In situ Activation of Molecular Oxygen at Intermetallic Spacing-Optimized Iron Network-Like Sites for Boosting Electrocatalytic Oxygen Reduction.

The oxygen reduction reaction (ORR) catalyzed by transition-metal single-atom catalysts (SACs) is promising for practical applications in energy-conversion devices, but great challenges still remain due to the sluggish kinetics of O═O cleavage. Herein, a kind of high-density iron network-like sites catalysts are constructed with optimized intermetallic distances on an amino-functionalized carbon matrix (Fe-HDNSs). Quasi-in situ soft X-ray absorption spectroscopy and in situ synchrotron infrared characterizations demonstrate that the optimized intermetallic distances in Fe-HDNSs can in situ activate the molecular oxygen by fast electron compensation through the hybridized Fe 3d-O 2p, which efficiently facilitates the cleavage of the O═O bond to *O species and highly suppresses the side reactions for an accelerated kinetics of the 4e- ORR. As a result, the well-designed Fe-HDNSs catalysts exhibit superior performances with a half-wave potential of 0.89 V versus reversible hydrogen electrode (RHE) and a kinetic current density of 72 mA cm-2 @0.80 V versus RHE, exceeding most of the noble-metal-free ORR catalysts. This work offers some new insights into the understanding of 4e- ORR kinetics and reaction pathways to boost electrochemical performances of SACs.

Observation on the effect of periodontal treatment on patients with combined periodontal-pulpal lesions.

OBJECTIVE: To evaluate the effect of periodontal treatment on combined periodontal-pulpal lesions. METHODS: A total of 327 patients with periodontal-pulpal lesions (360 affected teeth) were selected, and all affected teeth were treated with a complete root canal, and assigned into group A (periodontal treatment group, 180 affected teeth) and group B (non-periodontal treatment group, 180 affected teeth). Group A received periodontal basic treatment for 2 weeks after the completion of root canal treatment; 6 weeks later, if there were still more than 5 mm periodontal pockets and bleeding after detection, flap treatment was performed. Group B received root canal treatment and supragingival scaling. Follow-up was conducted at 3, 6, 12 and 24 months after surgery by observing the periodontal depth (PD), alveolar bone resorption and tooth mobility (TM). RESULT: In group A, the PDs before operation and 2 years after operation were (5.966±1.877) mm and (5.133±1.935) mm, and the PD was significantly decreased. In group B, the PDs before operation and 2 years after operation were (5.533±1.856) mm and (6.167±1.927) mm, and the PD was increased. There was no statistical difference in preoperative TM between the two groups (P>0.05). Two years after operation, TM in group A was significantly lower than that in group B (P<0.05). In terms of X-ray performance, there was no significant change in alveolar bone resorption in group A two years after operation compared with that before operation (P>0.05); two years after operation, alveolar bone resorption in group B was significantly reduced compared with that before operation (P<0.05). CONCLUSION: Periodontal treatment is a promising technique for patients with combined periodontal-pulpal lesions.

Sox2 promotes tumor aggressiveness and epithelial­mesenchymal transition in tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is highly malignant and poorly differentiated, resulting in a high frequency of local recurrence and distant metastases. Sox2 (Sry­box2), an important factor in embryonic development and cell differentiation, has been shown to associate with malignant phenotypes and epithelial­mesenchymal transition (EMT) progression in numerous types of human tumors. However, the clinical relevance and molecular mechanisms of Sox2 in TSCC remain unclear. In the present study, the expression levels of Sox2 were assessed in 61 pairs of TSCC samples and corresponding adjacent non-cancerous tissues using immunohistochemical methods. Associations between Sox2 expression and clinicopathological features were evaluated. Furthermore, Sox2 was overexpressed and inhibited using full-length Sox2 cDNA and short hairpin RNA (shRNA) transfection in UM2 and Cal27 cell lines, respectively. The malignant phenotypes were assessed by plate clone formation assays, wound-healing assays and Transwell assays. EMT markers (E­cadherin, vimentin, Twist, Slug and Snail) and ß­catenin were detected by reverse transcription­polymerase chain reaction and western blot analysis following the alterations of Sox2 expression. The results indicated that Sox2 expression was markedly upregulated in TSCC samples and was significantly associated with tumor growth (pT stage), cell differentiation, lymphatic metastasis (pN stage) and clinical stage (pTNM stage). Cal27­shRNA­Sox2 cells not only exhibited a decreased capacity for cell proliferation, but also suppressed cell migration and invasion, and an attenuated colony formation capacity. By contrast, UM2­Sox2 cells exhibited accelerated cell malignant phenotypes and EMT progression. Moreover, when the expression of Sox2 was decreased by shRNA transduction, ß­catenin expression was attenuated. An opposing phenomenon was observed in UM2­Sox2 cells. In conclusion, this study suggests that Sox2 expression serves a role in TSCC malignant phenotypes and EMT progression, and that ß­catenin may act as a modulated factor in this progression.

Upregulation of proline rich 11 is an independent unfavorable prognostic factor for survival of tongue squamous cell carcinoma patients.

Proline rich 11 (PRR11) serves an important role in the development and progression of a number of types of human cancer. However, the clinical role of PRR11 in tongue squamous cell carcinoma (TSCC) remains unknown. The present study aimed to investigate the expression and clinicopathological significance of PRR11 in TSCC. The Cancer Genome Atlas analysis demonstrated that the upregulation of PRR11 in TSCC correlated with poor prognosis. The data of the present study revealed that PRR11 mRNA and protein expression was markedly upregulated in human TSCC tissues. Immunohistochemistry on 72 archived paraffin-embedded TSCC specimens suggested that high levels of PRR11 expression were significantly associated with clinical stage (P<0.001), T classification (P=0.009), N classification (P=0.017) and vital status (P=0.010). In addition, patients with TSCC with higher PRR11 expression exhibited substantially shorter survival times compared with patients with lower PRR11 expression (P<0.001). Univariate and multivariate analyses indicated that PRR11 upregulation may be an independent prognostic factor for patients with TSCC (P=0.001). Taken together, and to the best of our knowledge, the results of the present study demonstrated for the first time that PRR11 is involved in the development and progression of TSCC, and may serve as a useful prognostic marker and an effective target for treating TSCC.

MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway.

Accumulating data suggest that microRNAs (miRNAs) play a pivotal role in the regulation of tumor cell sensitivity to chemotherapeutic agents. Although the roles of a few miRNAs have been identified in cisplatin resistance, little is known in regards to the concerted contribution of miRNA­mediated biological networks. In the present study, we demonstrated that microRNA-218 (miR-218) was significantly upregulated in cisplatin-resistant oral cancer cells. The results of cell viability and apoptosis assay showed that ectopic expression of miR-218 induced cell survival and resistance to cisplatin, whereas suppression of miR-218 caused apoptosis and enhanced sensitivity to cisplatin. Moreover, we identified PPP2R5A as a new direct target of miR-218 by using the dual luciferase reporter assay. Overexpression of miR-218 led to inhibition of PPP2R5A expression, whereas knockdown of miR-218 increased PPP2R5A levels. Introduction of PPP2R5A abrogated miR­218-mediated cell survival and drug resistance. Furthermore, suppression of miR-218 or PPP2R5A significantly promoted or reduced cisplatin-induced apoptosis, respectively. Finally, PPP2R5A overexpression or ß-catenin knockdown inhibited miR-218-mediated Wnt activation and partially restored cell sensitivity. Our data revealed a molecular link between miR-218 and PPP2R5A/Wnt signaling and implicates miR-218 as a potential target for oral cancer therapy.

Overexpression of ß-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma.

Abnormal expression of ß-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression of ß-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect of ß-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines with ß-catenin knockin and knockdown. In this study, we found that higher expression level of ß-catenin can be observed in CDDP-treated cell lines as compared with the control group. Furthermore, the expression levels of ß-catenin increased in both a concentration- and time-dependent manner with the cisplatin treatment. More importantly, the nuclear translocation of ß-catenin could also be observed by confocal microscope analysis. Stable cell lines with CTNNB1 knockin and knockdown were established to further investigate the potential role and mechanism of ß-catenin in the chemoresistance of OSCC in vitro and in vivo. Our findings indicated that overexpression of ß-catenin promoted cisplatin resistance in OSCC in vitro and in vivo. We confirmed that GSK-3ß, C-myc, Bcl-2, P-gp, and MRP-1 were involved in ß-catenin-mediated drug resistance. Our findings indicate that the Wnt/ß-catenin signaling pathway may play important roles in cisplatin resistance in OSCC.

Role of the Accessory Parotid Gland in the Etiology of Parotitis: Statistical Analysis of Sialographic Features.

This retrospective study aimed to identify if the existence of the accessory parotid gland correlated with the etiology of parotitis. This may aid the development of better treatment strategies in the future. Sialographic features of cases with parotitis and healthy subjects were reviewed. The chi-square test was used to compare the incidence of accessory parotid gland between the groups. The Student's t test was used to compare the length of Stensen's duct, the length from the orifice to the confluence of the accessory duct, and the angle between the accessory duct and Stensen's duct between the groups. The incidence of accessory parotid gland in patients with parotitis was 71.8% (28/39), which was significantly higher than that in healthy subjects (P = 0.005). Patients with parotitis had a longer Stensen's duct than healthy subjects (P = 0.003). There was no significant difference in the length from the orifice to the confluence of the accessory duct or the angle between the accessory duct and Stensen's duct (P = 0.136 and 0.511, respectively) between the groups. The accessory parotid gland might play a role in the pathogenesis of parotitis. The existence of an accessory parotid gland is likely to interfere with salivary flow. Computational fluid dynamics analysis of salivary flow in the ductal system would be useful in future etiologic studies on parotitis.

Clinical Characteristics of Radiation-Induced Sarcoma of the Head and Neck: Review of 15 Cases and 323 Cases in the Literature.

PURPOSE: This retrospective study aimed to identify the clinical characteristics of radiation-induced sarcoma of the head and neck (RISHN) that could help in the early diagnosis of this rare disease. MATERIALS AND METHODS: From August 1995 through October 2014, 15 cases of RISHN presenting at the authors' department and 323 cases in the literature were reviewed. RESULTS: The incidence of RISHN was higher in men than in women (male-to-female ratio, 2.4:1). The mean latency was long (9.3 yr), and the tumor often occurred in middle age (50.0 yr old). Osteosarcoma was the predominant pathologic diagnosis (34.1%). The prognosis of RISHN was poor. CONCLUSION: RISHN is a serious long-term complication of radiotherapy and its incidence has been increasing in recent years. Owing to the long latency period, its early diagnosis is difficult to make. RISHN should be considered when a patient who has undergone radiotherapy presents with a mass, pain, or trismus in the irradiated field.

Clinicopathological features and prognostic implications of Raf kinase inhibitor protein downregulation in tongue squamous cell carcinoma.

Raf kinase inhibitor protein (RKIP) is recognized as a suppressor of metastasis, and the downregulation of RKIP is associated with aggressive events and a poor outcome in a variety of solid tumors. However, the clinical relevance of RKIP expression in tongue squamous cell carcinoma (TSCC) remains unclear. In the present study, the expression of RKIP in 85 pairs of TSCC and corresponding adjacent non-cancerous tissues, 30 matched metastatic lesions from the cervical lymph nodes and 32 oral leukoplakia samples were assessed using immunohistochemical methods. The association between RKIP expression and clinicopathological features was then evaluated. Kaplan-Meier survival analysis and Cox proportional hazards model were used to estimate the effect of RKIP expression on the survival time of patients with TSCC. The results revealed that RKIP expression was dramatically downregulated in TSCC, and to an even greater extent in metastatic lesions. RKIP downregulation was significantly associated with the presence of lymphatic metastasis and the clinical stage of TSCC. Furthermore, patients with low RKIP expression demonstrated a significantly shorter overall survival time. Multivariate analysis indicated that RKIP expression may be an independent prognostic factor in TSCC. In conclusion, the present findings indicate that the lack of RKIP expression is of clinical significance and may serve as a prognostic biomarker in TSCC.

Blockade of telomerase reverse transcriptase enhances chemosensitivity in head and neck cancers through inhibition of AKT/ERK signaling pathways.

Head and Neck squamous cell carcinomas (HNSCC), characterized by the high frequency of local recurrence and distant metastases, is mostly related to highly malignant and resistant to apoptosis, resulting in significant insensitivity to chemotherapy. Telomerase reverse transcriptase (TERT), as the catalytic subunit of telomerase, was implicated in the telomerase-mediated cellular transformation, proliferation, stemness and cell survival. Moreover, overexpression of human TERT (hTERT) is reported to be correlated with advanced invasive stage of the tumor progression and poor prognosis. Here, we show that hTERT potentially mediated the apoptotic resistance and blockade of telomerase reverse transcriptase could enhance chemosensitivity in head and neck cancers. Mechanistically, hTERT interacts with the phosphorylation of AKT and ERK to suppress the expression of p53, ultimately, leading to modulation of the cellular sensitivity to chemotherapy. Thus, these findings suggest that hTERT targeting could be an attractive approach in combination with conventional chemotherapies for patients suffering from chemoinsensitivity or refractory HNSCC.

Dissociation of E-cadherin/ß-catenin complex by MG132 and bortezomib enhances CDDP induced cell death in oral cancer SCC-25 cells.

E-cadherin/ß-catenin complex plays an important role in maintaining the homeostasis of tissues and regulating cell proliferation, survival and apoptosis. To address the relationships between the change of E-cadherin/ß-catenin complex and cell apoptosis, human oral squamous carcinoma SCC-25 cells were used to investigate whether the dissociation of the E-cadherin/ß-catenin complex was the main reason of MG132- or bortezomib-induced apoptosis. We found that MG132 or bortezomib alone induced remarkable loss of cell integrity and contact, inhibited cell growth, survival, migration and caused cell cycle arrest, intracellular ROS production. Further experiments showed that colony formations were significantly decreased by MG132 and bortezomib alone or plus cis-diaminedichloroplatinum (CDDP). Immunofluorescence staining showed that SCC-25 cells exhibited remarkable accumulations of ß-catenin in cytoplasm and few E-cadherin in cell membranes after MG132 or bortezomib treatment. Western blot results showed that MG132 or bortezomib induced high accumulation of ubiquitinated proteins and activation of apoptosis related protein caspase-3. Meanwhile, the combinational use of MG132 or bortezomib with CDDP led to synergistic effects on SCC-25 cells. However, knockdown of ß-catenin could decrease MG132 or bortezomib induced cell death. Taken together, our data suggest that the regulation of E-cadherin/ß-catenin complex could be a promising therapeutic target to overcome the multidrug resistance of oral cancer.

Telomerase reverse transcriptase potentially promotes the progression of oral squamous cell carcinoma through induction of epithelial-mesenchymal transition.

In recent years, researchers have found the critical role of telomerase in cellular transformation, proliferation, stemness and cell survival. High levels of telomerase reverse transcriptase (TERT) expression and telomerase activation have been reported in most cancer cells. Moreover, overexpression of human TERT (hTERT) is reported to be correlated with advanced invasive stage of the tumor progression and poor prognosis. Epithelial-mesenchymal transition (EMT), characterized by the loss of the cell-cell contact of epithelial cells and the acquisition of migratory and motile properties, is known to be a central mechanism responsible for invasiveness and metastasis of various cancers. Thus, we investigated whether hTERT plays a potential role in the development of EMT. As we expected, our clinical results showed that hTERT is overexpressed in oral epithelial dysplasia (OED) and OSCC tissues and correlates with clinical aggressiveness of oral squamous cell carcinoma (OSCC) patients. We then overexpressed hTERT in primary human oral epithelial cells (HOECS) and found that hTERT has the potential to prolong the lifespan, a process confering the characteristics of EMT by activating the Wnt/ß-catenin pathway. Our findings provided an explanation for the aggressive nature of human tumors overexpressing hTERT and the possibly mechanism that links hTERT to EMT property, which represents a possible therapeutic target in highly metastatic cancers.

BMI-1 activation is crucial in hTERT-induced epithelial-mesenchymal transition of oral epithelial cells.

BMI-1 (B lymphoma Mo-MLV insertion region 1 homolog) has been reported to be over-expressed in cell immortalisation and the epithelial-mesenchymal transition (EMT) of cancer cells. The aim of this study is to study the roles of BMI-1 in the human telomerase reverse transcriptase (hTERT)-induced immortalisation and EMT. In this study, hTERT(+)-OME cells and hTERT(+)-HaCaT cells were acquired by viral transduction of hTERT to primary cultured oral keratinocytes and HaCaT cells (skin epidermal cells). siRNA transduction was used for the inhibition of BMI-1 expression. RT-PCR and Western blots were performed to detect the expressions of twist, vimentin, BMI-1, hTERT and p16INK4a in these cell lines. EMT was assessed by immunohistochemistry (expressions of cytokertin & vimentin), Western blots (expressions of Twist, vimentin & E-cadherin) and RT-PCR (expression of Twist). The results indicated that hTERT(+)-OME cells and hTERT(+)-HaCaT cells underwent EMT spontaneously with high expression of Twist. p16INK4a was silenced in both hTERT-transduced cells but could be detected in HaCaT cells. Moreover, BMI-1 was highly expressed in hTERT(+)-OME and hTERT(+)-HaCaT cells but was negative in HaCaT cells. When the expression of BMI-1 was blocked by siRNA transduction, the proliferations of hTERT(+)-OME and hTERT(+)-HaCaT cells were inhibited and the mono-spheroid colony formation of these hTERT-transduced cells was decreased. In addition, the expression of p16INK4a was regained while the expressions of EMT markers (twist and vimentin) were down-regulated in these two BMI-1 blocking cell lines. To conclude, this study suggests BMI-1 expression plays a role in hTERT-induced immortalisation and EMT.

Diagnosis and treatment of primary synovial cell sarcoma that occurred in the left mandible body: a case report and literature review.

OBJECTIVE: The authors describe a case of synovial sarcoma in the left mandible body. STUDY DESIGN: The primary tumor was investigated morphologically and immunohistochemically. The patient was treated with madibulectomy and lymph node dissection, which was followed by an immediate reconstruction of the left mandible with a revascularized osteomyocutaneous fibula free flap. RESULTS: The primary tumor was described as gingival sarcoma. The initial preoperative biopsy showed positive staining for cytokeratin, vimentin, smooth muscle actin, and desmin by immunohistochemistry. The definitive diagnosis of monophasic synovial sarcoma was established following postoperative excision biopsy. Antigens of S-100 and CD99 displayed positive staining but epithelial membrane antigen, Bcl-2, and CD34 were negative. Also, no metastasis or other bone swelling was observed by radionuclide survey suggesting the left mandible was the primary lesion of occurrence. CONCLUSIONS: Synovial sarcoma is an uncommon soft tissue malignant neoplasm. This is the sixth case of primary synovial sarcoma occurring in the jaw.