Microfibril-associated protein 2 is activated by POU class 2 homeobox 1 and promotes tumor growth and metastasis in tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) represents the most frequent malignancy of the oral cavity, characterized by a high metastasis rate and poor prognosis. Microfibril-associated protein 2 (MFAP2), as an extracellular matrix protein, has been found to drive tumor progression. The function and underlying mechanism of MFAP2 in TSCC remain unknown. The expression levels of MFAP2 were analyzed in tissue samples from 30 TSCC patients by real time-polymerase chain reaction and western blot assays. Our results revealed that the expression of MFAP2 mRNA and protein was upregulated in TSCC tissue samples compared with that in the matched para-carcinoma tissue samples. By performing in vitro gain-of-function or loss-of-function experiments and in vivo mouse xenograft experiments, we found that overexpression of MFAP2 induced proliferation and promoted transition from G1 to S phase of TSCC cells. Stronger invasive and migratory capabilities were observed in MFAP2-overexpressing TSCC cells. In contrast, knockdown of MFAP2 exhibited anti-proliferative, apoptosis-promoting and pro-migratory roles in TSCC cells. Knockdown of MFAP2 significantly inhibited xenograft tumor growth. Mechanistically, POU class 2 homeobox 1 (POU2F1) was recruited to the region of MFAP2 promoter and upregulates the expression of MFAP2. Silencing of MFAP2 effectively blocked the proliferation, migration, and invasion of TSCC cells caused by POU2F1 overexpression. Our results indicate that the role of MFAP2 in TSCC may attribute to transcriptional regulation of POU2F1.

Rheumatoid arthritis risk in periodontitis patients: A systematic review and meta-analysis.

OBJECTIVE: Many clinical studies have been carried out to investigate the relationship between periodontitis and rheumatoid arthritis (RA). Owing to limited evidence and inconsistent findings among these studies, it is unclear whether periodontitis would increase the risk for RA. This meta-analysis was performed to evaluate whether periodontitis represents a risk factor for RA. METHODS: PubMed, Cochrane Library, Embase, Web of Science, and Wanfang were searched for eligible studies that compared periodontitis patients with controls. A pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the association between periodontitis and RA. RESULTS: Thirteen studies including a total of 706611 periodontitis patients and 349983 control subjects were included. The pooled OR of RA risk between periodontitis and controls was (OR: 1.69; 95% CI: 1.31-2.17; P<0.0001), indicating that the patients in periodontitis group had a 69% greater risk for RA than people in control group. When stratified by disease type, the pooled results showed periodontitis represents a risk factor for incident RA (OR=1.70, 95%CI: 0.75-3.85, P<0.001) and mixed RA (OR=1.61, 95%CI: 1.26-2.06; P<0.001). When stratified by disease duration, the pooled results showed periodontitis represents a risk factor for RA disease duration>5 years (OR=2.88, 95%CI: 0.66-12.62, P=0.018), disease duration<5 years (OR=2.59, 95%CI: 0.83-8.11, P<0.001), mixed disease duration (OR=1.53; 95%CI: 1.05-2.22, P<0.001). CONCLUSION: Our meta-analysis revealed an increased risk of RA in patients with periodontitis compared to healthy controls. Moreover, when stratified by disease type, there was a higher risk between incident RA and periodontitis. When stratified by disease duration, the patients with periodontitis might be more closely associated with the RA patients with disease duration >5 years.

TUG1/miR-133b/CXCR4 axis regulates cisplatin resistance in human tongue squamous cell carcinoma.

BACKGROUND: Long noncoding RNA taurine upregulated 1 (TUG1) has been reported to play an important role in human cancers. However, little is known about the role of TUG1 in drug resistance and its mechanism in tongue squamous cell carcinoma (TSCC). METHODS: Twenty-one cisplatin-sensitive or resistant TSCC patients were enrolled in this study. Cisplatin-resistant cells (SCC25/CDDP and CAL27/CDDP) were used for experiments in vitro. Transfection was performed using Lipofectamine 2000 transfection reagent. The levels of TUG1, microRNA-133b (miR-133b) and cysteine-X-cysteine chemokine receptor 4 (CXCR4) were measured by quantitative real-time polymerase chain reaction or western blot. The cisplatin resistance was investigated by cell viability, transwell invasion and apoptosis assays. The interactions among TUG1, miR-133b and CXCR4 were evaluated by luciferase reporter assay and RNA immunoprecipitation. Murine xenograft model was established using the stably transfected CAL27/CDDP cells. RESULTS: TUG1 expression was elevated in cisplatin-resistant TSCC tissues and cells compared with that in sensitive group and its knockdown inhibited cisplatin resistance to SCC25/CDDP and CAL27/CDDP cells. miR-133b was targeted via TUG1 and its overexpression suppressed cisplatin resistance. Moreover, CXCR4 was a target of miR-133b. CXCR4 silence repressed cisplatin resistance, which was reversed by miR-133b knockdown. The level of CXCR4 protein was decreased by inhibition of TUG1 and recuperated by miR-133b knockdown. Besides, interference of TUG1 attenuated tumor growth by regulating miR-133b and CXCR4 in vivo. CONCLUSION: Downregulation of TUG1 impeded cisplatin resistance in TSCC-resistant cells by mediating miR-133b and CXCR4, indicating TUG1 as a promising target for TSCC chemotherapy.

Suppression of puerarin on polymethylmethacrylate-induced lesion of peri-implant by inhibiting NF-κB activation in vitro and in vivo.

Puerarin (PR), a natural isoflavone isolated from Chinese traditional plant pueraria lobata, has attracted considerable attention due to its important biological and pharmacological activities. However, its effects on lesion of peri-implant and related mechanism of action are still not clear, which require further investigation. In this study, we evaluated the effects of PR on polymethylmethacrylate (PMMA)-induced lesion of peri-implant in vitro and in vivo, and explored its possible mechanism of action. Our results indicated that PR could inhibit PMMA-induced osteoclastogenesis in RAW264.7 cells with a dose-dependent manner in vitro and effectively down-regulate mRNA and protein expressions of matrix metalloprotein 9 (MMP-9), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and receptor activator of nuclear factor (NF)-κB (RANK), primarily via the suppression of NF-κB signaling. Furthermore, we found that PMMA induction could directly cause the phosphorylation of IκB and significantly promote the nuclear translocation of p65 in RAW264.7 cells. In other words, PR was able to dose-dependently attenuate the PMMA-induced nuclear translocation of p65 in RAW264.7 cells. In vivo, PR was observed to attenuate PMMA-induced osteoclastogenesis, osteolysis, mRNA expressions of receptor activator of nuclear factor (NF)-κB ligand (RANKL) and RANK, as well as protein levels of MMP-9, TNF-α, IL-6, and p65 in a murine calvarial osteolysis model. These findings suggested that PR might be a potential therapeutic drug to lesion of peri-implant, and provided new insights for understanding its possible mechanism.

Genome-wide profiles of metastasis-associated mRNAs and microRNAs in salivary adenoid cystic carcinoma.

Salivary adenoid cystic carcinoma (SACC) is often accompanied with poor prognosis due to local recurrence, distant metastasis, and perineural invasion. The mechanism involved in SACC metastasis is not yet fully understood. In this study, we profiled the expression of messenger RNA (mRNA) and microRNA (miRNA) in a SACC cell line, ACC-2, and a highly metastatic SACC cell line, ACC-M, using high-throughput sequencing. We discovered that: (1) differentially expressed (DE) mRNAs and DE miRNAs are potentially involved in SACC metastasis; (2) multiple regulatory interactions between DE miRNAs and DE mRNAs exist; and (3) miR-338-5p/3p target LAMC2 to impair motility and invasion of ACC-M and MDA-MB-231 cells. In conclusion, our study integrated the regulatory effects of miRNAs and mRNAs on SACC metastasis and provided a potential application for miRNAs in future therapeutic intervention.

A Precisely Assembled Carbon Source to Synthesize Fluorescent Carbon Quantum Dots for Sensing Probes and Bioimaging Agents.

A broad range of carbon sources have been used to fabricate varieties of carbon quantum dots (CQDs). However, the majority of these studies concern the influence of primary structures and chemical compositions of precursors on the CQDs; it is still unclear whether or not the superstructures of carbon sources have effects on the physiochemical properties of the synthetic CQDs. In this work, the concept of molecular assembly is first introduced into the design of a new carbon source. Compared with the tropocollagen molecules, the hierarchically assembled collagen scaffolds, as a new carbon source, immobilize functional groups of the precursors through hydrogen bonds, electrostatic attraction, and hydrophobic forces. Moreover, the accumulation of functional groups in collagen self-assembly further promotes the covalent bond formation in the obtained CQDs through a hydrothermal process. Both of these two chemical superiorities give rise to high quality CQDs with enhanced emission. The assembled collagen scaffold-based CQDs with heteroatom doping exhibit superior stability, and could be further applied as effective fluorescent probes for Fe3+ detection and cellular cytosol imaging. These findings open a wealth of possibilities to explore more nanocarbons from precursors with assembled superstructures.

Thermochemotherapy of lower lip squamous cell carcinoma without metastases: an experience of 31 cases.

INTRODUCTION: The aim of this study was to evaluate the efficacy, functional and aesthetic results, and safety of a novel treatment, thermochemotherapy, for lower lip squamous cell carcinoma (LLSCC) without metastases. PATIENTS AND METHODS: A combination of local hyperthermia delivered by a 915MHz microwave heating system and the chemotherapy of pingyangmycin (bleomycin A(5) hydrochloride) (PYM) and methotrexate (MTX), was administered to 31 patients of LLSCC twice per week for a period of 4.5-7.5 weeks. Patients with complete response (CR) have been followed up for a full five-year period, whereas partial response (PR) patients were excluded for further analysis. The local control of tumour, functional and cosmetic outcomes, recurrence, regional lymph node and distant metastases, and complications were assessed by clinical and imaging examination. RESULTS: Clinical CR was observed in twenty-nine (93.55%) patients and PR in two (6.45%), the total response rate was 100%, while the adverse effects were extremely minimal and tolerable in all 31 patients including 6 elderly patients with a compromised general condition. All 29 CR, including 8 extensive lesions, achieved excellent cosmetic and functional preservation. During the follow-up period, local relapse was seen in 1 case, 1 patient died, and the remainder obtained a complete remission. CONCLUSION: This clinical study suggests that thermochemotherapy may be a feasible treatment for primary LLSCC without cervical metastases, especially for patients with extensive lesions and a compromised general condition.

[The study of apoptosis induction effect of vitamin E succinate on Tca8113 human tongue cancer cells].

OBJECTIVE: To investigate the apoptosis induction effect of vitamin E succinate (VES) on Tca8113 cells and its possible mechanisms. METHODS: The proliferative activity of Tca8113 was assessed by methyl thiazolyl tetrazolium (MTT) assay. After Tca8113 cells were treated with different concentrations of VES, apoptotic rates were analyzed by flow cytometry (FCM). Fas monoclonal antibody was used for the blocking test. Fas expression was detected by immuocytochemistry(SABC assay) and FCM. RESULTS: VES demonstrated a significant growth inhibitory effect and apoptosis induced effect on the Tca8113 cells in a dose- and time-dependent manner. Fas neutralizing antibody can block the apoptosis induced by VES. After the administration of VES, the expression of Fas protein increased and the kytoplasm staining enhanced. Proteinum quantitative analysis showed that the mean fluorescence intensity increased. CONCLUSION: VES can induce apoptosis in human tongue cancer cells, and the up-regulation of the cell surface Fas protein may play an important role in the process.

[Relationship between the expression of cyclooxygenase-2 and microvessel density in oral squamnous cell carcinoma].

OBJECTIVE: To detective the relationship between cyclooxygenase-2 (COX-2) and angiogenesis in oral squamous cell carcinoma (OSCC) and its clinical significance through observing the expression of COX-2 and determining microvessel density (MVD) in OSCC. METHODS: PV-9000 immunohistochemistry was used to determine the expression of COX-2 and CD34, which was used to determine MVD, in 76 OSCC tissues and 12 normal oral mucosa tissues. RESULTS: Overexpression of COX-2 was detected in OSCC, and was more intense compared with normal epithelium (P < 0.001). The high expression of COX-2 in OSCC was related to neck lymphnode metastasis, tumor size, TNM stage and histological grade (P <0.05). The MVD value in COX-2-positive group was much higher than that in COX-2-negative group (P < 0.01) and that in normal oral mucosa tissues (P < 0.01). CONCLUSION: The high expression of COX-2 in OSCC was significantly associated with MVD, neck lymphnode metastasis, tumor size, TNM stage and histological grade. COX-2 might be one of the important factors in the angiogenesis of OSCC.

[Expression and significance of cyclin D1 in human adenoid cystic carcinoma].

OBJECTIVE: To observe the expression of cyclin D1 in human adnoid cystic carcinoma and its correlation with clinical characters. METHODS: The expression of cycline D1 was evaluated with immunohistochemical method in forty-one cases of human adnoid cystic carcinoma, 15 cases of PA and 12 cases of normal salivary gland tissue. RESULTS: The expression of cyclin D1 in normal tissue was negative, significantly different from PA and ACC (P < 0.05). The expression level of PA was significantly lower than ACC (P < 0.05). High expression of cyclin D1 was correlated with clinical stage and histological classification (P < 0.05), but not with sex, age, tumor site, recurrence, metastasis. CONCLUSION: High expression of cyclin D1 promotes the formation and development of ACC.