With the development of tissue engineering and the shortage of autologous nerve grafts in nerve reconstruction, cell transplantation in a conduit is an alternative strategy to improve nerve regeneration. The present study evaluated the effects and mechanism of brain-derived neural stem cells (NSCs) on sciatic nerve injury in rats. At the transection of the sciatic nerve, a 10-mm gap between the nerve stumps was bridged with a silicon conduit filled with 5 × 10(5) NSCs. In control experiments, the conduit was filled with nerve growth factor (NGF) or normal saline (NS). The functional and morphological properties of regenerated nerves were investigated, and expression of hepatocyte growth factor (HGF) and NGF was measured. One week later, there was no connection through the conduit. Four or eight weeks later, fibrous connections were evident between the proximal and distal segments. Motor function was revealed by measurement of the sciatic functional index (SFI) and sciatic nerve conduction velocity (NCV). Functional recovery in the NSC and NGF groups was significantly more advanced than that in the NS group. NSCs showed significant improvement in axon myelination of the regenerated nerves. Expression of NGF and HGF in the injured sciatic nerve was significantly lower in the NS group than in the NSCs and NGF groups. These results and other advantages of NSCs, such as ease of harvest and relative abundance, suggest that NSCs could be used clinically to enhance peripheral nerve repair.
Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) has been identified as a crucial immune suppressor in human cancers, comparable to programmed cell death 1 ligand (PD-L1). However, the regulatory mechanisms underlying its transcriptional upregulation in human cancers remain largely unknown. Here, we show that the transcription factors ETS-1 and ETS-2 bound to the Siglec-15 promoter to enhance transcription and expression of Siglec-15 in hepatocellular carcinoma (HCC) cells and that transforming growth factor β-1 (TGF-β1) upregulated the expression of ETS-1 and ETS-2 and facilitated the binding of ETS-1 and ETS-2 to the Siglec-15 promoter. We further demonstrate that TGF-β1 activated the Ras/C-Raf/MEK/ERK1/2 signaling pathway, leading to phosphorylation of ETS-1 and ETS-2, which consequently upregulates the transcription and expression of Siglec-15. Our study defines a detailed molecular profile of how Siglec-15 is transcriptionally regulated which may offer significant opportunity for therapeutic intervention on HCC immunotherapy.
Objective. During orthodontic treatment, a higher caries risk has been reported, so fluorides and other remineralizing compounds have been proposed. Currently, fluoride varnish is commonly available in conventional and light-curable forms. This in vitro study was performed to evaluate the effectiveness of two different materials, Clinpro™ XT (light-curable forms) and Duraphat (conventional forms) varnish, whose main active principle according to their manufacturers is fluoride in preventing tooth discoloration during orthodontic treatment with appliances attached with metal brackets or resin. Materials and Methods. This study included 120 premolars free of white spot lesions and caries that were randomly divided into the following six groups (n = 20): resin control (RCTR), resin Clinpro (RC), resin Duraphat (RD), bracket control (BCTR), bracket Clinpro (BC), and bracket Duraphat (BD). All the samples were exposed to 180 ml of coffee (4 times × 5 min/day) for 7 or 28 days. When not immersed in coffee, the teeth were stored in artificial saliva, which was replaced every day. The lightness ( L ∗ ), red/green axis ( a ∗ ), and yellow/blue axis ( b ∗ ) values were recorded with a dental spectrophotometer (Easy shade Advance 4.0) on days 0 (baseline), 7, and 28. The color difference ( Δ E ∗ ) on days 7 and 28 was also calculated. Results. The data were statistically analyzed using one-way ANOVA and Bonferroni’s test (α = 0.05). Significant differences were observed between the Δ E ∗ , L ∗ , a ∗ , and b ∗ values of the Clinpro™ XT and Duraphat groups and those of the control groups after 7 and 28 days regardless of the attachment type ( P < 0.001). On day 7, no significant differences were observed between the Clinpro™ XT and Duraphat groups, whereas on day 28, the Duraphat groups with metal and resin attachments exhibited significant differences from the Clinpro™ XT groups ( P < 0.001). No significant differences correlated to the attachment type were observed throughout the discoloration procedure. Conclusions. The application of fluoride varnish during orthodontic treatment can significantly reduce tooth discoloration caused by the staining solution. Clinpro™ XT varnish showed a longer period of efficacy in protecting teeth from discoloration than Duraphat. No differences in tooth discoloration were observed between the groups with fixed and clear appliances.
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