Silica nanoparticles are a class of molecules commonly used in drug or gene delivery systems that either facilitate the delivery of therapeutics to specific drug targets or enable the efficient delivery of constructed gene products into biological systems. Some in vivo or in vitro studies have demonstrated the toxic effects of silica nanoparticles. Despite the availability of risk management tools in response to the growing use of synthetic silica in commercial products, the molecular mechanism of toxicity induced by silica nanoparticles is not well characterized. The purpose of this study was to elucidate the effects of silica nanoparticle exposure in three types of cells including human aortic endothelial cells, mouse-derived macrophages, and A549 non-small cell lung cancer cells using toxicogenomic analysis. The results indicated that among all three cell types, the TNF and MAPK signaling pathways were the common pathways upregulated by silica nanoparticles. These findings may provide insight into the effects of silica nanoparticle exposure in the human body and the possible mechanism of toxicity.

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Brachial-ankle pulse wave velocity (baPWV) is a noninvasive clinical test that provides quantification for the stiffness of both the aorta and peripheral arteries by measuring the brachial and tibial arterial wave velocities. The temporal pattern of baPWV values during aging was investigated in this paper. A gradual increase in baPWV with respect to age was observed, suggesting an increase in the stiffness of arterial vessels as age increases. The ΔbaPWV value, defined as the absolute value of the difference between bilateral baPWV, also showed a positive correlation with aging. Many underlying physiological conditions such as hyperlipidemia, hypertension, diabetes, and hyperglycemia have previously been shown to elevate baPWV and contribute to the decline of arterial function. The effect of factors including biological sex, blood pressure, and blood glucose levels on the baPWV temporal pattern were also investigated. Between the ages of 18 and 50, men in the study had significantly higher baPWV readings than females of comparable age on average. However, after the age of 50, mean baPWV values increased at a greater rate in females than in males. In addition, blood pressure and blood glucose were shown to be associated with baPWV values. The results will improve existing prediction models for future cardiovascular episodes induced by arterial hardening in different age groups.

Background: Bradycardia is a physiological condition characterized by a decrease in heart rate and is a side effect of many drug classes. Bradycardia has been reported as an adverse event for patients receiving donepezil for Alzheimer’s disease (AD) treatment. Objective: The purpose of the paper is to systematically investigate the association between the occurrence of bradycardia in adults and the usage of donepezil using clinical data derived from the FDA Adverse Event Reporting System (FAERS) database. Methods: The risk of bradycardia in patients who only took donepezil was compared with those of patients who only took over-the-counter medications, multiple arrhythmia drugs, or other medications for AD treatment. In addition, this study sought to determine if this heightened bradycardia risk was influenced by sex, age, and dosage. Results: The results indicated that there was a significant greater likelihood of reporting bradycardia in patients administered donepezil than most of the drugs investigated. There was no significant association between age or the dosage of donepezil and the likelihood of reporting bradycardia. However, males were found to be more likely than females to report bradycardia as an adverse event. Tumor necrosis factor inhibition and stimulation of endothelial nitric oxide synthase were proposed to be the primary mechanism of actions which confer elevated bradycardia risk when using donepezil. Conclusion: These findings identified strong association between the usage of donepezil and bradycardia in adults as well as provide insight into the underlying molecular mechanisms that induce bradycardia by donepezil.