Tertiary lymphoid structures in oral lichen planus and oral epithelial dysplasia with lichenoid features: A comparative study.

OBJECTIVE: Tertiary lymphoid structures (TLSs) provide sites for antigen presentation and activation of lymphocytes, promoting their infiltration; thus, enhancing specific immune responses. The aim of this comparative cross-sectional study was to reveal the characteristics and influence of TLSs in oral lichen planus (OLP) and oral epithelial dysplasia (OED) with lichenoid features. METHODS: Clinical information and samples of 51 OLP and 19 OED with lichenoid features were collected. Immunohistochemistry was performed, and the structures where CD20+ B cells and CD3+ T cells aggregated with peripheral lymph node addressin positive (PNAd+) vessels were defined as TLSs. The results and clinical information were analysed. RESULT: TLS were found in 44 (86.3%) patients with OLP and 19 (100%) patients with OED. The TLS score was higher in OED group (p = 0.023), accompanied by an increased number of PNAd+ vessels. The TLS was significantly correlated with PNAd+ vessels (p = 0.027), CD20+ B (p < 0.001) and CD208+ dendritic cells (p = 0.001). Foxp3+ Treg cells but not CD8+ T cells infiltrated more severely in OED (p = 0.003) and increased when TLS score was high (p = 0.002). CONCLUSIONS: This study revealed the widespread development of TLSs in the OLP and OED. The presence of TLSs showed a close relationship with dysplasia and may increase malignant potency by over-inducing Treg cells.

Influence of PD-1/PD-L1 on immune microenvironment in oral leukoplakia and oral squamous cell carcinoma.

OBJECTIVE: To evaluate the relation between the expression of PD-1, PD-L1, CD3, CD8, Foxp3 and clinicopathological features in patients with oral leukoplakia (OLK) and oral squamous cell carcinomas (OSCC) as well as the malignant outcome in OLK patients, and to study the effect of PD-1 and PD-L1 on immune microenvironment in the progression of oral carcinogenesis. METHODS: We evaluated the expression of PD-1/PD-L1 and composition of CD3+ , CD8+ and Foxp3+ T lymphocytes in OLK and OSCC samples by immunohistochemical (IHC) staining and analyzed their relation with clinical information and malignant transformation in OLK patients. RESULTS: IHC staining demonstrated that the expression of PD-1 was significantly increased in the high-grade OLK group than in the low-grade OLK group, while PD-L1 was detected mainly in OSCC. The expression of CD3, CD8, and Foxp3 was found higher in the high-grade OLK group than in the low-grade OLK group, and the Foxp3+ cells were found more in the OSCC group than in the high-grade OLK group. PD-1 was significantly correlated with CD3 (p < 0.05, R = 0.52), CD8 (p < 0.05, R = 0.46), and Foxp3 (p < 0.05, R = 0.46), and the low PD-1-expression group showed a better malignant-free survival than high PD-1 expression group in the OLK (p < 0.05). CONCLUSION: The PD-1/PD-L1 may induce immune suppression in OLK and accelerate the progress of malignant transformation.

Cancer-associated fibroblasts promote oral squamous cell carcinoma progression through LOX-mediated matrix stiffness.

BACKGROUND: Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, have prominent roles in the development of solid tumors as stromal targets. However, the underlying mechanism of CAFs' function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we investigated the role of lysyl oxidase (LOX) expression in CAFs in tumor stromal remodeling and the mechanism of its effect on OSCC progression. METHODS: Multiple immunohistochemistry (IHC) staining was performed to detect the correlation of CAFs and LOX in the stroma of OSCC specimens, as well as the correlation with clinicopathological parameters and prognosis. The expression of LOX in CAFs were detected by RT-qPCR and western blot. The effects of LOX in CAFs on the biological characteristics of OSCC cell line were investigated using CCK-8, wound-healing and transwell assay. CAFs were co-cultured with type I collagen in vitro, and collagen contraction test, microstructure observation and rheometer were used to detect the effect of CAFs on remodeling collagen matrix. Then, collagen with different stiffness were established to investigate the effect of matrix stiffness on the progression of OSCC. Moreover, we used focal adhesion kinase (FAK) phosphorylation inhibitors to explored whether the increase in matrix stiffness promote the progression of OSCC through activating FAK phosphorylation pathway. RESULTS: LOX was colocalized with CAFs in the stroma of OSCC tissues, and its expression was significantly related to the degree of malignant differentiation and poor prognosis in OSCC. LOX was highly expressed in CAFs, and its knockdown impaired the proliferation, migration, invasion and EMT process of OSCC cells. The expression of LOX in CAFs can catalyze collagen crosslinking and increase matrix stiffness. Furthermore, CAFs-derived LOX-mediated increase in collagen stiffness induced morphological changes and promoted invasion and EMT process in OSCC cells by activating FAK phosphorylation pathway. CONCLUSIONS: Our findings suggest that CAFs highly express LOX in the stroma of OSCC and can remodel the matrix collagen microenvironment, and the increase in matrix stiffness mediated by CAFs-derived LOX promotes OSCC development through FAK phosphorylation pathway. Thus, LOX may be a potential target for the early diagnosis and therapeutic treatment of OSCC.

Heat shock factor 1 in cancer-associated fibroblasts is a potential prognostic factor and drives progression of oral squamous cell carcinoma.

Heat shock factor 1 (HSF1) is highly expressed in various malignancies and is a potential modulator of tumor progression. Emerging evidence suggests that HSF1 activation in stromal cells is closely related to poor patient prognosis. However, the role of HSF1 in oral squamous cell carcinoma (OSCC) remains elusive. We aimed to investigate the function of HSF1 in cancer-associated fibroblasts (CAFs) of the tumor microenvironment (TME) and in tumor development. In the present study, we found that HSF1 was highly expressed in both CAFs and tumor cells, and was significantly correlated with poor prognosis and overall survival. Moreover, HSF1 overexpression in CAFs resulted in a fibroblast-like phenotype of Cal27 cells, induced epithelial-mesenchymal transition (EMT), and promoted proliferation, migration and invasion in Cal27 cells. HSF1 knockdown attenuated features of CAFs and reduced EMT, proliferation, migration and invasion in Cal27 cells. Furthermore, HSF1 in CAFs promoted tumor growth in nude mice. Taken together, these data suggest that HSF1 expression in CAFs drive OSCC progression, and could serve as an independent prognostic marker of patients with OSCC. Thus, HSF1 is a potent mediator of OSCC malignancy.

Membrane Type 1 Matrix Metalloproteinase induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells.

BACKGROUND: Tissue invasion and metastasis are acquired abilities of cancer and related to the death in oral squamous cell carcinoma (OSCC). Emerging observations indicate that the epithelial-to-mesenchymal transition (EMT) is associated with tumor progression and the generation of cells with cancer stem cells (CSCs) properties. Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) is a cell surface proteinase, which is involved in degrading extracellular matrix components that can promote tumor invasion and cell migration. METHODS: In the current study, we utilized SCC9 cells stably transfected with an empty vector (SCC9-N) or a vector encoding human MT1-MMP (SCC9-M) to study the role of MT1-MMP in EMT development. RESULTS: Upon up-regulation of MT1-MMP, SCC9-M cells underwent EMT, in which they presented a fibroblast-like phenotype and had a decreased expression of epithelial markers (E-cadherin, cytokeratin18 and ß-catenin) and an increased expression of mesenchymal markers (vimentin and fibronectin). We further demonstrated that MT1-MMP-induced morphologic changes increased the level of Twist and ZEB, and were dependent on repressing the transcription of E-cadherin. These activities resulted in low adhesive, high invasive abilities of the SCC9-M cells. Furthermore, MT1-MMP-induced transformed cells exhibited cancer stem cell (CSC)-like characteristics, such as low proliferation, self-renewal ability, resistance to chemotherapeutic drugs and apoptosis, and expression of CSCs surface markers. CONCLUSIONS: In conclusion, our study indicates that overexpression of MT1-MMP induces EMT and results in the acquisition of CSC-like properties in SCC9 cells. Our growing understanding of the mechanism regulating EMT may provide new targets against invasion and metastasis in OSCC.

A hybrid SERS sensing platform constructed by porous carbon/Ag nanoparticles for efficient imatinib detection in bio-environment.

Surface enhanced Raman scattering (SERS) is a rapid and non-destructive spectral detection technique, and has been widely implemented on trace-level molecule detection. In this work, a hybrid SERS substrate constructed by porous carbon film and silver nanoparticles (PCs/Ag NPs) was developed and then used for imatinib (IMT) detection in bio-environment. The PCs/Ag NPs was prepared by direct carbonizing the gelatin-AgNO3 film in the air atmosphere, and an enhancement factor (EF) of 106 was achieved with R6G as the Raman reporter. Hereafter, this SERS substrate was used as the label-free sensing platform to detect the IMT in the serum, and the experimental results indicate that the substrate is conducive to eliminating the interference from the complex biological molecules in the serum, and the characteristic Raman peaks belonging to IMT (10-4 M) are accurately resolved. Furthermore, the SERS substrate was used to trace the IMT in the whole blood, the trace of ultra-low concertation of IMT is rapidly discovered without any pretreatment. Thus, this work finally suggests that the proposed sensing platform provides a rapid and reliable method for IMT detection in the bio-environment and offers a potential for its application in therapeutic drug monitoring.

Ag NC and Ag NP/PorC Film-Based Surface-Enhanced Raman Spectroscopy-Type Immunoassay for Ultrasensitive Prostate-Specific Antigen Detection.

Surface-enhanced Raman scattering (SERS) is a spectral detection technology with high sensitivity and detectivity and can be used to detect the fingerprint information of the molecules with ultralow concentration. Herein, a kind of immunostructure constructed by Ag nanoparticle/porous carbon (Ag NP/PorC) films as the immunosubstrate and Ag NCs as the immunoprobes was presented for ultralow level prostate-specific antigen (PSA) detection. Experimentally, the Ag NP/PorC film was first prepared with a facile method by carbonizing the gelatin-AgNO3 film in air, and Ag NCs were synthesized by the hydrothermal method. Then, the Ag NP/PorC film was modified by PSA antibodies as the substrate, while Ag NCs were decorated by R6G and PSA antibodies for probes. The sandwiched SERS detection embodiment was constructed by the immunoreaction between the PSA and PSA antibody predecorated on the substrate and probes. Our results show that the proposed SERS-type immunoassay is highly sensitive and selective to a wide range of PSA concentrations from 10-5 to 10-12 g/mL. Thereafter, it was also implemented to detect the PSA level in human serum, and the results successfully reproduce the PSA levels as those measured by the chemiluminescence method with a recovery rate above 90%. All in all, this SERS-type immunoassay provides a promising method for the early diagnosis of prostate cancer.

Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells.

Local invasiveness and distant metastasis are critical factors that contribute to oral squamous cell carcinoma-related deaths. Increasing evidence has shown that the epithelial to mesenchymal transition (EMT) is involved in cancer progression and is associated with the 'stemness' of cancer cells. Snail is a transcriptional factor that can induce EMT and preserve stem-cell function, which may induce resistance to radio- and chemotherapies in the cells. In the present study, SCC9 cells were transfected with an empty vector or a vector encoding human Snail (SCC9-S). Overexpression of Snail induced SCC9 cells to undergo EMT, in which the cells presented a fibroblast-like appearance, downregulated the epithelial markers E-cadherin and ß-catenin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Furthermore, the induction of EMT promoted cancer stem cell (CSC)-like characteristics in the SCC9-S cells, such as low proliferation, self-renewal, and CSC-like markers expression. These results indicate that overexpression of Snail induces EMT and promotes CSC-like traits in the SCC9 cells. Further understanding the role of Snail in cancer progression may reveal new targets for the prevention or therapy of oral cancers.

Constructing the Mo2C@MoOx Heterostructure for Improved SERS Application.

Surface-enhanced Raman scattering (SERS) is a non-destructive spectra analysis technique. It has the virtues of high detectivity and sensitivity, and has been extensively studied for low-trace molecule detection. Presently, a non-noble-metal-based SERS substrate with excellent enhancement capabilities and environmental stability is available for performing advanced biomolecule detection. Herein, a type of molybdenum carbide/molybdenum oxide (Mo2C@MoOx) heterostructure is constructed, and attractive SERS performance is achieved through the promotion of the charge transfer. Experimentally, Mo2C was first prepared by calcinating the ammonium molybdate tetrahydrate and gelatin mixture in an argon atmosphere. Then, the obtained Mo2C was further annealed in the air to obtain the Mo2C@MoOx heterostructure. The SERS performance was evaluated by using a 532 nm laser as an excitation source and a rhodamine 6G (R6G) molecule as the Raman reporter. This process demonstrates that attractive SERS performance with a Raman enhancement factor (EF) of 1.445 × 108 (R6G@10-8 M) and a limit of detection of 10-8 M can be achieved. Furthermore, the mechanism of SERS performance improvement with the Mo2C@MoOx is also investigated. HRTEM detection and XPS spectra reveal that part of the Mo2C is oxidized into MoOx during the air-annealing process, and generates metal-semiconductor mixing energy bands in the heterojunction. Under the Raman laser irradiation, considerable hole-electron pairs are generated in the heterojunction, and then the hot electrons move towards MoOx and subsequently transfer to the molecules, which ultimately boosts the Raman signal intensity.

Upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complex in oral squamous cell carcinomas: correlation with the clinicopathological features and patient outcome.

Oral squamous cell carcinoma is a challenging oncology problem. A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined. Using quantitative immunohistochemistry, we examined the expression of vimentin, E-cadherin, and beta-catenin in 83 oral squamous cell carcinoma patients, and the relationships between the expression of these markers and specific clinicopathological features were analysed. The high expression of vimentin was observed in 23 of 43 (53%) tumours from patients who eventually developed a recurrent tumour and was associated with recurrence and death (P<0.001 and <0.001, respectively). The decreased expression of E-cadherin was observed in 36 of 43 (84%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence and death (P<0.001 and <0.001, respectively). Although no correlation between beta-catenin expression in whole-tumour sections and clinicopathological features was observed, decreased beta-catenin expression at the tumour invasive front was closely associated with recurrence and death (P=0.002 and 0.002, respectively). The expression of vimentin and that of E-cadherin were associated with survival and were independent prognostic factors in univariate and multivariate analyses. Our data show that the overexpression of vimentin was closely associated with recurrence and death in oral squamous cell carcinoma patients. The combination of the upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complexes at the tumour invasive front may provide a useful prognostic marker in oral squamous cell carcinoma.

Upregulation of CSF-1 is correlated with elevated TAM infiltration and poor prognosis in oral squamous cell carcinoma.

Mounting lines of evidence indicated that the "colony stimulating factor-1 (CSF-1)/tumor-associated macrophage (TAM)" signature plays an important role in the progression, invasion and metastasis of multiple tumors. However, the potential role of CSF-1/TAM in oral squamous cell carcinoma (OSCC) remains largely unknown. In the present study, the expression of CSF-1 from 99 OSCC specimens and its correlation with clinicopathological features and patient outcomes were investigated. Meanwhile, the correlation between CSF-1 expression and TAM infiltration was also explored. To investigate the potential effect of CSF-1 on tumor growth, nude mice were subcutaneously injected with Cal27 cell line and a small molecule inhibitor of CSF-1 (BZL945). The results showed that the high expression rate of CSF-1 (52%) was found in OSCC, and the upregulation of CSF-1 was closely correlated with lymph node metastasis and clinical stage. Additionally, there was a positive correlation between a high CSF-1 level and elevated TAM infiltration. The xenograft model study showed that CSF-1 signal blockade inhibited tumor growth, with a significant synchronous decrease in CSF-1 expression and TAM infiltration. Overall, our findings indicated that CSF-1 plays a crucial role in TAMs-mediated OSCC tumor progression and invasion. The "CSF-1/TAM" signaling axis may serve as a prospective target for anti-tumor therapy of OSCC.

TLR2 deficiency enhances susceptibility to oral carcinogenesis by promoting an inflammatory environment.

Inflammation is closely related to oral squamous cell carcinoma (OSCC). However, its mechanism is still obscure. Toll-like receptor 2 (TLR2) plays an important role in oral chronic inflammatory diseases, but the role of TLR2 in OSCC is unclear. Here, we investigated the expression of TLR2 expression in OSCCs and examined the potential role of TLR2 in OSCC through its association with clinicopathological features and patient outcome. We used 4-nitroquinoline 1-oxide (4-NQO) to induce a tongue cancer model in TLR2-/- and wild type (WT) mice. Histological and clinical results both indicated that TLR2 played a protective role in oral tumorigenesis. The results of a cytometric bead array (CBA) indicated that TLR2 deficiency resulted in Th1 and Th2 cytokine abnormalities, especially Th2 abnormalities. Immunohistochemistry also showed that TLR2 deficiency increases the number of tongue-infiltrating M2 macrophages. Overall, our results demonstrated that TLR2 plays an important role in the prevention of oral tumorigenesis and affects the levels of Th2 cytokines and tongue-infiltrating M2 macrophages; therefore, it may be used to prevent the development of oral cancer.

Chitosan-phosphorylated chitosan polyelectrolyte complex hydrogel as an osteoblast carrier.

To simulate extra-cellular matrix, a novel three-dimensional scaffold of polyelectrolyte complex (PEC) hydrogel as an osteoblast carrier was synthesized. First, chitosan, a natural glycosaminoglycan, was modified by phosphorylation to obtain a water-soluble phosphorylated chitosan (P-content: 10.7 mass%). The PEC hydrogel was then formed from equal volumes of 0.173 mass% phosphorylated chitosan in water and 1 mass% chitosan in 1% (V/V) acetic acid solution. Rat osteoblasts were seeded in the hydrogel. The PEC hydrogel had a three-dimensional hierarchically-porous structure and good cytobiocompatibility for osteoblasts in vitro. It is concluded that the PEC hydrogel is a promising material as an osteoblast carrier.

[Expression of deltaNp63 in salivary gland tumours].

OBJECTIVE: To detect the expression of deltaNp63 in human salivary gland tumor and analyze its role in the malignant salivary gland tumors. METHODS: Collecting the samples from 68 cases of pathologically proven salivary gland tumours and investigating the microscopic sections with HE stain and immunohistochemical-SP stain. RESULTS: It was found that the expression of deltaNp63 is gradually increased in the malignant tumours, the myoepithelial cells and the basal cells of the salivary gland tumors are positive, and the expression of deltaNp63 is correlated directly with benign and malignant tumor. CONCLUSION: deltaNp63 plays an important role in salivary gland tumours. deltaNp63 possesses some special activity that is characteristic of oncogene. p63 is a sensitive and highly specific marker of myoepithelial cells in salivary gland tumours and an additional marker for defining myoepithelial histogenesis. p63 is of definite clinical value in falicitating diagnosis and differential diagnosis.

Nanofibrous biomimetic mesh can be used for pelvic reconstructive surgery: A randomized study.

BACKGROUND: Implantation of nonabsorbable polypropylene (PP) mesh in the vagina is the main surgical treatment for pelvic organ prolapse (POP); however, clinical outcomes remain controversial and far from satisfactory. In particular, reducing the exposure or erosion of vaginal implants to obtain improved functional reconstruction is challenging. There is an urgent need for the development of new materials and/or products for POP treatment. A nanofibrous biomimetic mesh was recently developed to address this issue. OBJECTIVE: In this study, the basic properties of the newly developed mesh, including structural characteristics, mechanical properties, biological response of human umbilical cord mesenchymal stem cells in vitro, and tissue regeneration and biocompatibility in vivo, were evaluated and compared with those of Gynemesh™PS. METHODS: Scanning electron microscopy and uniaxial tensile methods were used to evaluate microstructure and mechanical properties, respectively. Mesenchymal stem cell growth on the meshes was observed by fluorescence microscopy to visualize the expression of enhanced red fluorescent protein. Twenty-four mature female Sprague Dawley rats were randomly assigned to two groups: group 1 (nanofibrous biomimetic mesh, Medprin, Germany, n=12) and group 2 (Gynemesh(TM)PS, Ethicon, USA; n=12). The posterior vaginal wall was incised from the introitus, and the mesh was then implanted. Three implants of each type were tested for 1, 4, 8 and 12 weeks. Connective tissue organization, inflammation, vascularization, and regenerated tissue were histologically assessed. RESULTS: The nanofibrous biomimetic mesh is a relatively heavy material and exhibited lower porosity than Gynemesh(TM)PS. The new mesh was stiffer than Gynemesh(TM)PS (p<0.001) but supported human umbilical cord mesenchymal stem cell attachment. Erosion of the grafts did not occur in any animal. The nanofibrous biomimetic mesh was encapsulated by a thicker layer of connective tissue and was associated with significantly greater inflammatory scores compared with Gynemesh(TM)PS. At 12 weeks, the vascularization of the new mesh was greater than that of Gynemesh(TM)PS (p<0.05). No significant difference in the thickness of the smooth muscle layer following implantation was observed between the two groups (p>0.05). CONCLUSIONS: The nanofibrous biomimetic mesh is a candidate for reinforcing pelvic reconstruction. The mesh could be improved by decreasing its weight and stiffness and increasing its porosity. This mesh could serve as a carrier for stem cells in future regenerative medicine and tissue engineering research.

The overexpressed functional transient receptor potential channel TRPM2 in oral squamous cell carcinoma.

TRPM2, one member of the transient receptor potential (TRP) protein super-family, is a Ca2+-permeable channel that is activated by oxidative stress and confers susceptibility to cell death. In the human tongue specimens of carcinoma and the tongue carcinoma SCC cell lines, we observed the enhanced expression of TRPM2. By means of the whole-cell electrophysiological recording, the ADPR-induced currents mediated by TRPM2 were recorded in cultured SCC9 cells. Moreover, after H2O2 treatment for 24 hours, the apoptotic number of SCC9 cells was significantly increased. However, the selectively knocked-down TRPM2 with the small interfering RNA technique inhibited the survival and migration of the SCC9 cancer cells, which was independent of the p53-p21 pathway, since the expression of p21 was enhanced after TRPM2 knockdown. Furthermore, the sub-cellular localization of TRPM2 was remarkably different between cancerous and non-cancerous cells. A significant amount of the TRPM2 proteins were located in the nuclei in cancer cells. All these data suggest that TRPM2 is essential for the survival and migration of SCC cancer cells and may be a potential target for the selective treatment of tongue cancer.

Tumor-associated macrophages correlate with the clinicopathological features and poor outcomes via inducing epithelial to mesenchymal transition in oral squamous cell carcinoma.

BACKGROUND: Both tumor-associated macrophages (TAMs) and the epithelial to mesenchymal transition (EMT) of cancer cells play key roles in promoting tumor progression. However, whether TAMs could induce EMT in the progression of oral squamous cell carcinoma (OSCC) remains undefined. RESULTS: Here we detected the expression of macrophages markers CD68 and CD163, epithelial marker E-cadherin and mesenchymal marker vimentin in 127 OSCC patients by using semi-quantitative immunohistochemistry. CD68 and CD163 expression was not confined to the infiltrating TAMs, but also detected in cancer cells. The high number of CD68-positive macrophages was correlated with poor overall survival. Meanwhile, the expression of CD163 both in macrophages and in cancer cells was associated with poor overall survival and had a significant prognostic impact in OSCC. Importantly, the expression of CD163 in cancer cells had a significant relationship with E-cadherin and vimentin. Furthermore, the incubation of TAMs conditioned medium resulted in a fibroblast-like appearance of cancer cells (HN4, HN6 and SCC9) together with the decreased/increased expression of E-cadherin/ vimentin, which were correlated with the enhanced ability of migration and invasion. CONCLUSIONS: Our results indicate that TAMs could promote the EMT of cancer cells, thereby leading to the progression of oral cancer.

Snail interacts with Id2 in the regulation of TNF-α-induced cancer cell invasion and migration in OSCC.

The inflammatory tumor microenvironment has been identified to play a pivotal role in tumor development and metastasis. Tumor necrosis factor-α (TNF-α) is one of the key cytokines that regulate the inflammatory processes in tumor promotion. In the current study, we treated three oral squamous cell carcinoma (OSCC) cell lines with TNF-α to study its role in inflammation-induced tumor progression. Here we show that TNF-α induces stabilization of the transcriptional repressor Snail and activates NF-κB pathway in the three OSCC cell lines. These activities resulted in the increased motility and invasiveness of three OSCC cell lines. In addition, upon dealing with TNF-α for the indicated time, three OSCC cell lines underwent epithelial-to-mesenchymal transition (EMT), in which they presented a fibroblast-like phenotype and had a decreased expression of epithelial marker (E-cadherin) and an increased expression of mesenchymal marker (vimentin). We further demonstrated that TNF-α can up-regulate the expression of Id2 while inducing an EMT in oral cancer cells. Finally, we showed that Id2 interacted with Snail which may constrain Snail-dependent suppression of E-cadherin. In conclusion, our study indicates that TNF-α induces Snail stabilization is dependent on the activation of NF-κB pathway and results in increasing cell invasion and migration in OSCC cells. Id2 may contribute to regulate the function of Snail during TNF-α-mediated EMT in OSCC. These findings have significant implications for inflammation-induced tumor promotion in OSCC.

Biomimetic mineralization of dentin induced by agarose gel loaded with calcium phosphate.

A novel biomimetic mineralization system was designed to induce a layer of hydroxyapatite on a demineralized dentin surface. This system was constructed as follows. A layer of 0.5% agarose gel containing 0.26M Na(2) HPO(4) was used to cover acid-etched dentin slices, followed by a layer of agarose gel without phosphate ions. Then a neutral 0.13M CaCl(2) solution was added onto the ion-free gel surface. The mineralization system (dentin-agarose gel containing phosphate ions-CaCl(2) solution) was kept in a water bath at 37°C, and the gel and CaCl(2) solution were replaced at various intervals. The results showed that the deposited hydroxyapatite crystals densely packed to each other, completely covered the dentin surface, and occluded the dentinal tubules after 10 days of biomimetic mineralization in vitro. Therefore, this method may provide the experimental basis for dentin remineralization and for a new method to treat dentin hypersensitivity and dental caries.

[Effect of Roux-en-Y gastric bypass on quality of life in non-obese patients with type 2 diabetes mellitus].

OBJECTIVE: To observe the impact of Roux-en-Y gastric bypass on quality of life in non-obese patients with type 2 diabetes mellitus. METHODS: Thirty-seven non-obese patients with type 2 diabetes mellitus who underwent Roux-en-Y gastric bypass were prospectively studied. A 36-item short form healthy survey questionnaire(SF36), the diabetes treatment satisfaction questionnaire(DTSQ), and quality of life scale for patients with type 2 diabetes mellitus(DMQLS) were used to evaluate the quality of life for all the non-obese patients with type 2 diabetes mellitus preoperatively and 12 months postoperatively. RESULT: The blood glucose and lipid indexes were significantly decreased after operation(all P<0.05). SF36 showed the physical and mental synthesis scores at 12 month after operation were 74.6±18.3 and 79.8±14.9 respectively, higher than those at one week before operation(54.9±15.1 and 56.4±17.8, both P<0.01). DTSQ showed treatment satisfaction score was increaced significantly after operation(29.2±7.1 vs. 15.4±5.6, P<0.01). The quality of life evaluated by DMQLS, was also significantly improved(P<0.01). CONCLUSION: Roux-en-Y gastric bypass can significantly improve the quality of life for non-obese patients with type 2 diabetes mellitus.