X were: d-Ala (a), d-Arg (r), d-Ile (i), d-Glu (e), d-Ser (s), d-Trp (w) or d-Pro (p). The assays used comprised the in vitro cell-based BBB assay (mimicking both active and passive transport) and the PAMPA (mimicking only passive diffusion). The identification of candidates was determined using a two-step mass spectrometry approach combining LTQ-Orbitrap and Q-trap mass spectrometers. Identified sequences were postulated to cross the BBB models. We hypothesized that some sequences cross the BBB through passive diffusion mechanisms and others through other mechanisms, including paracellular flux and active transport. These results provide a new set of BBB shuttle peptide families. Furthermore, the methodology described is proposed as a consistent approach to search for protease-resistant therapeutic peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

all-D proline-rich cell-penetrating peptides: a preliminary in vivo internalization study.

Proline-rich cell-penetrating peptides, particularly the SAP (sweet arrow peptide), (VRLPPP)(3), have been proposed to be useful intracellular delivery vectors, as a result of their lack of cytotoxicity combined with their capacity to be internalized by cells. A common limitation of the therapeutic use of peptides is metabolic instability. In general, peptides are quickly degraded by proteases upon entry into the bloodstream. The use of all-D-peptide derivatives is emerging as a fruitful strategy to circumvent this degradation problem. In this context, we report on the internalization behaviour, protease-resistance enhancement and self-assembly properties of an all-D version of SAP [(vrlppp)(3)]. The cellular uptake of (vrlppp)(3) was evaluated in an in vivo assay in mice. Both flow cytometry and confocal laser-scanning microscopy experiments showed that a carboxyfluoresceinated version of the molecule, carboxyfluorescein-(vrlppp)(3), is internalized rapidly in white blood cells and kidney cells. Significant fluorescence was also detected in other organs such as the spleen and the liver. Finally, the toxicity of (vrlppp)(3) was examined, and no significant differences in the main biochemical parameters nor in weight were detected compared with controls.