Transcription factors play crucial roles in governing gene expression and are implicated in various physiological and pathological processes. Here, we propose a novel electrochemiluminescence (ECL) biosensor for the sensitive and specific detection of the transcription factor NF-kB p50, utilizing CRISPR/Cas12a-assisted hyperbranched rolling circle amplification (HRCA) technology. The biosensor achieves a remarkable limit of detection (LOD) of 3.6 fM and demonstrates excellent specificity against interfering proteins. Optimization of experimental parameters further enhances the biosensor’s performance, ensuring its reliability and accuracy. In addition, validation in real biological samples confirms the feasibility of biosensor for practical applications, offering a promising tool for clinical trials and disease diagnosis.
Specifically inhibiting the proliferation of activated macrophages and clearing the high levels of reactive oxygen species (ROS) secreted by macrophages is crucial for osteoarthritis (OA) treatment. Moreover, if the clearance of these high levels of ROS can be simultaneously used to induce oxidation-responsive release of anti-inflammatory drugs, the therapeutic effect of OA may be further improved. Here, a multifunctional anti-inflammatory drug (CPHs) based on a peptide dendrimer nanogel was constructed by physically encapsulating CORM-401 and wrapping its surface with folic acid (FA)-modified hyaluronic acid (HA). CPHs is capable of efficiently entering activated macrophages via FA- and HA-mediated specific targeting effects and then rapidly release large amounts of CO by massive consumption of H 2 O 2 . The generated CO effectively suppresses the secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α by inhibiting cell proliferation ; inducing the activation of heme oxygenase (HO-1), and downregulating the expression of p38 MAPK , NF-kB (p50/p65) and TLR-2. In vivo experiments further confirmed that CPHs can massively deplete ROS in OA joints and effectively suppress the degradation of articular cartilage and their extracellular matrix. More importantly, CPHs is non-toxic to normal macrophages, and the high levels of CO generated in the joints do not result in notable changes in the HbCO levels in blood. Together, these results show that CPHs is an effective and safe anti-inflammatory drug and has essential application prospects in OA treatment.
危险品化学品经营许可证（带存储）