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Logan Carson posted an update 1 year, 5 months ago
In this perspective article, we delineate the connection between aging, epigenetics, and environmental exposures. We discuss why it is essential to consider age when researching how an organism interacts with its environment. We describe recent advances in understanding how the chemical environment affects aging and the gap in research on how age affects an organism’s response to the environment. Finally, we highlight how model organisms and network approaches can help fill this crucial gap. Taken together, systemic changes that occur in the epigenome with age indicate that adult organisms cannot be treated as a homogeneous population and that there are discrete mechanisms modulating the aging epigenome that we do not yet understand.Phthalate plasticizers are ubiquitous chemicals linked to several cardiovascular diseases in animal models and humans. Despite this, the mechanisms by which phthalate exposures cause adverse cardiac health outcomes are unclear. In particular, whether phthalate exposures during pregnancy interfere with normal developmental programming of the cardiovascular system, and the resulting implications this may have for long-term disease risk, are unknown. Recent studies suggest that the effects of phthalates on metabolic and neurobehavioral outcomes are sex-specific. However, the influence of sex on cardiac susceptibility to phthalate exposures has not been investigated. One mechanism by which developmental exposures may influence long-term health is through altered programming of DNA methylation. In this work, we utilized an established mouse model of human-relevant perinatal exposure and enhanced reduced representation bisulfite sequencing to investigate the long-term effects of diethylhexyl phthalate (DEHP) exposure on DNA methylation in the hearts of adult male and female offspring at 5 months of age (n = 5-7 mice per sex and exposure). Perinatal DEHP exposure led to hundreds of sex-specific, differentially methylated cytosines (DMCs) and differentially methylated regions (DMRs) in the heart. Pathway analysis of DMCs revealed enrichment for several pathways in females, including insulin signaling, regulation of histone methylation, and tyrosine phosphatase activity. In males, DMCs were enriched for glucose transport, energy generation, and developmental programs. Notably, many sex-specific genes differentially methylated with DEHP exposure in our mouse model were also differentially methylated in published data of heart tissues collected from human heart failure patients. Together, these data highlight the potential role for DNA methylation in DEHP-induced cardiac effects and emphasize the importance of sex as a biological variable in environmental health studies.In living systems, the biomolecules that coat nanoparticles (NPs) alter the NP biological identity and response. Although some biomolecules are more effective in mediating NP stability or biological fate, it is difficult to monitor an individual biomolecule within the complexity of the biota. To understand the dependence of protein-NP interactions on common variations in blood, we have evaluated binding between silica NPs and a model gamma-fibrinogen (GF) peptide. Fibrinogen is commonly identified within the protein corona fingerprint of human serum, but its abundance on the NP varies. To assess the relative importance of human serum and solution conditions, GF peptide and silica NP interactions were evaluated with and without serum across pH, NaCl concentrations, and glucose concentrations. Initial evaluation of the GF peptide and silica NP complexes using circular dichroism and dynamic light scattering show little change in the secondary structure of the peptide and no significant agglomeration of NPs, suggesting peptide-NP complexes are stable across study conditions. Fluorescence anisotropy was used to monitor GF peptide-NP binding. Both with and without serum, binding constants for the gamma-fibrinogen peptide vary significantly upon addition of diluted HS (1500) and 29 mM sodium chloride. PCB chemical price Yet, results indicated that gamma-fibrinogen binding interactions with silica NPs are comparatively insensitive to physiologically relevant pH changes and dramatic increases in glucose concentrations. Results highlight the importance of blood chemistries, which vary across individuals and disease states, in mediating protein corona formation.
Takotsubo syndrome (TTS) is a reversible cardiomyopathy. Little is known regarding its basal form and possible complications.
A 31-year-old woman with no medical history was hospitalized for attempted suicide by ingestion of cocaine, benzodiazepine, and methadone. Initially, the patient received intensive care for coma and bradypnoea. After naloxone administration, the neurological situation improved, but the patient developed acute pulmonary oedema. Transthoracic echocardiography (TTE) revealed left ventricular systolic dysfunction with the basal wall’s akinesia associated with moderate to severe restrictive mitral regurgitation. Global longitudinal strain (GLS) was impaired mainly in the basal segments. A coronary computed tomography ruled out coronary artery disease. Symptoms improved quickly under diuretic treatment. Transthoracic echocardiography at Day 6 showed improved basal wall contraction, with a left ventricular ejection fraction (LVEF) of 50% and moderate mitral regurgitation. TTE at Day 30 confirmed the diagnosis of myocardial infarction with non-obstructive coronary arteries related to a basal TTS after complete recovery of the LVEF, normalization of the wall motion and GLS, and the absence of residual mitral regurgitation.
We report a case of acute pulmonary oedema due to basal TTS complicated by severe transient mitral regurgitation associated with moderate left ventricular dysfunction. Measuring strain by speckle-tracking can be useful to diagnose and monitor this entity. The use of coronary computed tomography is informative in young patients to rule-out coronary artery disease.
We report a case of acute pulmonary oedema due to basal TTS complicated by severe transient mitral regurgitation associated with moderate left ventricular dysfunction. Measuring strain by speckle-tracking can be useful to diagnose and monitor this entity. The use of coronary computed tomography is informative in young patients to rule-out coronary artery disease.

