bioRxiv Science⌕ Search

Biology subjects

Applegate, C. C.

Publications and source records attributed to Applegate, C. C..

2 recordsLinked to original sources

The Role of the Receptor for Advanced Glycation End-Products in Cancer: Evidence from a Systematic Review and Meta-Analysis

The Receptor for Advanced Glycation End-products (RAGE) has been implicated in driving cancer growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarize and analyze current clinical and preclinical data to provide insight into the relationship between RAGE and cancer, cancer grade, metastasis, patient survival, and cellular processes. A multi-database search was performed to identify original clinical and preclinical research studies examining RAGE expression in cancer. After screening and review, 53 clinical and 233 preclinical studies were included. Associations of RAGE with clinical cancer outcomes were estimated using odds ratio (OR) and associated 95% confidence intervals (CI). The meta-analysis found that RAGE expression was highly correlated with cancerous tissue when compared to controls; high-grade tumors; regional lymph node invasion; and was somewhat negatively associated with patient survival. In addition, meta-analysis estimates of preclinical studies found positive associations between RAGE expression/activation and cancer growth, metastatic potential, evasion of apoptosis, and activated NF-{kappa}B expression. This systematic review and meta-analysis is the first comprehensive study through which both preclinical and clinical research in all available cancer types are assessed for correlations with RAGE expression and activation, demonstrating that RAGE does indeed play a significant role in cancer progression and that further research is warranted.

cancer biology↗

Lipid Nanoparticle Barcoding for Multiplexed Single-Cell RNA Sequencing

Sample multiplexing is an emerging method in single-cell RNA sequencing (scRNA-seq) that addresses high costs and batch effects. Current multiplexing schemes use DNA labels to barcode cell samples but are limited in their stability and extent of labeling across heterogeneous cell populations. Here, we introduce Nanocoding using lipid nanoparticles (LNPs) for high barcode labeling density in multiplexed scRNA-seq. LNPs reduce dependencies on cell surface labeling mechanisms due to multiple controllable means of cell uptake, amplifying barcode loading 10-100-fold and allowing both protection and efficient release by dissolution. In cultured cell lines and heterogeneous cells from tissue digests, Nanocoding occurs in 40 minutes with stability after sample mixing and requires only commercially available reagents without novel chemical modifications. In spleen digests, 6-plex barcoded samples show minimal unlabeled cells, with all barcodes giving bimodal count distributions. Challenging samples containing lipid-rich debris and heterogeneous cells from adipose tissue of obese rodents show more than 95% labeling with all known subtypes identified. Using Nanocoding, we investigate gene expression changes related to aging in adipose tissue, profiling cells that could not be readily identified with current direct conjugate methods using lipid or antibody conjugates. This ease of generating and tuning these constructs may afford efficient and robust whole-sample multiplexing with minimal sample crosstalk.

bioengineering↗