Carcinogenesis promotion in oral squamous cell carcinoma: KDM4A complex-mediated gene transcriptional suppression by LEF1.

Oral squamous cell carcinoma (OSCC) is the most prevalent cancer of the mouth, characterised by rapid progression and poor prognosis. Hence, an urgent need exists for the development of predictive targets for early diagnosis, prognosis determination, and clinical therapy. Dysregulation of lymphoid enhancer-binding factor 1 (LEF1), an important transcription factor involved in the Wnt-ß-catenin pathway, contributes to the poor prognosis of OSCC. Herein, we aimed to explore the correlation between LEF1 and histone lysine demethylase 4 A (KDM4A). Results show that the KDM4A complex is recruited by LEF1 and specifically binds the LATS2 promoter region, thereby inhibiting its expression, and consequently promoting cell proliferation and impeding apoptosis in OSCC. We also established NOD/SCID mouse xenograft models using CAL-27 cells to conduct an in vivo analysis of the roles of LEF1 and KDM4A in tumour growth, and our findings show that cells stably suppressing LEF1 or KDM4A have markedly decreased tumour-initiating capacity. Overall, the results of this study demonstrate that LEF1 plays a pivotal role in OSCC development and has potential to serve as a target for early diagnosis and treatment of OSCC.

Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation.

Osteoradionecrosis of the jaw (ORNJ) is an infrequent yet potentially devastating complication of head and neck radiation therapy. Low-intensity pulsed ultrasound (LIPUS) has been widely accepted as a promising method for the successful management of ORNJ, but the mechanism remains unclear. In this study, the effects of LIPUS on cytoskeletal reorganization, cell viability, and osteogenic differentiation capacity of rat mandible-derived bone marrow mesenchymal stem cells (M-BMMSCs) induced by radiation were determined by immunofluorescence staining, CCK-8 cell proliferation assay, quantification of alkaline phosphatase (ALP) activity, alizarin red staining, and real-time RT-PCR, respectively. Moreover, the involvement of the RhoA/ROCK signaling pathway underlying this process was investigated via western blot analysis. We found that radiation induced significant damage to the cytoskeleton, cell viability, and osteogenic differentiation capacity of M-BMMSCs and downregulated their expression of RhoA, ROCK, and vinculin while increasing FAK expression. LIPUS treatment effectively rescued the disordered cytoskeleton and redistributed vinculin. Furthermore, the cell viability and osteogenic differentiation capacity were also significantly recovered. More importantly, it could reverse the aberrant expression of the key molecules induced by radiation. Inhibition of RhoA/ROCK signaling remarkably aggravated the inhibitory effect of radiation and attenuated the therapeutic effect of LIPUS. In the light of these findings, the RhoA/ROCK signaling pathway might be a promising target for modifying the therapeutic effect of LIPUS on osteoradionecrosis.

Application of IMF screws to assist internal rigid fixation of jaw fractures: our experiences of 168 cases.

Intermaxillary fixation (IMF) screws were first introduced to achieve IMF as a kind of bone borne appliance for jaw fractures in 1989. Because this method can overcome many disadvantages associated with tooth borne appliance, IMF screws have been popularly used for jaw fractures since then. From March 2011 to February 2014, we treated 168 cases with single or multiple jaw fractures by open reduction and a total of 705 IMF screws were intraoperatively applied in all the cases to achieve IMF and maintain dental occlusion as an adjuvant to open reduction. The numbers, implantation sites and complications of IMF screws were retrospectively analyzed. In our experience, we found that IMF screws were important to assist open reduction of jaw fractures but their roles should be objectively assessed and the reliability of open reduction and internal rigid fixation must be emphasized. Much attention should be paid when implanting.

Melatonin attenuates inflammation of acute pulpitis subjected to dental pulp injury.

Acute pulpitis (AP), one of the most common diseases in the endodontics, usually causes severe pain to the patients, which makes the search for therapeutic target of AP essential in clinic. Toll-like receptor 4 (TLR4) signaling is widely involved in the mechanism of pulp inflammation, while melatonin has been reported to have an inhibition for a various kinds of inflammation. We hereby studied whether melatonin can regulate the expression of TLR4/NF-ĸB signaling in the pulp tissue of AP and in human dental pulp cells (HDPCs). Two left dental pulps of the adult rat were drilled open to establish the AP model, and the serum levels of melatonin and pro-inflammatory cytokines, including interleukin 1ß (IL-1ß), interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α), were assessed at 1, 3 and 5 d post injury. At the same time points, the expression of TLR4 signaling in the pulp was explored by quantitative real-time PCR and immunohistochemistry. The AP rats were administered an abdominal injection of melatonin to assess whether melatonin rescued AP and TLR4/NF-ĸB signaling. Dental pulp injury led to an approximately five-day period acute pulp inflammation and necrosis in the pulp and a significant up-regulation of IL-1ß, IL-18 and TNF-α in the serum. ELISA results showed that the level of melatonin in the serum decreased due to AP, while an abdominal injection of melatonin suppressed the increase in serum cytokines and the percentage of necrosis at the 5 d of the injured pulp. Consistent with the inflammation in AP rats, TLR4, NF-ĸB, TNF-α and IL-1ß in the pulp were increased post AP compared with the baseline expression. And melatonin showed an inhibition on TLR4/NF-ĸB signaling as well as IL-1ß and TNF-α production in the pulp of AP rats. Furthermore, melatonin could also regulate the expression of TLR4/NF-ĸB signaling in LPS-stimulated HDPCs. These data suggested that dental pulp injury induced AP and reduced the serum level of melatonin and that supplementation with melatonin may have a protective effect on AP by modulating TLR4/NF-ĸB signaling in the pulp and in pulp cells.

A new model of blast injury from a spherical explosive and its special wound in the maxillofacial region.

OBJECTIVE: The goal of this study was to establish an efficient explosive model with spherical explosives for the study of blast injury and its wound characteristics in the maxillofacial region. METHODS: Different spherical explosives were used to produce blast waves and to establish the wound model. Fresh sheep heads as the targets were used for the study of wound characteristics. The wounding parameters and the injuries of targets after explosion were observed. RESULTS: The overpressure values of blast waves decreased exponentially along with the increase of distances to explosives and so did the tissue damage. The blast injury is quite different from other injuries and is more serious. A kind of special "split fracture" of the mandibles was found. CONCLUSIONS: The new explosive wound model with spherical explosives can be used for the study of blast injury in the laboratory. The injury manner of blast wave and the local anatomy of tissues resulted in the special wound characteristics.

Distraction osteogenesis in the dog mandible under 60-Gy irradiation.

OBJECTIVE: The objective of this study was to explore the probability of distraction osteogenesis (DO) in the irradiated dog mandible after 60-Gy irradiation. STUDY DESIGN: Fourteen Chinese dogs were randomly divided into 2 groups. Twelve dogs received a preoperative unilateral irradiation from (60)Co (group R) in the mandible with a total dose of 24.8 Gy in four 6.2-Gy fractions (biologically equivalent to 60 Gy/25 fractions). The other 2 dogs without irradiation served as the control (group C). Bilateral corticotomies were made 6 months after completion of irradiation. Bone distraction was activated at a rate of 0.5 mm twice daily for 10 days after a 1-week latency period, followed by a consolidation phase of 8 weeks. The inferior alveolar nerve (IAN) underwent electrophysiologic analysis. Dog mandibles were subsequently subjected to histologic and radiographic analysis. RESULTS: All the animals had successful distractions. After 8 weeks of consolidation, no difference was found between the percentage area of new bone in both groups. New bone was more mature and organized in group C than in group R. The action potential of IAN showed corresponding alternation during the irradiation and distraction process. CONCLUSIONS: Based on this study it seems that DO may be feasible in dog mandible under 60-Gy irradiation. Further research is indicated.