Insight from atomistic molecular dynamics simulations into the supramolecular assembly of the aldo-keto reductase from Trypanosoma cruzi.

Context: Currently, Chagas disease represents an important public health problem affecting more than 8 million people worldwide. The vector of this disease is the Trypanosoma cruzi (Tc) parasite. Our research specifically focuses on the structure and aggregation states of the enzyme aldo-keto reductase of Tc (TcAKR) reported in this parasite.

Cellular Uptake Mechanism of Nucleic Acid Nanocapsules and Their DNA-Surfactant Building Blocks.

Nucleic acid nanocapsules (NANs) are enzyme-responsive DNA-functionalized micelles built for the controlled release of DNA-surfactant conjugates (DSCs) that present sequences with demonstrated therapeutic potential. Here, we investigate the mechanisms by which DSCs gain access to intracellular space and determine the effects of serum on the overall uptake and internalization mechanism of NANs. Using pharmacological inhibitors to selectively block certain pathways, we show, through confocal visualization of cellular distribution and flow cytometry quantification of total cellular association, that scavenger receptor-mediated, caveolae-dependent endocytosis is the major cellular uptake pathway of NANs in the presence and absence of serum.

First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study.

Current hepatic locoregional therapies are limited in terms of effectiveness and toxicities. Given promising pre-clinical results, a first in-human trial was designed to assess the technical effectiveness and safety profile of histotripsy, a noninvasive, non-thermal, non-ionizing focused ultrasound therapy that creates precise, predictable tissue destruction, in patients with primary and secondary liver tumors. A multicenter phase I trial (Theresa Study) was performed in a single country with 8 weeks of planned follow-up.

Liver Histotripsy Mediated Abscopal Effect-Case Report.

We present a case report that shows an abscopal effect in the context of a safety and efficacy clinical trial for histotripsy as ablation technique in liver tumors. The abscopal effect appears in the form of reduction in the volume of nontreated tumor lesions in the same organ, as well as sustained reduction of tumor marker [carcinoembryonic antigen (CEA)] that extends weeks away of the procedure. Histotripsy is a novel noninvasive, nonthermal, and nonionizing precise ablation technique for tissue destruction guided by ultrasonography.

Contrast-Enhanced Ultrasound: A Useful Tool to Study and Monitor Hepatic Tumors Treated With Histotripsy.

Histotripsy is a novel noninvasive nonthermal, nonionizing, and precise treatment technique for tissue destruction. Contrast-enhanced ultrasound (CEUS) improves the detection, characterization, and follow-up of hepatic lesions because it depicts accurately the vascular perfusion of both normal hepatic tissue and hepatic tumors. We present the spectrum of imaging findings of CEUS after histotripsy treatment of hepatic tumors.