Enhanced Label-Free Nanoplasmonic Cytokine Detection in SARS-CoV-2 Induced Inflammation Using Rationally Designed Peptide Aptamer.

Rapid and precise serum cytokine quantification provides immense clinical significance in monitoring the immune status of patients in rapidly evolving infectious/inflammatory disorders, examplified by the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, real-time information on predictive cytokine biomarkers to guide targetable immune pathways in pathogenic inflammation is critically lacking, because of the insufficient detection range and detection limit in current label-free cytokine immunoassays. In this work, we report a highly sensitive localized surface plasmon resonance imaging (LSPRi) immunoassay for label-free Interleukin 6 (IL-6) detection utilizing rationally designed peptide aptamers as the capture interface. Benefiting from its characteristically smaller dimension and direct functionalization on the sensing surface via Au-S bonding, the peptide-aptamer-based LSPRi immunoassay achieved enhanced label-free serum IL-6 detection with a record-breaking limit of detection down to 4.6 pg/mL, and a wide dynamic range of ∼6 orders of magnitude (values from 4.6 to 1 × 106 pg/mL were observed). The immunoassay was validated in vitro for label-free analysis of SARS-CoV-2 induced inflammation, and further applied in rapid quantification of serum IL-6 profiles in COVID-19 patients. Our peptide aptamer LSPRi immunoassay demonstrates great potency in label-free cytokine detection with unprecedented sensing capability to provide accurate and timely interpretation of the inflammatory status and disease progression, and determination of prognosis.

Long, Noncoding RNA Dysregulation in Glioblastoma.

Transcription occurs across more than 70% of the human genome and more than half of currently annotated genes produce functional noncoding RNAs. Of these transcripts, the majority-long, noncoding RNAs (lncRNAs)-are greater than 200 nucleotides in length and are necessary for various roles in the cell. It is increasingly appreciated that these lncRNAs are relevant in both health and disease states, with the brain expressing the largest number of lncRNAs compared to other organs. Glioblastoma (GBM) is an aggressive, fatal brain tumor that demonstrates remarkable intratumoral heterogeneity, which has made the development of effective therapies challenging. The cooperation between genetic and epigenetic alterations drives rapid adaptation that allows therapeutic evasion and recurrence. Given the large repertoire of lncRNAs in normal brain tissue and the well-described roles of lncRNAs in molecular and cellular processes, these transcripts are important to consider in the context of GBM heterogeneity and treatment resistance. Herein, we review the general mechanisms and biological roles of lncRNAs, with a focus on GBM, as well as RNA-based therapeutics currently in development.