PLEK2 promotes cancer stemness and tumorigenesis of head and neck squamous cell carcinoma via the c-Myc-mediated positive feedback loop.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis, high lymph node metastasis and early recurrence. However, the molecular events regulating HNSCC tumorigenesis remain poorly understood. Therefore, uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC. In this study, we aimed to explore the role of pleckstrin-2 (PLEK2) in regulating HNSCC tumorigenesis. METHODS: The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort. In vitro and in vivo experiments, including cell proliferation, colony formation, Matrigel invasion, tumor sphere formation, ALDEFLUOR, Western blotting assays and xenograft mouse models, were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells. The underlying molecular mechanisms for the tumor-promoting role of PLEK2 were elucidated using co-immunoprecipitation, cycloheximide chase analysis, ubiquitination assays, chromatin immunoprecipitation-quantitative polymerase chain reaction, luciferase reporter assays and rescue experiments. RESULTS: The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues, and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance. Additionally, PLEK2 was important for maintaining the proliferation, invasion, epithelial-mesenchymal transition, cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells. Mechanistically, PLEK2 interacted with c-Myc and reduced the association of F-box and WD repeat domain containing 7 (FBXW7) with c-Myc, thereby avoiding ubiquitination and subsequent proteasome-mediated degradation of c-Myc. Moreover, the c-Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells. c-Myc also directly bounded to the PLEK2 promoter and activated its transcription, forming a positive feedback loop. CONCLUSIONS: Collectively, these findings uncover a previously unknown molecular basis of PLEK2-enhanced c-Myc signaling in HNSCC, suggesting that PLEK2 may represent a promising therapeutic target for treating HNSCC.

Accuracy of half-way mucosa-supported implant guides for edentulous jaws: a retrospective study with a median follow-up of 2 years.

OBJECTIVE: To assess the accuracy of half-way digital mucosa-supported implant guides (HDMIGs) for edentulous jaws. METHODS: Ninety-five consecutive patients (859 implants) with edentulous jaws who underwent implant placement using an HDMIG from July 2012 to June 2018 were retrospectively identified. The primary endpoint was implant-related complications (nerve injury and unexpected perforation), and the secondary endpoints were the faciolingual distance, mesiodistal distance, buccolingual angle, and mesiodistal angle. Follow-ups occurred at 1 month, 2 months, and then every 2 months following implant placement. RESULTS: Twenty-seven (28.4%) patients met the exclusion criteria, leaving 68 eligible patients (636 implants) for the final analysis. The median follow-up was 24 months (range, 18-27 months). No patients developed nerve injury, revision, or unexpected perforation. At the final follow-up, the mean faciolingual distance was 0.65 ± 0.16 mm, the mean mesiodistal distance was 1.16 ± 0.61 mm, the mean buccolingual angle was 4.04° ± 2.26°, and the mean mesiodistal angle was 3.75° ± 2.56°. In the comparison of the first month after surgery and the last follow-up, no significant differences were detected in any of the four measured variables. CONCLUSION: Use of an HDMIG may be a convenient and safe method to ensure correct implantation.

Association of Periodontitis with Rheumatoid Arthritis and the Effect of Non-Surgical Periodontal Treatment on Disease Activity in Patients with Rheumatoid Arthritis.

BACKGROUND The association of periodontitis (PD) with the prevalence of rheumatoid arthritis (RA) remains controversial. Therefore, the aim of this study was to evaluate their correlation and investigate the effects of non-surgical periodontal treatment on RA. MATERIAL AND METHODS A total of 64 patients were enrolled in this study and divided into 4 groups: 18 PD patients (PD+RA-), 18 RA patients (PD-RA+), 18 RA with PD patients (PD+RA+), and 10 healthy controls (PD-RA-). Periodontal and rheumatologic parameters were examined at baseline and 1 month following non-surgical periodontal treatment. RESULTS Our results showed that RA patients had similar periodontal status. However, patients in the PD+RA+ group had significantly higher levels of rheumatologic parameters such as C-reactive protein (CRP), anti-cyclic citrulline peptide antibody (ACPA), erythrocyte sedimentation rate (ESR), and Disease Activity Score 28 (DAS28) than those in the PD-RA+ group. In addition, non-surgical periodontal treatment was efficacious in improving rheumatologic parameters of patients in the PD+RA+ group. CONCLUSIONS The presence of PD might contribute to the progression of RA, while RA might have little effect on accelerating the development of PD. In addition, RA patients with PD receiving non-surgical periodontal treatment resulted in noteworthy improvement in the clinical outcome for RA.

Accuracy of using computer-aided rapid prototyping templates for mandible reconstruction with an iliac crest graft.

BACKGROUND: This study aimed to evaluate the accuracy of surgical outcomes in free iliac crest mandibular reconstructions that were carried out with virtual surgical plans and rapid prototyping templates. METHODS: This study evaluated eight patients who underwent mandibular osteotomy and reconstruction with free iliac crest grafts using virtual surgical planning and designed guiding templates. Operations were performed using the prefabricated guiding templates. Postoperative three-dimensional computer models were overlaid and compared with the preoperatively designed models in the same coordinate system. RESULTS: Compared to the virtual osteotomy, the mean error of distance of the actual mandibular osteotomy was 2.06 ± 0.86 mm. When compared to the virtual harvested grafts, the mean error volume of the actual harvested grafts was 1412.22 ± 439.24 mm3 (9.12% ± 2.84%). The mean error between the volume of the actual harvested grafts and the shaped grafts was 2094.35 ± 929.12 mm3 (12.40% ± 5.50%). CONCLUSIONS: The use of computer-aided rapid prototyping templates for virtual surgical planning appears to positively influence the accuracy of mandibular reconstruction.

Digital surgical templates for managing high-energy zygomaticomaxillary complex injuries associated with orbital volume change: a quantitative assessment.

PURPOSE: This study sought to introduce 3-dimensional (3D) virtual surgical planning and digital rapid-prototyping templates for zygomaticomaxillary complex (ZMC) injuries associated with orbital volume change and to evaluate the surgical outcomes quantitatively. PATIENTS AND METHODS: Eight patients who underwent open reduction and fixation for a ZMC injury with orbital volume change were studied. Computed tomographic (CT) scan of the zygomaticomaxillary area was performed before the operation in each case. Scanned data were converted into 3D models using Mimics software (Materialise, Brussels, Belgium) for surgical designs. Virtual surgical reductions and correlated guiding templates were designed using Mimics and Magics software (Materialise). The operations were performed with the help of prefabricated templates to reduce the fractures. A postoperative CT scan of each patient was obtained within 2 weeks after surgery, and quantitative measurements were made to assess the surgical outcomes. Preoperative volumes of the bilateral orbits were compared, and concordance with postoperative volumes of the bilateral orbits was assessed. Twenty-one pairs of distances from 7 marker points to 3 reference planes were measured to assess postoperative facial symmetry. RESULTS: Volumes of the injured orbits were significantly different from volumes of the uninjured orbits preoperatively (P < .05), whereas bilateral orbital volumes showed no statistically significant difference postoperatively (P > .05). In addition, 19 of the 21 pairs of bilateral distances showed no significant difference postoperatively (P > .05). CONCLUSIONS: Quantitative assessment showed that digitally designed, rapid-prototyping templates for ZMC fractures have a positive impact on restoring facial symmetry and concordance of bilateral orbital volumes.

Superior biocompatibility and osteogenic efficacy of micro-arc oxidation-treated titanium implants in the canine mandible.

The aim of this paper is to test implantation outcomes and osteogenic efficacy of plasma micro-arc oxidation (MAO)-treated titanium implants in dogs. Thirty-six pure titanium implants (18 MAO-treated, 18 untreated) were inserted into the mandibles of nine adult beagles and allowed to heal under non-weight-bearing conditions. Implant stability and interface characteristics were evaluated at 4, 8 and 12 weeks post-implantation. Methods included scanning electron microscopy, mechanical testing, histological analysis and computer-quantified tissue morphology. Osseointegration was achieved in both groups, but occurred earlier and more extensively in the MAO group. Areas of direct bone/implant contact were approximately nine times higher in the MAO group than in the control group at 12 weeks (65.85% versus 7.37%, respectively; p < 0.01). Bone-implant shear strength in the MAO group (71.4, 147.2 and 266.3 MPa at weeks 4, 8 and 12, respectively) was higher than in the control group (4.3, 7.1, and 11.8 MPa at weeks 4, 8 and 12, respectively), at all assessments (all, p < 0.01). MAO treatment of titanium implants promotes more rapid formation of new bone, and increases bone-implant shear strength compared to untreated titanium implants.