Transcriptional landscape of human microglia implicates age, sex, and APOE-related immunometabolic pathway perturbations.

Microglia have fundamental roles in health and disease; however, effects of age, sex, and genetic factors on human microglia have not been fully explored. We applied bulk and single-cell approaches to comprehensively characterize human microglia transcriptomes and their associations with age, sex, and APOE. We identified a novel microglial signature, characterized its expression in bulk tissue and single-cell microglia transcriptomes. We discovered microglial co-expression network modules associated with age, sex, and APOE-ε4 that are enriched for lipid and carbohydrate metabolism genes. Integrated analyses of modules with single-cell transcriptomes revealed significant overlap between age-associated module genes and both pro-inflammatory and disease-associated microglial clusters. These modules and clusters harbor known neurodegenerative disease genes including APOE, PLCG2, and BIN1. Meta-analyses with published bulk and single-cell microglial datasets further supported our findings. Thus, these data represent a well-characterized human microglial transcriptome resource and highlight age, sex, and APOE-related microglial immunometabolism perturbations with potential relevance in neurodegeneration.

Chitosan-Based Non-viral Gene and Drug Delivery Systems for Brain Cancer.

Central nervous system (CNS) tumors are a leading source of morbidity and mortality worldwide. Today, different strategies have been developed to allow targeted and controlled drug delivery into the brain. Gene therapy is a system based on the modification of patient's cells through the introduction of genetic material to exert a specific action. Administration of the foreign genetic material can be done through viral-mediated delivery or non-viral delivery via physical or mechanical systems. For brain cancer specifically, gene therapy can overcome the actual challenge of blood brain barrier penetration, the main reason for therapeutic failure. Chitosan (CS), a natural based biodegradable polymer obtained from the exoskeleton of crustaceans such as crab, shrimp, and lobster, has been used as a delivery vehicle in several non-viral modification strategies. This cationic polysaccharide is highly suitable for gene delivery mainly due to its chemical properties, its non-toxic nature, its capacity to protect nucleic acids through the formation of complexes with the genetic material, and its ease of degradation in organic environments. Recent evidence supports the use of CS as an alternative gene delivery system for cancer treatment. This review will describe multiple studies highlighting the advantages and challenges of CS-based delivery structures for the treatment of brain tumors. Furthermore, this review will provide insight on the translational potential of various CS based-strategies in current clinical cancer studies. Specifically, CS-based nanostructures including nanocapsules, nanospheres, solid-gel formulations, and nanoemulsions, also microshperes and micelles will be evaluated.