Development and optimisation of in vitro sonodynamic therapy for glioblastoma.

Sonodynamic therapy (SDT) is currently on critical path for glioblastoma therapeutics. SDT is a non-invasive approach utilising focused ultrasound to activate photosensitisers like 5-ALA to impede tumour growth. Unfortunately, the molecular mechanisms underlying the therapeutic functions of SDT remain enigmatic. This is primarily due to the lack of intricately optimised instrumentation capable of modulating SDT delivery to glioma cells in vitro. Consequently, very little information is available on the effects of SDT on glioma stem cells which are key drivers of gliomagenesis and recurrence. To address this, the current study has developed and validated an automated in vitro SDT system to allow the application and mapping of focused ultrasound fields under varied exposure conditions and setup configurations. The study optimizes ultrasound frequency, intensity, plate base material, thermal effect, and the integration of live cells. Indeed, in the presence of 5-ALA, focused ultrasound induces apoptotic cell death in primary patient-derived glioma cells with concurrent upregulation of intracellular reactive oxygen species. Intriguingly, primary glioma stem neurospheres also exhibit remarkably reduced 3D growth upon SDT exposure. Taken together, the study reports an in vitro system for SDT applications on tissue culture-based disease models to potentially benchmark the novel approach to the current standard-of-care.

Peptidomics comparison of plant-based meat alternatives and processed meat after in vitro digestion.

Plant-based meat alternatives (PMAs) is a new type of food that meets people's health needs, but the lack of awareness of its nutritional properties limits product development and promotion. Here, we compared the similarities and differences of the nutritional properties of PMAs and meat before and after in vitro simulation of gastrointestinal digestion by chemical composition analysis, peptidomics and bioactivity tests. The molecular weights of Plant-based meat alternatives derived peptides (PDPs) as well as meat-derived peptides (MDPs) in the beef and pork groups were mainly concentrated in the low mass range from 800 Da to 1500 Da. The principal component analysis indicated that the composition of MDPs in the beef and pork groups significantly differed from PDPs but overlapped slightly with the chicken group. Also, there were very few common peptides among them. The proportion of high-biological-scoring peptides (33.3%-40%) in PDPs was more than that in MDPs (4.8%-20.8%). PDPs were predicted to have higher antibacterial activity than others. PDPs and MDPs showed a certain antioxidant capacity and angiotensin converting enzyme inhibitory activity (62.2%-92.5%) in vitro. Some peptides weakly inhibited the growth of Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) while promoting the growth of probiotics. This research provides a theoretical basis for in-depth exploration of the nutritional characteristics of PMAs.