Pusan National University Dental Hospital

PURPOSE: Artificial intelligence (AI), represented by deep learning, can be used for real-life problems and is applied across all sectors of society including medical and dental field. The purpose of this study is to review articles about deep learning that were applied to the field of oral and maxillofacial radiology. MATERIALS AND METHODS: A systematic review was performed using Pubmed, Scopus, and IEEE explore databases to identify articles using deep learning in English literature. The variables from 25 articles included network architecture, number of training data, evaluation result, pros and cons, study object and imaging modality. RESULTS: Convolutional Neural network (CNN) was used as a main network component. The number of published paper and training datasets tended to increase, dealing with various field of dentistry. CONCLUSION: Dental public datasets need to be constructed and data standardization is necessary for clinical application of deep learning in dental field.

Recently, graphene-based nanomaterials, in the form of two dimensional substrates or three dimensional foams, have attracted considerable attention as bioactive scaffolds to promote the differentiation of various stem cells towards specific lineages. On the other hand, the potential advantages of using graphene-based hybrid composites directly as factors inducing cellular differentiation as well as tissue regeneration are unclear. This study examined whether nanocomposites of reduced graphene oxide (rGO) and hydroxyapatite (HAp) (rGO/HAp NCs) could enhance the osteogenesis of MC3T3-E1 preosteoblasts and promote new bone formation. When combined with HAp, rGO synergistically promoted the spontaneous osteodifferentiation of MC3T3-E1 cells without hindering their proliferation. This enhanced osteogenesis was corroborated from determination of alkaline phosphatase activity as early stage markers of osteodifferentiation and mineralization of calcium and phosphate as late stage markers. Immunoblot analysis showed that rGO/HAp NCs increase the expression levels of osteopontin and osteocalcin significantly. Furthermore, rGO/HAp grafts were found to significantly enhance new bone formation in full-thickness calvarial defects without inflammatory responses. These results suggest that rGO/HAp NCs can be exploited to craft a range of strategies for the development of novel dental and orthopedic bone grafts to accelerate bone regeneration because these graphene-based composite materials have potentials to stimulate osteogenesis.

Three bioceramic sealers (EndoSequence BC sealer, EndoSeal MTA, and MTA Fillapex) and three epoxy resin-based sealers (AH-Plus, AD Seal, and Radic-Sealer) were tested to evaluate the physicochemical properties: flow, final setting time, radiopacity, dimensional stability, and pH change. The one-way ANOVA and Tukey’s post hoc test were used to analyze the data (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0</mml:mn><mml:mo>.</mml:mo><mml:mn fontstyle="italic">05</mml:mn></mml:math>). The MTA Fillapex sealer had a highest flow and the BC Sealer presented a flow significantly lower than the others (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn fontstyle="italic">0.05</mml:mn></mml:math>). The BC Sealer and MTA Fillapex samples were not set in humid incubator condition even after one month. EndoSeal MTA had the longest setting time among the measurable materials and Radic-Sealer and AD Seal showed shorter setting time than the AH-Plus (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn fontstyle="italic">0.05</mml:mn></mml:math>). AH-Plus and EndoSeal MTA showed statistically higher values and MTA Fillapex showed statistically lower radiopacity (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn fontstyle="italic">0.05</mml:mn></mml:math>). BC Sealer showed the highest alkaline pH in all evaluation periods. Set samples of 3 epoxy resin-based sealers and EndoSeal MTA presented a significant increase of pH over experimental time for 4 weeks. In conclusion, the bioceramic sealer and epoxy resin-based sealers showed clinical acceptable physicochemical properties, but BC Sealer and MTA Fillapex were not set completely.

The practicability of deep learning techniques has been demonstrated by their successful implementation in varied fields, including diagnostic imaging for clinicians. In accordance with the increasing demands in the healthcare industry, techniques for automatic prediction and detection are being widely researched. Particularly in dentistry, for various reasons, automated mandibular canal detection has become highly desirable. The positioning of the inferior alveolar nerve (IAN), which is one of the major structures in the mandible, is crucial to prevent nerve injury during surgical procedures. However, automatic segmentation using Cone beam computed tomography (CBCT) poses certain difficulties, such as the complex appearance of the human skull, limited number of datasets, unclear edges, and noisy images. Using work-in-progress automation software, experiments were conducted with models based on 2D SegNet, 2D and 3D U-Nets as preliminary research for a dental segmentation automation tool. The 2D U-Net with adjacent images demonstrates higher global accuracy of 0.82 than naïve U-Net variants. The 2D SegNet showed the second highest global accuracy of 0.96, and the 3D U-Net showed the best global accuracy of 0.99. The automated canal detection system through deep learning will contribute significantly to efficient treatment planning and to reducing patients' discomfort by a dentist. This study will be a preliminary report and an opportunity to explore the application of deep learning to other dental fields.

Mesenchymal stem cells (MSCs) have been reported to possess regulatory functions on immune cells which make them alternative therapeutics for the treatment of inflammatory and autoimmune diseases. The interaction between MSCs and immune cells through paracrine factors might be crucial for these immunomodulatory effects of MSCs. Extracellular vesicles (EVs) are defined as bilayer membrane structures including exosomes and microvesicles which contain bioactive paracrine molecules affecting the characteristics of target cells. Recently, several studies have revealed that EVs derived from MSCs (MSC-EVs) can reproduce similar therapeutic impacts of parent MSCs; MSC-EVs could regulate proliferation, maturation, polarization, and migration of various immune effector cells and modulate the immune microenvironment depending on the context by delivering inflammatory cytokines, transcription factors, and microRNAs. Therefore, MSC-EVs can be applied as novel and promising tools for the treatment of immune-related disorders to overcome the limitations of conventional cell therapy regarding efficacy and toxicity issues. In this review, we will discuss current insights regarding the major outcomes in the evaluation of MSC-EV function against inflammatory disease models, as well as immune cells.

In the absence of accurate medical records, it is critical to correctly classify implant fixture systems using periapical radiographs to provide accurate diagnoses and treatments to patients or to respond to complications. The purpose of this study was to evaluate whether deep neural networks can identify four different types of implants on intraoral radiographs. In this study, images of 801 patients who underwent periapical radiographs between 2005 and 2019 at Yonsei University Dental Hospital were used. Images containing the following four types of implants were selected: Brånemark Mk TiUnite, Dentium Implantium, Straumann Bone Level, and Straumann Tissue Level. SqueezeNet, GoogLeNet, ResNet-18, MobileNet-v2, and ResNet-50 were tested to determine the optimal pre-trained network architecture. The accuracy, precision, recall, and F1 score were calculated for each network using a confusion matrix. All five models showed a test accuracy exceeding 90%. SqueezeNet and MobileNet-v2, which are small networks with less than four million parameters, showed an accuracy of approximately 96% and 97%, respectively. The results of this study confirmed that convolutional neural networks can classify the four implant fixtures with high accuracy even with a relatively small network and a small number of images. This may solve the inconveniences associated with unnecessary treatments and medical expenses caused by lack of knowledge about the exact type of implant.

This study was conducted to compare 3D-printed polycaprolactone (PCL) and polycaprolactone/β-tricalcium phosphate (PCL/β-TCP) membranes with a conventional commercial collagen membrane in terms of their abilities to facilitate guided bone regeneration (GBR). Fabricated membranes were tested for dry and wet mechanical properties. Fibroblasts and preosteoblasts were seeded into the membranes and rates and patterns of proliferation were analyzed using a kit-8 assay and by scanning electron microscopy. Osteogenic differentiation was verified by alizarin red S and alkaline phosphatase (ALP) staining. An in vivo experiment was performed using an alveolar bone defect beagle model, in which defects in three dogs were covered with different membranes. CT and histological analyses at eight weeks after surgery revealed that 3D-printed PCL/β-TCP membranes were more effective than 3D-printed PCL, and substantially better than conventional collagen membranes in terms of biocompatibility and bone regeneration and, thus, at facilitating GBR.

OBJECTIVES: This study evaluated the effects of the resin thickness on the microhardness and optical properties of bulk-fill resin composites. METHODS: Four bulk-fill (Venus Bulk Fill, Heraeus Kulzer; SDR, Dentsply Caulk; Tetric N-Ceram Bulk Fill, Ivoclar vivadent; SonicFill, Kerr) and two regular resin composites (Charisma flow, Heraeus Kulzer; Tetric N-Ceram, Ivoclar vivadent) were used. Sixty acrylic cylindrical molds were prepared for each thickness (2, 3 and 4 mm). The molds were divided into six groups for resin composites. The microhardness was measured on the top and bottom surfaces, and the colors were measured using Commission Internationale d'Eclairage (CIE) L (*) a (*) b (*) system. Color differences according to the thickness and translucency parameters and the correlations between the microhardness and translucency parameter were analyzed. The microhardness and color differences were analyzed by ANOVA and Scheffe's post hoc test, and a student t-test, respectively. The level of significance was set to α = 0.05. RESULTS: The microhardness decreased with increasing resin thickness. The bulk-fill resin composites showed a bottom/top hardness ratio of almost 80% or more in 4 mm thick specimens. The highest translucency parameter was observed in Venus Bulk Fill. All resin composites used in this study except for Venus Bulk Fill showed linear correlations between the microhardness and translucency parameter according to the thickness. CONCLUSIONS: Within the limitations of this study, the bulk-fill resin composites used in this study can be placed and cured properly in the 4 mm bulk.

Numerous approaches have been introduced to regenerate artificial dental tissues. However, conventional approaches are limited when producing a construct with three-dimensional patient-specific shapes and compositions of heterogeneous dental tissue. In this research, bioprinting technology was applied to produce a three-dimensional dentin-pulp complex with patient-specific shapes by inducing localized differentiation of human dental pulp stem cells within a single structure. A fibrin-based bio-ink was designed for bioprinting with the human dental pulp stem cells. The effects of fibrinogen concentration within the bio-ink were investigated in terms of printability, human dental pulp stem cell compatibility, and differentiation. The results show that micro-patterns with human dental pulp stem cells could be achieved with more than 88% viability. Its odontogenic differentiation was also regulated according to the fibrinogen concentration. Based on these results, a dentin-pulp complex having patient-specific shape was produced by co-printing the human dental pulp stem cell-laden bio-inks with polycaprolactone, which is a bio-thermoplastic used for producing the overall shape. After culturing with differentiation medium for 15 days, localized differentiation of human dental pulp stem cells in the outer region of the three-dimensional cellular construct was successfully achieved with localized mineralization. This result demonstrates the possibility to produce patient-specific composite tissues for tooth tissue engineering using three-dimensional bioprinting technology.

Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PCL/PLGA/β-TCP) membranes with the widely used collagen membranes for guided bone regeneration (GBR) in beagle implant models. For mechanical property comparison in dry and wet conditions and cytocompatibility determination, we analyzed the rate and pattern of cell proliferation of seeded fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning electron microscopy. Osteogenic differentiation was verified using alizarin red S staining. At 8 weeks following implantation in vivo using beagle dogs, computed tomography and histological analyses were performed after sacrifice. Cell proliferation rates in vitro indicated that early cell attachment was higher in collagen than in PCL/PLGA/β-TCP membranes; however, the difference subsided by day 7. Similar outcomes were found for osteogenic differentiation, with approximately 2.5 times greater staining in collagen than PCL/PLGA/β-TCP, but without significant difference by day 14. In vivo, bone regeneration in the defect area, represented by new bone formation and bone-to-implant contact, paralleled those associated with collagen membranes. However, tensile testing revealed that whereas the PCL/PLGA/β-TCP membrane mechanical properties were conserved in both wet and dry states, the tensile property of collagen was reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo that PCL/PLGA/β-TCP membranes have similar levels of biocompatibility and bone regeneration as collagen membranes. In particular, considering that GBR is always applied to a wet environment (e.g. blood, saliva), we demonstrated that PCL/PLGA/β-TCP membranes maintained their form more reliably than collagen membranes in a wet setting, confirming their appropriateness as a GBR membrane.

Kaempferol, a flavonoid compound, is derived from the rhizome of Kaempferia galanga L., which is used in traditional medicine in Asia. Autophagy has pleiotropic functions that are involved in cell growth, survival, nutrient supply under starvation, defense against pathogens, and antigen presentation. There are many studies dealing with the inhibitory effects of natural flavonoids in bone resorption. However, no studies have explained the relationship between the autophagic and inhibitory processes of osteoclastogenesis by natural flavonoids. The present study was undertaken to investigate the inhibitory effects of osteoclastogenesis through the autophagy inhibition process stimulated by kaempferol in murin macrophage (RAW 264.7) cells. The cytotoxic effect of Kaempferol was investigated by MTT assay. The osteoclast differentiation and autophagic process were confirmed via tartrate-resistant acid phosphatase (TRAP) staining, pit formation assay, western blot, and real-time PCR. Kaempferol controlled the expression of autophagy-related factors and in particular, it strongly inhibited the expression of p62/SQSTM1. In the western blot and real time-PCR analysis, when autophagy was suppressed with the application of 3-Methyladenine (3-MA) only, osteoclast and apoptosis related factors were not significantly affected. However, we found that after cells were treated with kaempferol, these factors inhibited autophagy and activated apoptosis. Therefore, we presume that kaempferol-inhibited autophagy activated apoptosis by degradation of p62/SQSTM1. Further study of the p62/SQSTM1 gene as a target in the autophagy mechanism, may help to delineate the potential role of kaempferol in the treatment of bone metabolism disorders.

PURPOSE: This study was conducted to evaluate the effects of full-coverage all-ceramic zirconia, lithium disilicate glass-ceramic, leucite glass-ceramic, or stainless steel crowns on antagonistic primary tooth wear. MATERIALS AND METHODS: There were four study groups: the stainless steel (Steel) group, the leucite glass-ceramic (Leucite) group, the lithium disilicate glass-ceramic (Lithium) group, and the monolithic zirconia (Zirconia) group. Ten flat crown specimens were prepared per group; opposing teeth were prepared using primary canines. A wear test was conducted over 100,000 chewing cycles using a dual-axis chewing simulator and a 50 N masticating force, and wear losses of antagonistic teeth and restorative materials were calculated using a three-dimensional profiling system and an electronic scale, respectively. Statistical significance was determined using One-way ANOVA and Tukey's test (P<.05). RESULTS: The Leucite group (2.670±1.471 mm(3)) showed the greatest amount of antagonist tooth wear, followed by in decreasing order by the Lithium (2.042±0.696 mm(3)), Zirconia (1.426±0.477 mm(3)), and Steel groups (0.397±0.192 mm(3)). Mean volume losses in the Leucite and Lithium groups were significantly greater than in the Steel group (P<.05). No significant difference was observed between mean volume losses in the Zirconia and Steel groups (P>.05). CONCLUSION: Leucite glass-ceramic and lithium disilicate glass-ceramic cause more primary tooth wear than stainless steel or zirconia.

BACKGROUND: Kaempferol, a kind of flavonol, has been reported to possess various osteogenic biological activities, such as inhibiting bone resorption of osteoclasts and promoting the differentiation and mineralization of preosteoblasts. However, the precise cellular mechanism of action of kaempferol in osteogenesis is elusive. Autophagy is a major intracellular degradation system, which plays an important role in cell growth, survival, differentiation and homeostasis in mammals. Recent studies showed that autophagy appeared to be involved in the degradation of osteoclasts, osteoblasts and osteocytes, potentially pointing to a new pathogenic mechanism of bone homeostasis and bone marrow disease. The potential correlation between autophagy, osteogenesis and flavonoids is unclear. METHODS: The present study verified that kaempferol promoted osteogenic differentiation and mineralization and that it elevated osteogenic gene expression based on alkaline phosphatase (ALP) activity, alizarin red staining and quantitative PCR. And then we found that kaempferol induced autophagy by acridine orange (AO) and monodansylcadaverine (MDC) staining and autophagy-related protein expression. The correlation between kaempferol-induced autophagy and the osteogenic process was confirmed by the autophagy inhibitor 3-methyladenine (3-MA). RESULTS: Kaempferol promoted the proliferation, differentiation and mineralization of osteoblasts at a concentration of 10 μM. Kaempferol showed cytotoxic properties at concentrations above 50 μM. Concentrations above 10 μM decreased ALP activity, whereas those up to 10 μM increased ALP activity. Kaempferol at concentrations up to 10 μM also increased the expression of the osteoblast- activated factors RUNX-2, osterix, BMP-2 and collagen I according to RT-PCR analyses. 10 μM or less, the higher of the concentration and over time, kaempferol promoted the activity of osteoblasts. Kaempferol induced autophagy. It also increased the expression of the autophagy-related factors beclin-1, SQSTM1/p62 and the conversion of LC3-II from LC3-I. The application of 3-MA decreased the activity of ALP and the autophagy induced by kaempferol. In the RT-PCR analysis, the expression of RUNX-2, osterix, BMP-2 and collagen I was decreased. CONCLUSION: The present study showed that kaempferol stimulated the osteogenic differentiation of cultured osteoblasts by inducing autophagy.

The effects of dentin wetness on the bond strength and adhesive interface morphology of universal adhesives have been investigated using micro-tensile bond strength (μTBS) testing and confocal laser scanning microscopy (CLSM). Seventy-two human third molars were wet ground to expose flat dentin surfaces. They were divided into three groups according to the air-drying time of the dentin surfaces: 0 (without air drying), 5, and 10 s. The dentin surfaces were then treated with three universal adhesives: G-Premio Bond, Single Bond Universal, and All-Bond Universal in self-etch or etch-and-rinse mode. After composite build up, a μTBS test was performed. One additional tooth was prepared for each group by staining the adhesives with 0.01 wt % of Rhodamine B fluorescent dye for CLSM analysis. The data were analyzed statistically using ANOVA and Tukey’s post hoc tests (α = 0.05). Two-way ANOVA showed significant differences among the adhesive systems and dentin moisture conditions. An interaction effect was also observed (p &lt; 0.05). One-way ANOVA showed that All-Bond Universal was the only material influenced by the wetness of the dentin surfaces. Wetness of the dentin surface is a factor influencing the micro-tensile bond strength of universal adhesives.

Periodontitis is a widespread chronic inflammatory disease caused by interactions between periodontal bacteria and homeostasis in the host. We aimed to investigate the performance and reliability of machine learning models in predicting the severity of chronic periodontitis. Mouthwash samples from 692 subjects (144 healthy controls and 548 generalized chronic periodontitis patients) were collected, the genomic DNA was isolated, and the copy numbers of nine pathogens were measured using multiplex qPCR. The nine pathogens are as follows: Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Campylobacter rectus (Cr), Aggregatibacter actinomycetemcomitans (Aa), Peptostreptococcus anaerobius (Pa), and Eikenella corrodens (Ec). By adding the species one by one in order of high accuracy to find the optimal combination of input features, we developed an algorithm that predicts the severity of periodontitis using four machine learning techniques. The accuracy was the highest when the models classified “healthy” and “moderate or severe” periodontitis (H vs. M-S, average accuracy of four models: 0.93, AUC = 0.96, sensitivity of 0.96, and specificity of 0.81, diagnostic odds ratio = 112.75). One or two red complex pathogens were used in three models to distinguish slight chronic periodontitis patients from healthy controls (average accuracy of 0.78, AUC = 0.82, sensitivity of 0.71, and specificity of 0.84, diagnostic odds ratio = 12.85). Although the overall accuracy was slightly reduced, the models showed reliability in predicting the severity of chronic periodontitis from 45 newly obtained samples. Our results suggest that a well-designed combination of salivary bacteria can be used as a biomarker for classifying between a periodontally healthy group and a chronic periodontitis group.

AIM: To examine the effect of several standard geometric characteristics of rotary instruments on the 'screw-in' forces and stresses generated on root dentine using 3D finite element analysis (FEA). METHODOLOGY: Four cross-sectional designs (triangular, slender-rectangular, rectangular and square) were evaluated. The area of the triangular cross-section and of the slender-rectangular model were the same. Another rectangular model had the same centre-core diameter as the triangular one. Each design was twisted into a file model with 5, 10 or 15 threads over its 16-mm-long working section. Three curved root canals were simulated as rigid surface models: θ = 15 degrees/R = 36 mm radius; θ = 30/R = 18; and θ = 45/R = 12. A commercial FEA package was used to simulate the file rotating in the canal to determine the 'screw-in' force and reaction torque on the instrument. RESULTS: Instruments of a square cross-section had the highest 'screw-in' force and reaction torsional stresses followed by the rectangle, the triangle design and the slender-rectangle design, respectively. The file with closer pitch generated lower stresses, compared with that with longer pitch. The greater the root canal curvature, the higher the 'screw-in' force and reaction torque generated. CONCLUSION: This study demonstrated that the 'screw-in' tendency depends on both the instrument geometry and canal curvature. Clinicians should be aware that certain instrument designs are prone to develop high 'screw-in' forces, requiring the operator to maintain control of the handpiece or to use a brushing action to prevent instruments being pulled into the canal.

The purpose of this study was to compare the oral health related quality of life (OHRQoL) between older Korean adults with complete and partial removable dentures using oral health impact profile (OHIP). A pool of 4250 Korean older adults was identified by random stratification by area from the sample cohort of Korean National Survey of Oral Health in the year of 2000. Out of the potential pool, 445 subjects with removable partial dentures (RPDs) or complete dentures (CDs) agreed to be interviewed by telephone. Each question in the survey was about how frequently each event was experienced during the past 12 months. To analyse the association between OHIP scores and removable denture status, bivariable analysis and multiple linear regression analysis were used. RPD users showed higher scores on eight items than CD users. They were 'breath stale', 'food catching', 'sensitive teeth', 'toothache', 'tense', 'unable to brush teeth', 'less tolerant to family members' and 'irritable with others'. RPD users might be associated with higher scores of functional limitation, physical pain and psychological discomfort than CD users. RPD users had slight tendency to be associated with higher OHIP-49 score than CD users, but it was not statistically significant. The findings of the present study confirm that there is no general OHRQoL difference between RPD and CD users. But in the items and subscales of OHIP, RPD users might experience more impaired OHRQoL than CD users.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a genetic and epigenetic disease. There is growing evidence to suggest that environmental factors due to epigenetic changes can be involved in the OSCC pathogenesis. Although tumor suppressor genes (TSGs) are commonly inactivated by promoter hypermethylation in human cancers, the epigenetic changes and the mechanism of TSGs in human OSCC remain unclear. We therefore assessed the methylation status of the TSGs, which are associated with epigenetic silencing in human cancers, OSCC cell lines, primary tumors, and normal oral mucosa. RESULTS: We used 14 TSGs that were originally identified in colon cancer to investigate the aberrant hypermethylation of these genes associated with transcriptional silencing in 10 OSCC cell lines. We found three TSGs, TFPI2, SOX17, and GATA4, that are robustly hypermethylated and are associated with transcriptional silencing in OSCC cell lines. The re-expression of the three genes was induced by 5-aza-2'-deoxycytidine (5-aza-dC) in cells in which these genes were not expressed or had a lack of expression. In 33 cases of primary OSCC tumors, promoter hypermethylation was detected for the TFPI2, SOX17, and GATA4 genes at (32/33) 97%, (22/33) 67%, and (11/33) 33%, respectively. Eleven normal oral mucosa samples showed no promoter hypermethylation for all three genes, which suggests that this promoter hypermethylation is cancer-specific. Bisulfite sequencing analysis confirmed the cancer-specific methylation of the TFPI2, SOX17, and GATA4 promoters in the OSCC cell lines and tumors but not in the normal oral mucosa samples. More importantly, the methylation status of TFPI2, GATA4, and SOX17 was significantly associated with OSCC patients' overall survival through TCGA DNA methylation database. CONCLUSIONS: We identified that TFPI2, SOX17, and GATA4 are frequently hypermethylated in human OSCC cells in a cancer-specific manner and that the transcriptional expression of these genes is regulated by promoter hypermethylation in OSCC. Our results highlight the great potential used as a synergistic biomarker set to improve the prognosis and therapeutic treatment for patients with OSCC.

The authors describe a new type of titanium (Ti) implant as a Modi-anodized (ANO) Ti implant, the surface of which was treated by sandblasting, acid etching (SLA), and anodized techniques. The aim of the present study was to evaluate the adhesion of MG-63 cells to Modi-ANO surface treated Ti in vitro and to investigate its osseointegration characteristics in vivo. Four different types of Ti implants were examined, that is, machined Ti (control), SLA, anodized, and Modi-ANO Ti. In the cell adhesion study, Modi-ANO Ti showed higher initial MG-63 cell adhesion and induced greater filopodia growth than other groups. In vivo study in a beagle model revealed the bone-to-implant contact (BIC) of Modi-ANO Ti (74.20%±10.89%) was much greater than those of machined (33.58%±8.63%), SLA (58.47%±12.89), or ANO Ti (59.62%±18.30%). In conclusion, this study demonstrates that Modi-ANO Ti implants produced by sandblasting, acid etching, and anodizing improve cell adhesion and bone ongrowth as compared with machined, SLA, or ANO Ti implants. These findings suggest that the application of Modi-ANO surface treatment could improve the osseointegration of dental implant.

Osteoblastic differentiation and bone-forming capacity are known to be suppressed under hypoxic conditions. Melatonin has been shown to influence cell differentiation. A number of in vitro and in vivo studies have suggested that melatonin also has an anabolic effect on bone, by promoting osteoblastic differentiation. However, the precise mechanisms and the signaling pathways involved in this process, particularly under hypoxic conditions, are unknown. This study investigated whether melatonin could promote osteoblastic differentiation and mineralization of preosteoblastic MC3T3-E1 cells under hypoxic conditions. Additionally, we examined the molecular signaling pathways by which melatonin mediates this process. We found that melatonin is capable of promoting differentiation and mineralization of MC3T3-E1 cells cultured under hypoxic conditions. Melatonin upregulated ALP activity and mRNA levels of Alp, Osx, Col1, and Ocn in a time- and concentration-dependent manner. Alizarin red S staining showed that the mineralized matrix in hypoxic MC3T3-E1 cells formed in a manner that was dependent on melatonin concentration. Moreover, melatonin stimulated phosphorylation of p38 Mapk and Prkd1 in these MC3T3-E1 cells. We concluded that melatonin promotes osteoblastic differentiation of MC3T3-E1 cells under hypoxic conditions via the p38 Mapk and Prkd1 signaling pathways.