RESUMEN
Neuregulin-1ß (NRG-1ß) is a growth and differentiation factor with pleiotropic systemic effects. Because NRG-1ß has therapeutic potential for heart failure and has known growth effects in skeletal muscle, we hypothesized that it might affect heart failure-associated cachexia, a severe co-morbidity characterized by a loss of muscle mass. We therefore assessed NRG-1ß's effect on intercostal skeletal muscle gene expression in a swine model of heart failure using recombinant glial growth factor 2 (USAN-cimaglermin alfa), a version of NRG-1ß that has been tested in humans with systolic heart failure. Animals received one of two intravenous doses (0.67 or 2 mg/kg) of NRG-1ß bi-weekly for 4 weeks, beginning one week after infarct. Based on paired-end RNA sequencing, NRG-1ß treatment altered the intercostal muscle gene expression of 581 transcripts, including genes required for myofiber growth, maintenance and survival, such as MYH3, MYHC, MYL6B, KY and HES1. Importantly, NRG-1ß altered the directionality of at least 85 genes associated with cachexia, including myostatin, which negatively regulates myoblast differentiation by down-regulating MyoD expression. Consistent with this, MyoD was increased in NRG-1ß-treated animals. In vitro experiments with myoblast cell lines confirmed that NRG-1ß induces ERBB-dependent differentiation. These findings suggest a NRG-1ß-mediated anti-atrophic, anti-cachexia effect that may provide additional benefits to this potential therapy in heart failure.
RESUMEN
The detection of early-stage cancer offers patients the best chance of treatment and could help reduce cancer mortality rates. However, cancer cells or biomarkers are present in extremely small amounts in the early stages of cancer, requiring high-precision quantitative approaches with high sensitivity for accurate detection. With the advantages of simplicity, rapid response, reusability, and a low cost, aptamer-based electrochemical biosensors have received considerable attention as a promising approach for the clinical diagnosis of early-stage cancer. Various methods for developing highly sensitive aptasensors for the early detection of cancers in clinical samples are in progress. In this article, we discuss recent advances in the development of electrochemical aptasensors for the early detection of different cancer biomarkers and cells based on different detection strategies. Clinical applications of the aptasensors and future perspectives are also discussed.
