Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation

Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.

Evolution of the ErbB gene family and analysis of regulators of Egfr expression during development of the rat spinal cord

Egfr,a member of the ErbB gene family,plays a critical role in tissue development and homeostasis,wound healing,and disease.However,expression and regulators of Egfr during spinal cord development remain poorly understood.In this study,we investigated ErbB evolution and analyzed co-expression modules,miRNAs,and transcription factors that may regulate Egfr expression in rats.We found that ErbB family members formed via Egfr duplication in the ancient ve rtebrates but dive rged after speciation of gnathostomes.We identified a module that was co-expressed with Egfr,which involved cell proliferation and blood vessel development.We predicted 25 miRNAs and nine transcription factors that may regulate Egfr expression.Dual-luciferase reporter assays showed six out of nine transcription factors significantly affected Egfr promoter reporter activity.Two of these transcription factors(KLF1 and STAT3)inhibited the Egfr promoter repo rter,whereas four transcription factors(including FOXA2)activated the Egfr promoter reporter.Real-time PCR and immunofluorescence expe riments showed high expression of FOXA2 during the embryonic period and FOXA2 was expressed in the floor plate of the spinal cord,suggesting the importance of FOXA2 during embryonic spinal cord development.Considering the importance of Egfr in embryonic spinal cord development,wound healing,and disease(specifically in cancer),regulatory elements identified in this study may provide candidate targets for nerve regeneration and disease treatment in the future.

Biocompatibility and biosafety of butterfly wings for the clinical use of tissue-engineered nerve grafts

In a previous study, we used natural butterfly wings as a cell growth matrix for tissue engineering materials and found that the surface of different butterfly wings had different ultramicrostructures, which can affect the qualitative growth of cells and regulate cell growth, metabolism, and gene expression. However, the biocompatibility and biosafety of butterfly wings must be studied. In this study, we found that Sprague-Dawley rat dorsal root ganglion neurons could grow along the structural stripes of butterfly wings, and Schwann cells could normally attach to and proliferate on different species of butterfly wings. The biocompatibility and biosafety of butterfly wings were further examined through subcutaneous implantation in Sprague-Dawley rats, intraperitoneal injection in Institute of Cancer Research mice, intradermal injection in rabbits, and external application to guinea pigs. Our results showed that butterfly wings did not induce toxicity, and all examined animals exhibited normal behaviors and no symptoms, such as erythema or edema. These findings suggested that butterfly wings possess excellent biocompatibility and biosafety and can be used as a type of tissue engineering material. This study was approved by the Experimental Animal Ethics Committee of Jiangsu Province of China(approval No. 20190303-18) on March 3, 2019.

Composition characterization and transformation mechanism of dissolved organic phosphorus in wastewater treatment using 31P NMR spectroscopy

The migration and transformation of phosphorus components in wastewater treatment plants(WWTPs)play a crucial role in the convergence and circulation of phosphorus.However,the composition and variation of dissolved organic phosphorus(DOP)in WWTPs were unclear because of its complex nature,hindering its efficient detection.In this study,the DOP species and their transformation during the treatment process in WWTP were comprehensively analyzed.First,two enrichment methods were assessed for their effectiveness at facilitating wastewater analysis:lyophilization and aluminum salt precipitation.Aluminum salt precipitation was found to be better because its application allowed 31P nuclear magnetic resonance(31P NMR)spectroscopy to identify more species in the secondary effluent:orthophosphate(Ortho-P)(81.1%–89.3%of the dissolved total phosphorus),pyrophosphates(Pyro-P)(0%–2.3%),orthophosphate monoesters(Mono-P)(7.0%–10.77%),orthophosphate diesters(Di-P)(1.0%–2.96%),and phosphonate(Phos-P)(1.7%–5.16%).Furthermore,the variation and transformation mechanism of phosphorus,particularly those of DOP,during the entire sewage-treatment process were elucidated.Among the treatment steps,biological treatment combined tertiary treatment achieved better DOP removal efficiencies.Therein,biological treatment mainly removed Mono-P and Di-P with removal efficiencies of 33.3%and 41.7%compared with the effluent of the grit chamber.Di-P has higher bioavailability and is more easily converted and utilized by microorganisms than Mono-P.However,Phos-P,with low bioavailability,was hardly utilized by microorganisms,which showed only 18.4%removal efficiency in biological treatment.In tertiary treatment,coagulation process exhibited higher removal ability of Ortho-P(69.1%)and partial removal efficiencies of DOP,resulting in an increase in the DOP proportion in TP.In addition,Phos-P could not be effectively removed through the biological treatment and was only partially reduced via the adsorption process by large particles,zoogloea or multinuclear hydroxyl complexes.The results of this study can provide a theoretical basis for efficient phosphorus removal in WWTPs.