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Hypertension is a prevalent systemic disease in the elderly, who can suffer from several pathological skeletal conditions simultaneously, including osteoporosis. Benidipine (BD), which is widely used to treat hypertension, has been proved to have a beneficial effect on bone metabolism. In order to confirm the osteogenic effects of BD, we investigated its osteogenic function using mouse MC3T3-E1 preosteoblast cells in vitro. The proliferative ability of MC3T3-E1 cells was significantly associated with the concentration of BD, as measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell cycle assay. With BD treatment, the osteogenic differentiation and maturation of MC3T3-E1 cells were increased, as established by the alkaline phosphatase (ALP) activity test, matrix mineralized nodules formation, osteogenic genetic test, and protein expression analyses. Moreover, our data showed that the BMP2/Smad pathway could be the partial mechanism for the promotion of osteogenesis by BD, while BD might suppress the possible function of osteoclasts through the OPG/RANKL/RANK (receptor activator of nuclear factor-κB (NF-κB)) pathway. The hypothesis that BD bears a considerable potential in further research on its dual therapeutic effect on hypertensive patients with poor skeletal conditions was proved within the limitations of the present study.

As a core kinase of antiviral immunity, the activity and stability of TANK-binding kinase 1 (TBK1) is tightly controlled by multiple post-translational modifications. Although it has been demonstrated that TBK1 stability can be regulated by ubiquitin-dependent proteasome pathway, it is unclear whether another important protein degradation pathway, autophagosome pathway, can specifically affect TBK1 degradation by cargo receptors. Here we report that E3 ubiquitin ligase NEDD4 functions as a negative regulator of type I interferon (IFN) signaling by targeting TBK1 for degradation at the late stage of viral infection, to prevent the host from excessive immune response. Mechanically NEDD4 catalyzes the K27-linked poly-ubiquitination of TBK1 at K344, which serves as a recognition signal for cargo receptor NDP52-mediated selective autophagic degradation. Taken together, our study reveals the regulatory role of NEDD4 in balancing TBK1-centered type I IFN activation and provides insights into the crosstalk between selective autophagy and antiviral signaling.

To investigate the early bone formation in beagles with mini-lateral window sinus floor elevation and simultaneous implant placement.Six beagles were selected for the split-mouth design procedures. In each animal, one maxillary recess received a 5 mm-diameter mini-round lateral osteotomy (test group), and the contralateral maxillary recess received a large rectangular osteotomy (10 mm long and 8 mm wide), (control group). Simultaneous implant installation was executed on bilateral maxillary recesses. Tetracycline and calcein dyes were administered on the 14th, 13th days and the 4th, 3rd days prior to sacrifice, respectively. After 8 weeks of healing, the beagles were euthanized for fluorescent labeling and histomorphometric analyses.In both groups, new bone formation initiated from the circumferential native bone of the maxillary recesses and extended toward the central sub-recess cavities. The maxillary recesses with the mini-window procedures exhibited superior mineral apposition rate, bone formation rate, and the percentage of new bone area to those of the group exposed to large osteotomy procedure (p .05). While there was no significant difference in the value of bone-to-implant contact, the mini-window group displayed a tendency for an increase in this aspect (p .05). Bone formation rate and new bone amount were not statistically correlated with bone-to-implant contact (p .05).The hypothesis that mini-lateral window sinus floor elevation with simultaneous implant placement would improve early new bone formation in augmented sinus compared with large lateral window procedure is accepted.

ObjectiveThis study was performed to establish an optimized beagle model for maxillary sinus floor augmentation via a mini-lateral window with simultaneous implant placement.MethodsTwelve beagles underwent maxillary sinus floor augmentation via a mini-lateral window with simultaneous implant placement through sites selected by analyzing preoperative cone beam computed tomography (CBCT) images. During the experiment, no maxillary teeth were extracted and the infraorbital nerve was not severed. The osteotomy was only 5 mm in diameter. The implant stability quotient was measured, and postoperative CBCT was used to detect the condition of the sinus membrane and bone augmentation.ResultsThe site corresponding to the tip of the highest dental cusp of the maxillary fourth premolar was suitable for the procedure, and the implant site was on the palatal bone plate. All implants achieved good primary stability. Postoperative CBCT showed no sinus membrane perforation, and the implants penetrated into the sinus cavity surrounded by bone substitute.ConclusionThe herein-described optimized model with mini-lateral osteotomy and without extraction or severing of the infraorbital nerve was minimally invasive, retained more lateral bone of the sinus, and achieved good sinus floor-lifting results. This model is highly reproducible and merits wider application.