Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease

Background The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic of Alzheimer's disease (AD), at the same time, it is possible alterations of liver function could affect brain Aβ levels through changes in blood Aβ concentration. Over the last decade, a number of reports have shown that P-glycoprotein (encoded by ABC1B1) actively mediates the efflux transport of Aβ peptides. However, the mechanism by which Aβ peptides enter the cells is not clear. In the preliminary study, we found that the protein expression of organic anion transporting Polypeptide 1a4 (OATP1B1) in the liver tissue of mice with AD was significantly higher than that in the normal mice. In contrast, the protein expression of Oatp1a4 in the brain significantly decreased in mice with AD. OATP1B1, an important drug transporter might be related to the pathophysiology of AD. Results In this study, we established an OATP1B1-GFP-HEK293T cell model to confirm the OATP1B1 mediated transport of Aβ1-42. Compared to the control group of GFP-HEK293Tcells, the uptake of Aβ1-42 protein in the OATP1B1-GFP-HEK293T group increased significantly with the increase in concentration of Aβ1-42, and also increased significantly with an increase in the duration of incubation. Similar results were observed in the flow cytometry experiment, and the uptake of Aβ1-42in HEK293T-OATP1B1 cells was almost twice that in the control group. These results indicate that OATPs may act as an important “carrier” for the transport of Aβ1-42 from the blood to the tissues, including liver and brain. Conclusions This is a novel and interesting finding and OATP1B1 can be investigated as a new treatment target for AD.

Protective effect of Boldine against neuroinflammation in spinal cord injury in rats

The successful clinical management of spinal cord injury (SCI) is still a unmet medical need. Despite advances in novel therapeutics, the multifactorial etiology of SCI still poses significant challenge to the mankind. Thus, in the present study, we intend to scrutinize the protective effect of Boldine (BOL), an alkaloid obtained from the boldo tree against experimental spinal cord injury. The effect of BOL was investigated on locomotor function of rats with various biomarkers of oxidative stress (MDA, SOD and GSH), inflammation (TNF-α, IL-1β and IL-6), and apoptosis. Results suggest that BOL showed improvement in locomotor function (on BBB scale) of rats with does-dependent reduction in oxidative stress and inflammation. It also reduces neuronal apoptosis in flow cytometry experiment. The study successfully demonstrated the possible clinical utility of BOL against SCI.

Uptake of Aβ by OATPs Might Be a New Pathophysiological Mechanism of Alzheimer Disease

BackgroundThe accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic of Alzheimer's disease (AD). Over the last decade, a number of reports have shown that P-glycoprotein (encoded by ABCB1) actively mediates the efflux transport of Aβ peptides. However, the mechanism by which Aβ peptides enter the cells is not clear. We found that the protein expression oforganic anion transporting Polypeptide 2 (Oatp2) in the liver tissue of mice with AD was significantly higher than that in the normal mice. In contrast, the protein expression of Oatp2 in the brain significantly decreased in mice with AD. OATP1B1, an important drug transporter might be related to the pathophysiology of AD. ResultsIn this study, we established an OATP1B1-GFP-HEK293T cell model to confirm the OATP1B1 mediated transport ofAβ1-42.Compared to the control group of GFP-HEK293Tcells, the uptake of Aβ1-42 protein in the OATP1B1-GFP-HEK293T group increased significantly with the increase in concentration of Aβ1-42, and also increased significantly with an increase in the duration of incubation. Similar results were observed in the flow cytometry experiment, and the uptake of Aβ1-42in HEK239T-OATP1B1 cells was almost twice that in the control group. These results indicate that OATP1B1 acts as an important “carrier” for the transport of Aβ1-42 from the blood to the tissues, including liver and brain. ConclusionsThis is a novel and interesting finding and OATP1B1 can be investigated as a new treatment target for AD.

Microbubble Resonators for All-Optical Photoacoustics of Flowing Contrast Agents

In this paper, we implement a Whispering Gallery mode microbubble resonator (MBR) as an optical transducer to detect the photoacoustic (PA) signal generated by plasmonic nanoparticles. We simulate a flow cytometry experiment by letting the nanoparticles run through the MBR during measurements and we estimate PA intensity by a Fourier analysis of the read-out signal. This method exploits the peaks associated with the MBR mechanical eigenmodes, allowing the PA response of the nanoparticles to be decoupled from the noise associated with the particle flow whilst also increasing the signal-to-noise ratio. The photostability curve of a known contrast agent is correctly reconstructed, validating the proposed analysis and proving quantitative PA detection. The experiment was run to demonstrate the feasible implementation of the MBR system in a flow cytometry application (e.g., the detection of venous thrombi or circulating tumor cells), particularly regarding wearable appliances. Indeed, these devices could also benefit from other MBR features, such as the extreme compactness, the direct implementation in a microfluidic circuit, and the absence of impedance-matching material.