From Apoptosis to Regulated Necrosis: An Evolving Understanding of Acute Kidney Injury

Acute kidney injury (AKI) is a prevailing health threat around the world with high mortalities and heavy economic burdens. In the past, apoptosis was recognized as the main contributor to the pathogenesis of AKI. However, recent evidence has suggested that regulated necrosis also plays an important role in the pathologic process of various types of renal damages, improving our limited understanding of the complex mechanisms underlying AKI. Regulated necrosis is a newly identified type of “programed cell death” with morphologic features of necrosis, which includes necroptosis, ferroptosis, parthanatos, pyroptosis, etc. In this chapter, we summarized the molecular pathways of both apoptosis and regulated necrosis, and reviewed the potential roles and corresponding mechanisms of various cell deaths in AKI based on recent advances. We also discussed the therapeutic potentials and clinical implications based on manipulating regulated cell death. Taken together, the progress in this field lays the ground for better prevention and management of AKI in the future

Facile and Label-Free Electrochemical Biosensors for MicroRNA Detection based on DNA Origami Nanostructures

MicroRNAs (miRNAs) have emerged as the promising molecular biomarkers for early diagnosis and enhanced understanding of the molecular pathogenesis of cancers as well as certain diseases. Here, a facile, label-free, and amplification-free electrochemical biosensor was developed to detect miRNA by using DNA origami nanostructure-supported DNA probes, with methylene blue (MB) serving as the hybridization redox indicator, for the first time. Specifically, the use of cross-shaped DNA origami nanostructures containing multiple single-stranded DNA probes at preselected locations on each DNA nanostructure could increase the accessibility and the recognition efficiency of the probes (due to the rational controlled density of DNA probes). The successful immobilization of DNA origami probes and their hybridization with targeted miRNA-21 molecules was confirmed by electrochemical impedance spectroscopy and cyclic voltammetry methods. A differential pulse voltammetry technique was employed to record the oxidation peak current of MB before and after target hybridization. The linear detection range of this biosensor was from 0.1 pM to 10.0 nM, with a lower detection limit of 79.8 fM. The selectivity of the miRNA biosensor was also studied by observing the discrimination ability of single-base mismatched sequences. Because of the larger surface area and unprecedented customizability of DNA origami nanostructures, this strategy demonstrated great potential for sensitive, selective, and label-free determination of miRNA for translational biomedical research and clinical applications