The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin’s but not resveratrol’s anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.
Activating Transcription Factor 3 ; Adipocytes ; Adiponectin ; Adipose Tissue, White ; Animals ; Diet* ; Insulin Resistance ; Metabolic Diseases* ; Mice ; Mice, Obese* ; Microarray Analysis ; Obesity* ; RNA, Messenger

PURPOSE: The purpose of the present study was to validate an experimental model for assessing tissue integration of titanium and zirconia implants with and without buccal dehiscence defects. METHODS: In 3 dogs, 5 implants were randomly placed on both sides of the mandibles: 1) Z1: a zirconia implant (modified surface) within the bony housing, 2) Z2: a zirconia implant (standard surface) within the bony housing, 3) T: a titanium implant within the bony housing, 4) Z1_D: a Z1 implant placed with a buccal bone dehiscence defect (3 mm), and 5) T_D: a titanium implant placed with a buccal bone dehiscence defect (3 mm). The healing times were 2 weeks (one side of the mandible) and 6 weeks (the opposite side). RESULTS: The dimensions of the peri-implant soft tissue varied depending on the implant and the healing time. The level of the mucosal margin was located more apically at 6 weeks than at 2 weeks in all groups, except group T. The presence of a buccal dehiscence defect did not result in a decrease in the overall soft tissue dimensions between 2 and 6 weeks (4.80±1.31 and 4.3 mm in group Z1_D, and 4.47±1.06 and 4.5±1.37 mm in group T_D, respectively). The bone-to-implant contact (BIC) values were highest in group Z1 at both time points (34.15%±21.23% at 2 weeks, 84.08%±1.33% at 6 weeks). The buccal dehiscence defects in groups Z1_D and T_D showed no further bone loss at 6 weeks compared to 2 weeks. CONCLUSIONS: The modified surface of Z1 demonstrated higher BIC values than the surface of Z2. There were minimal differences in the mucosal margin between 2 and 6 weeks in the presence of a dehiscence defect. The present model can serve as a useful tool for studying peri-implant dehiscence defects at the hard and soft tissue levels.
Animals ; Dental Implants ; Dogs ; Housing ; Mandible ; Models, Theoretical ; Mouth Mucosa ; Osseointegration ; Surface Properties ; Titanium

PURPOSE: The aim of this study was to determine the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded synthetic bone substitute on implants that were simultaneously placed with sinus augmentation in rabbits. METHODS: In this study, a circular access window was prepared in the maxillary sinus of rabbits (n=5) for a bone graft around an implant (Ø 3×6 mm) that was simultaneously placed anterior to the window. Synthetic bone substitute loaded with rhBMP-2 was placed on one side of the sinus to form the experimental group, and saline-soaked synthetic bone substitute was placed on the other side of the sinus to form the control group. After 4 weeks, sections were obtained for analysis by micro-computed tomography and histology. RESULTS: Volumetric analysis showed that the median amount of newly formed bone was significantly greater in the BMP group than in the control group (51.6 mm3 and 46.6 mm3, respectively; P=0.019). In the histometric analysis, the osseointegration height was also significantly greater in the BMP group at the medial surface of the implant (5.2 mm and 4.3 mm, respectively; P=0.037). CONCLUSIONS: In conclusion, an implant simultaneously placed with sinus augmentation using rhBMP-2-loaded synthetic bone substitute can be successfully osseointegrated, even when only a limited bone height is available during the early stage of healing.
Bone Substitutes* ; Collagen ; Dental Implants ; Humans ; Maxillary Sinus ; Osseointegration ; Rabbits* ; Sinus Floor Augmentation ; Transplants

PURPOSE: The aim of this pilot study was to determine the osteoconductivity and dimensional stability of augmented sinuses using different ratios of biphasic calcium phosphate (BCP) in a rabbit sinus model. METHODS: Each sinus of New Zealand white rabbits (2.5-3.5 kg) was assigned to one of two groups: BCP with a hydroxyapatite to beta-tricalcium phosphate (HA:beta-TCP) ratio of 70:30 (group TCP30) and BCP with an HA:beta-TCP ratio of 30:70 (group TCP70). After preparing a window in the antral wall of a sinus, the Schneiderian membrane was elevated, and the applicable material was grafted. A fluorochrome calcein green was injected five days before euthanizing the animals at four months post-surgery. The specimens were analyzed histologically, histomorphometrically, and by using micro-computed tomography (micro-CT). RESULTS: Micro-CT analysis revealed that the total augmented volume and the new bone volume did not differ significantly between the two groups whereas the resorption of materials was greater in the TCP70 group. The trabecular thickness, number, and separation also did not differ significantly between the two groups. Histomorphometrically, the areas of total augmentation, new bone, and residual material, as well as the ratio of new-bone-material contact did not differ significantly between the groups. Histologically, the residual particles were more scattered in the TCP70 group than in the TCP30 group. The fluorescence of the calcein green did not differ notably between the two groups. CONCLUSIONS: The osteoconductivity and dimensional stability of the two BCPs with different ratios tested in this study were comparable after four months of healing. Therefore, we conclude that both BCPs show promise as a bone substitute for sinus augmentation.
Animals ; Bone Regeneration ; Bone Substitutes ; Calcium* ; Durapatite ; Fluorescence ; Nasal Mucosa ; Pilot Projects* ; Rabbits ; Transplants

PURPOSE: Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. MATERIALS AND METHODS: Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. RESULTS: Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. CONCLUSION: In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.
Animals ; Anoxia ; Cell Death ; Cell Survival ; Colonic Neoplasms ; DNA Nucleotidylexotransferase ; In Vitro Techniques ; Mice ; Nanoparticles* ; Radiotherapy* ; Reactive Oxygen Species ; Silicon Dioxide

Lower extremity deep vein thrombosis is a serious medical condition that can result in death or major disability due to pulmonary embolism or post-thrombotic syndrome. Appropriate diagnosis and treatment are required to improve symptoms and salvage the affected limb. Early thrombus clearance rapidly resolves symptoms related to venous obstruction, restores valve function and reduces the incidence of post-thrombotic syndrome. Recently, endovascular treatment has been established as a standard method for early thrombus removal. However, there are a variety of views regarding the indications and procedures among medical institutions and operators. Therefore, we intend to provide evidence-based guidelines for diagnosis and treatment of lower extremity deep vein thrombosis by multidisciplinary consensus. These guidelines are the result of a close collaboration between interventional radiologists and vascular surgeons. The goals of these guidelines are to improve treatment, to serve as a guide to the clinician, and consequently to contribute to public health care.
Consensus ; Cooperative Behavior ; Diagnosis* ; Extremities ; Incidence ; Lower Extremity* ; Methods ; Public Health ; Pulmonary Embolism ; Surgeons ; Thrombosis ; Venous Thrombosis*

The authors recently found a mistake in their previously published article and sincerely regret these errors.

PURPOSE: Decision-making by dental and medical experts can be influenced by their biases, interests, and experiences, and academic arguments about controversial issues may additionally be considered indirect experiences capable of affecting decision-making. This study reports on the use of interactive communication devices to evaluate preferences and flexibility in decision-making among dental care providers who attended two distinct academic conferences. METHODS: Two debates were presented by a team of two lecturers at two academic conferences (focusing on periodontology and implant dentistry, respectively) and the audience members of each session were surveyed. Before each lecture, two case modules about the diagnosis and treatment of multirooted molar lesions were provided, and interactive communication devices were used to collect responses about decision-making preferences in treatment planning immediately before and after a debate about treatment strategies. RESULTS: In total, 81 and 84 completed answers from both conferences were obtained for the first and second case modules, respectively. The preferred treatment plan differed significantly according to the focus of the conference, and a tendency emerged for the clinicians participating in each conference to express uniform preferences. However, attending the debates resulted in significant changes in decision-making preferences regardless of the conference focus or the characteristics of the participants. CONCLUSIONS: Our findings suggest that providing continuing education via debates on controversial issues may be effective in widening conceptual knowledge and reducing biases among experts in the dental and medical fields.
Bias (Epidemiology) ; Clinical Protocols ; Congresses as Topic* ; Decision Making ; Dental Care ; Dental Implants ; Dentistry ; Diagnosis ; Education, Continuing ; Education, Dental, Continuing ; Molar ; Periodontics ; Pliability* ; Tooth*

PURPOSE: This study evaluated the mechanical and structural properties of biphasic calcium phosphate (BCP) blocks processed using a modified extrusion method, and assessed their in vivo effectiveness using a rabbit calvarial defect model. METHODS: BCP blocks with three distinct ratios of hydroxyapatite (HA):tricalcium phosphate (TCP) were produced using a modified extrusion method:HA8 (8%:92%), HA48 (48%:52%), and HA80 (80%:20%). The blocks were examined using scanning electron microscopy, X-ray diffractometry, and a universal test machine. Four circular defects 8 mm in diameter were made in 12 rabbits. One defect in each animal served as a control, and the other three defects received the BCP blocks. The rabbits were sacrificed at either two weeks (n=6) or eight weeks (n=6) postoperatively. RESULTS: The pore size, porosity, and compressive strength of the three types of bone block were 140-170 microm, >70%, and 4-9 MPa, respectively. Histologic and histomorphometric observations revealed that the augmented space was well maintained, but limited bone formation was observed around the defect base and defect margins. No significant differences were found in the amount of new bone formation, graft material resorption, or bone infiltration among the three types of BCP block at either of the postoperative healing points. CONCLUSIONS: Block bone substitutes with three distinct compositions (i.e., HA:TCP ratios) processed by a modified extrusion method exhibited limited osteoconductive potency, but excellent space-maintaining capability. Further investigations are required to improve the processing method.
Animals ; Bone Regeneration ; Bone Substitutes* ; Calcium* ; Compressive Strength ; Durapatite ; Microscopy, Electron, Scanning ; Osteogenesis ; Porosity ; Rabbits ; Transplants

PURPOSE: The objective of this study was to comparatively assess the bone regenerative capacity of absorbable collagen sponge (ACS), biphasic calcium phosphate block (BCP) and collagenated biphasic calcium phosphate (CBCP) loaded with a low dose of recombinant human bone morphogenetic protein-2 (rhBMP-2). METHODS: The CBCP was characterized by X-ray diffraction and scanning electron microscopy. In rabbit calvaria, four circular 8-mm-diameter defects were created and assigned to one of four groups: (1) blood-filled group (control), (2) rhBMP-2-soaked absorbable collagen sponge (0.05 mg/mL, 0.1 mL; CS group), (3) rhBMP-2-loaded BCP (BCP group), or (4) rhBMP-2-loaded CBCP (CBCP group). The animals were sacrificed either 2 weeks or 8 weeks postoperatively. Histological and histomorphometric analyses were performed. RESULTS: The CBCP showed web-like collagen fibrils on and between particles. Greater dimensional stability was observed in the BCP and CBCP groups than in the control and the CS groups at 2 and 8 weeks. The new bone formation was significantly greater in the BCP and CBCP groups than in the control and CS groups at 2 weeks, but did not significantly differ among the four groups at 8 week. The CBCP group exhibited more new bone formation in the intergranular space and in the center of the defect compared to the BCP group at 2 weeks, but a similar histologic appearance was observed in both groups at 8 weeks. CONCLUSIONS: The dose of rhBMP-2 in the present study enhanced bone regeneration in the early healing period when loaded on BCP and CBCP in rabbit calvarial defects.
Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins* ; Bone Regeneration ; Calcium ; Collagen ; Humans ; Microscopy, Electron, Scanning ; Osteogenesis ; Porifera ; Skull ; X-Ray Diffraction