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Bilobalide isolated from the leaves of Ginkgo biloba has several pharmacological activities such as neuroprotective, anti-inflammatory, and anticonvulsant. However, the effect of bilobalide on cancer has not been clearly established. The main purpose of this study was to investigate the effect of bilobalide on cell growth and apoptosis induction in FaDu human pharyngeal squamous cell carcinoma. This was examined by 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide assay, nuclear 4′,6-diamidino-2-phenylindole dihydrochloride staining, DNA fragmentation analysis, and immunoblotting. Bilobalide inhibited the growth of FaDu cells in dose- and time-dependent manners. Treatment with bilobalide resulted in nuclear condensation and DNA fragmentation in FaDu cells. Furthermore, it promoted the proteolytic cleavage of procaspase-3/-7/-8/-9 with increase in the amount of cleaved caspase-3/-7/-8/-9. Bilobalide-induced apoptosis in FaDu cells was mediated by the expression of Fas and the activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting revealed that the antiapoptotic mitochondrial protein Bcl-2 was downregulated, but the proapoptotic protein Bax was upregulated by bilobalide in FaDu cells. Bilobalide significantly increased Bax/Bcl-2 ratio. These results suggest that bilobalide inhibits cell proliferation and induces apoptosis in FaDu human pharyngeal squamous cell carcinoma via both the death receptor-mediated extrinsic apoptotic pathway and the mitochondrial-mediated intrinsic apoptotic pathway.

Purpose: This study examines the properties and potential commercial value of the pine cones extract when used as bioactive and cosmetics ingredients. Methods: Pine cones were extracted with hot water (WE), 70% ethanol (EE), and supercritical fluid extraction (SFE) to examine their antioxidant properties on the basis of their total polyphenol content, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and gas chromatography-mass spectrometry (GC-MS) analysis. The antibacterial properties of the pine cone extract were also studied on 2 types of bacteria. In addition, this study examined the nitric oxide (NO) inhibition effect using RAW 264.7 cells, in which the inflammatory reaction was induced by lipopolysaccharides (LPS), and cell migration activity in the HeCaT cells. Results: The extract obtained with SFE exhibited high antioxidative ability even at low concentration (0.125%). The antimicrobial activity of the of SFE pine cone extract was 12.1±1.04 mm for Staphylococcus aureus (S. aureus ) and 11.8±0.45 mm for Staphylococcus epidermidis (S. epidermidis ). Cytotoxicity evaluation showed cell viability above 80% in all extracts. During the antiinflammatory test, the nitric oxide expression level was low, and it was confirmed by the antiinflammatory effect. The results of the stability test showed that emulsions containing SFE extract were very stable. The pH and high temperature (40℃) of each emulsion containing SFE extract did not considerably change for 30 days. Conclusion: These findings suggest that SFE extract is a possible cosmeceutical material with potent skin regeneration and antiinflammatory properties.

Purpose The purpose of this study was to evaluate the effects of the growth factor within platelet-rich fibrin (PRF) in proliferation and differentiation of osteoblast and to observe the effectiveness of PRF. Materials and methods The colorimetric MTT assay, cell live and dead assay, alkaline phosphatase staining and activity assay, alizarine red S, and von Kossa staining were performed. Finally, the alterations of biomarkers associated with bone formation were verified at the mRNA level by quantitative polymerase chain reaction (PCR) and quantitative real-time PCR. In in vivo study, 6 adult mongrel dogs were used. The defect was performed and divided into 3 groups: (1) defect left unfilled, (2) defect filled with only 0.25-g Bio-Oss, and (3) defect filled with 0.25-g Bio-Oss mixed with PRF. Results MTT and cell live and dead assay showed that PRF did not affect the cell viability in MG-63 cells. The alkaline phosphatase activity, calcification, and mineralization were gradually increased in the MG-63 cells treated with PRF. Furthermore, the mRNA levels of biomarker gene in the MG-63 cells treated with PRF were significantly higher than those of control. In in vivo study, both radiographical and histological evaluations showed that the new bone formations were significantly increased in the defecting bone region transplanted with Bio-Oss and PRF compared with Bio-Oss only at 2 weeks after transplantation. Conclusion PRF can promote the bone regeneration without any complications.

This study investigates the potential of propolis-embedded zeolite nanocomposites for dental implant application. Propolis-embedded zeolite nanocomposites were fabricated by complexation of propolis and zeolites. Then, they were pelleted with Poly(L-lactide) (PLA)/poly(e-caprolactone) (PCL) polymer for the fabrication of a dental implant. The chemical properties of propolis were not changed during the fabrication of propolis-embedded zeolite nanocomposites in attenuated total reflection-fourier transform infra-red (ATR FT-IR) spectroscopy measurements. Propolis was continuously released from propolis-embedded zeolite nanocomposites over one month. PLA/PCL pellets containing propolis-embedded zeolite nanocomposites showed longer sustained release behavior compared to propolis-embedded zeolite nanocomposites. Propolis-embedded zeolite nanocomposite powder showed similar antibacterial activity against C. albicans in an agar plate and formed an inhibition zone as well as chlorohexidine (CHX) powder. Eluted propolis solution from PLA/PCL pellets also maintained antibacterial activity as well as CHX solution. Furthermore, eluted propolis solution from PLA/PCL pellets showed significant antibacterial efficacy against C. albicans, S. mutans and S. sobrinus. Dental implants fabricated from PLA/PCl polymer and propolis-embedded zeolite nanocomposites also have antibacterial efficacy and negligible cytotoxicity against normal cells. We suggest that PLA/PCl pellets containing propolis-embedded zeolite nanocomposites are promising candidates for dental implants.

Background/aim MicroRNAs (miRNAs) are closely associated with a number of cellular processes, including cell development, differentiation, proliferation, carcinogenesis, and apoptosis. The aim of the present study was to elucidate the molecular mechanisms underlying the tumor suppressor activity of miRNA-203 (miR-203) in YD-38 human oral cancer cells. Materials and methods Polymerase chain reaction analysis, MTT assay, DNA fragmentation assay, fluorescence-activated cell-sorting analysis, gene array, immunoblotting, and luciferase assay were carried out in YD-38 cells. Results miR-203 expression was significantly down-regulated in YD-38 cells compared to expression levels in normal human oral keratinocytes. miR-203 decreased the viability of YD-38 cells in a time- and dose-dependent manner. In addition, over-expression of miR-203 significantly increased not only DNA segmentation, but also the apoptotic population of YD-38 cells. These results indicate that miR-203 overexpression induces apoptosis in YD-38 cells. Target gene array analysis revealed that the expression of the polycomb complex protein gene Bmi-1, a representative oncogene, was significantly down-regulated by miR-203 in YD-38 cells. Moreover, both mRNA and protein levels of Bmi-1 were significantly reduced in YD-38 cells transfected with miR-203. These results indicate that Bmi-1 is a target gene of miR-203. A luciferase reporter assay confirmed that miR-203 suppressed Bmi-1 expression by directly targeting the 3'-untranslated region. Conclusion miR-203 induces apoptosis in YD-38 cells by directly targeting Bmi-1, which suggests its possible application as an anti-cancer therapeutic.

The inferior alveolar nerve block is the most common method of local anesthesia for intraoral surgery at the posterior mandibular region. However, unexpected complications may occur when administering the local anesthesia. One of these uncommon complications is the fracture of the needle. If the injection needle is broken during the surgery, it should be removed immediately. However, this is one of the most difficult procedures. In this report, we present two cases of needle fracture during the procedure, and its successful removal under general/local anesthesia administration.

Metformin (1,1-dimethylbiguanide hydrochloride), derived from French lilac (Galega officinalis), is a first-line drug prescribed for patients with type 2 diabetes. It has been reported to have anti-cancer effects in a variety of cancer cells. However, effects of metformin on oral cancer cells have not been clearly established. The main goal of this study was to investigate the effect of metformin on cell growth and apoptosis induction in oral cancer cells derived from Korean patients. The effect of metformin on cell growth and apoptosis induction in oral cancer cells was examined by inhibition of cell growth, DNA fragmentation analysis and immunoblotting in YD-38 human oral cancer cells derived from Korean patients. Treatment with metformin induced inhibition of cell growth depending on the metformin treatment time and concentration in YD-38 human oral cancer cells. Treatment with metformin induced nuclear fragmentation in YD-38 human oral cancer cells. Metformin promoted proteolytic cleavage of procaspase-3 with an increase in the amount of cleaved caspase-3. Cleaved PARP was increased by metformin in YD-38 human oral cancer cells. Treatment of YD-38 human oral cancer cells with metformin increased the level of Bax, but it decreased the level of Bcl-2. These results suggest that metformin can induce suppression of cell growth and cell apoptosis in YD-38 human oral cancer cells derived from Korean patients.

Background/aim The present study aimed to investigate the apoptotic effects of phenformin, a therapeutic agent for diabetes, on head and neck squamous cell carcinoma (HNSCC). Materials and methods Cytotoxicity was measured by the MTT and live/dead cell assay. Phenformin-induced apoptotic FaDu cell death and its associated cellular signaling pathways were investigated by hematoxylin and eosin staining, 4',6-diamidino-2-phenylindole staining, caspase-3 activity assay, fluorescence-activated cell sorting analysis, and western blotting. Results Phenformin promoted death of and apoptotic processes in FaDu cells, including morphological alterations and nuclear condensation. Furthermore, treatment with phenformin increased caspase-3 activity and apoptotic populations via the caspase cascade through cleavage of capspase-8, -9, and -3 and poly(ADP-ribose) polymerase in FaDu cells. Moreover, phosphorylation levels of mitogen-activated protein kinases, nuclear factor-κB, and AKT were down-regulated in FaDu cells by phenformin. Conclusion Phenformin induced death of FaDu cells via caspase-dependent extrinsic and intrinsic apoptosis pathways and is a promising novel therapeutic agent for HNSCC.

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is characterized by various embryological deformities and carcinoma formation. It is caused by PTCHI gene mutations and is autosomal dominantly inherited. Some of the main symptoms of NBCCS are multiple basal cell carcinomas, multiple keratocystic odontogenic tumors (KCOTs) of the mandible, hyperkeratosis of the palmar and plantar, skeletal deformity, calcification of the falx cerebri, and facial defomity. Recurrent KCOT is the main symptom of NBCCS and is present in approximately 90% of patients. In NBCCS, KCOTs typically occur in multiples. KCOTs can be detected in patients under the age of 10, and new and recurring cysts develop until approximately the age of 30. The postoperation recurrence rate is approximately 60%. This case report presents a 14-year-old female patient with a chief complaint of a cyst found in the maxilla and mandible. The patient was diagnosed with NBCCS, and following treatment of marsupialization and enucleation, the clinical results were satisfactory.

Objectives: If teeth are missing, super-eruption of teeth in the opposing arch can occur in the area and can change the occlusal plane. When missing teeth are replaced with implants, the oral surgeon must determine whether or not the super-erupted teeth need to be treated in order to normalize the occlusal plane. In this study, we evaluated the clinical prognosis of dentition after implant placement and prosthetic treatment were completed in an occlusal plane altered by super-erupted teeth in the opposing arch without additional treatment of the super-erupted teeth. Materials and Methods: Twenty-two patients (9 males, 13 females) were treated with implants and prosthetics without addressing the super-erupted opposing dentition from April 2004 to August 2012 at Seoul National University Bundang Hospital. A total of 33 implants were placed. Values of crestal bone loss, survival rates, and surgical and prosthetic complications for an average of 29.6 months after prosthetic loading were recorded. Results: In one case, the cover screw was exposed after implant surgery. The mean crestal bone loss was 0.09±0.30 mm. Of the 33 implants, 31 survived, a survival rate of 93.94%. A prosthetic complication occurred in one case but functioned well after correction. Conclusion: Favorable clinical results from prosthetic complications, crestal bone loss, and implant survival rates were exhibited in implants next to a super-erupted opposing tooth.

MicroRNAs (miRNAs) are closely associated with a number of cellular processes, including cell development, differentiation, proliferation, carcinogenesis, and apoptosis. The aim of the present study was to elucidate the molecular mechanisms underlying the tumor suppressor activity of miRNA-203 (miR-203) in YD-38 human oral cancer cells.Polymerase chain reaction analysis, MTT assay, DNA fragmentation assay, fluorescence-activated cell-sorting analysis, gene array, immunoblotting, and luciferase assay were carried out in YD-38 cells.miR-203 expression was significantly down-regulated in YD-38 cells compared to expression levels in normal human oral keratinocytes. miR-203 decreased the viability of YD-38 cells in a time- and dose-dependent manner. In addition, over-expression of miR-203 significantly increased not only DNA segmentation, but also the apoptotic population of YD-38 cells. These results indicate that miR-203 overexpression induces apoptosis in YD-38 cells. Target gene array analysis revealed that the expression of the polycomb complex protein gene Bmi-1, a representative oncogene, was significantly down-regulated by miR-203 in YD-38 cells. Moreover, both mRNA and protein levels of Bmi-1 were significantly reduced in YD-38 cells transfected with miR-203. These results indicate that Bmi-1 is a target gene of miR-203. A luciferase reporter assay confirmed that miR-203 suppressed Bmi-1 expression by directly targeting the 3'-untranslated region.miR-203 induces apoptosis in YD-38 cells by directly targeting Bmi-1, which suggests its possible application as an anti-cancer therapeutic.

In the present study, we investigated berberine‑induced apoptosis and the signaling pathways underlying its activity in FaDu head and neck squamous cell carcinoma cells. Berberine did not affect the viability of primary human normal oral keratinocytes. In contrast, the cytotoxicity of berberine was significantly increased in FaDu cells stimulated with berberine for 24 h. Furthermore, berberine increased nuclear condensation and apoptosis rates in FaDu cells than those in untreated control cells. Berberine also induced the upregulation of apoptotic ligands, such as FasL and TNF-related apoptosis-inducing ligand, and triggered the activation of caspase-8, -7 and -3, and poly(ADP ribose) polymerase, characteristic of death receptor-dependent extrinsic apoptosis. Moreover, berberine activated the mitochondria‑dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bax, Bad, Apaf-1, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. In addition, berberine increased the expression of the tumor suppressor p53 in FaDu cells. The pan-caspase inhibitor Z-VAD-fmk suppressed the activation of caspase-3 and prevented cytotoxicity in FaDu cells treated with berberine. Interestingly, berberine suppressed cell migration through downregulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38, components of the mitogen-activated protein kinase pathway that are associated with the expression of MMP and VEGF, was suppressed in FaDu cells treated with berberine for 24 h. Therefore, these data suggested that berberine exerted anticancer effects in FaDu cells through induction of apoptosis and suppression of migration. Berberine may have potential applications as a chemotherapeutic agent for the management of head and neck squamous carcinoma.

We report generation and characterization of pain-related behavior in a minimally invasive facet joint degeneration (FJD) animal model in rats. FJD was produced by a non-open percutaneous puncture-induced injury on the right lumbar FJs at three consecutive levels. Pressure hyperalgesia in the lower back was assessed by measuring the vocalization response to pressure from a force transducer. After hyperalgesia was established, pathological changes in lumbar FJs and alterations of intervertebral foramen size were assessed by histological and imaging analyses. To investigate treatment options for lumber FJ osteoarthritis-induced pain, animals with established hyperalgesia were administered with analgesic drugs, such as morphine, a selective COX-2 inhibitor, a non-steroidal anti-inflammatory drug (NSAID) (ketorolac), or pregabalin. Effects were assessed by behavioral pain responses. One week after percutaneous puncture-induced injury of the lumbar FJs, ipsilateral primary pressure hyperalgesia developed and was maintained for at least 12 weeks without foraminal stenosis. Animals showed decreased spontaneous activity, but no secondary hyperalgesia in the hind paws. Histopathological and microfocus X-ray computed tomography analyses demonstrated that the percutaneous puncture injury resulted in osteoarthritis-like structural changes in the FJs cartilage and subchondral bone. Pressure hyperalgesia was completely reversed by morphine. The administration of celecoxib produced moderate pain reduction with no statistical significance while the administration of ketorolac and pregabalin produced no analgesic effect on FJ osteoarthritis-induced back pain. Our animal model of non-open percutanous puncture-induced injury of the lumbar FJs in rats shows similar characteristics of low back pain produced by human facet arthropathy.

Purpose: The aim of the present study is to assess the importance of proper treatment timing for dental emergency patients by characterizing current patient care in the emergency room. Materials and Methods: A retrospective chart review of 3,211 patients who visited the Chosun University Hospital’s dental emergency department (Gwangju, Korea) was conducted from January 1, 2011 to May 31, 2014. Information regarding age, gender, onset date, main causes, and diagnoses were collected and analyzed. The main causes were divided into six categories: assault, household/play, sports, traffic, work, and others. Result: Emergency visits were more common for men (69%), and the ratio of males to females was 2.2:1 On average, the major cause was household/play (49.8%), followed by others (18.9%), traffic (16.6%), assault (9.1%), sports (2.9%), and work (2.6%). The most frequent diagnosis on average was dental trauma with 82.4%, followed by infection (10.7%), others (4.7%), and bleeding (2.2%). Conclusion: The main reasons for visits to the dental emergency department are dental trauma, dental infection, bleeding, and others. The most frequent reason for dental emergency patients to visit the emergency department was dental trauma (82.4%).

We investigated Licochalcone-A (Lico-A)-induced apoptosis and the pathway underlying its activity in a pharyngeal squamous carcinoma FaDu cell line. Lico-A purified from root of Glycyrrhiza inflata had cytotoxic effects, significantly increasing cell death in FaDu cells. Using a cell viability assay, we determined that the IC50 value of Lico-A in FaDu cells was approximately 100 µM. Chromatin condensation was observed in FaDu cells treated with Lico-A for 24 h. Consistent with this finding, the number of apoptotic cells increased in a time-dependent manner when FaDu cells were treated with Lico-A. TRAIL was significantly up-regulated in Lico-A-treated FaDu cells in a dose-dependent manner. Apoptotic factors such as caspases and PARP polymerase were subsequently activated in a caspase-dependent manner. In addition, levels of pro-apoptotic factors increased significantly in response to Lico-A treatment, while levels of anti-apoptotic factors decreased. Lico-A-induced TRAIL expression was mediated in part by a MAPK signaling pathway involving ERK1/2 and p38. Lastly, in an in vivo xenograft mouse model, Lico-A treatment effectively suppressed the growth of FaDu cell xenografts by activating caspase-3, without affecting the body weight of mice. Taken together, these data suggest that Lico-A has potential chemopreventive effects and should therefore be developed as a chemotherapeutic agent for pharyngeal squamous carcinoma.

In the present study, we examined the anticancer properties of berberine in KB oral cancer cells with a specific focus on its cellular mechanism. Berberine did not affect the cell viability of the primary human normal oral keratinocytes that were used as a control. However, the viability of KB cells was found to decrease significantly in the presence of berberine in a dose-dependent manner. Furthermore, in KB cells, berberine induced the fragmentation of genomic DNA, changes in cell morphology, and nuclear condensation. In addition, caspase-3 and -7 activation, and an increase in apoptosis were observed. Berberine was also found to upregulate significantly the expression of the death receptor ligand, FasL. In turn, this upregulation triggered the activation of pro-apoptotic factors such as caspase-8, -9 and -3 and poly(ADP-ribose) polymerase (PARP). Furthermore, pro-apoptotic factors such as Bax, Bad and Apaf-1 were also significantly upregulated by berberine. Anti-apoptotic factors such as Bcl-2 and Bcl-xL were downregulated. Z-VAD-FMK, a cell-permeable pan-caspase inhibitor, suppressed the activation of caspase-3 and PARP. These results clearly indicate that berberine-induced cell death of KB oral cancer cells was mediated by both extrinsic death receptor-dependent and intrinsic mitochondrial-dependent apoptotic signaling pathways. In addition, berberine-induced upregulation of FasL was shown to be mediated by the p38 MAPK signaling pathway. We also found that berberine-induced migration suppression was mediated by downregulation of MMP-2 and MMP-9 through phosphorylation of p38 MAPK. In summary, berberine has the potential to be used as a chemotherapeutic agent, with limited side-effects, for the management of oral cancer.

BACKGROUND/AIM The purpose of this study was to elucidate the molecular mechanism underlying regulation of semaphorin-6A (SEMA6A) involving microRNA-203 (miR-203) as a tumor suppressor in YD-38 human oral cancer cells. MATERIALS AND METHODS miRNA arrays, polymerase chain reaction analyses, MTT assays, immunoblotting, and luciferase assays were carried out in YD-38 cells. RESULTS MiRNA microarray results showed that expression of miR-203 was significantly down-regulated in YD-38 cells compared to normal human oral keratinocytes. The viability of YD-38 cells was reduced by miR-203 in time- and dose-dependent manners. Overexpression of miR-203 increased the nuclear condensation of YD-38 cells and activated the apoptotic signaling pathway by up-regulating pro-apoptotic factors, such as BCL-2-associated X protein (BAX) and BCL-2 homologous antagonist killer (BAK), and the active forms of caspase-9, caspase-3, and poly-(ADP-ribose)-polymerase (PARP). Furthermore, target gene array analyses revealed that the expression of class 6 semaphorin A (SEMA6A) was down-regulated by miR-203 in YD-38 cells. Both the mRNA and protein levels of SEMA6A were reduced in YD-38 cells transfected with miR-203. Luciferase activity assay confirmed that miR-203 directly targets the SEMA6A 3'-untranslated region to suppress gene expression. CONCLUSION Our results indicate that miR-203 induces the apoptosis of YD-38 human oral cancer cells by directly targeting SEMA6A, suggesting its potential application in anticancer therapeutics.

Background Codium fragile (Suringar) Hariot has been used as a potential remedy in traditional medicine because of its anti-inflammatory and anti-oxidant effects. Osteoarthritis is a chronic progressive joint disease, characterized by complex mechanisms related to inflammation and degeneration of articular cartilage. In this study, we aimed to evaluate the cartilage protective effect of an aqueous extract of Codium fragile (AECF) using rat primary chondrocytes and the osteoarthritis animal model induced by destabilization of the medial meniscus (DMM). Methods In vitro, rat primary cultured chondrocytes were pre-treated with AECF (0.5, 1, and 2 mg/mL) for 1 h and then incubated with interleukin-1β (10 ng/mL) for 24 h. Nitrite production was detected by the Griess reagent. Alteration of the protein levels of iNOS, MMP-13, ADAMTS-4, ADAMTS-5, mitogen-activated protein kinases (MAPKs), and nuclear factor-κB (NF-κB) was detected by western blotting. In vivo, osteoarthritis was induced by DMM of Sprague Dawley (SD) rats. The rats subjected to destabilization of the medial meniscus (DMM) surgery were orally administered with AECF (50, 100, and 200 mg/kg bodyweight) or distilled water for 8 w. The severity of cartilage lesions was evaluated by safranin O staining and the Osteoarthritis Research Society International (OARSI) score. Results These results demonstrated that AECF significantly inhibited nitrite production and inhibited the levels of iNOS, MMP-13, ADAMTS-4, and ADAMTS-5 in interleukin-1β-induced rat primary cultured chondrocytes. Moreover, AECF suppressed interleukin-1β-induced NF-κB activation in the nucleus and phosphorylation of ERK1/2 and JNK in the cytosol. In vivo, the cartilage lesions in AECF‐treated osteoarthritis rats exhibited less proteoglycan loss and lower OARSI scores. Conclusions These results suggested that AECF is a potential therapeutic agent for the alleviation of osteoarthritis progression.

The aim of the present study was to investigate biochanin-A-induced anticancer effects and their cellular signaling pathway in FaDu pharyngeal squamous carcinoma cells. Biochanin-A induced cell death through increased cytotoxicity of FaDu cells in a dose- and time-dependent manner. The number of cells with nucleus condensation and the apoptotic population were increased in the FaDu cells stimulated with biochanin-A for 24 h. Furthermore, extrinsic apoptotic factors such as FasL and their downstream target caspase-8 were increased and activated in the FaDu cells treated with biochanin-A in a dose-dependent manner. Moreover, biochanin-A decreased the expression of intrinsic anti-apoptotic factors such as Bcl-2 and Bcl-xL, and increased the level and activation of intrinsic apoptotic factors such as Bad and caspase-9. Finally, biochanin-A induced the activation of caspase-3 and Poly(ADP ribose) polymerase (PARP) in FaDu cells. Our results suggest that biochanin-A-induced apoptosis was mediated by death receptor mediated-extrinsic and mitochondria-dependent intrinsic apoptotic signaling pathways. Biochanin-A also inhibited wound healing migration and proliferation of FaDu cells via the downregulation and inactivation of matrix metalloproteinase-2 and -9 that are mediated by the suppression of p38, mitogen activated protein kinase (MAPK), NF-κB and Akt cellular signaling pathways. Therefore, these data suggest that the biochanin-A may act as a potential chemotherapeutic compound to treat head and neck cancer.

The aim of the present study was to investigate licochalcone-E (Lico-E)-induced apoptosis and the associated apoptotic signaling pathway in FaDu cells, a human pharyngeal squamous carcinoma cell line. Treatment with Lico-E exhibited significant cytotoxicity on FaDu cells in a concentration-dependent manner. The IC50 value of Lico-E in FaDu cells was ~50 µM. Treatment with Lico-E increased the number of dead FaDu cells. Furthermore, chromatin condensation, which is associated with apoptotic cell death, was observed in FaDu cells treated with Lico-E for 24 h. By contrast, Lico-E did not produce cytotoxicity or increase the number of dead cells when applied to human normal oral keratinocytes (hNOKs). Furthermore, chromatin condensation was not observed in hNOKs treated with Lico-E. Treatment with Lico-E increased the expression of Fas ligand and the cleaved form of caspase-8 in FaDu cells. Furthermore, treatment with Lico-E increased the expression of pro-apoptotic factors, including apoptosis regulator BAX, Bcl-2-associated agonist of cell death, apoptotic protease-activating factor 1, caspase-9 and tumor suppressor p53, while decreasing the expression of anti-apoptotic factors, including apoptosis regulator Bcl-2 and Bcl-2-like protein 1 in FaDu cells. The expression of cleaved caspases-3 and poly (ADP-ribose) polymerase was significantly upregulated following treatment with Lico-E in FaDu cells, while Lico-E-induced apoptotic FaDu cell death was partially suppressed by treatment with Z-VAD-FMK, a pan caspase inhibitor. Therefore, Lico-E-induced oral cancer (OC) cell-specific apoptosis is mediated by the death receptor-dependent extrinsic and mitochondrial-dependent intrinsic apoptotic signaling pathways. In conclusion, these data suggested that Lico-E exhibits potential chemopreventive effects and warrants further developed as a chemotherapeutic agent against OC.

Purpose: To establish management protocol for mandibular angle fracture, we describe pertinent factors including cause, impacted third molar and recent treatment tendency. Methods: We examined the records of 62 patients who had unilateral mandibular angle fracture. Sixty patients who had open reduction surgery were examined at postoperative weeks 1, 4, 8, 12, and 28. Results: Left mandibular angle fracture is frequent in younger males. Presence of the mandibular third molar can increase fracture risk. Because of attached muscle, favorable fractures occurred primarily in the mandibular angle area. Conclusion: Extracting the mandibular third molar can prevent angle fractures, and open reduction with only one plate adaptation is generally the proper treatment method for mandibular angle fracture.

The aim of the present study was to investigate and compare the effects of diferuloylmethane (curcumin) and diphenyldifluoroketone (EF-24) on cell growth and apoptosis induction in human osteogenic sarcoma cells. This was examined by MTT assay, nuclear DAPI staining, caspase-activation assay, flow cytometry analysis and immunoblotting in Saos2 human osteogenic sarcoma cells. Curcumin and EF-24 inhibited the growth of Saos2 cells in a dose-dependent manner. The apparent potency of EF-24 was more than 3-fold higher that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in the cells. The caspase-3/-7 activities were detected in living cells treated with curcumin or EF-24. Flow cytometry showed that the rate of apoptosis was increased by curcumin and EF-24 compared to the control. Curcumin and EF-24 promoted the proteolytic cleavages of procaspase-3/-7/-8/-9 with increases in the amount of cleaved caspase-3/-7/-8/-9. The curcumin- or EF-24-induced apoptosis in the Saos2 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3 and poly(ADP-ribose) polymerase. Immunoblotting revealed the Bid and Bcl-2 proteins to be downregulated, and truncated-Bid, Bax and p53 proteins to be upregulated by curcumin and EF-24. Curcumin and EF-24 increased the Bax/Bcl-2 ratio significantly. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptotic cell death in Saos2 human osteogenic sarcoma cells via both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway, and may have potential properties for anti-osteosarcoma drug discovery.

Osteoradionecrosis is one of the most serious complications of patients receiving radiation therapy. It is characterized by hypovascularity, hypocellularity, and hypoxia-inducing necrosis of bone and soft tissue following delayed healing. In this case, a 72-year-old man was referred to the Department of Oral and Maxillofacial Surgery complaining of trismus following extraction three months before first visit. He had a history of right tonsillectomy, radical neck dissection and radiotherapy performed due to right tonsillar cancer seven years prior. After the diagnosis of osteoradionecrosis on right mandibular body and angle, conservative antibiotic therapy was used first, but an orocutaneous fistula gradually formed, and extensive bony destruction and sequestrum were observed. Sequestrectomy, free particulated iliac bone and umbilical fat pad graft were performed via a submandibular approach under general anesthesia. Preoperative regular exams and delicate wound care led to secondary healing of the wound without vascularized free flap reconstruction.

Keratocystic odontogenic tumor (KCOT) is a benign cystic intraosseous tumor of odontogenic origin. An infection of a KCOT is not common because KCOT is a benign developmental neoplasm. Moreover, a severe deep neck space infection with compromised airway caused by infected KCOT is rare. This report presents a 60-year-old male patient with a severe deep neck space infection related to an infected KCOT due to cortical bone perforation and rupture of the exudate. Treatment of the deep neck space infection and KCOT are reported.

Recently, clinical application of autogenous tooth bone-graft materials has been reported. Autogenous tooth bone graft has been used in implant surgery. Familial tooth bone graft is a more advanced procedure than autogenous teeth bone graft in that extracted teeth can be used for bone graft materials of implant and teeth donation between siblings is possible. We used autogenous tooth and familial tooth bone-graft materials for ridge augmentation and sinus bone graft and obtained satisfactory results. The cases are presented herein.

Objectives: The aim of this study was to retrospectively evaluate the clinical survival rate of Astra Tech implants in the maxillary molar region performed with sinus lift and bone graft. Materials and Methods: Ninety-nine Astra Tech implants (Osseospeed) placed in the maxillary molar region using sinus lift from September 2009 to February 2012 were selected with a minimum follow-up period of 1 year. The height of alveolar bone, sinus approach technique, bone material and implant survival rate were evaluated. Results: Of the 99 implants, the survival rate was 90.9%; 8 implants failed within 1 year after implant placement, and 1 implant failed 1 year after implant loading. All failed implants were placed with sinus lift simultaneously. The average height of alveolar bone before implant placement was 6.9 mm, while the height of alveolar bone of failed implants was 2.1 mm, on average. Conclusion: Astra Tech implants placed in the maxillary molar region had generally good survival rates, but the relationship between reduced preimplant alveolar bone height and implant failure requires further attention.

Compared to most normal cells that express L-type amino acid transporter 2, L-type amino acid transporter 1 is highly expressed in cancer cells and presumed to support their elevated growth and proliferation. This study examined JPH203, a potent and selective L-type amino acid transporter 1 inhibitor, and its ability to suppress YD-38 human oral cancer cell growth. The YD-38 cells express L-type amino acid transporter 1 with its associating protein 4F2 heavy chain, but not L-type amino acid transporter 2. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, completely inhibited l-leucine uptake in YD-38 cells. As expected, the intrinsic affinity of JPH203 to inhibit l-leucine uptake was far more efficient than BCH. Likewise, JPH203 and BCH inhibited YD-38 cell growth, with JPH203 being superior to BCH. JPH203 up-regulated the population of apoptotic YD-38 cells through the activation of apoptotic factors, including caspases and PARP. These results suggest that the inhibition of L-type amino acid transporter 1 activity via JPH203, which may act as a potential novel anti–oral-cancer agent, leads to apoptosis by inducing the intracellular depletion of the neutral amino acids essential for cancer cell growth in YD-38 human oral cancer cells. Keywords:: JPH203, L-type amino acid transporter 1, apoptosis, oral cancer cell, anti-cancer therapy

The objective of this study was to examine whether altered expression of microRNAs in central nervous system components is pathologically linked to chronic knee joint pain in osteoarthritis. A surgical animal model for knee joint OA was generated by medial meniscus transection in rats followed by behavioral pain tests. Relationships between pathological changes in knee joint and development of chronic joint pain were examined by histology and imaging analyses. Alterations in microRNAs associated with OA-evoked pain sensation were determined in bilateral lumbar dorsal root ganglia (DRG) and the spinal dorsal horn by microRNA array followed by individual microRNA analyses. Gain- and loss-of-function studies of selected microRNAs (miR-146a and miR-183 cluster) were conducted to identify target pain mediators regulated by these selective microRNAs in glial cells. The ipsilateral hind leg displayed significantly increased hyperalgesia after 4 weeks of surgery, and sensitivity was sustained for the remainder of the 8-week experimental period (F = 341, p < 0.001). The development of OA-induced chronic pain was correlated with pathological changes in the knee joints as assessed by histological and imaging analyses. MicroRNA analyses showed that miR-146a and the miR-183 cluster were markedly reduced in the sensory neurons in DRG (L4/L5) and spinal cord from animals experiencing knee joint OA pain. The downregulation of miR-146a and/or the miR-183 cluster in the central compartments (DRG and spinal cord) are closely associated with the upregulation of inflammatory pain mediators. The corroboration between decreases in these signature microRNAs and their specific target pain mediators were further confirmed by gain- and loss-of-function analyses in glia, the major cellular component of the central nervous system (CNS). MicroRNA therapy using miR-146a and the miR-183 cluster could be powerful therapeutic intervention for OA in alleviating joint pain and concomitantly regenerating peripheral knee joint cartilage.

Maxillary sinus membrane elevation and bone graft have been performed routinely in alveolar bone with insufficient residual bone height. There are a number of causes for development of maxillary sinusitis after these procedures. When maxillary sinusitis is caused by sinus membrane elevation, bone graft, and implant placement, various treatment such as medication, incision and drainage (I&D), implant removal, and the Caldwell-Luc procedure can be considered. Removal of an implant or the Caldwell-Luc procedure can be harmful if inflammation is not present in the oral cavity and survival of grafted bone and implant osseointegration can be expected despite the presence of maxillary sinusitis. In this case, functional endoscopic sinus surgery, which was often used in the otorhinolaryngology department, was performed without removal of the implant for a patient with maxillary sinusitis after one month following implant placement. Thus, we report on this case with a review of the literature.

Bone-morphogenetic protein-7 (BMP7) is a well-known anabolic and anti-catabolic growth factor on intervertebral disc (IVD) matrix and cell homeostasis. Similarly, Lactoferricin B (LfcinB) has recently been shown to have pro-anabolic, anti-catabolic, anti-oxidative and/or anti-inflammatory effects in bovine disc cells in vitro. In this study, we investigated the potential benefits of using combined peptide therapy with LfcinB and BMP7 for intervertebral disc matrix repair and to understand cellular and signaling mechanisms controlled by these factors. We studied the effects of BMP7 and LfcinB as individual treatments and combined therapy on bovine nucleus pulposus (NP) cells by assessing proteoglycan (PG) accumulation and synthesis, and the gene expression of matrix protein aggrecan and transcription factor SOX-9. We also analyzed the role of Noggin, a BMP antagonist, in IVD tissue and examined its effect after stimulation with LfcinB. To understand the molecular mechanisms by which LfcinB synergizes with BMP7, we investigated the ERK-SP1 axis as a downstream intracellular signaling regulator involved in BMP7 and LfcinB-mediated activities. Treatment of bovine NP cells cultured in alginate with LfcinB plus BMP7 synergistically stimulates PG synthesis and accumulation in part by upregulation of aggrecan gene expression. The synergism results from LfcinB-mediated activation of Sp1 and SMAD signaling pathways by (i) phosphorylation of SMAD 1/5/8; (ii) downregulation of SMAD inhibitory factors [i.e., noggin and SMAD6 (inhibitory SMAD)]; and (iii) upregulation of SMAD4 (universal co-SMAD). These data indicate that LfcinB-suppression of Noggin may eliminate the negative feedback of BMP7, thereby maximizing biological activity of BMP7 and ultimately shifting homeostasis to a pro-anabolic state in disc cells. We propose that combination growth factor therapy using BMP7 and LfcinB may be beneficial for treatment of disc degeneration.

Purpose: The purpose of this study is to evaluate the difference between open reduction and internal fixation (ORIF) and intermaxillary fixation (IMF) of mandibular fractures. Methods: A total of one hundred twenty-seven patients who were treated for mandibular fractures at Chosun University Dental Hospital, from January 2008 to December 2010, and analyzed their prognoses based on the use of IMF at the time of fracture reduction. The patients were divided into two groups; the manual reduction group without IMF and IMF group. Results: After reduction of the mandibular fracture, good results were obtained with majority patients. Nonetheless, seven patients (13.0%) in manual reduction method without arch bars or IMF, developed complications after surgery. Three patients underwent IMF due to occlusal instability after surgery, while one patient underwent re-operation. Thus, a significant difference was not observed between the IMF and manual reduction groups. Conclusion: Manual reduction and IMF at mandibular simple fracture could produce good results. In case of mandibular simple fracture, it was recommended with only manual reduction without IMF or IMF during a short period.

Background The utilization of a cone-beam computed tomography (CT)-assisted surgical template allows for predictable results because implant placement plans can be performed in the actual surgery. In order to assess the accuracy of the CT-guided surgery, angular errors and shoulder/apex distance errors were evaluated by data fusion from before and after the placement. Methods Computer-guided implant surgery was performed in five patients with 19 implants. In order to analyze differences of the implant fixture body between preoperative planned implant and postoperative placed implant, angular error and distance errors were evaluated. Results The mean angular errors between the preoperative planned and postoperative placed implant was 3.84° ± 1.49°; the mean distance errors between the planned and placed implants were 0.45 ± 0.48 mm horizontally and 0.63 ± 0.51 mm vertically at the implant neck and 0.70 ± 0.63 mm horizontally and 0.64 ± 0.57 mm vertically at the implant apex for all 19 implants. Conclusions It is important to be able to utilize these methods in actual clinical settings by improving the various problems, including the considerations of patient mouth opening limitations, surgical guide preparation, and fixation.

The purpose of this study was to examine the toothbrushing behavior of the citizens, their use of dentifrice, awareness of the importance of dentifrice purchase and consciousness of dentifrice containing the extract of Chamaecyparis obtusa in the city of Gwangju. It`s basically meant to provide some informations on the development of oral health supplies involving dentifrice containing the extract of Chamaecyparis obtusa in that city in an effort to help the city serve as a hub of the dental industry. The subjects in this study were the selected citizens in the city of Gwangju. As a result of analyzing their awareness of the importance of the considerations for the purchase and use of dentifrice, they gave 68.2% overall. They gave the highest marks of 83.3% to the importance of effect. As for the importance of each item, they gave the highest marks of 85.1% to the importance of the prevention of dental caries. Concerning differences in awareness of the importance of the external purchase factors according to age, every age group placed the most importance on inspection by the certification authorities except for those who were in their 40s and 60s, and the respondents who were in their 40s and 60s attached more importance to price than the other items. Regarding differences in awareness of the importance of effectiveness according to age, those who were under the age of 20 gave the highest marks of 79.8% to the importance of dental-caries prevention and whitening effects. As a result of asking them whether they had an intention to use dentifrice containing the extract of Chamaecyparis obtusa if this dentifrice would be developed, 54.6% replied they had the intention. When they were asked another question whether they thought this dentifrice would have an effect on oral health, 55.1% answered they thought so. 33.8% expected this dentifrice to have a primary effect on the prevention of dental caries. Given the findings of the study, full-scale R&D efforts should be directed into the development of dentifrice containing the extract of chamaecyparis obtusa in the future.

MyD88 is an adapter protein that links toll-like receptors (TLRs) and Interleukin-1 receptors (IL-1Rs) with downstream signaling molecules. The MyD88 has been found to be an essential mediator in the development of osteoarthritis in articular cartilage. However, the role of the MyD88 pathway has yet to be elucidated in the intervertebral disk (IVD). Using in vitro techniques, we analyzed the effect of MyD88 pathway-specific inhibition on the potent inflammatory and catabolic mediator LPS and IL-1 in bovine and human nucleus pulposus (NP) cells by assessing matrix-degrading enzyme expression, including matrix metalloproteases (MMPs) and a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS family). We also analyzed inhibition of MyD88 in the regulation of inducible nitric oxide synthase and TLR-2. Finally, we used an ex vivo organ culture model to assess the effects of MyD88 inhibitor (MyD88i) on catabolic factor-induced disk degeneration in mice lumbar disks. In bovine NP cells, MyD88i potently antagonizes LPS- or IL-1-mediated induction of cartilage-degrading enzyme production, including MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5. MyD88i also attenuates the LPS- or IL-1-mediated induction of iNOS and TLR-2 gene expression. Our ex vivo findings reveal inhibition of MyD88 via counteraction of IL-1-mediated proteoglycan depletion. The findings from this study demonstrate the potent anti-inflammatory and anti-catabolic effects of inhibition of MyD88 pathway inhibition on IVD homeostasis, suggesting a potential therapeutic benefit of a MyD88i in degenerative disk disease in the future.

The purpose of this study was to examine the satisfaction of dental hygiene students receiving dental hygiene education with their major, their view of profession and the correlation between their satisfaction with major and view of profession in an attempt to provide some information on how to teach students to accept the occupation of dental hygienist as a profession. 1. As for satisfaction with major, the dental hygiene students were most satisfied with awareness of dental hygienist, and they were least satisfied with courses. 2. The major satisfaction score was 3.51. The students whose academic standing was higher and who wanted to work in a general hospital or university hospital expressed more satisfaction with their major(p