Potential role of Schwann cells in neuropathic pain.

Neuropathic pain (NPP) is a common syndrome associated with most forms of disease, which poses a serious threat to human health. NPP may persist even after the nociceptive stimulation is eliminated, and treatment is extremely challenging in such cases. Schwann cells (SCs) form the myelin sheaths around neuronal axons and play a crucial role in neural information transmission. SCs can secrete trophic factors to nourish and protect axons, and can further secrete pain-related factors to induce pain. SCs may be activated by peripheral nerve injury, triggering the transformation of myelinated and non-myelinated SCs into cell phenotypes that specifically promote repair. These differentiated SCs provide necessary signals and spatial clues for survival, axonal regeneration, and nerve regeneration of damaged neurons. They can further change the microenvironment around the regions of nerve injury, and relieve the pain by repairing the injured nerve. Herein, we provide a comprehensive overview of the biological characteristics of SCs, discuss the relationship between SCs and nerve injury, and explore the potential mechanism of SCs and the occurrence of NPP. Moreover, we summarize the feasible strategies of SCs in the treatment of NPP, and attempt to elucidate the deficiencies and defects of SCs in the treatment of NPP.

Finite element analysis of the effect of power arm locations on tooth movement in extraction space closure with miniscrew anchorage in customized lingual orthodontic treatment.

INTRODUCTION: More patients are choosing customized orthodontic appliances because of their excellent esthetics. It is essential that clinicians understand the biomechanics of the tooth movement tendency in customized lingual orthodontics. This study aimed to evaluate the tooth movement tendency during space closure in maxillary anterior teeth with the use of miniscrew anchorage in customized lingual orthodontics with various power arm locations. METHODS: Three-dimensional finite element models of the maxilla were created with miniscrews and power arms; the positions were varied to change the force directions. A retraction force (1.5 N) was applied from the top of the miniscrews to the selected points on the power arm, and the initial displacements of the reference nodes of the maxillary teeth were analyzed. RESULTS: After applying force in different directions, power arms located at the distal side of the canines led to larger initial lingual crown tipping and occlusal crown extrusion of the maxillary incisors compared with power arms located at the midpoint between the lateral incisors and canines, and caused a decreasing trend of the intercanine width. CONCLUSIONS: In customized lingual orthodontic treatment, power arms located at the distal side of the canines are unfavorable for anterior teeth torque control and intercanine width control. Power arms located at the midpoint between the lateral incisors and canines can get better torque control, but still cannot achieve excepted torque without extra torque control methods, no matter whether its force application point is higher than, lower than, or equal to the level of the top of the miniscrews.

MicroRNA-29b inhibits peritoneal fibrosis in a mouse model of peritoneal dialysis.

TGF-ß/Smad3 signaling plays a pivotal role in the pathogenesis of peritoneal fibrosis associated with peritoneal dialysis (PD). MicroRNA-29 (miR-29) is known as a potent downstream inhibitor of TGF-ß/Smad3 in renal fibrosis. In this study, we examined the therapeutic potential for miR-29b on PD-related peritoneal fibrosis in a mouse model of PD induced by daily infusion of 4.25% dextrose-containing PD fluid (PDF). MiR-29b-expressing plasmid was delivered into the peritoneum via an ultrasound-microbubble-mediated system before and at day 14 after PDF. We found that mice on PD developed peritoneal fibrosis with impaired peritoneal function, which was associated with a loss of miR-29b. In contrast, overexpression of miR-29b before the PDF infusion showed a protective effect on peritoneal fibrosis including EMT and prevented peritoneal dysfunction. Moreover, delayed miR-29b treatment until peritoneal fibrosis was established at day 14 also halted the progression of peritoneal fibrosis at day 28. Further studies identified that blockade of the Sp1-TGF-ß/Smad3 pathway may be a mechanism by which miR-29b inhibited peritoneal fibrosis. In conclusion, treatment with miR-29b may represent a novel and effective therapy for PD-associated peritoneal fibrosis.

Opposing roles for Smad2 and Smad3 in peritoneal fibrosis in vivo and in vitro.

Peritoneal fibrosis is a major cause of ultrafiltration failure in patients receiving continuous ambulatory peritoneal dialysis. Transforming growth factor (TGF)-ß1 is an important mediator in this process; however, its signaling mechanisms had not been explored. Thus, we examined TGF-ß1/Smad signaling in human peritoneal biopsy specimens associated with continuous ambulatory peritoneal dialysis. We found that TGF-ß/Smad2/3 signaling was highly activated in patients with increased collagen deposition and thickening of the peritoneal membrane who were receiving continuous ambulatory peritoneal dialysis. Long-term exposure of wild-type mice to 4.25% peritoneal dialysis solution for 30 days induced significant peritoneal fibrosis with impaired peritoneal equilibrium, which was prevented in Smad3 knockout mice. In contrast, conditional Smad2 gene deletion in the peritoneum exacerbated peritoneal fibrosis and dysfunction. The contrasting roles of Smad2 and Smad3 in peritoneal fibrosis were also examined in vitro. Cultured mesothelial cells from Smad3 knockout mice were resistant to TGF-ß1-induced collagen I production and the transition toward a myofibroblast phenotype as seen in wild-type cells, whereas Smad2 deficiency in mesothelial cells failed to modulate the profibrotic response to TGF-ß1. In conclusion, this study found activation of TGF-ß/Smad signaling in peritoneal fibrosis in patients receiving continuous ambulatory peritoneal dialysis and identifies opposing roles for Smad2 and Smad3 in peritoneal dialysis-associated peritoneal fibrosis. These findings provide a mechanistic basis for future therapies targeting TGF-ß/Smad signaling in peritoneal fibrosis.

Re-examination of the genotoxic activity of water taken from the Songhua River in P. R. China.

The Songhua River, in northeast China, has heavy organic contamination due to domestic sewage and industrial wastewater. Thus, it is important to further determine its genotoxic activity, which is a potential hazard for human health. Short-term genotoxic bioassays using Salmonella, the cytokinesis-block micronucleus cytome assay, and mouse liver cell comet assay were employed to further examine the genotoxic activity of diethyl ether extracts of water samples taken from the Songhua River. Ames test results showed that there were still frame-shift mutagens, both direct and indirect, in water samples at doses of 5.0 or 7.0 L water equivalent/plate. The mutagenicity seems to be less when compared with the results from 2002 to 2003. A dose-response relationship was also obtained between DNA damage in mouse liver cells by comet assay and micronuclei formation by CBMN assay. These results indicate that the water samples showed genotoxic activity with a mutagenic potency. 88 and 104 compounds, respectively, were identified in summer and winter water sample extracts by gas chromatography-mass spectrometry analysis. Four priority pollutants listed by the United States Environmental Protection Agency and six priority pollutants listed by the Chinese Environment Protection Agency were found in summer or winter water samples, respectively. The results indicate that the diethyl ether extracts of surface water samples taken from the Songhua River still show genotoxic activity (≥3.0 L water). The risks of potential carcinogenicity for human health in the Songhua River should be studied further.