Protein-enriched extracts from housefly (Musca domestica) maggots alleviates atherosclerosis in apolipoprotein E-deficient mice by promoting bile acid production and consequent cholesterol consumption.

Currently, atherosclerosis control is important to prevent future heart attacks or strokes. Protein-enriched extract (PE) from housefly maggots (Musca domestica) can inhibit the development of atherosclerosis partially through its antioxidant effects. Whether PE exerts other anti-atherosclerosis functions remains unclear. Here, PE was found to simultaneously promote cholesterol metabolism effects in apolipoprotein E knockout (ApoE-/- ) mice. Bile acid synthesis plays a key role in regulating cholesterol homeostasis in atherosclerosis. Whether PE alleviates atherosclerosis by promoting bile acid production and consequent cholesterol consumption was further explored. First, 8-week-old male ApoE-/- mice were recruited and fed on a cholesterol-enriched diet. After 8 weeks, these mice were divided into three groups and received gavage administration of PE, simvastatin, and saline for another 8 weeks. Atherosclerosis severity was then assessed. Real-time quantitative polymerase chain reaction and western blot were employed to determine the expression of hepatic ATP-binding cassette transporter A1 (ABCA1), liver X receptor α (LXRα), and peroxisome proliferator-activated receptor-γ (PPAR-γ). Serum levels of high-density lipoprotein-cholesterol (HDL), low-density lipoprotein-cholesterol (LDL), and total cholesterol (TC) were determined by enzyme-linked immunoassay. Results revealed that PE reversed the formation of atherosclerotic lesion; increased the expression of PPAR-γ, LXRα, and ABCA1; increased the amount of bile flow and total bile acid; reduced the serum level of LDL and TC; and increased the level of HDL. In conclusion, enhancement on bile acid production and consequent cholesterol consumption may partially contribute to the anti-atherosclerotic effects of PE. The reversal of PPARγ-LXRα-ABCA1 signaling pathway may be involved in this process.

Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo.

Non-small cell lung cancer (NSCLC) is a highly lethal disease and the majority of NSCLC patients are desperate for therapies that can effectively target their cancer and ultimately improve their overall survival. Docetaxel (DTX) represents the first-line of the antitumor agent that is used to treat NSCLC; however, it has poor solubility in water and unsatisfactory encapsulation efficiency. In our study, exosomes were isolated from A549 cancer cells by ultracentrifugation and then characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot (WB). The particle size changes of EXO and EXO-DTX were measured daily for seven days to test the stability. DTX was selected payload by electroporation (EXO-DTX). For the in vitro evaluation, cell proliferation, cell cycle, cell apoptosis, reactive oxygen species (ROS) assay and cellular uptake were evaluated in the A549 cells. Also, this study evaluated the target and therapeutic effect of DTX as an antitumor agent in vivo. As a result, EXO-DTX with a particle size of 149.5 nm were successfully prepared and the cytotoxicity of the EXO-DTX was much greater than that of DTX monomers. Exosomes significantly increased the cellular uptake in vitro evaluation and showed better targeting to tumor tissue compared to the free DTX in the mice. We also explored the potential of tumor cell-derived exosomes as a drug delivery agent to target the parent cancer. Hence, we conclude that exosomes might be used as a potential antitumor drug delivery system (DDS).