Emodin derivatives as promising multi-aspect intervention agents for amyloid aggregation: molecular docking/dynamics simulation, bioactivities evaluation, and cytoprotection.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with complex pathogenesis. Despite the pathogenesis is unknown, the misfolding and accumulation of ß-amyloid (Aß) peptide play the important role in the occurrence and development of AD. Hence, multi-aspect intervention of the misfolded Aß peptides aggregation is a promising therapy for AD. In previous work, we obtained the emodin derivatives (a-d) with multifunctional anti-AD activities, including metal ions chelation, cholinesterase inhibition, and hydroxyl/superoxide anion radical elimination. In this work, we predicted the interaction of emodin derivatives (a-d) with Aß by combining molecular docking simulation and molecular dynamics simulation, and evaluated the ability to intervene with the self-, Cu2+- and AChE-induced Aß aggregation via in vitro methods. The results indicated that a-d could act as the potent multi-aspect intervention agents for Aß aggregation. In addition, a-d could effectively eliminate peroxyl radical, had virtually no neurotoxicity, and protect cells from oxidative and Aß-induced damage. The prediction results of ADMET properties showed that a-d had suitable pharmacokinetic characteristics. It suggested that a-d could act as the promising multi-targeted directed ligands (MTDLs) for AD. These results may provide meaningful information for the development of the potential MTDLs for AD which are modified from natural-origin scaffolds.

The Proangiogenic Potential of Rat Adipose-Derived Stromal Cells with and without Cell-Sheet Induction: A Comparative Study.

A functional vasculature for survival remains a challenge for tissue regeneration, which is indispensable for oxygen and nutrient supply. Utilizing mesenchymal stromal cells (MSCs) to alleviate tissue ischemia and repair dysfunctional or damaged endothelium is a promising strategy. Compared to other populations of MSCs, adipose-derived stromal cells (ASCs) possess a more significant proangiogenic potential and are abundantly available. Cell sheet technology has recently been widely utilized in bone engineering. Compared to conventional methods of seeding seed cell suspension onto biological scaffolds, cell sheet technology prevents cell loss and preserves the extracellular matrix (ECM). Nevertheless, the proangiogenic potential of ASC sheets remains unknown. In this study, rat ASC sheets were constructed, and their macro- and microstructures were examined. In addition, we investigated the effects of ASCs and ASC sheets on the biological properties and angiogenic capacity of endothelial cells (ECs). The results demonstrated that the ASC sheets gradually thickened as the number of cells and ECM increased over time and that the cells were in an active state of secretion. Similar to ASC-CM, the conditioned medium (CM) of ASC sheets could significantly enhance the proliferative capacity of ECs. ASC sheet-CM has significant advantages over ASC-CM in promoting the migration and angiogenesis of ECs, where the exosomes secreted by ASC sheets play an essential role. Therefore, using ASC sheets for therapeutic tissue and organ regeneration angiogenesis may be a valuable strategy.

Construction and performance of exendin-4-loaded chitosan-PLGA microspheres for enhancing implant osseointegration in type 2 diabetic rats.

The updating and optimization of drug delivery systems is critical for better in vivo behaviors of drugs, as well as for improving impaired implant osseointegration in diabetes. Numerous studies have reported the benefits of exendin-4 on diabetic bone, with the potential to enhance osseointegration in diabetes. To construct an appropriate sustained-release system of exendin-4 targeting implant osseointegration in diabetes, this study fabricated exendin-4-loaded microspheres using poly(lactic-co-glycolic acid) (PLGA) and chitosan. The morphology, size, encapsulation efficiency, and drug release behavior of microspheres were investigated. The bioactivity of drug-loaded microspheres on cell proliferation and osteogenic differentiation of diabetic BMSCs was investigated to examine the pharmacologic action of exendin-4 loaded into chitosan-PLGA microspheres. Further, the influence of microspheres on osseointegration was evaluated using type 2 diabetes mellitus (T2DM) rat implant model. After 4 weeks, the samples were evaluated by radiological and histological analysis. The results of in vitro experiments showed that the prepared exendin-4-loaded chitosan-PLGA microspheres have good properties as a drug delivery system, and the chitosan could improve the encapsulation efficiency and drug release of PLGA microspheres. In addition, exendin-4-loaded microspheres could enhance the proliferation and osteogenic differentiation of diabetic BMSCs. The results of in vivo experiments showed the exendin-4-loaded microspheres significantly improved the impaired osseointegration and bone formation around implants in T2DM rats without affecting blood glucose levels. Thus, the local application of exendin-4-loaded chitosan-PLGA microspheres might be a promising therapeutic strategy for improving the efficacy of dental implants in T2DM individuals.

A novel microfluidic capture and monitoring method for assessing physiological damage of C. elegans under microgravity.

Spatial microgravity is a significant factor affecting and causing physiological changes of organisms in space environment. On-site assessment of the damage associated to microgravity is very important for future long-term space exploration of mankind. In this paper, a new microfluidic device for analyzing the damage of microgravity on Caenorhabditis elegans (C. elegans) has been developed. This device is mainly composed of a microfluidic chip, a dual imaging module, and an imaging acquisition and processing module, which are integrated into a compact system. The microfluidic chip is designed as a platform for monitoring C. elegans, which is captured in an imaging region through a suction structure in the microfluidic chip. A dual imaging module is designed to obtain the images of bright field and fluorescence of C. elegans. The behaviors of C. elegans are analyzed based on the dual-mode imaging of bright field and fluorescence to assess the degree of damage due to microgravity. A comparative study using a commercial microscope is also conducted to demonstrate the unique advantage of the developed system under the simulated microgravity. The results show that the developed system can evaluate the damage of C. elegans under microgravity accurately and conveniently. Furthermore, this device has compact size and weight, easy operation, and low-cost, which could be highly advantageous for on-site evaluation of the damage to microorganisms under microgravity in a space station.

Neural Correlates of Emotion Processing in Word Detection Task.

In our previous study, we have proposed a three-stage model of emotion processing; in the current study, we investigated whether the ERP component may be different when the emotional content of stimuli is task-irrelevant. In this study, a dual-target rapid serial visual presentation (RSVP) task was used to investigate how the emotional content of words modulates the time course of neural dynamics. Participants performed the task in which affectively positive, negative, and neutral adjectives were rapidly presented while event-related potentials (ERPs) were recorded from 18 undergraduates. The N170 component was enhanced for negative words relative to positive and neutral words. This indicates that automatic processing of negative information occurred at an early perceptual processing stage. In addition, later brain potentials such as the late positive potential (LPP) were only enhanced for positive words in the 480-580-ms post-stimulus window, while a relatively large amplitude signal was elicited by positive and negative words between 580 and 680 ms. These results indicate that different types of emotional content are processed distinctly at different time windows of the LPP, which is in contrast with the results of studies on task-relevant emotional processing. More generally, these findings suggest that a negativity bias to negative words remains to be found in emotion-irrelevant tasks, and that the LPP component reflects dynamic separation of emotion valence.

The influence of spatial frequency content on facial expression processing: An ERP study using rapid serial visual presentation.

Spatial frequency (SF) contents have been shown to play an important role in emotion perception. This study employed event-related potentials (ERPs) to explore the time course of neural dynamics involved in the processing of facial expression conveying specific SF information. Participants completed a dual-target rapid serial visual presentation (RSVP) task, in which SF-filtered happy, fearful, and neutral faces were presented. The face-sensitive N170 component distinguished emotional (happy and fearful) faces from neutral faces in a low spatial frequency (LSF) condition, while only happy faces were distinguished from neutral faces in a high spatial frequency (HSF) condition. The later P3 component differentiated between the three types of emotional faces in both LSF and HSF conditions. Furthermore, LSF information elicited larger P1 amplitudes than did HSF information, while HSF information elicited larger N170 and P3 amplitudes than did LSF information. Taken together, these results suggest that emotion perception is selectively tuned to distinctive SF contents at different temporal processing stages.

A New Microfluidic Device for Classification of Microalgae Cells Based on Simultaneous Analysis of Chlorophyll Fluorescence, Side Light Scattering, Resistance Pulse Sensing.

Fast on-site monitoring of foreign microalgae species carried by ship ballast water has drawn more and more attention. In this paper, we presented a new method and a compact device of classification of microalgae cells by simultaneous detection of three kinds of signals of single microalgae cells in a disposable microfluidic chip. The microfluidic classification device has advantages of fast detection, low cost, and portability. The species of a single microalgae cell can be identified by simultaneous detection of three signals of chlorophyll fluorescence (CF), side light scattering (SLS), and resistance pulse sensing (RPS) of the microalgae cell. These three signals represent the different characteristics of a microalgae cell. A compact device was designed to detect these three signals of a microalgae cell simultaneously. In order to demonstrate the performance of the developed system, the comparison experiments of the mixed samples of three different species of microalgae cells between the developed system and a commercial flow cytometer were conducted. The results show that three kinds of microalgae cells can be distinguished clearly by our developed system and the commercial flow cytometer and both results have good agreement.