Innovation of dental education system for researcher, dentist, dental hygienist and dental technician in Hiroshima University

Hiroshima University Faculty of Dentistry's goal is to become the worldwide research and education center in Dentistry. It seems to constitute the dental education by two missions: core and characteristic. Hiroshima University Faculty of Dentistry has clarified their characteristic mission and improved dental education system to reinforce the innovative part of the education. We started two programs to cultivate researchers/educators who will be a world-wide leader of dental research and education in addition to excellent dental practitioners, the frontier dental science course and the advanced dental clinician course in 2000. The students who completed new education system gave good score to the frontier dental science. The basic clinical knowledge level of students is the same between two courses before starting clinical training. Hiroshima University Faculty of Dentistry had School for Dental Hygienists and Dental Technicians School. These two schools are integrated and reorganized to the School of Oral Health Science in 2005. Hiroshima University firstly established the School of Oral Health Science with four-year programs for dental hygienists and dental technicians in Japan. The liberal arts education is reinforced in both four-year programs. The purpose of our four-year program in oral health science is to cultivate educators in dental hygienists school, researchers in Universities, and nursing teachers who work sickbay of elementary or junior high school. The purpose of our four-year program in oral health engineering is to cultivate educators in dental technicians school and researchers in Universities or dental materials/products companies in addition to excellent dental technicians

Microbe-Dependent Exacerbated Alveolar Bone Destruction in Heterozygous Cherubism Mice

Cherubism (OMIM#118400) is a craniofacial disorder characterized by destructive jaw expansion. Gain‐of‐function mutations in SH3‐domain binding protein 2 (SH3BP2) are responsible for this rare disorder. We have previously shown that homozygous knock‐in (KI) mice (Sh3bp2 KI/KI) recapitulate human cherubism by developing inflammatory lesions in the jaw. However, it remains unknown why heterozygous KI mice (Sh3bp2 KI/+) do not recapitulate the excessive jawbone destruction in human cherubism, even though all mutations are heterozygous in humans. We hypothesized that Sh3bp2 KI/+ mice need to be challenged for developing exacerbated jawbone destruction and that bacterial stimulation in the oral cavity may be involved in the mechanism. In this study, we applied a ligature‐induced periodontitis model to Sh3bp2 KI/+ mice to induce inflammatory alveolar bone destruction. Ligature placement induced alveolar bone resorption with gingival inflammation. Quantification of alveolar bone volume revealed that Sh3bp2 KI/+ mice developed more severe bone loss (male: 43.0% ± 10.6%, female: 42.6% ± 10.4%) compared with Sh3bp2 +/+ mice (male: 25.8% ± 4.0%, female: 30.9% ± 6.5%). Measurement of bone loss by the cement‐enamel junction–alveolar bone crest distance showed no difference between Sh3bp2 KI/+ and Sh3bp2 +/+ mice. The number of osteoclasts on the alveolar bone surface was higher in male Sh3bp2 KI/+ mice, but not in females, compared with Sh3bp2 +/+ mice. In contrast, inflammatory cytokine levels in gingiva were comparable between Sh3bp2 KI/+ and Sh3bp2 +/+ mice with ligatures. Genetic deletion of the spleen tyrosine kinase in myeloid cells and antibiotic treatment suppressed alveolar bone loss in Sh3bp2 KI/+ mice, suggesting that increased osteoclast differentiation and function mediated by SYK and accumulation of oral bacteria are responsible for the increased alveolar bone loss in Sh3bp2 KI/+ mice with ligature‐induced periodontitis. High amounts of oral bacterial load caused by insufficient oral hygiene could be a trigger for the initiation of jawbone destruction in human cherubism

RUNX3 Has an Oncogenic Role in Head and Neck Cancer

Background: Runt-related transcription factor 3 (RUNX3) is a tumor suppressor of cancer and appears to be an important component of the transforming growth factor-beta (TGF-ß)-induced tumor suppression pathway. Surprisingly, we found that RUNX3 expression level in head and neck squamous cell carcinoma (HNSCC) tissues, which is one of the most common types of human cancer, was higher than that in normal tissues by a previously published microarray dataset in our preliminary study. Therefore, here we examined the oncogenic role of RUNX3 in HNSCC. Principal Findings: Frequent RUNX3 expression and its correlation with malignant behavior were observed in HNSCC. Ectopic RUNX3 overexpression promoted cell growth and inhibited serum starvation-induced apoptosis and chemotherapeutic drug induced apoptosis in HNSCC cells. These findings were confirmed by RUNX3 knockdown. Moreover, RUNX3 overexpression enhanced tumorsphere formation. RUNX3 expression level was well correlated with the methylation status in HNSCC cells. Moreover, RUNX3 expression was low due to the methylation of its promoter in normal oral epithelial cells. Conclusions/Significance: Our findings suggest that i) RUNX3 has an oncogenic role in HNSCC, ii) RUNX3 expression observed in HNSCC may be caused in part by demethylation during cancer development, and iii) RUNX3 expression can b

RUNX3 Has an Oncogenic Role

Background: Runt-related transcription factor 3 (RUNX3) is a tumor suppressor of cancer and appears to be an important component of the transforming growth factor-beta (TGF-ß)-induced tumor suppression pathway. Surprisingly, we found that RUNX3 expression level in head and neck squamous cell carcinoma (HNSCC) tissues, which is one of the most common types of human cancer, was higher than that in normal tissues by a previously published microarray dataset in our preliminary study. Therefore, here we examined the oncogenic role of RUNX3 in HNSCC. Principal Findings: Frequent RUNX3 expression and its correlation with malignant behavior were observed in HNSCC. Ectopic RUNX3 overexpression promoted cell growth and inhibited serum starvation-induced apoptosis and chemotherapeutic drug induced apoptosis in HNSCC cells. These findings were confirmed by RUNX3 knockdown. Moreover, RUNX3 overexpression enhanced tumorsphere formation. RUNX3 expression level was well correlated with the methylation status in HNSCC cells. Moreover, RUNX3 expression was low due to the methylation of its promoter in normal oral epithelial cells. Conclusions/Significance: Our findings suggest that i) RUNX3 has an oncogenic role in HNSCC, ii) RUNX3 expression observed in HNSCC may be caused in part by demethylation during cancer development, and iii) RUNX3 expression can be a useful marker for predicting malignant behavior and the effect of chemotherapeutic drugs in HNSCC

Expression levels of novel cytokine IL-32 in periodontitis and its role in the suppression of IL-8 production by human gingival fibroblasts stimulated with Porphyromonas gingivalis

Background:IL-32 was recently found to be elevated in the tissue of rheumatoid arthritis and inflammatory bowel disease. Periodontitis is a chronic inflammatory disease caused by polymicrobial infections that result in soft tissue destruction and alveolar bone loss. Although IL-32 is also thought to be associated with periodontal disease, its expression and possible role in periodontal tissue remain unclear. Therefore, this study investigated the expression patterns of IL-32 in healthy and periodontally diseased gingival tissue. The expression of IL-32 in cultured human gingival fibroblasts (HGF) as well as effects of autocrine IL-32 on IL-8 production from HGF were also examined.Methods:Periodontal tissue was collected from both healthy volunteers and periodontitis patients, and immunofluorescent staining was performed in order to determine the production of IL-32. Using real-time PCR and ELISA, mRNA expression and protein production of IL-32 in HGF, stimulated by Porphyromonas gingivalis (Pg), were also investigated.Results:Contrary to our expectation, the production of IL-32 in the periodontitis patients was significantly lower than in the healthy volunteers. According to immunofluorescent microscopy, positive staining for IL-32 was detected in prickle and basal cell layers in the epithelium as well as fibroblastic cells in connective tissue. Addition of fixed Pg in vitro was found to suppress the otherwise constitutive expression of IL-32 mRNA and protein in HGF. However, recombinant IL-32 in vitro inhibited the expression of IL-8 mRNA by HGF stimulated with Pg. Interestingly, anti-IL-32 neutralizing antibody upregulated the IL-8 mRNA expression in non-stimulated HGF, indicating that constitutive expression of IL-32 in HGF suppressed IL-8 mRNA expression in the absence of bacterial stimulation.Conclusion:These results indicate that IL-32 is constitutively produced by HGF which can be suppressed by Pg and may play a role in the downregulation of inflammatory responses, such as IL-8 production, in periodontal tissue

Induction of functional xeno-free MSCs from human iPSCs via a neural crest cell lineage

iPS細胞から間葉系幹細胞の誘導方法を確立 --動物由来成分を含まず再生医療への利用に期待. 京都大学プレスリリース. 2022-09-15.A new method for inducing mesenchymal stem cells from iPS cells without using animal-derived components. 京都大学プレスリリース. 2022-09-27.Mesenchymal stem/stromal cells (MSCs) are adult multipotent stem cells. Here, we induced MSCs from human induced pluripotent stem cells (iPSCs) via a neural crest cell (NCC) lineage under xeno-free conditions and evaluated their in vivo functions. We modified a previous MSC induction method to work under xeno-free conditions. Bovine serum albumin-containing NCC induction medium and fetal bovine serum-containing MSC induction medium were replaced with xeno-free medium. Through our optimized method, iPSCs differentiated into MSCs with high efficiency. To evaluate their in vivo activities, we transplanted the xeno-free-induced MSCs (XF-iMSCs) into mouse models for bone and skeletal muscle regeneration and confirmed their regenerative potency. These XF-iMSCs mainly promoted the regeneration of surrounding host cells, suggesting that they secrete soluble factors into affected regions. We also found that the peroxidasin and IGF2 secreted by the XF-iMSCs partially contributed to myotube differentiation. These results suggest that XF-iMSCs are important for future applications in regenerative medicine

Alveolar bone protection by targeting the SH3BP2-SYK axis in osteoclasts

Periodontitis is a bacterially induced chronic inflammatory condition of the oral cavity where tooth-supporting tissues including alveolar bone are destructed. Previously, we have shown that the adaptor protein SH3-domain binding protein 2 (SH3BP2) plays a critical role in inflammatory response and osteoclastogenesis of myeloid lineage cells through spleen tyrosine kinase (SYK). In this study, we show that SH3BP2 is a novel regulator for alveolar bone resorption in periodontitis. Micro-CT analysis of SH3BP2-deficient (Sh3bp2 -/- ) mice challenged with ligature-induced periodontitis revealed that Sh3bp2 -/- mice develop decreased alveolar bone loss (male 14.9% ± 10.2%; female 19.0% ± 6.0%) compared with wild-type control mice (male 25.3% ± 5.8%; female 30.8% ± 5.8%). Lack of SH3BP2 did not change the inflammatory cytokine expression and osteoclast induction. Conditional knockout of SH3BP2 and SYK in myeloid lineage cells with LysM-Cre mice recapitulated the reduced bone loss without affecting both inflammatory cytokine expression and osteoclast induction, suggesting that the SH3BP2-SYK axis plays a key role in regulating alveolar bone loss by mechanisms that regulate the bone-resorbing function of osteoclasts rather than differentiation. Administration of a new SYK inhibitor GS-9973 before or after periodontitis induction reduced bone resorption without affecting inflammatory reaction in gingival tissues. In vitro, GS-9973 treatment of bone marrow-derived M-CSF-dependent macrophages suppressed tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation with decreased mineral resorption capacity even when GS-9973 was added after RANKL stimulation. Thus, the data suggest that SH3BP2-SYK is a novel signaling axis for regulating alveolar bone loss in periodontitis and that SYK can be a potential therapeutic target to suppress alveolar bone resorption in periodontal diseases

Application of mesenchymal stem cells (MSC) to regenerative dentistry and identification of molecular markers for MSC

We characterized human bone marrow-derived mesenchymal stem cells (MSC) by identification of molecular markers and used these markers in clinical studies for treatment of periodontal disease: Auto-transplantation of MSC into periodontal defects enhanced regeneration of cementum, periodontal ligament and alveolar bone. Stem cell therapy could be a new frontier in dentistry

Diseño de sistema de alcantarillado sanitario y ampliación del sistema de agua potable del Barrio Villa Vallarta en la Ciudad de Managua

El presente estudio monográfico denominado "DISEÑO DEL SISTEMA DE ALCANTARILLADO SANITARIO Y AMPLIACIÓN DEL SISTEMA DE AGUA POTABLE EN EL BARRIO VILLA VALLARTA'', tiene como propósito mejorar las condiciones higiénico-sanitarias de la población, djsminuir el índice de mortalidad infantil y promover cambios de comportamientos en los miembros de las familias beneficiadas, para que mejoren su nivel de vida. EI Barrio Villa Vallarta se encuentra ubicado en la parie Nor-Este de la ciudad de Managua, localizándose en la zona alta del Acueducto de Managua; específicamente está ubicado en el Distrito No. Vl de la municipalidad de Managua. Se caracteriza por ser una zona de alta densidad debido que en dicho Barrio se encuentran construcciones sencillas y lotes con dimensiones y áreas homogéneas, de aproximadamente | 05 m2. Esta conformado por 393 viviendas,13 manzanas, 9 calles y 3 avenidas, alcanzando un área total de aproximadamente 67, 327.81 m2, incluyendo calles, avenidas y un área comunal de 1,575.45 m2 La calles miden aproximadamente 750.45 m2 Para formular el estudio monográfico, primeramente se realizó un diagnóstico situacional a través de ntrevistas y encuesta dirigidas. a funcionarios, líderes comunales y familias del Barrio. Posteriormente se efectuará el estudio topográfico y el estudio de suelo para conocer las características del terreno y la clasificación o tipo de suelo que predomina en el Barrio. Además se realizó la valoración del Sistema de Alcantarillado Sanitario y Sistema de Agua Potable existente