No abstract

Nerve injury-induced neuropathic pain is difficult to treat. In this study, we used exosomes derived from human umbilical cord mesenchymal stem cell (UCMSC) as a cell-free therapy for nerve injury-induced pain in rats. Isolated UCMSC exosomes range in size from 30 to 160 nm and contain CD63, HSP60, and CD81 exosome markers. After L5/6 spinal nerve ligation surgery, single intrathecal injection of exosomes reversed nerve ligation-induced mechanical and thermal hypersensitivities of right hindpaw of rats at initial and well-developed pain stages. Moreover, continuous intrathecal infusion of exosomes achieved excellent preventive and reversal effects for nerve ligation-induced pain. In immunofluorescent study, lots of Exo-green-labelled exosomes could be found majorly in the ipsilateral L5 spinal dorsal horn, dorsal root ganglion, and peripheral axons, suggesting the homing ability of UCMSC exosomes. They also appeared in the central terminals or cell bodies of IB4, CGRP, and NF200 sensory neurons. In addition, exosome treatment suppressed nerve ligation-induced upregulation of c-Fos, CNPase, GFAP, and Iba1. All these data suggest that the analgesic effects of exosomes may involve their actions on neuron and glial cells. Exosomes also inhibited the level of TNF-α and IL-1β, while enhanced the level of IL-10, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in the ipsilateral L5/6 dorsal root ganglion of nerve-ligated rats, indicating anti-inflammatory and proneurotrophic abilities. Protein analysis revealed the content of vascular endothelial growth factor C, angiopoietin-2, and fibroblast growth factor-2 in the exosomes. In summary, intrathecal infusion of exosomes from UCMSCs may be considered as a novel therapeutic approach for nerve injury-induced pain.

We define a new property which contains the property (EA) for a hybrid pair of single- and multivalued maps and give some new common fixed point theorems under hybrid contractive conditions. Our results extend previous ones. As an application, we give a partial answer to the problem raised by Singh and Mishra

MicroRNA (miRNA) functions are tightly regulated by their sub‐compartmental location in living cells, and the ability to imaging of mitochondrial miRNAs (mitomiRs) is essential for understanding of the related pathological processes. However, most existing DNA‐based methods could not be used for this purpose. Here, we report the development of a DNA nanoreporter technology for imaging of mitomiRs in living cells through near‐infrared (NIR) light‐controlled DNA strand displacement reactions. The sensing function of the DNA nanoreporters are silent (OFF) during the delivery process, but can be photoactivated (ON) with NIR light after targeted mitochondrial localization, enabling spatially‐restricted imaging of two types of cancer‐related mitomiRs with improved detection accuracy. Furthermore, we demonstrate imaging of mitomiRs in vivo through spatiotemporally‐controlled delivery and activation. Therefore, this study illustrates a simple methodology that may be broadly applicable for investigating the mitomiRs‐associated physiological events.

Polyetherimide (PEI) is a kind of high-performance polymer, which possesses a high glass transition temperature ( Tg), excellent flame retardancy, low smoke generation, and good mechanical properties. In this article, PEI was applied in the fused deposition modeling (FDM)–based 3-D printing for the first time. The entire process from filament extrusion to printing was studied. It was observed that the filament orientation and nozzle temperature were closely related to the mechanical properties of printed samples. When the nozzle temperature is 370°C, the mean tensile strength of FDM printing parts can reach to 104 MPa, which is only 7% lower than that of injection molded parts. It can be seen that the 0° orientation set of samples show the highest storage modulus (2492 MPa) followed by the 45° samples, and the 90° orientation set of samples show the minimum storage modulus (1420 MPa) at room temperature. The above results indicated that this technique allows the production of parts with adequate mechanical performance, which does not need to be restricted to the production of mock-ups and prototypes. Our work broke the limitations of traditional FDM technology and expanded the types of material available for FDM to the high-temperature engineering plastics.