Study of an Ultrasensitive Label-Free Electrochemiluminescent Immunosensor Fabricated with a Composite Electrode for Detecting the Glutamate Decarboxylase Antibody.

Antibody testing for the glutamic acid decarboxylase 65 antibody (GADA) is widely used as a golden standard for autoimmune diabetes diagnosis, while current methods for antibody testing are not sensitive enough for clinical usage. Here, a label-free electrochemiluminescent (ECL) immunosensor for detecting GADA in autoimmune diabetes is fabricated and investigated. In the designed immunosensor, a composite film including the multiwalled carbon nanotubes (MWCNTs), zinc oxide (ZnO), and Au nanoparticles (AuNPs) was prepared through nanofabrication processes to improve the performance of sensor. The MWCNTs, which can provide a larger specific surface area, ZnO as a good photocatalytic material, and AuNPs that can enhance the ECL signal of luminol and immobilize the GAD65 antigen were applied to prefunctionalize indium tin oxide (ITO) glass based on a nanofabrication process. The GADA concentration was detected using the ECL immunosensor after incubating with GAD65 antigen-coated prefunctionalized ITO glass. After a direct immunoreaction, it is found that the degree of decreased ECL intensity has a good linear regression toward the logarithm of the GADA concentration in the range of 0.01 to 50 ng mL-1 with a detection limit down to 10 pg mL-1. Human serum samples positive or negative for GADA all nicely fell in the expected area. The fabricated immunosensor with excellent sensitivity, specificity, and stability has potential capability for clinical usage in GADA detection.

Disruption of MAP7D1 Gene Function Increases the Risk of Doxorubicin-Induced Cardiomyopathy and Heart Failure.

Doxorubicin is a cornerstone chemotherapeutic drug widely used to treat various cancers; its dose-dependent cardiomyopathy, however, is one of the leading causes of treatment-associated mortality in cancer survivors. Patients' threshold doses leading to doxorubicin-induced cardiomyopathy (DIC) and heart failure are highly variable, mostly due to genetic variations in individuals' genomes. However, genetic susceptibility to DIC remains largely unidentified. Here, we combined a genetic approach in the zebrafish (Danio rerio) animal model with a genome-wide association study (GWAS) in humans to identify genetic susceptibility to DIC and heart failure. We firstly reported the cardiac and skeletal muscle-specific expression and sarcomeric localization of the microtubule-associated protein 7 domain-containing protein 1b (Map7d1b) in zebrafish, followed by expression validation in mice. We then revealed that disruption of the map7d1b gene function exaggerated DIC effects in adult zebrafish. Mechanistically, the exacerbated DIC are likely conveyed by impaired autophagic degradation and elevated protein aggregation. Lastly, we identified 2 MAP7D1 gene variants associated with cardiac functional decline and heart failure in cancer patients who received doxorubicin therapy. Together, this study identifies MAP7D1 as a clinically relevant susceptibility gene to DIC and heart failure, providing useful information to stratify cancer patients with a high risk of incurring severe cardiomyopathy and heart failure after receiving chemotherapy.