Therapeutic Effect of HDAC5 Binding and Cell Penetrating Peptide for the Treatment of Inflammatory Bowel Disease

BACKGROUND@#Inflammatory bowel disease (IBD) is an incurable disease that negatively influences the quality of life of patients. Current and emerging therapies target proinflammatory cytokines and/or receptors to downregulate proinflammatory responses, but insufficient remission requires other therapeutic agents. Herein, we report that the synthetic antiinflammatory peptide 15 (SAP15) is capable of cell penetration and anti-inflammatory activity in human macrophages. @*METHODS@#SAP15 was labeled with fluorescence and administered to human leukemia monocytic cells (THP-1) cells for cell penetration analysis. Using biolayer interferometry analysis, the binding affinity of SAP15 with histone deacetylase 5 (HDAC5) was measured. SAP15-treated THP-1 cells were analyzed by protein phosphorylation assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In addition, in vivo analysis of the therapeutic effect on IBD was observed in a dextran sulfate sodium (DSS)-induced model. Samples from SAP15-treated mice were analyzed at both the macroscopic and microscopic levels using ELISA, myeloperoxidase (MPO) assays, and histological evaluations. @*RESULTS@#SAP15 was internalized within the cytosol and nucleus of THP-1 cells and bound to the HDAC5 protein. SAP15-treated macrophages were assessed for protein phosphorylation and showed inhibited phosphorylation of HDAC5 and other immune-related proteins, which led to increased M2-like macrophage markers and decreased M1-like macrophage markers and tumor necrosis factor-a and interleukin-6 cytokine levels. The SAP15 treatment on IBD model showed significant recovery of colon length. Further histological analysis of colon demonstrated the therapeutic effect of SAP15 on mucosal layer. Moreover, proinflammatory cytokine levels and MPO activity from the plasma show that SAP15 is effective in reduced proinflammatory responses. @*CONCLUSION@#These findings suggest that SAP15 is a novel peptide with a novel cell-penetrating peptide with antiinflammatory property that can be used as a therapeutic agent for IBD and other inflammatory diseases.

The clinical effects of a hydroxyapatite containing toothpaste for dentine hypersensitivity / 대한치주과학회지

PURPOSE: The aim of this study was to compare the effectiveness of hydroxyapatite containing toothpaste with positive control toothpastes in reducing dentine hypersensitivity. MATERIALS AND METHODS: This clinical trial was a double-blind, randomized, parallel group comparison of two, namely hydroxyapatite containing toothpaste and strontium chloride containing toothpaste. A total of 55 subjects were included in this study. The subjects were given randomly assigned one of the two toothpastes after received tooth brushing instruction at baseline. Some clinical indices(PI, GI, PD), verbal rating score(VRS) for sensitivity to stimulus, the effect in relieving sensitivity and visual analogue scale(VAS) for sensitivity at baseline, week 2, week 4 and week 8 were assessed. All data were evaluated by intention-to-treat analysis. RESULTS: Overall, PI and GI scores were significantly reduced compare baseline in all groups(p0.05). CONCLUSION: This study demonstrated that the new hydroxyapatite containing toothpaste was similarly effective in reducing dentine hypersensitivity with pre-existing benchmark toothpaste.

Effects of enamel matrix derivatives on biologic activities of human periodontal fibloblasts to demineralized root surface / 대한치주과학회지

PURPOSE: The aim of this study was to investigate the effects of EMD on demineralized root surface using human periodontal ligament cells and compare the effects of root conditioning materials(tetracycline(TCN), EDTA). MATERIAL AND METHODS: Dentin slices were prepared from the extracted teeth and demineralized with TCN and EDTA. Demineralized dentin slices were incubated at culture plate with 25, 50 and 100 microgram/ml concentration of EMD. Cell attachment, alkaline phosphatase activity test, protein synthesis assay and scanning electronic microscopic examination were done. RESULTS: Cells were attached significantly higher in EMD treated group at 7 and 14 days. Cell numbers were significantly higher in EMD treated group. Alkaline phosphatase activity was significantly higher in EMD treated group at 7 and 14 days. Protein synthesis was significantly higher in EMD treated group at 7 and 14 days. CONCLUSION: Enamel matrix derivatives enhance the biologic activities of human periodontal ligament cells on demineralized root surface and its effects are dependent on the concentration of EMD.

Change of plaque removal ability by worn toothbrush / 대한치주과학회지

No abstract available.

studies of Osseointegrated Implant-Models on Stress Distribution / 대한치과보철학회지

Finite element analyses were performed to study effects on stress distribution generated in jaw bone for various shapes of dental implants: plateau type, plateau with small radius of curvature, triangular thread screw type in accordance with ISO regulations and square thread screw filleted with small radius partially. It was found that square thread screw filleted with small radius was more effective on stress distribution than other dental implants used in analyses. Additional analyses were performed on the implant with square thread screw filleted with small radius for verying design parameters, such as the width of thread end, the height of the thread of the implant and load direction, to determine the optimum dimensions of the implant. The highest stress concentration occurred at the region in jaw bone adjacent to the first thread of the implant. The maximum effective stress induced by a 15 degree oblique load of 100 N was twice as high as the maximum effective stress caused by an equal amount of vertical load. Stress distribution was more effective in the case when the width of thread end and the height of thread were p/2 and 0.46p, respectively, where p is the pitch of thread. At last, using tensile force calculated from the possible insert torque without breading bone thread, finite element analysis was performed on the implant to calculate pre-stress when the primary fixation of the implant was operated in jaw bone. The maximum effective stress was 136.8 MPa which proven to be safe.

Development of moldable bone regenerating therapeutics using partially purified porcine bone morphogenetic protein and bioresorbable polymer

The purpose of this study was to develop an osteogenic, biodegradable material using polymer and BMP. It was designed to have structural function and be moldable, for the reconstruction of load bearing areas and deformities of various configurations. Bone apatite was added to Poly(L-lactide)(PLLA) and made porous for osteoconductability and ease of BMP loading. The materials, with or without BMP purified from porcine bone matrix, were evaluated in cranial bone defect models in rats for biocompatibility and bone regeneration capability. The following results were obtained: The PLLA-BMP material with BMP added to the polymer showed 30% healing of cranial bone defects in rats during the 2 weeks to 3 months period of observation. The moldable PLLA agent without BMP also showed 25% bone healing capacity. Although new bone formation was incomplete in the critical size defect of rat cranium, it can be concluded that the unique moldability of those agents makes them useful for the reconstruction of various bone defects and maxillofacial deformities.

Guided Bone Regeneration with a PDGF-BB-loaded Resorbable Membrane in the Dehisced Implant of the Beagle Dog / 대한치주과학회지

4 beagle dogs aged over one and half years and weighed 15 to 16 Kg were utilized in this study. Experimental dehiscent defects were made in the mandibular edentulous area after removal of lower premolar. e-PTFE membrane resorbable membrane, and PDGF-BB-loaded resorbable membrane were covered at the dehiscent defects around the dental implants respectively. Animal was sacrificed at 1, 2, 3 months respectively. Non-decalicifed specimens were made and mutiple-stained for light microscopic study. The results were as follows: 1. Dehiscent defects around the implant installed in the beagle dog were an excellent defect model for studying guided bone regeneration. 2. Fibroblasts penetrated into expanded-PTFE membrane was observed and inflammatory cell infiltration was also observed around the membrane. 3. Resorbable membrane was degradaded and resorbed at 1 month after application to the dehiscent defect. Though multinucleated giant cells were observed adjacent to the membrane, that had no reverse effect on the bone regeneration. 4. PDGF-BB-loaded resorbable membrane was same capability as the resorbable membrane and e-PTFE membrane in the guided bone regeneration. 5. PDGF-BB-loaded resorbable membrane-applied site was better than resorbable membrane-applied site in the speed and maturity of bone formation. Within the above results, it was suggested that PDGF-BB-loaded resorbable membrane might have same bone regeneration capacity as nonresorbable membrane in the dehisced implant of the beagle dog and potentiality to use in human subjects.

The factors related with the failure in GBR and GTR technique / 대한치주과학회지

Using barrier membrane, guided bone regeneration(GBR) and guided tissue regeneration(GTR) of periodontal tissue are now widely studied and good results were reported. In bone regeneration, not all cases gained good results and in some cases using GTR, bone were less regenerated than that of control. The purpose of this study is to search for the method to improve the success rate of GBR and GTR by examination of the cause of the failure. For these study, rats and beagle dogs were used. In rat study, 5mm diameter round hole was made on parietal bone of the rat and 10mm diameter of bioresorbable membrane was placed on the bone defects and sutured. In 1, 2, 4 weeks later, the rats were sacrificed and Masson-Trichrome staining was done and inspected under light microscope for guided bone regeneration. In dog study, 3x4mm2 Grade III furcation defect was made at the 3rd and 4th premolar on mandible of 6 beagle dogs. The defects were covered by bioresorbable membrane extending 2-3mm from the defect margin. The membrane was sutured and buccal flap was covered the defect perfectly. In 2, 4, 8 weeks later, the animals were sacrificed and undecalcified specimens were made and stained by multiple staining method. In rats, there was much amount of new bone formation at 2 weeks, and in 4 weeks specimen, bony defect was perfectly closed and plenty amount of new bone marrow was developed. In some cases, there were failures of guided bone regeneration. In beagle dogs, guided tissue regeneration was incomplete when the defect was collapsed by the membrane itself and when the rate of resorption was so rapid than expected. The cause of the failure in GBR and GTR procedure is that 1) the membrane was not tightly seal the bony defects. If the sealing was not perfect, fibrous connective tissue infiltrate into the defect and inhibit the new bone formation and regeneration. 2) the membrane was too tightly attached to the tissue and then there was no space to be regenerated. In conclusion, the requirements of the membrane for periodontal tissue and bone regeneration are the biocompatibility, degree of sealingness, malleability, space making and manipulation. In this animal study, space making for new bone and periodontal ligament, and sealing the space might be the most important point for successful accomplishment of GBR and GTR.

Effects of Ethanolic Extracts of Scutellaria Radix on the alveolar bone formation in the extract socket of rat / 대한치주과학회지

The purpose of this study was to evaluate the effects of ethanolic extracts of Scutellaria Radix on the alveolar bone formation in the extract socket of rat. Thirty-six Sprague-dawley rats were used in this study. Mean body weight of rat was 130+/-5g. Experimental animal were administered 0.4% beta-aminopropionitril(Sigma, USA) with the solid commercial food for 5 days. All the maxillary 1st molar of the rats were extracted by using of the tissue forcep under the general anesthesia with Pentobarbital sodium(Tokyo Chemical Co., Japan) injection into intraperitoneal space. All the extracted rats were divided into two group, experimental group which were feeded the solid food mixed ethanolic extracts of Scutellaria Radix, and control group which were feeded same food without reagent. At 1, 3, 5, 7, 9 and 14th days after tooth extraction, rats in both groups were serially sacrificed respectively. All the specimen were treated as usual method and prepared Hematoxylin-eosin stain for the light microscopic observation. The results were as follows : 1. Bone formation of extracted socket starts from the area on remained periodontal ligament than other area. 2. In the case of administration of the extracted Scutellaria Radix showed rapid healing process of connective tissue than non-administrated group. 3. In the case of administration of the extracted Scutellaria Radixshowed rapid osteogenesis than non-administrated With above results, it was concluded that ethanolic extracts of Scutellaria Radix may play a favorable role on the healing process of exatraction socket after extraction in rats. It was suggested that further study to evaluate the different concentration and administration method of ethanolic extracts of the Scutellaria Radix into same experimental model.