Optimization Analysis of Two-Factor Continuous Variable between Thread Depth and Pitch of Microimplant under Toque Force.

Microimplant, an anchorage device, is widely applied in clinical orthodontic treatment. Since tooth torque is required to be controlled during orthodontic tooth movement, a novel microimplant needs to be developed to apply better torque force during orthodontic. In this study, the optimal value ranges of thread depth and pitch under toque force were studied for choosing microimplant with relevant value ranges in clinical design from biomechanical perspective. Finite element analysis (FEA) and optimization design technology were used for accessing the optimal value ranges of thread depth and pitch under toque force. Thread depth (D) (0.1 mm to 0.4 mm) and pitch (P) (0.4 mm to 1 mm) were used as continuous variables, with the other parameters as constant, and the optimal value ranges were obtained by analyzing the tangent slope and sensitivity of the response curve. When a torque force of 6 Nmm was applied on the microimplant, the maximum equivalent stress (Max EQV) of cortical bone and maximum displacements (Max DM) of microimplant were analysis indexes. When 0.55 mm ≤ P ≤ 1 mm, the Max EQV of cortical bone was relatively smaller with less variation range. When 0.1 mm ≤ D ≤ 0.35 mm, the Max DM of microimplant was relatively smaller with less variation range. So in conclusion, the initial stability of microimplants with pitch 0.55 mm ≤ P ≤ 1 mm and thread depth 0.1 mm ≤ D ≤ 0.35 mm was better with the torque force applied.

A Novel Prognostic Model for Oral Squamous Cell Carcinoma: The Functions and Prognostic Values of RNA-Binding Proteins.

PURPOSE: The biological roles and clinical significance of RNA-binding proteins (RBPs) in oral squamous cell carcinoma (OSCC) are not fully understood. We investigated the prognostic value of RBPs in OSCC using several bioinformatic strategies. MATERIALS AND METHODS: OSCC data were obtained from a public online database, the Limma R package was used to identify differentially expressed RBPs, and functional enrichment analysis was performed to elucidate the biological functions of the above RBPs in OSCC. We performed protein-protein interaction (PPI) network and Cox regression analyses to extract prognosis-related hub RBPs. Next, we established and validated a prognostic model based on the hub RBPs using Cox regression and risk score analyses. RESULTS: We found that the differentially expressed RBPs were closely related to the defense response to viruses and multiple RNA processes. We identified 10 prognosis-related hub RBPs (ZC3H12D, OAS2, INTS10, ACO1, PCBP4, RNASE3, PTGES3L-AARSD1, RNASE13, DDX4, and PCF11) and effectively predicted the overall survival of OSCC patients. The area under the receiver operating characteristic (ROC) curve (AUC) of the risk score model was 0.781, suggesting that our model exhibited excellent prognostic performance. Finally, we built a nomogram integrating the 10 RBPs. The internal validation cohort results showed a reliable predictive capability of the nomogram for OSCC. CONCLUSION: We established a novel 10-RBP-based model for OSCC that could enable precise individual treatment and follow-up management strategies in the future.

Comparison of postoperative cytokine and hormone between endoscopically assisted and open parotid tumor resection.

OBJECTIVE: Endoscopically assisted extracapsular dissection through a single incision along the cephaloauricular furrow has been adapted as a method of access for operating on benign parotid gland tumors. However, no study has compared the immune and stress responses after surgery between the endoscopic procedure and conventional open surgery. METHODS: Through a randomized method, 50 patients with benign parotid gland tumors were assigned to undergo either endoscopically assisted extracapsular dissection or open parotidectomy. The postoperative inflammatory changes and hormonal response in the patients were analyzed at serum level during the preoperative period and at 12, 24, and 72 hr after either surgery. RESULTS: Twenty-three patients received an endoscopic procedure, while 27 underwent open surgery. The size of the incision, amount of intraoperative bleeding, volume of drainage, postoperative pain score, and satisfaction with appearance were all improved in the endoscopic procedure group. Additionally, the serum levels of C-reactive protein, interleukin (IL)-6, IL-10, and cortisol were significantly lower in the endoscopy group in comparison with those in the open surgery group. CONCLUSION: Endoscopically assisted extracapsular dissection on patients with benign parotid gland tumors is associated with lower inflammatory changes and hormone responses than open surgery, thereby reducing perioperative pathophysiological disturbance and enhancing recovery after surgery.

Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expression.

BACKGROUND: Arecoline is an alkaloid natural product found in the areca nut that can induce oral submucous fibrosis and subsequent development of cancer. However, numerous studies have shown that arecoline may inhibit fibroblast proliferation and prevent collagen synthesis. RESULTS: High doses of arecoline (> 32 µg/ml) could inhibit human oral fibroblast proliferation, while low doses of arecoline (< 16 µg/ml) could promote the proliferation of human oral fibroblasts. Wnt5a was found to be both sufficient and necessary for the promotion of fibroblast proliferation. Egr-1 could mediate the expression of Wnt5a in fibroblasts, while NF-κB, FOXO1, Smad2, and Smad3 did not. Treatment with siRNAs specific to Egr-1, Egr inhibitors, or Wnt5a antibody treatment could all inhibit arecoline-induced Wnt5a upregulation and fibroblast proliferation. CONCLUSIONS: Egr-1 mediates the effect of low dose arecoline treatment on human oral mucosa fibroblast proliferation by transactivating the expression of Wnt5a. Therefore, Egr inhibitors and Wnt5a antibodies are potential therapies for treatment of oral submucosal fibrosis and oral cancer.

Tumor necrosis factor receptor-associated factor 6 mediated the promotion of salivary adenoid cystic carcinoma progression through Smad-p38-JNK signaling pathway induced by TGF-ß.

BACKGROUND: Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) has been proved to play an important role in tumorigenesis, invasion, and metastasis. However, its precise role salivary adenoid cystic carcinoma (SACC) has not been determined. The aim of this study was to explore the role of TRAF6 in SACC including invasion and metastasis of SACC cells. MATERIALS AND METHODS: Immunohistochemistry and quantitative real-time PCR were performed in SACC tissues paired with their adjacent normal tissues to analyze the expression of TRAF6. Downstream proteins expression was explored when TRAF6 was knockdown by siRNA. RESULTS: The results show that TRAF6 is upregulated in SACC samples, especially in SACC with metastasis, which is closely correlated with an aggressive phenotype (P = .0073) and shorter life survival span (P = .0061) in SACC patients. Knockdown of TRAF6 can attenuate the promotion effect of SACC cell invasion induced by TGF-ß. Western blot results also showed that silencing TRAF6 expression can inhibit the activation of SMAD2, SMAD3, ERK, p38, and JNK induced by TGF-ß in SACC cells. CONCLUSION: These data suggested that TRAF6 regulates TGF-ß-mediated SACC progression through SMAD2/3-ERK-p38-JNK cascades.

Down-regulation of miR-125a-5p is associated with salivary adenoid cystic carcinoma progression via targeting p38/JNK/ERK signal pathway.

Salivary adenoid cystic carcinoma (SACC) is a relatively uncommon epithelial-like malignancy that can occur in the head and neck region. Despite its slow growth, this aggressive salivary gland tumor frequently recurs and metastasizes to distant organs since lacking effective chemotherapy treatment. MicroRNAs are key regulators in tumor metastasis and progression, but their roles during SACC progression have not been illustrated. In current study, we demonstrate that miR-125a-5p is down-regulated in SACC and closely related to the metastasis and progression in human SACC specimens. In vitro, miR-125a-5p mimic can suppress SACC cell migration and invasion; while blocking miR-125a-5p can relieve the inhibition effect. By using dual-luciferase assay, we confirmed that miR-125a-5p directly targeted to p38 and tissue samples of patients indicated the negative correlation between miR-125a-5p and p38; clinical analysis also showed that low level expression of miR-125a-5p is closely associated with poor prognosis of SACC. Furthermore, down-regulation of miR-125a-5p triggered downstream p38/JNK/ERK activation. Taken together, our results indicate that down-regulation of miR-125a-5p promotes SACC progression through p38 signal pathway and miR-125a-5p can be a potential therapeutic target of SACC.

Mesenchymal stem cell-derived CCN2 promotes the proliferation, migration and invasion of human tongue squamous cell carcinoma cells.

Recent studies have demonstrated that mesenchymal stem cells (MSC) exhibit a tropism to tumors and form the tumor stroma. In addition, we found that MSC can secrete different types of factors. However, the involvement of MSC-derived factors in human tongue squamous cell carcinoma (TSCC) growth has not been clearly addressed. The CCN family includes multifunctional signaling molecules that affect the initiation and development events of various tumors. In our study, we report that CCN2/connective tissue growth factor (CTGF) was the most highly induced among the CCN family members in MSC that were co-cultured with TSCC cells. To evaluate the relationship between CCN2 and TSCC growth, we downregulated MSC-derived CCN2 expression with shRNA targeting CCN2 and found that MSC-secreted CCN2 promotes TSCC cell proliferation, migration and invasion. We also confirmed that MSC-derived CCN2 partially accelerated tumor growth in vitro. Taken together, these results suggest that MSC-derived CCN2 contributes to the promotion of proliferation, migration and invasion of TSCC cells and may be a possible therapy target in the future.

Overexpression of HMGA2 promotes tongue cancer metastasis through EMT pathway.

BACKGROUND: Metastasis to long distance organs is the main reason leading to morality of tongue squamous cell carcinoma (TSCC); however, the molecular mechanisms are still unknown. High mobility group AT-hook 2 (HMGA2) is highly expressed in multiple metastatic carcinomas, in which it contributes to cancer progression, metastasis and poor prognosis by upregulating Snail expression and inducing epithelial mesenchymal transition (EMT). This study focuses on investigating the role and mechanism of regulation of HMGA2 in the metastasis of TSCC. METHODS: HMGA2 mRNA and protein expression were examined in TSCC specimens by quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry (IHC). Western blotting, IHC and immunofluorescence were also used to measure the expression and localization of EMT marker E-Cadherin and Vimentin both in TSCC cells and tissues. Knockdown assay was performed in vitro in TSCC cell lines using small interfering RNAs and the functional assay was carried out to determine the role of HMGA2 in TSCC cell migration and invasion. RESULTS: TSCC mRNA and protein expression were significantly up-regulated in tumor tissues when compared to adjacent non-tumor tissues, and the overexpression of HMGA2 was closely correlated with lymph nodes metastasis. Clinicopathological analysis indicated that HMGA2 expression was associated with clinical stage (P = 0.001), lymph node metastasis (P = 0.000), histological differentiation (P = 0.002) and survival (P = 0.000). Silencing the HMGA2 expression in Cal27 and UM1 resulted in the inhibition of cell migration and invasion, meanwhile down-regulation of HMGA2 impaired the phenotype of EMT in TSCC cell lines and tissues. The Multivariate survival analysis indicates that HMGA2 can be an independent prognosis biomarker in TSCC. CONCLUSION: Our findings demonstrate that HMGA2 promotes TSCC invasion and metastasis; additionally, HMGA2 is an independent prognostic factor which implied that HMGA2 can be a biomarker both for prognosis and therapeutic target of TSCC.

FGF1-FGFR1 axis promotes tongue squamous cell carcinoma (TSCC) metastasis through epithelial-mesenchymal transition (EMT).

Increasing evidences suggest a close association between tumor metastasis and the inflammatory factors secreted by tumor microenvironment. It has been reported that epithelial mesenchymal-transition (EMT) plays a significant role during multiple types of tumor metastasis and progression induced by inflammatory factor from tumor microenvironment. Previous researches implied that fibroblast growth factor 1 (FGF1) can promote tumor progression and cause poor prognosis in several types of malignant tumors via interacting with its receptor fibroblast growth factor receptor 1 (FGFR1). However, the effects of FGF1-FGFR1 on tongue squamous cell carcinoma (TSCC) are not yet completely understood. In the present study, we evaluated the effects and function of FGF1-FGFR1 axis on TSCC metastasis. In addition, we investigated whether the EMT pathway is involved in these effects, thus modulating the TSCC progression. The expression of FGFR1 was measured both in tongue cancer cell lines and tissues by qRT-PCR and western blot. We found that FGFR1 was up-regulated in TSCC tissues compared to non-neoplastic tongue tissues. Additionally, overexpression of FGFR1 is positively associated with poor differentiation and metastasis potential. Furthermore, the function of FGF1-FGFR1 was examined in TSCC cell line. The results implied that FGF1 can obviously promote Cal27 cells migration and invasion abilities through FGFR1, while the motile and invasive capabilities can be severely attenuated when knockdown the expression of FGFR1 by specific siRNAs. Further investigation results show that FGF1-FGFR1 axis promotes TSCC metastasis by modulating EMT pathway. However, this effect can be inhibited by blocking the FGF1-FGFR1 axis using FGFR1 specific siRNAs. In conclusion, our findings of the present study provide the evidences that FGF1-FGFR1 axis promotes the TSCC metastasis through the EMT pathway.

Anesthetic efficacy of inferior alveolar nerve block plus buccal infiltration or periodontal ligament injections with articaine in patients with irreversible pulpitis in the mandibular first molar.

OBJECTIVE: We compared the anesthetic efficacy of inferior alveolar nerve block (IANB) plus buccal infiltration (BI) and IANB plus periodontal ligament (PDL) articaine injections in patients with irreversible pulpitis in the mandibular first molar. STUDY DESIGN: Fifty-seven volunteers, patients with irreversible pulpitis in the mandibular first molar admitted to the Department of Stomatology, Second Affiliated Hospital, Sun Yat-Sen University, randomly received conventional IANB, containing 1.7 mL 4% articaine/HCl with 1:100,000 epinephrine, plus either BI or PDL injections containing 0.4 mL articaine/HCl with 1:100,000 epinephrine. The patients recorded the pain of the injections and endodontic access on a Heft-Parker visual analog scale (VAS). RESULTS: According to the VAS scores, all patients experienced no or mild pain with BI and PDL injections after the application of IANB. Anesthetic success occurred in 81.48% for IANB plus BI (IANB/BI) compared with 83.33% for IANB plus PDL injection (IANB/PDL injection). None of the observed differences between the 2 groups was significant (P > .05). CONCLUSION: Both injection combinations resulted in high anesthetic success in patients with irreversible pulpitis in the mandibular first molar.