Smartphone use and schema-based learning in dentomaxillofacial radiology practice: a case report from one College of Dentistry.

OBJECTIVES: This study investigates the students' satisfaction and awareness of competency towards smartphone use and schema-based learning in dental radiology practice. METHODS: Third year students undertaking a dental radiology practicum at a dental school were divided into two groups: one group received traditional clinical training, whereas the other group used smartphones in classes and received new training using schema assignments. At the end of the course, students' satisfaction with the training and self-awareness of their competency were surveyed, and their achievement was assessed. RESULTS: Although students' satisfaction with smartphone-based training was generally high, it was less than that of students trained by traditional instruction. However, most students that received smartphone-based training had higher self-scored competency before than after training. The smartphone group scored higher on true/false or multiple-choice questions, whereas the traditional group scored higher on short-answer questions. CONCLUSIONS: Smartphone education with schema based assignment proved to be attractive in dental radiology, but students showed less satisfaction, and need to meet the requirements of evidence-based practice. Although the full use of smartphone education with schema is not recommended in dental education, we think that it could be try to use as a supplementary approach with traditional didactic method to facilitate student's exploration and self-study to cope with rapid change in educational environment.

BST2 Mediates Osteoblast Differentiation via the BMP2 Signaling Pathway in Human Alveolar-Derived Bone Marrow Stromal Cells.

The molecular mechanisms controlling the differentiation of bone marrow stromal stem cells into osteoblasts remain largely unknown. In this study, we investigated whether bone marrow stromal antigen 2 (BST2) influences differentiation toward the osteoblasts lineage. BST2 mRNA expression in human alveolar-derived bone marrow stromal cells (hAD-BMSCs) increased during differentiation into osteoblasts. hAD-BMSCs differentiation into osteoblasts and the mRNA expression of the bone-specific markers alkaline phosphatase, collagen type α 1, bone sialoprotein, osteocalcin, and osterix were reduced by BST2 knockdown using siRNA. Furthermore, BST2 knockdown in hAD-BMSCs resulted in decreased RUNX2 mRNA and protein expression. We hypothesized that BST2 is involved in differentiation of into osteoblasts via the BMP2 signaling pathway. Accordingly, we evaluated the mRNA expression levels of BMP2, BMP receptors (BMPR1 and 2), and the downstream signaling molecules SMAD1, SMAD4, and p-SMAD1/5/8 in BST2 knockdown cells. BMP2 expression following the induction of differentiation was significantly lower in BST2 knockdown cells than in cells treated with a non-targeting control siRNA. Similar results were found for the knockdown of the BMP2 receptor- BMPR1A. We also identified significantly lower expression of SMAD1, SMAD4, and p-SMAD1/5/8 in the BST2 knockdown cells than control cells. Our data provide the first evidence that BST2 is involved in the osteogenic differentiation of bone marrow stromal cells via the regulation of the BMP2 signaling pathway.

The regulatory mechanism of 4-phenylbutyric acid against ER stress-induced autophagy in human gingival fibroblasts.

Endoplasmic reticulum (ER) stress is closely connected to autophagy. When cells are exposed to ER stress, cells exhibit enhanced protein degradation and form autophagosomes. In this study, we demonstrate that the chemical chaperone, 4-phenylbutyric acid (4-PBA), regulates ER stressinduced cell death and autophagy in human gingival fibroblasts. We found that 4-PBA protected cells against thapsigargin-induced apoptotic cell death but did not affect the reduced cell proliferation. ER stress induced by thapsigargin was alleviated by 4-PBA through the regulation of several ER stress-inducible, unfolded protein response related proteins including GRP78, GRP94, C/EBP homologous protein, phospho-eIF-2α, eIF-2α, phospho-JNK1 (p46) and phospho-JNK2/3 (p54), JNK1, IRE-1α, PERK, and sXBP-1. Compared with cells treated with thapsigargin alone, cells treated with both 4-PBA and thapsigargin showed lower levels of Beclin-1, LC-3II and autophagic vacuoles, indicating that 4-PBA also inhibited autophagy induced by ER stress. This study suggests that 4-PBA may be a potential therapeutic agent against ER stress-associated pathologic situations.

Cytoprotective and anti-inflammatory effects of melatonin in hydrogen peroxide-stimulated CHON-001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway.

Melatonin has potent antioxidant, analgesic, and antinociceptive properties. However, the effects of melatonin against oxidative stress-induced cytotoxicity and inflammatory mediators in human chondrocytes remain poorly understood. This study examined the effects and underlying mechanism of melatonin in hydrogen peroxide (H(2) O(2) )-stimulated human chondrocytes and rabbit osteoarthritis (OA) model. Melatonin markedly inhibited hydrogen peroxide (H(2) O(2) )-stimulated cytotoxicity, iNOS, and COX-2 protein and mRNA expression, as well as the downstream products, NO and PGE(2) . Incubation of cells with melatonin decreased H(2) O(2) -induced Sirtuin 1 (SIRT1) mRNA and protein expression. SIRT1 inhibition by sirtinol or Sirt1 siRNA reversed the effects of melatonin on H(2) O(2) -mediated induction of pro-inflammatory cytokines (NO, PGE(2) , TNF-α, IL-1ß, and IL-8) and the expression of iNOS, COX-2, and cartilage destruction molecules. Melatonin blocked H(2) O(2) -induced phosphorylation of PI3K/Akt, p38, ERK, JNK, and MAPK, as well as activation of NF-κB, which was reversed by sirtinol and SIRT1 siRNA. In rabbit with OA, intra-articular injection of melatonin significantly reduced cartilage degradation, which was reversed by sirtinol. Taken together, this study shows that melatonin exerts cytoprotective and anti-inflammatory effects in an oxidative stress-stimulated chondrocyte model and rabbit OA model, and that the SIRT1 pathway is strongly involved in this effect.

4-phenylbutyric Acid Regulates Collagen Synthesis and Secretion Induced by High Concentrations of Glucose in Human Gingival Fibroblasts.

High glucose leads to physio/pathological alterations in diabetes patients. We investigated collagen production in human gingival cells that were cultured in high concentrations of glucose. Collagen synthesis and secretion were increased when the cells were exposed to high concentrations of glucose. We examined endoplasmic reticulum (ER) stress response because glucose metabolism is related to ER functional status. An ER stress response including the expression of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), inositol requiring enzyme alpha (IRE-1α) and phosphoreukaryotic initiation factor alpha (p-eIF-2α) was activated in the presence of high glucose. Activating transcription factor 4 (ATF-4), a downstream protein of p-eIF-2α as well as a transcription factor for collagen, was also phosphorylated and translocalized into the nucleus. The chemical chaperone 4-PBA inhibited the ER stress response and ATF-4 phosphorylation as well as nuclear translocation. Our results suggest that high concentrations of glucose-induced collagen are linked to ER stress and the associated phosphorylation and nuclear translocation of ATF-4.

Isoliquiritigenin 2'-methyl ether induces growth inhibition and apoptosis in oral cancer cells via heme oxygenase-1.

We previously reported that a chloroform extract of Caesalpinia sappan L. induces apoptosis in oral cancer cells but not in normal epithelial cell lines. In the present study, we explored the effects of a single compound isolated from C. sappan heartwood, isoliquiritigenin 2'-methyl ether (ILME), on cultured primary and metastatic oral cancer cell lines using MTT assays, fluorescence microscopy, flow cytometry, and Western blotting. ILME inhibited the growth of the oral cancer cells in a time- and dose-dependent manner. The major mechanism of growth inhibition was apoptosis induction, as shown by flow cytometric analysis of sub-G(1)-phase arrest and by annexin V-FITC and propidium iodide staining. ILME time-dependently activated NF-kappaB transcription factors, phospholated the MAP kinases JNK (c-Jun N-terminal kinase) and ERK (extracellular signal-regulated kinase). Furthermore, ILME treatment upregulated HO-1 expression though activation of Nrf2 (NF-E2-related factor 2) pathway, and induced the expression of heme oxygenase-1 (HO-1). Tin protoporphyrin, an HO-1 inhibitor, dose-dependently attenuated the growth-inhibitory effect of ILME and blocked ILME-induced expression of the p21 and p53 cell cycle-regulatory proteins. These results provide the first evidence that the anti-oral cancer effects of ILME may involve a mechanism in which HO-1 is upregulated via a pathway involving MAP kinases, NF-kappaB, and Nrf2. Thus, ILME could be considered to be a potential chemotherapeutic target for anti-oral cancer treatment strategies.

Iron chelator differentially activates macrophage inflammatory protein-3alpha/CCL20 in immortalized and malignant human oral keratinocytes.

Macrophage inflammatory protein-3alpha (MIP-3alpha or CCL20) is an intriguing molecule in cancer immunotherapy, but MIP-3alpha expression and signalling are not well understood in oral cancer cells. We investigated CCL20 expression and signal transduction by treating immortalized human oral keratinocyte (IHOK) and oral cancer (HN4) cells with deferoxamine (DFO) and examined the mRNA expression of CCL20 using RT-PCR and ELISA. IHOK and HN4 cells treated with DFO showed increased mRNA and protein expression of CCL20, and the upregulation of DFO-induced CCL20 expression was higher in IHOK cells than in HN4 cells. Selective inhibitors of p38 and ERK1/2 abolished DFO-induced CCL20 expression in both IHOK and HN12 cells, and p38 and ERK1/2 inhibitors prevented DFO-induced degradation of I-kappaB and NF-kappaB activation. Activation of c-fos and c-jun also occurred following DFO treatment in IHOK and HN4 cells. Collectively, these results suggest that DFO-induced MIP-3alpha, which is involved in the MAP kinase, c-fos, c-jun, and NF-kappaB pathways, may be an important mediator of the antitumour immune response in oral keratinocytes and warrants consideration as a target molecule for oral cancer treatment.

Anti-cancer activity of highly purified sulfur in immortalized and malignant human oral keratinocytes.

Sulfur is commonly used in Asia as an herbal medicine to treat inflammation and cancer, and potent chemopreventive effects have been demonstrated in various in vivo and in vitro models for sulfur-containing compounds found in naturally occurring products. Here, we report the growth inhibitory and apoptosis-related effects of a newly developed highly purified sulfur (HPS) on immortalized human oral keratinocytes (IHOKs) and on oral cancer cells representing two stages of oral cancer (HN4, HN12) based on a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Western blotting, cell cycle analysis, and nuclear staining. The purity of the sulfur preparation was verified by high-performance liquid chromatography. HPS inhibited the proliferation of immortalized and malignant oral keratinocytes in a dose- and time-dependent manner. FITC-annexin V staining, DNA fragmentation testing, and Hoechst 33258 staining revealed that HPS inhibited cell growth via apoptosis. HPS increased the sub-G1 cell cycle fraction, with decreased expression of cyclins D1, D2, and E and their activating partners cdk2, cdk4, and cdk6, and a concomitant induction of p53 and p21/WAF1. Furthermore, HPS treatment increased the cytosolic level of cytochrome c and resulted in caspase-3 activation; this effect was correlated with Bax up-regulation and Bcl-2 down-regulation. Thus, these data suggest that HPS is a potential candidate for anti-cancer therapy in oral cancer.