Antiviral effects of liposome-encapsulated PolyICLC against Dengue virus in a mouse model.

This study presents the first investigation of the antiviral effects of the liposome-encapsulated PolyICLC (LE-PolyICLC) on Dengue virus (DENV) in a mouse model. In vivo efficacy studies showed that LE-PolyICLC acted to increase antiviral mechanisms mainly through promoting cytokine expression associated with innate immunity, such as IFN-γ. In addition, the pro-inflammatory cytokine TNF-α was also increased, while IL-6 level was decreased in serum. The titers of total antibodies against DENV2 in mice were also elevated. Administration of LE-PolyICLC not only alleviated the loss of body weight, degree of morbidity, and pathological damage in brains, but also reduced the viral titers and expression of viral E protein in the brain. Notably, the effectiveness of LE-PolyICLC was better than PolyICLC on the basis of the data presented in this study. These results, therefore, set a foundation for further development of LE-PolyICLC as an attractive candidate of antiviral agents to be used in both prophylactic and therapeutic settings in DENV diseases.

Knockdown of TRPM2 promotes osteogenic differentiation of human periodontal ligament stem cells by modulating NF-κB /NLRP3 pathway.

Periodontitis is characterized by periodontal destruction triggered by chronic inflammation. The optimal treatment for periodontitis is to improve the periodontal microenvironment, reduce inflammation and achieve periodontal regeneration. Recently, the role of TRPM2 in inflammatory diseases has been reported. However, the function of TRPM2 in periodontal disease and the biological mechanism remain elusive. Therefore, this study aimed to identify the role and explore the underlying mechanisms of TRPM2 in periodontal disease. Here, we first identified the characterization of human periodontal ligament stem cells (PDLSCs). Oil Red O Staining and Alizarin Red mineralized matrix were used to evaluate the multi-differentiation capacity of cells. Flow cytometry was employed to detect MSC-specific surface markers of hPDLSCs. hPDLSCs were treated with 0, 5, 10 or 40 µg/mL of TNF-α for 72 h. Western blot assay were performed to examine the expression of Transient receptor potential cation channel, subfamily M, member 2 (TRPM2) in hPDLSCs. CCK8 and colony formation assays were used to detect the cell viability and proliferation of hPDLSCs, which revealed that TRPM2 knockdown promoted hPDLSCs proliferation. Then, ALP activity in hPDLSCs was detected by ALP activity detection kit. Next, the expression of ALP and Runx2 in hPDLSCs was detected by immunofluorescence staining. The result showed that TRPM2 knockdown promoted osteogenic differentiation and affected the genes expression of osteogenic. Finally, the expressions of p-p65, p65, p-IκBα, IκBα and NLRP3 in hPDLSCs were detected by western blot assay. Together, these results suggested that knockdown of TRPM2 accelerated osteogenic differentiation of hPDLSCs through mediating NF-κB /NLRP3 pathway.

Research on a novel digital tooth sectioning guide system for tooth sectioning during mandibular third molar extraction: An in vitro study.

OBJECTIVE: To construct a novel portable tooth sectioning guide to improve the accuracy of mandibular third molar extraction. METHODS: First, 72 samples of an identical 3D-printed double-rooted mandibular third molar were obtained and used in 36 mandibular models. Three different models were constructed (class B vertical, mesial, and horizontal impaction). Then, we made the tooth sectioning guides. mimicking clinical tooth sectioning conditions, two dental surgeons with different levels of experience used both the digital guided technique and the traditional empirical technique during surgery. Accuracy indicators, including apical deviation and angle deviation, were analyzed and compared on postoperative cone-beam computed tomographic scanning and via image reconstruction. Descriptive statistical analyses were performed. A p-value of 0.05 indicated statistically significant differences among the groups. RESULTS: Overall, the mean apical deviation of experienced/inexperienced operators using the conventional section technique was 1.120 mm (0.7 mm, 2.3 mm) and 1.54± 0.84 mm, respectively. Correspondingly, the mean apical deviation under the guided section technique was 0.28 mm (0.2 mm, 0.4 mm) and 0.32±0.16 mm, respectively. The mean angle deviations of experienced/inexperienced operators under the conventional section technique were 8.015° (3.5°, 10.5°) and 6.570° (5.5°, 14.9°). Correspondingly, the mean apical deviation using the guided section technique was 1.880° (0.4°, 2.9°) and 1.470° (0.7°, 3.1°), respectively. The conventional and guided techniques were significantly different (P < 0.001). CONCLUSIONS: In the digital guide technique, sectioning is more predictable and accurate, and the success of the operation is achievable with different proficiencies among dental surgeons. CLINICAL SIGNIFICANCE: This technique will not only reduce the difficulty of tooth extraction but also reduce the risk of damage to the surrounding soft and hard tissues, especially damage to the inferior alveolar nerve.

Fabrication of chondrocytes/chondrocyte-microtissues laden fibrin gel auricular scaffold for microtia reconstruction.

Fibrin gel-based scaffolds have promising potential for microtia reconstruction. Autologous chondrocytes and chondrocyte cell sheets are frequently used seed cell sources for cartilage tissue engineering. However, the aesthetic outcome of chondrocyte-based microtia reconstruction is still not satisfactory. In this study, we aimed to fabricate the chondrocytes/chondrocyte-microtissues laden fibrin gel auricular scaffold for microtia reconstruction. We designed a unique auricular mold that could fabricate a fibrin gel scaffold resembling human auricle anatomy. Primary chondrocytes were harvested from rabbit auricular cartilage, and chondrocyte cell sheets were developed. Chondrocyte-microtissues were prepared from the cell sheets. The mixture of chondrocytes/chondrocyte-microtissues was laden in fibrin gel during the auricular scaffold fabrication. The protrusions and recessed structure in the auricular scaffold surface were still clearly distinguishable. After a one-week in vitro culture, the 3 D structure and auricular anatomy of the scaffold were retained. And followed by eight-week subcutaneous implantation, cartilaginous tissue was regenerated in the artificial auricular structure as indicated by the results of H&E, Toluidine blue, Safranin O, and type II collagen (immunohistochemistry) staining. Protrusions and depressions of the auricular scaffold were slightly deformed, but the overall auricular anatomy was maintained after 8-week in vivo implantation. Extracellular matrix components content were similar in artificial auricular cartilage and rabbit native auricular cartilage. In conclusion, the mixture of chondrocytes/chondrocyte-microtissues laden fibrin gel auricular scaffold showed a promising potential for cartilaginous tissue regeneration, suggesting this as an effective approach for autologous chondrocyte-based microtia reconstruction.