Microbubbles in combination with focused ultrasound for the delivery of quercetin-modified sulfur nanoparticles through the blood brain barrier into the brain parenchyma and relief of endoplasmic reticulum stress to treat Alzheimer's disease.

The delivery of drugs across the blood-brain barrier (BBB) effectively and safely is one of the major challenges in the treatment of neurodegenerative diseases. In this work, we constructed a nano-system using microbubbles to promote the crossing of drugs across the BBB, where microbubbles in combination with focused ultrasound were used to mediate the transient opening of the BBB and delivery of nanomedicines. This system (Qc@SNPs-MB) was formed by embedding quercetin-modified sulfur nanoparticles (Qc@SNPs) in microbubbles (MB). Qc@SNPs-MB was destroyed instantly when exposed to ultrasonic pulses, and it enhanced the permeability of the blood vessels, resulting in the brief opening of the BBB owing to the "sonoporation" effect. Also, Qc@SNPs were released from the outer shell of the microbubbles and entered the brain across the open BBB, accumulating in the brain parenchyma. Due to the rapid accumulation of Qc@SNPs in the brain, it effectively reduced neuronal apoptosis, inflammatory response, calcium homeostasis imbalance, and oxidative stress, which are all mediated by endoplasmic reticulum stress, and protected nerve cells, thus treating Alzheimer's disease (AD) effectively. The Morris water maze experiment showed that the learning ability and memory ability of the AD mice treated with Qc@SNPs were significantly improved, and no obvious side effects were found. Therefore, Qc@SNPs-MB combined with ultrasound can provide an effective and safe drug delivery method for the treatment of neurodegenerative diseases and a promising strategy for endoplasmic reticulum stress therapy.

Contrast echocardiography: clinical utility for the evaluation of left ventricular systolic function.

Despite continued improvements in imaging technology, transthoracic echocardiography does not reliably provide images adequate for interpretation in all patients. In these patients, the administration of ultrasound contrast agents can markedly enhance the diagnostic utility of the test. Contrast echocardiography relies on the ultrasound detection of contrast agents composed of encapsulated microbubbles that are generally smaller than red blood cells. Intravenous administration of microbubble contrast agents results in left ventricular opacification and facilitates delineation of the endocardial border. This procedure has been shown to consistently increase the number of myocardial segments that can be interpreted, to improve accuracy of assessing regional and global left ventricular function, to decrease interinterpreter variability, to increase interpreter confidence, and to be a cost-effective strategy. Accordingly, patient selection for contrast echocardiography should be based not only on adequacy of the baseline images, but also on the clinical question being asked.