Proteolytic cleavage of amyloid precursor protein by ADAM10 promotes proliferation and migration via activating MAPKs pathway in tongue squamous cell carcinoma in vitro.

APP, well-studied in the development of Alzheimer's disease, has been recently identified as the key gene correlated with TSCC. Here, we investigate the function of APP and its proteolytic cleavage by ADAM10 in the pathogenesis of TSCC. A total of 63 TSCC patients and 30 healthy controls were included and the results of IHC assay showed high expressions of ADAM10 and APP in TSCC tissues compared to paired para-carcinoma tissues. Interestingly, APP expression in TSCC patients was correlated with ADAM10 expression and their combined expression was related to the poor patients' survival. We found that APP was ɑ-cleaved in TSCC cells to form sAPPα, and the serum level of sAPPα but not sAPPß in TSCC patients was higher than healthy controls. Both overexpression with full-length APP and sAPPα promoted TSCC cell proliferation, migration and invasion. Downregulation of APP or ADAM10 by siRNA decreased the generation of sAPPα and inhibited the activity of ERK1/2 and p38 pathways, thereby reducing TSCC cell proliferation, migration and invasion. Treatment with ERK1/2 or p38 agonist or sAPPα overexpression reversed the effects of APP or ADAM10 knockdown. In conclusion, our data demonstrated the pathogenic roles of APP cleaved by ADAM10 to activate ERK1/2 and p38 pathways in TSCC cells. Both high expressions of ADAM10 and APP were related to poor prognosis. Targeting APP cleaved by ADAM10 might be a potential strategy in TSCC treatment.

Inhibitory effect of baicalin on orthodontically induced inflammatory root resorption in rats.

OBJECTIVE: This study investigated the inhibitory effect of baicalin on orthodontically induced inflammatory root resorption in rats. METHODS: Forty-five male Wistar rats were randomly divided into three groups of 15 rats each. Fifty grams of force was used to establish an orthodontic tooth movement model. Baicalin (40 mg/kg) was locally injected into rats in the baicalin group at 3-day intervals; concurrently, normal saline was injected into rats in the negative control group. On the 21st day after orthodontic treatment, the tooth movement distance and root resorption area ratio were measured. Histomorphology changes were observed by hematoxylin and eosin staining and immunohistochemistry. RESULTS: There was no significant difference in tooth movement distance between groups. The root resorption area ratio was significantly lower in the baicalin group than in the negative control group. Runx-2 expression was significantly higher in the baicalin group than in the negative control group, while tumor necrosis factor (TNF)-α expression was significantly lower in the baicalin group than in the negative control group. CONCLUSIONS: Baicalin inhibits orthodontically induced inflammatory root resorption by enhancing the expression of Runx-2 and reducing the expression of TNF-α, but does not affect tooth movement distance.

Genetic susceptibility of common polymorphisms in NIN and SIGLEC5 to chronic periodontitis.

Chronic periodontitis (CP) is a common oral disease characterized by the slow progression of alveolar attachment loss and bone destruction. Genetic components have been reported to play an important role in the onset and development of CP. In the present study, we aimed to replicate the association signals of NIN and SIGLEC5 identified in previous genome-wide association studies (GWASs) of samples from Chinese Han individuals. Association signals between clinical severity indicators of CP and relevant single nucleotide polymorphisms (SNPs) were also examined. A total of 3,160 study subjects, including 1,076 CP patients and 2,084 healthy controls, were recruited. A total of 32 SNPs, including 22 from NIN and 10 from SIGLEC5, were selected for genotyping. SNPs rs12883458 (OR = 1.45, P = 1.22 × 10-5, NIN) and rs4284742 (OR = 0.75, P = 1.69 × 10-5, SIGLEC5) were significantly associated with CP disease status. rs4284742 was significantly associated with all 3 clinical severity indicators, including bleeding on probing (BOP), probing depth (PD) and clinical attachment loss (CAL). According to evidence from bioinformatics analyses, both significant SNPs, rs12883458 and rs4284742, are likely surrogates of underlying variants with true effects. In summary, our findings provide direct evidence for the association of NIN and SIGLEC5 with CP susceptibility.

MiR-106a* inhibits oral squamous cell carcinoma progression by directly targeting MeCP2 and suppressing the Wnt/ß-Catenin signaling pathway.

MicroRNAs (miRNAs) play critical roles in the tumorigenesis and progression of oral squamous cell carcinoma (OSCC). MiR-106a* functions as a tumor suppressor miRNA in several cancers; however, its role in OSCC has not been elucidated. We investigated the role of miR-106a* in human OSCC and explored its relevant mechanisms. The expression of miR-106a* was significantly downregulated in OSCC tissues and cell lines. The overexpression of miR-106a* inhibited OSCC cell proliferation and the cell cycle G1-S transition, and induced apoptosis. In contrast, inhibition of miR-106a* promoted cell proliferation and G1-S transition and suppressed apoptosis. The expression of miR-106a* inversely correlated with methyl-CpG binding protein 2 (MeCP2) expression in OSCC tissues. Using a luciferase reporter assay, MeCP2 was determined to be a direct target of miR-106a*. Overexpression of miR-106a* decreased MeCP2 expression at both the mRNA and protein levels, while inhibition of miR-106a* increased MeCP2 expression. Importantly, overexpression of MeCP2 eliminated the effects of miR-106a* overexpression in OSCC cells and silencing of MeCP2 recapitulated the cellular and molecular effects observed with miR-106a* overexpression. MeCP2 may promote OSCC cell proliferation by activating the Wnt/ß-Catenin signaling pathway. Taken together, our study demonstrated that miR-106a* inhibited OSCC cell proliferation by suppression of the Wnt/ß-Catenin signaling pathway and induced apoptosis through regulation of Caspase 3/9 expression via targeting MeCP2. These findings suggest that miR-106a* acted as a tumor suppressor in the progression of OSCC and may be a potential new target for OSCC diagnosis and therapy.

Apoptosis Inducing Factor Is Involved in Stretch-Induced Apoptosis of Myoblast via a Caspase-9 Independent Pathway.

The apoptosis of myoblast in response to excessive cyclic stretch is crucial in adaptive construction of skeletal muscles in orthopedic functional therapy. Mitochondria signaling pathway is the central links in the execution of the intrinsic apoptotic cascade, but its molecular mechanism in stretch-induced apoptosis in myoblasts remains incompletely understood. The aim of this study was to investigate the mechanobiological roles of caspase-9 and Apoptosis Inducing Factor (AIF), two important components in mitochondrial pathway, in stretch-induced apoptosis of myoblast. Hoechst 33258 was used to observe apoptotic cells morphologically and flow cytometry to analyze apoptosis rate of myoblasts. Protein and mRNA of caspase-9 and AIF were detected by Western blotting and RT-PCR. Furthermore, caspase-9 specific inhibitor z-LEHD-fmk was applied to clear the mechanism of caspase-9 pathway in stretch-induced apoptosis. We found that apoptotic rate induced by cyclic stretch increased in a time-dependent manner, and the same tendency of mRNA and protein of caspase-9 and AIF. Caspase-9 inhibition reduced stretch-induced apoptosis, but had no effect on expression of AIF. We concluded that caspase-9 and AIF played an important role in stretch-induced apoptosis in myoblast, and AIF was involved in the process in a caspase-9 independent way. J. Cell. Biochem. 118: 829-838, 2017. © 2016 Wiley Periodicals, Inc.

[Crown cutting mode selection in extracting the mandible third molar by dental drilling system].

OBJECTIVE: To investigate the influence of different crown cutting mode on operation time and post-operation trauma in extracting the mandible third molar by dental drilling system. METHODS: According to different impaction types, the patients were divided into vertical impaction, horizontal impaction, and mesioangular impaction groups. The operation time, mouth opening, swelling, and pain degrees were recorded during traditional extraction, crown "T"-shaped cutting, crown three section cutting, and crown-root cutting in the extraction of mandibular wisdom teeth. RESULTS: In the vertical impaction group, the operation time, the degree of swelling, limitation of mouth opening and the pain degree were (8.2 ± 2.5) min, (14.7 ± 2.0) mm, (3.9 ± 2.4) mm and 3.4 ± 1.8, respectively using crown cutting, and (14.0 ± 2.7) min, (18.2 ± 1.9) mm, (9. 7 ± 3.6) mm and 6.9 ± 2.3 using traditional extraction method (P < 0.05). In the horizontal impaction group, the operation time, degree of swelling, limitation of mouth opening and pain degree (14.0 ± 2.0) min, (19.2 ± 3.9) mm, (9.5 ± 2.5) mm, 5.6 ± 1.7 respectively using crown "T"-shaped cutting, and (18.0 ± 3.1) min, (23.6 ± 3.5) mm, (9.8 ± 2.7) mm and 8.5 ± 2.3 using crown three section cutting. There was significant difference in operation time, degree of swelling and pain (P < 0.05), but no significant difference in the limitation of mouth opening (P > 0.05). In mesioangular impaction group, operation time, degree of swelling, limitation of mouth opening and pain degree were (10.2 ± 2.6) min, (18.4 ± 2.9) mm, (6.4 ± 2.5) mm and 4.8 ± 1.8, respectively using "T"-shaped cutting, and (15.0 ± 3.5) min, (18.9 ± 3.0) mm, (7.0 ± 3.7) mm and 7.6 ± 2.3 using crown- root cutting. The operation time and pain degree were significantly different (P < 0.05), but not different in limitation of mouth opening and swelling degree (P > 0.05). CONCLUSIONS: Different impaction types of wisdom teeth should choose different cutting mode. Vertical impacted tooth uses distal crown cutting. "T"-shaped cutting is preferred with horizontal impaction. According to the angle and depth of the mesioangular impaction, "T"-shaped cutting or the crown-root cutting can be selectively used.

[Effects of premolar extractions on Bolton index overall ratios].

PURPOSE: To investigate the effect of premolar extraction on Bolton index overall ratios. METHODS: Bolton index overall ratios were measured in 198 randomly chosen dental casts of three types of Angle's malocclusions before and after 4 combinations of hypothetical premolar extractions. The data was processed using SPSS 17.0 software package. RESULTS: The overall ratios decreased in each class of Angle's malocclusion after all combinations of premolars extraction, and the decreases in combinations of 5/5 and 5/4 extractions were significantly greater than that of 4/4 and 4/5 combinations (P<0.05), but no significant difference was found between different types of malocclusion (P>0.05). CONCLUSIONS: When formulating a treatment plan involving premolar extractions, orthodontists should consider that the Bolton overall ratios may decrease.