Gut-brain axis through the lens of gut microbiota and their relationships with Alzheimer's disease pathology: Review and recommendations.

Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. Growing evidence suggests that the gut microbiome (GM) plays a pivotal role in the pathogenesis of AD through the microbiota-gut-brain axis (MGB). Alterations in GM composition and diversity have been observed in both animal models and in human patients with AD. GM dysbiosis has been implicated in increased intestinal permeability, blood-brain barrier (BBB) impairment, neuroinflammation and the development of hallmarks of AD. Further elucidation of the role of GM in AD could pave way for the development of holistic predictive methods for determining AD risk and progression of disease. Furthermore, accumulating evidence suggests that GM modulation could alleviate adverse symptoms of AD or serve as a preventive measure. In addition, increasing evidence shows that Type 2 Diabetes Mellitus (T2DM) is often comorbid with AD, with common GM alterations and inflammatory response, which could chart the development of GM-related treatment interventions for both diseases. We conclude by exploring the therapeutic potential of GM in alleviating symptoms of AD and in reducing risk. Furthermore, we also propose future directions in AD research, namely fecal microbiota transplantation (FMT) and precision medicine.

Materials for Improving Immune Cell Transfection.

Chimeric antigen receptor T cell (CAR-T) therapy holds great promise for preventing and treating deadly diseases such as cancer. However, it remains challenging to transfect and engineer primary immune cells for clinical cell manufacturing. Conventional tools using viral vectors and bulk electroporation suffer from low efficiency while posing risks like viral transgene integration and excessive biological perturbations. Emerging techniques using microfluidics, nanoparticles, and high-aspect-ratio nanostructures can overcome these challenges, and on top of that, provide universal and high-throughput cargo delivery. Herein, the strengths and limitations of traditional and emerging materials for immune cell transfection, and commercial development of these tools, are discussed. To enhance the characterization of transfection techniques and uptake by the clinical community, a list of in vitro and in vivo assays to perform, along with relevant protocols, is recommended. The overall aim, herein, is to motivate the development of novel materials to meet rising demand in transfection for clinical CAR-T cell manufacturing.