Perspectives on RNA Interference in Immunopharmacology and Immunotherapy

RNA interference (RNAi), mediated by short interfering RNA (siRNA), vector-derived short hairpin RNA (shRNA) and microRNA (miRNA), brings about revolutionary features to basic biomedical research and clinical application. New drugs based on RNAi have been developed for therapeutic applications. The family of RNAi molecules are efficient agents to modulate mammalian immune system, and many studies reported that these molecules could manipulate immune defence, surveillance and homeostasis. Both perfect match of siRNA/shRNA and non-perfect match of miRNA could be beneficial for designing RNAi-based drugs for treatment of tumour and viral infection. This chapter provides a view to control or utilize the immune regulation of various small RNAs that should help researchers to understand the successful clinical application of RNAi

CD51/CD61+ Endothelial Microparticles Decrease in Diabetes Patients with Hypertension

Backgrounds: Type 2 Diabetes Mellitus (T2DM) and hypertension are commonly co-occurred and both diseases are related to endothelial dysfunction. Endothelial microparticles (EMPs) are shed from endothelial cells and can be found in condition of endothelial dysfunction. This study aimed to evaluate the circulating endothelial MPs (CD51/CD61+) levels in T2DM patients with or without hypertension and the correlation between endothelial MPs and clinical parameters. Methods and Results: 20 healthy control, 16 T2DM patients without hypertension and 11 T2DM patients with hypertension were recruited. CD51/CD61+ EMPs from all subjects were analyzed by flow cytometry. We found that, in the group of T2DM patients with hypertension, the absolute median number of CD51/CD61+EMPs was significantly decreased, compared with that in the healthy control and T2DM without hypertension groups. Furthermore, we conducted receiver operating characteristics (ROC) analysis to examine the accuracy of CD51/CD61+EMPs in the discrimination  between T2DM patients with hypertension and healthy control, showing the accuracy was 76.4%. In addition, we also found that the accuracy of CD51/CD61+EMPs was 83.5% in the discrimination between T2DM patients with hypertension or without hypertension Conclusion: These findings identify CD51/CD61+EMPs as a potential biomarker to monitor endothelial dysfunction in T2DM patients with hypertension

Development of an Improved Rotational Orthosis for Walking With Arm Swing and Active Ankle Control

Based on interlimb neural coupling, gait robotic systems should produce walking-like movement in both upper and lower limbs for effective walking restoration. Two orthoses were previously designed in our lab to provide passive walking with arm swing. However, an active system for walking with arm swing is desirable to serve as a testbed for investigation of interlimb neural coupling in response to voluntary input. Given the important function of the ankle joint during normal walking, this work aimed to develop an improved rotational orthosis for walking with arm swing, which is called ROWAS II, and especially to develop and evaluate the algorithms for active ankle control. After description of the mechanical structure and control schemes of the overall ROWAS II system, the closed-loop position control and adjustable admittance control algorithms were firstly deduced, then simulated in Matlab/Simulink and finally implemented in the ROWAS II system. Six able-bodied participants were recruited to use the ROWAS II system in passive mode, and then to estimate the active ankle mechanism. It was showed that the closed-loop position control algorithms enabled the ROWAS II system to track the target arm-leg walking movement patterns well in passive mode, with the tracking error of each joint <0.7°. The adjustable admittance control algorithms enabled the participants to voluntarily adjust the ankle movement by exerting various active force. Higher admittance gains enabled the participants to more easily adjust the movement trajectory of the ankle mechanism. The ROWAS II system is technically feasible to produce walking-like movement in the bilateral upper and lower limbs in passive mode, and the ankle mechanism has technical potential to provide various active ankle training during gait rehabilitation. This novel ROWAS II system can serve as a testbed for further investigation of interlimb neural coupling in response to voluntary ankle movement and is technically feasible to provide a new training paradigm of walking with arm swing and active ankle control

Efficiency Analysis and Comparison of Different Radon Progeny Measurement Methods

Radon exposure to the public contributes more than half of all the radiation doses caused by natural radiation; accurate measurement of radon progeny is quite essential for the dose evaluation of radon exposure in environment. For the purpose of establishing a radon progeny standard and controlling measurement quality of commercial devices, it is quite important to analyze the efficiency of different measurement methods and determine which would be the most appropriate for radon progeny measurements. Through theoretical analysis and experimental measurement, some commonly used measurement methods were compared in this study and the development trends of those methods were reviewed. Results show that for radon progeny measurement, the spectroscopic analysis method is better than the gross count method, while least-square calculation methods is better than traditional three-count or five-count method. Multiperiod counting of α plus β spectrum as well as using weighted least-square calculation method might be the best choice for accurate measurement on radon progeny in standard radon chamber when calibrating commercial radon progeny monitors

A Lipoprotein Lipase–Promoting Agent, NO-1886, Improves Glucose and Lipid Metabolism in High Fat, High Sucrose–Fed New Zealand White Rabbits

The synthetic compound NO-1886 is a lipoprotein lipase activator that lowers plasma triglycerides and elevates high-density lipoprotein cholesterol (HDL-C). Recently, the authors found that NO-1886 also had an action of reducing plasma glucose in high-fat/high-sucrose diet–induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 on insulin resistance and β-cell function in rabbits. Our results showed that high-fat/high-sucrose feeding increased plasma triglyceride, free fatty acid (FFA), and glucose levels and decreased HDL-C level. This diet also induced insulin resistance and impairment of acute insulin response to glucose loading. Supplementing 1% NO-1886 into the high-fat/high-sucrose diet resulted in decreased plasma triglyceride, FFA, and glucose levels and increased HDL-C level. The authors also found a clear increased glucose clearance and a protected acute insulin response to intravenous glucose loading by NO-1886 supplementation. These data suggest that NO-1886 suppresses the elevation of blood glucose in rabbits induced by feeding a high-fat/high-sucrose diet, probably through controlling lipid metabolism and improving insulin resistance

Vertical distributions of plutonium isotopes in marine sediment cores off the Fukushima coast after the Fukushima Dai-ichi Nuclear Power Plant accident

The Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident led to the release of large amounts of radionuclides into the atmosphere as well as direct discharges into the sea. In contrast to the intensive studies on the distribution of the released high volatility fission products, such as 131I, 134Cs and 137Cs, similar studies of the actinides, especially the Pu isotopes, are limited. To obtain the vertical distribution of Pu isotopes in marine sediments and to better assess the possible contamination of Pu from the FDNPP accident in the marine environment, we determined the activities of 239+240Pu and 241Pu as well as the atom ratios of 240Pu/239Pu and 241Pu/239Pu in sediment core samples collected in the western North Pacific off Fukushima from July 2011 to July 2012. We also measured surface sediment samples collected from seven Japanese estuaries before the FNDPP accident to establish the comprehensive background baseline data. The observed results of both the Pu activities and the Pu atom ratios for the sediments in the western North Pacific were comparable to the baseline data, suggesting that the FDNPP accident did not cause detectable Pu contamination to the studied regions prior to the sampling time. The Pu isotopes in the western North Pacific 30 km off Fukushima coast originated from global fallout and Pacific Proving Ground close-in fallout

Composite Hydrogels with the Simultaneous Release of VEGF and MCP-1 for Enhancing Angiogenesis for Bone Tissue Engineering Applications

Rapid new microvascular network induction was critical for bone regeneration, which required the spatiotemporal delivery of growth factors and transplantation of endothelial cells. In this study, the linear poly(d,l-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (PLGA-mPEG) block copolymer microspheres were prepared for simultaneously delivering vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1). Then, vascular endothelial cells (VECs) with growth factor loaded microspheres were composited into a star-shaped PLGA-mPEG block copolymer solution. After this, composite hydrogel (microspheres ratio: 5 wt%) was formed by increasing the temperature to 37 °C. The release profiles of VEGF and MCP-1 from composite hydrogels in 30 days were investigated to confirm the different simultaneous delivery systems. The VECs exhibited a good proliferation in the composite hydrogels, which proved that the composite hydrogels had a good cytocompatibility. Furthermore, in vivo animal experiments showed that the vessel density and the mean vessel diameters increased over weeks after the composite hydrogels were implanted into the necrosis site of the rabbit femoral head. The above results suggested that the VECs-laden hydrogel composited with the dual-growth factor simultaneous release system has the potential to enhance angiogenesis in bone tissue engineering

Non-coding RNAs: The recently accentuated molecules in the regulation of cell autophagy for ovarian cancer pathogenesis and therapeutic response

Autophagy is a self-recycling and conserved process, in which the senescent cytoplasmic components are degraded in cells and then recycled to maintain homeostatic balance. Emerging evidence has suggested the involvement of autophagy in oncogenesis and progression of various cancers, such as ovarian cancer (OC). Meanwhile, the non-coding RNAs (ncRNAs) frequently regulate the mRNA transcription and other functional signaling pathways in cell autophagy, displaying promising roles in human cancer pathogenesis and therapeutic response. This article mainly reviews the cutting-edge research advances about the interactions between ncRNAs and autophagy in OC. This review not only summarizes the underlying mechanisms of dynamic ncRNA-autophagy association in OC, but also discusses their prognostic implications and therapeutic biomarkers. The aim of this review was to provide a more in-depth knowledge framework exploring the ncRNA-autophagy crosstalk and highlight the promising treatment strategies for OC patients