Ganoderic Acid A Promotes Amyloid-ß Clearance (In Vitro) and Ameliorates Cognitive Deficiency in Alzheimer's Disease (Mouse Model) through Autophagy Induced by Activating Axl.

Alzheimer's disease (AD) is thought to be caused by amyloid-ß (Aß) accumulation in the central nervous system due to deficient clearance. The aim of the present study was to investigate the effect of ganoderic acid A (GAA) on Aß clearance in microglia and its anti-AD activity. Aß degradation in BV2 microglial cells was determined using an intracellular Aß clearance assay. GAA stimulated autophagosome formation via the Axl receptor tyrosine kinase (Axl)/RAC/CDC42-activated kinase 1 (Pak1) pathway was determined by Western blot analyses, and fluorescence-labeled Aß42 was localized in lysosomes in confocal laser microscopy images. The in vivo anti-AD activity of GAA was evaluated by object recognition and Morris water maze (MWM) tests in an AD mouse model following intracerebroventricular injection of aggregated Aß42. The autophagy level in the hippocampus was assayed by immunohistochemical assessment against microtubule-associated proteins 1A/1B light-chain 3B (LC3B). Intracellular Aß42 levels were significantly reduced by GAA treatment in microglial cells. Additionally, GAA activated autophagy according to increased LC3B-II levels, with this increased autophagy stimulated by upregulating Axl and Pak1 phosphorylation. The effect of eliminating Aß by GAA through autophagy was reversed by R428, an Axl inhibitor, or IPA-3, a Pak1 inhibitor. Consistent with the cell-based assay, GAA ameliorated cognitive deficiency and reduced Aß42 levels in an AD mouse model. Furthermore, LC3B expression in the hippocampus was up-regulated by GAA treatment, with these GAA-specific effects abolished by R428. GAA promoted Aß clearance by enhancing autophagy via the Axl/Pak1 signaling pathway in microglial cells and ameliorated cognitive deficiency in an AD mouse model.

Paper-based microfluidic devices based on 3D network polymer hydrogel for the determination of glucose in human whole blood.

In this study, optical microfluidic paper analytical devices (µPADs) for glucose detection from whole blood samples with a small sample volume (2 µL) have been developed on a single paper. In the proposed method, a mushroom-shaped analytical device contains a sample inlet zone and a detection zone. When blood is dripped onto the inlet region of a µPAD, the plasma diffuses to the detection region. The detection region is implanted with a metallic three-dimensional (3D) polymer hydrogel vehicle. The gel vehicle consists of a copper complex that responds to oxygen changes and glucose oxidase (GOx) immobilized inside the gel as a bioactivity preservative. The phosphorescence of the copper complex is enhanced by oxygen consumed by detection of glucose with a limit of detection (S/N = 3) of 0.44 mM, and the total analysis of the sample is completed within 1 min. The validity of the proposed research is demonstrated using control samples and real-world whole blood samples of glucose concentrations ranging from 3 to 200 mM, and the detection results are shown to be in agreement with those obtained using a glucometer. Attaining a simple device for analysing glucose in human whole blood without any pretreatment procedures and having a broad sensing range while consuming a small sample volume remain challenging; thus, our new analytical device is of great interest.

Determination of nitrite ions in environment analysis with a paper-based microfluidic device.

A new microfluidic paper-based analytical device, a (Ag-µPAD)-based chemiresistor composed of silver ink, has been developed for the selective, sensitive, and quantitative determination of nitrite ions in environmental analysis. The silver ink acts as an efficient transducer in terms of resistance changes due to nitrite initiating a diazo reaction and further reacting with the ink. The silver ink is synthesized onto the µPADs by pulsed light sintering from silver nanoparticles, a mixture of silver nanowires and nanoparticles. The resistance changes show two linear response ranges to nitrite in the concentration ranges of 1.0 × 10-8 M to 5.0 × 10-6 M and 1.0 × 10-5 M to 3.2 × 10-3 M, with a limit of detection of 8.5 × 10-11 M (S/N = 3). The sensor displays a wider linear range, a lower detection limit, a higher stability, high selectivity, low-volume sampling, and disposability for nitrite with respect to other nanoparticle- and paper-based sensors. The characterization of silver ink was verified by SEM, EDS, and IR studies, and the sensing mechanism is discussed. In addition, this paper-based sensor has been successfully employed to determine the nitrite content in tap, river and lake water samples.

A silver metal complex as a luminescent probe for enzymatic sensing of glucose in blood plasma and urine.

In this work, we present a facile preparation of a paper-based glucose assay for rapid, sensitive, and quantitative measurement of glucose in blood plasma and urine. Two copper phosphorescent complexes [Cu(2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline)(2,6-dimethylphenylisocyanide)2][B(C6H3(CF3)2)4] (Cu1) and [Cu(2,9-dimethyl-1,10-phenanthroline)(2,6-dimethylphenylisocyanide)2][B(C6H3(CF3)2)4] (Cu2) and a new silver congener [Ag(P3)CNAg(P3)][B(C6H3(CF3)2)4] (Ag3) (P3 = PPh2C6H4-PPh-C6H4PPh2 [bis(o-diphenylphosphinophenyl)phenylphosphine]) have been synthesized and their oxygen sensing abilities were investigated. The dimetallic phosphine-based Ag3 complex, having a high oxygen sensing ability, was employed as an efficient signal transducer in enzymatic reactions to recognize blood plasma glucose and urine glucose, which provided a wide linear response for a concentration range between 1.0 and 35 mM and a rapid response, with a limit of detection (LOD) of 0.09 mM for glucose. In practical application, this Ag3 paper-based device offers great analytical reliability and accuracy upon monitoring glucose concentrations in blood plasma.