Background: Bone marrow mesenchymal stem cells (MSCs) are one of the potential tools for treatment of the spinal cord injury; however, the survival and differentiation of MSCs in an injured spinal cord still need to be improved. In the present study, we investigated whether Governor Vessel electro-acupuncture (EA) could efficiently promote bone marrow mesenchymal stem cells (MSCs) survival and differentiation, axonal regeneration and finally, functional recovery in the transected spinal cord.

A self-healing hydrogel enriched with properties from a double-dynamic network (DDN) that has been prepared via two dynamic linkages (imine and borate ester) by using a single polymeric cross-linker. The four-component Ugi reaction was used for easily synthesizing multifunctional poly­(ethylene glycol) (MF-PEG) with a benzaldehyde group and phenylboronic acid group at each end of the chain. This MF-PEG simultaneously cross-linked with poly­(vinyl alcohol) through the borate ester and glycol chitosan via an imine to generate a self-healing hydrogel with a unique DDN structure in seconds under mild conditions (pH ≈ 7, 25 °C). The prepared hydrogel showed enhanced strength and mucoadhesive abilities because of the complimentary interpenetrating dynamic networks. The DDN hydrogel showed satisfying biocompatibility and was further used in an in vivo mouse model. The hydrogel was injected to successfully deliver an antitumor drug and achieved a superior performance compared to traditional delivery methods. To the best of our knowledge, this is the first report of using the Ugi reaction to prepare a DDN self-healing hydrogel. We hereby propose a general strategy for the facile preparation of self-healing materials with improved properties. The strategy also opens a new avenue for synthesizing multifunctional/reinforced materials with the combination of dynamic chemistry and multicomponent reactions.

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Study design: An animal model of transected spinal cord injury (SCI) was used to test the hypothesis that cografted neural stem cells (NSCs) and NT-3-SCs promote morphologic and functional recoveries of injured spinal cord. Objective: To explore whether cotransplant of NSCs and NT-3-SCs could promote the injured spinal cord repair. Setting: Zhongshan Medical College, Sun Yat-sen University, PR China. Methods: Female Sprague-Dawley (SD) rats weighing on 200-220 g were used to prepare SCI models. The spinal cord was transected between T 9 and T 10 , then NSCs, SCs þ NSCs, LacZSCs þ NSCs, or NT-3-SCs þ NSCs were grafted into the transected site. Results: (1) Part of NSCs could differentiate to neuron-like cells in the transected site and the percentage of differentiation was NT-3-SCs þ NSCs group4SCs þ NSCs group4NSCs group. (2) In the grafted groups, there were 5-HT, CGRP, and SP positive nerve fibres within the transected site. Some fluorogold (FG)-labeled cells were found in the spinal cord rostral to the transected site, the red nuclei and the inner pyramidal layer of sensorimotor cortex. (3) The cells grafted could enhance the injured neurons survival in inner pyramidal layer of sensorimotor cortex, red nuclei of midbrain, and Clark's nuclei of spinal cord's L1 segment, could decrease the latency and increase the amplitude of cortical somatosensory evoked potential (CSEP) and cortical motor evoked potential (CMEP), and could promote partly structural and functional recovery of the SCI rats.Conclusion: These results demonstrate that cografted NT-3-SCs and NSCs is a potential therapy for SCI.

Our previous study has reported that electroacupuncture (EA) promotes survival, differentiation of bone marrow mesenchymal stem cells (MSCs), and functional improvement in spinal cord-transected rats. In this study, we further investigated the structural bases of this functional improvement and the potential mechanisms of axonal regeneration in injured spinal cord after MSCs and EA treatment. Five experimental groups, 1) sham control (Sham-control); 2) operated control (Op-control); 3) electroacupuncture treatment (EA); 4) MSCs transplantation (MSCs), and 5) MSCs transplantation combined with electroacupuncture (MSCs + EA), were designed for this study. Western blots and immunohistochemical staining were used to assess the fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs) proteins expression. Basso, Beattie, Bresnahan (BBB) locomotion test, cortical motor evoked potentials (MEPs), and anterograde and retrograde tracing were utilized to assess cortical-spinal neuronal projection regeneration and functional recovery. In the MSCs + EA group, increased labeling descending corticospinal tract (CST) projections into the lesion site showed significantly improved BBB scales and enhanced motor evoked potentials after 10 weeks of MSCs transplant and EA treatment. The structural and functional recovery after MSCs + EA treatment may be due to downregulated GFAP and CSPGs protein expression, which prevented axonal degeneration as well as improved axonal regeneration.

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Our previous study indicated that electroacupuncture (EA) could increase neurotrophin-3 (NT-3) levels in the injured spinal cord, stimulate the differentiation of transplanted bone marrow mesenchymal stem cells (MSCs), and improve functional recovery in the injured spinal cord of rats. However, the number of neuron-like cells derived from the MSCs is limited. It is known that NT-3 promotes the survival and differentiation of neurons by preferentially binding to its receptor TrkC. In this study, we attempted to transplant TrkC gene-modified MSCs (TrkC-MSCs) into the spinal cord with transection to investigate whether EA treatment could promote NT-3 secretion in the injured spinal cord and to determine whether increased NT-3 could further enhance transplanted MSCs overexpressing TrkC to differentiate into neuron-like cells, resulting in increased axonal regeneration and functional improvement in the injured spinal cord. Our results showed that EA increased NT-3 levels; furthermore, it promoted neuron-phenotype differentiation, synaptogenesis, and myelin formation of transplanted TrkC-MSCs. In addition, TrkC-MSC transplantation combined with EA (the TrkC-MSCs + EA group) treatment promoted the growth of the descending BDA-labeled corticospinal tracts (CSTs) and 5-HT-positive axonal regeneration across the lesion site into the caudal cord. In addition, the conduction of cortical motorevoked potentials (MEPs) and hindlimb locomotor function increased as compared to controls (treated with the LacZ-MSCs, TrkC-MSCs, and LacZ-MSCs + EA groups). In the TrkC-MSCs + EA group, the injured spinal cord also showed upregulated expression of the proneurogenic factors laminin and GAP-43 and downregulated GFAP and chondroitin sulfate proteoglycans (CSPGs), major inhibitors of axonal growth. Together, our data suggest that TrkC-MSC transplantation combined with EA treatment spinal cord injury not only increased MSC survival and differentiation into neuron-like cells but also promoted CST regeneration across injured sites to the caudal cord and functional improvement, perhaps due to increase of NT-3 levels, upregulation of laminin and GAP-43, and downregulation of GFAP and CSPG proteins.

Daidzein (one of the major isoflavones) can be metabolized to equol in certain individuals. The effects of isoflavones alone and equol status on lipid profiles are still controversial. To evaluate the 6-mo effects of daidzein on cardiovascular risk factors in hypercholesterolemic individuals and the interactions of these effects with equol status and estrogen receptor (ESR) genotypes, we conducted a randomized, double-blind, placebo-controlled trial consisting of 210 hypercholesterolemic adults (40-65 y old). The participants were randomly assigned (177 completed) to consume placebo, 40 mg daidzein (DAI40), or 80 mg daidzein (DAI80) daily for 6 mo. Daidzein decreased serum triglycerides (TGs) by 0.15 ± 0.62 mmol/L (mean ± SD) and 0.24 ± 0.61 mmol/L and decreased serum uric acid by 23 ± 47 μmol/L and 29 ± 44 μmol/L in the DAI40 and DAI80 groups, respectively. These reductions in the DAI40 and DAI80 groups were greater than those in the placebo group (P < 0.05). Other blood lipids, glucose, insulin, or glycated hemoglobin did not significantly change after daidzein treatment. No dose-dependent effects of daidzein were found. The reduction of TGs was influenced by the ESR genotype, with a greater effect observed in participants with the GA genotype compared with those with the GG genotype of ESR-β RsaI. These effects were not influenced by equol status. Six-month supplementation of daidzein significantly decreased TGs and uric acid. ESR-β RsaI genotype, not equol status, influenced daidzein's effects on TGs. Daidzein consumption may be effective to improve cardiovascular risk factors, especially in adults with the GA genotype of ESR-β RsaI. This trial was registered at the Chinese clinical trial registry as ChiCTR-TRC-10001048.