Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model.

Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.

Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model

Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.

Maxillary molar root and canal morphology of Neolithic and modern Chinese.

OBJECTIVE: This study aimed to characterize Neolithic human maxillary molars from archeological remains at the Jiaojia site, Shandong, China, and compare their ultrastructural features with sex and age-matched modern locals. DESIGN: Maxillary first (n = 86) and second (n = 80) molars in 5000-year-old individuals (n = 50) from the Jiaojia site were scanned by cone-beam computed tomography (CBCT). Sex and age-matched control groups were assigned from oral surgical patients at Shandong University. Images were analyzed for crown size, root length, root morphology, canal inter-orifice distances, mesiobuccal canal morphology, and second mesiobuccal (MB2) canal prevalence and location. Neolithic and modern values were compared statistically using Chi-squared and Mann-Whitney test at p < .05. RESULTS: Crown and root size were smaller, and canal inter-orifice distances were shorter in Neolithic maxillary molars than their modern counterparts. For mesiobuccal roots, Weine's Type I single canals were the most prevalent in Neolithic and modern first and second molars. MB2 canal prevalence were not significantly different (p > .05) in Neolithic (53.3%) or modern (60.5%) first molars, and Neolithic (11.3%) or modern (21.3%) second molars. But, MB2 prevalence was significantly higher for modern than ancient male first (p = .032) and second (p = .005) molars. Additionally, MB2 were located more mesially and closer to MB1 in Neolithic than modern molars. CONCLUSIONS: Maxillary molar root and canal morphology of ancient 5000-year-old remains at the Jiaojia site resemble that of local patients. A trend towards larger tooth size, and more dispersed MB2 canals over this short evolutionary period warrants additional investigation.

Tunable quad-band transmission response, based on single-layer metamaterials.

We investigated the electromagnetically induced transparency (EIT)-like effects in planar metamaterials (MMs) at microwave (GHz) frequencies. The specific MMs that were used in this study consist of cut-wire resonator/ring resonator, which achieved the dual EIT-like effects in a single-layer through the bright- and quasi-dark-mode coupling and the lattice mode coupling. In addition, by varying the distance between the two resonators, the quad-band EIT spectral response in the microwave region was obtained, and the group refractive index at the EIT-like resonance of proposed design reached up to 4,000. This study provides the design approach to the multispectral EIT-like effects and might suggest potential applications in a variety of fields, for example, low-loss slow-light device, multiple switching sensor, and other sensing devices.

Switching and extension of transmission response, based on bending metamaterials.

The electromagnetically-induced transparency (EIT)-like effects in planar and non-planar metamaterials (MMs) were investigated for microwave (GHz) frequencies. The specific MMs used in this study consisted of a cut-wire resonator and a ring resonator, where were placed on the top and the bottom layers, respectively. A transmission window was produced, due to the interference between bright- and bright-mode coupling. Using the numerical and the experimental results, we demonstrate that the bending of MM leads to enhanced transmission and bandwidth, as well as an additional EIT-like peak. This provides an effective way of realizing the tunable devices, including the switching sensors.

Systematic review with meta-analysis: the efficacy and safety of tenofovir to prevent mother-to-child transmission of hepatitis B virus.

BACKGROUND: Preventing mother to child transmission of chronic hepatitis B infection in the setting of a high maternal viral load is challenging. The idea has emerged from antepartum tenofovir treatment with combination immunoprophylaxis. AIMS: To demonstrate the efficacy and safety of tenofovir to prevent mother to child transmission of hepatitis B virus. METHODS: PubMed, EMBASE, and Cochrane databases were searched through August 16, 2016. Comparative trials of second or third trimester tenofovir administration vs. controls for patients with chronic hepatitis B infection and non-comparative case series assessing mother to child transmission rates and evaluating maternal and foetal safety outcomes were included. RESULTS: Ten studies (one randomised controlled trial, four non-randomised controlled trials and five case series) that enrolled 733 women were included. The pooled results from comparative trials (599 pregnancies) showed that tenofovir significantly reduced the risk of infant hepatitis B surface antigen seropositivity by 77% (odds ratio=0.23, 95% confidence intervals=0.10-0.52, P=.0004) without heterogeneity (I2 =0%). In the case series analysis (134 pregnancies), only two cases (1.5%) of mother to child transmission with extremely high maternal viral load and non-compliance to treatment were identified. Maternal and foetal safety parameters including congenital malformation and foetal death were re-assuring. CONCLUSIONS: For pregnant women with high hepatitis B virus DNA levels, tenofovir administration in the second or third trimester can prevent mother to child transmission when combined with hepatitis B immunoglobulin and the hepatitis B vaccine. Tenofovir is safe and tolerable for both the mother and foetus.

The sphingosine-1-phosphate receptor 1 binding molecule FTY720 inhibits osteoclast formation in rats with ligature-induced periodontitis.

BACKGROUND AND OBJECTIVE: Osteoclast precursors (OPs) re-migrate from the bone surface into blood vessels through sphingosine-1-phosphate receptor 1 (S1PR1) expression. T cells also express S1PR1, mediating their migration from the lymph nodes into blood vessels. OP and T-cell migration are one of the sequential steps related to osteoclast formation. To characterize the role of S1PR1 in osteoclast formation induced by periodontitis, we investigated the effect of S1PR1-binding molecule FTY720 (FTY) on the number of OPs and T cells in periodontal tissue and peripheral blood of rats with ligature-induced periodontitis. MATERIAL AND METHODS: Rats were divided into four groups; control (Con), FTY, periodontitis (Peri), and periodontitis+FTY (Peri+FTY) groups. Ligatures were placed around the first molars in the left and right mandibles. The rats were intraperitoneally injected with vehicle or 3 mg/kg FTY daily until they were killed. The number of osteoclasts and cluster of differentiation (CD)11b, CD3 and receptor activator of NF-κB ligand (RANKL)-positive cells in first molar furcation were counted by tartrate-resistant acid phosphatase or immunohistochemistry staining. The number of CD11b- and CD3-positive cells in peripheral blood was estimated by flow cytometry. RESULTS: The number of osteoclasts in the Peri group was higher than Con, Peri+FTY and FTY groups (p < 0.05) and CD11b, CD3 and RANKL-positive cells were also higher in the Peri group than other groups in furcation (p < 0.05). While CD11b-positive cells in furcation of the Peri+FTY group were lower than the Peri group (p < 0.05), they were higher in peripheral blood (p < 0.05). Dissimilar to CD11b-positive cells, CD3-positive cells in the Peri+FTY group were lower in peripheral blood as well as furcation than the Peri group (p < 0.05). RANKL-positive cells in furcation of the Peri+FTY group were also lower than Peri group (p < 0.05). CONCLUSION: These results indicate that FTY may facilitate re-migration of OPs from the alveolar bone surface into blood vessels, blocking T-cell migration from the lymph nodes into blood vessels and subsequently reducing osteoclast formation induced by periodontitis. This suggests that S1PR1-S1P binding may play a role in osteoclast formation of periodontitis by modulating OP and T-cell migration.

Genome Sequences of Malonate-Positive Cronobacter sakazakii Serogroup O:2, Sequence Type 64 Strains CDC 1121-73 and GK1025, Isolated from Human Bronchial Wash and a Powdered Infant Formula Manufacturing Plant.

We introduce draft genome sequences of strains CDC1121-73 (human bronchial wash isolate) and GK1025 (powdered infant formula manufacturing facility isolate), which are both malonate-positive Cronobacter sakazakii serogroup O:2, sequence type 64. Assemblies for these strains have sizes of 4,442,307 and 4,599,266 bp and % G+C contents of 56.9 and 56.7, respectively.

Geometrical shape design of nanophotonic surfaces for thin film solar cells.

We present the effect of geometrical parameters, particularly shape, on optical absorption enhancement for thin film solar cells based on crystalline silicon (c-Si) and gallium arsenide (GaAs) using a rigorous coupled wave analysis (RCWA) method. It is discovered that the "sweet spot" that maximizes efficiency of solar cells exists for the design of nanophotonic surfaces. For the case of ultrathin, rod array is practical due to the effective optical resonances resulted from the optimum geometry whereas parabola array is viable for relatively thicker cells owing to the effective graded index profile. A specific value of thickness, which is the median value of other two devices tailored by rod and paraboloid, is optimized by truncated shape structure. It is therefore worth scanning the optimum shape of nanostructures in a given thickness in order to achieve high performance.

Periodontitis mainly increases osteoclast formation via enhancing the differentiation of quiescent osteoclast precursors into osteoclasts.

BACKGROUND AND OBJECTIVES: Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts are formed in sequential steps: proliferation and differentiation of hematopoietic progenitors into quiescent osteoclast precursors (QOPs), followed by fusion of QOPs. In this study, we investigated whether enhancement of osteoclast formation by periodontitis is derived from the stimulation of proliferation of hematopoietic progenitors or the differentiation of QOPs into osteoclasts. MATERIAL AND METHODS: Ligatures were placed around the first molars in the left mandibles of Fischer 344 inbred rats. The rats received drinking water containing bromodeoxyuridine (BrdU) (which can be incorporated into dividing nuclei) after ligation during the experimental period. The number of inflammatory cells in the distal area was counted. Alveolar bone loss was histologically estimated by measuring the distance from the cementoenamel junction to the alveolar bone crest in the distal area and determining the percentage of periodontal ligament area in the furcation. The number of osteoclasts and percentage of BrdU(+) nuclei in total osteoclasts nuclei were counted after TRAP and BrdU double labeling. RESULTS: The number of polymorphonuclear cells increased on day 1 and then rapidly decreased. The number of mononuclear cells increased in a time-dependent manner up to day 5 and remained the same until day 10. Alveolar bone loss of ligatured teeth increased in a time-dependent manner. The number of osteoclasts peaked on day 3 then gradually decreased. At peak, the percentage of BrdU(+) nuclei in total osteoclasts nuclei in the distal and furcation areas were 7.9% and 4.1%, respectively. CONCLUSION: These results indicate that most of the osteoclasts formed after periodontitis induction are derived from preformed QOPs, suggesting that enhancement of osteoclast formation by periodontitis might be mainly caused by stimulating the differentiation of QOPs into osteoclasts.

Three-dimensional modelling and concurrent measurements of root anatomy in mandibular first molar mesial roots using micro-computed tomography.

AIM: To obtain concurrent radicular measurements in the mesiobuccal (MB) and mesiolingual (ML) canals of mandibular first molars using scanned data of micro-computed tomography (µCT) with novel software. METHODOLOGY: The scanned data from 37 mandibular first molar mesial roots were reconstructed and analysed with custom-developed software (Kappa2). For each canal, three-dimensional (3D) surface models were re-sliced at 0.1-mm intervals perpendicular to the central axis. Dentine thicknesses, canal widths and 3D curvatures were measured automatically on each slice. Measurements were analysed statistically with anova for differences at each direction and at different levels of both canals. RESULTS: Lateral dentine thicknesses were significantly higher than mesial and distal thicknesses, at all the levels of both canals (P < 0.001). Mesial thicknesses were significantly higher than distal thicknesses in the coronal third of both canals (P < 0.001). Thinnest dentine thicknesses were mainly located on the disto-inside of both canals. Narrowest canal widths were 0.24 ± 0.10 and 0.22 ± 0.09 mm in MB and ML canals, respectively. Canal curvatures were greatest in the apical third of both canals (P < 0.001), and they were greater in the MB canals than in the ML canals (P < 0.05). CONCLUSIONS: Micro-computed tomography with novel software provided valuable anatomical information for optimizing instrumentation and minimizing mishaps in nonsurgical root canal treatment.

Diabetic characteristics and alveolar bone loss in streptozotocin- and streptozotocin-nicotinamide-treated rats with periodontitis.

BACKGROUND AND OBJECTIVE: Experimental models showing variable diabetic status are necessary to understand the relationship between diabetes and periodontitis. The streptozotocin (STZ)-induced diabetes model allows control of diabetic status by nicotinamide (NA), which protects against STZ-induced ß-cell necrosis. Therefore, we compared diabetic characteristics and alveolar bone loss in STZ- and STZ-NA-treated rats with periodontitis. MATERIAL AND METHODS: STZ-treated rats were generated by intravenous (IV) administration of STZ (50 mg/kg). STZ-NA-treated rats were induced by intraperitoneal administration of NA (270 mg/kg) 15 min before IV administration of STZ (65 mg/kg). Periodontitis was induced by ligature around the left mandibular first molar 1 wk after injection. Blood glucose level, glucose tolerance and serum insulin levels were determined at day 0 and/or 20 after ligature. At day 20, tibia bone loss was assessed using micro-computed tomography and hematoxylin and eosin staining. Alveolar bone loss was histologically measured as the distance of the cementoenamel junction to the alveolar bone crest in distal and the percentage of periodontal ligament area in the first molar furcation, respectively. The number of inflammatory cells, receptor activator of nuclear factor kappa-B ligand (RANKL)-positive cells and the area of osteoid were determined. RESULTS: In STZ-treated rats, obvious hyperglycemia over 300 mg/dL and severe body weight loss were observed. The insulin level was approximately 14% compared to that of control rats. STZ-NA-treated rats were impaired in glucose tolerance compared to control rats; however, body weight and insulin levels were not significantly different. Tibia bone loss was increased in STZ-treated rats, but significant change was not observed in STZ-NA-treated rats compared to control rats. In ligatured teeth, alveolar bone loss was increased in both STZ- and STZ-NA-treated rats compared to control rats. Alveolar bone loss, the number of inflammatory cells and RANKL-positive cells in STZ-treated rats were greater than in STZ-NA-treated rats. The area of osteoid decreased in STZ-treated rats compared to control, but not STZ-NA-treated rats. CONCLUSION: These results indicate that STZ- and STZ-NA-treated rats exhibit diabetic characteristics similar to type 1 diabetes mellitus and a pre-diabetic state, respectively. In addition, alveolar bone loss in response to periodontitis and tibia loss depend on diabetic status. Diabetic status-dependent bone remodeling imbalance and inflammation could affect the alveolar bone loss in the two models. Both STZ- and STZ-NA-treated rats may be useful to investigate differences in periodontitis sensitivity associated with diabetic status and to develop therapeutic agents for periodontitis in patients with diabetes.

Trace metal contents of three tricalcium silicate materials: MTA Angelus, Micro Mega MTA and Bioaggregate.

AIM: To investigate the levels of nine metals [aluminium (Al), antimony (Sb), arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), iron (Fe), lead (Pb) and molybdenum (Mo)] in MTA Angelus, Micro Mega MTA and Bioaggregate using inductively coupled plasma-optical emission spectrometry (ICP-OES). METHODOLOGY: Each material (0.2 g) was digested using a mixture of hydrochloric and nitric acids and then filtered. The levels of nine metals in the resulting filtrates were measured by ICP-OES. The results were statistically analysed using one-way anova and the Bonferroni test. RESULTS: MTA Angelus contained more aluminium, beryllium and chromium than Micro Mega MTA (P < 0.05), whilst their levels of arsenic, cadmium and iron were similar. Antimony, lead and molybdenum were not detected in any of the three tested cements. Bioaggregate contained trace amounts of aluminium. CONCLUSIONS: MTA Angelus and Micro Mega MTA contained small amounts of seven tested metal oxides. Bioaggregate only contained trace amounts of aluminium.

Autotransplantation of mesiodens for missing maxillary lateral incisor with cone-beam CT-fabricated model and orthodontics.

AIM: Autotransplantation is a viable treatment option for a missing tooth when there is a suitable donor, especially in adolescents with remaining facial growth. This report presents the aesthetic restoration of a missing maxillary lateral incisor through orthodontic treatment and autotransplantation of a mesiodens using a CBCT-fabricated rapid-prototyping model. SUMMARY: A 14-year-old male patient with a congenitally missing maxillary lateral incisor was referred from the Department of Orthodontics. The teeth were moved orthodontically to regain space for the missing lateral incisor and to close the space of the mesiodens after transplantation. A replica of the donor tooth was fabricated from a cone-beam computed tomography scan through a rapid-prototyping machine before autotransplantation surgery. The model was used to create a socket for the graft tooth, thereby shortening the extra-oral time and minimizing the damage to the root surface. After transplantation and orthodontic tooth movement, the mesiodens was finally restored with an aesthetic laminate restoration. Over 3 years, the aesthetics remained excellent, and the transplant functioned normally without any signs or symptoms of root resorption. KEY LEARNING POINT: Missing anterior teeth may be replaced through a combination of orthodontics, autotransplantation with a rapid-prototyping model and prosthodontic restoration, in growing patients.

The effect of orally administered epigallocatechin-3-gallate on ligature-induced periodontitis in rats.

BACKGROUND AND OBJECTIVE: Epigallocatechin-3-gallate (EGCG) is known for its beneficial properties, including anti-inflammatory and anti-oxidative activities. Recently, reports have suggested that EGCG plays a pivotal role in regulating cytokine expression and osteoclastic activity. In the present study, we investigated whether orally administered EGCG has a therapeutic effect on ligature-induced periodontitis. MATERIALS AND METHODS: Forty-eight Sprague-Dawley rats were treated with EGCG or phosphate-buffered saline. Periodontitis was induced by tying a ligature for 7 d. After removing ligation, EGCG (200 mg/kg) or phosphate-buffered saline was administered via oral gavage on a daily basis. Rats were killed after 1, 2 and 4 wk of administration. Histologic and histomorphometric analyses, tartrate resistant acid phosphatase staining and immunohistochemistry were carried out. RESULTS: In the control group, bone loss did not recover even after the causative factor of periodontitis was eliminated. On the other hand, distance from cemento-enamel junction to alveolar bone crest, long junctional epithelium and collagen destruction were reduced in the EGCG group. Decreased interleukin (IL)-6 expression was shown from the early stage of EGCG administration, followed by reduced tumor necrosis factor (TNF) expression at week 4 EGCG group. The CT area showed a higher decrease of IL-6 expression between the control and EGCG group than alveolar bone area. Downregulation of TNF and IL-6 expression led to a decrease in osteoclast number and activity, which resulted in reduced bone loss. CONCLUSIONS: Systemic administration of EGCG could have a therapeutic effect on damaged periodontal tissue. Inhibited cytokine expression, including TNF and IL-6 is responsible for the reduction in osteoclast formation, osteoclastic activity and collagen destruction.

Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-ß plaques.

Presently, co-culture of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) with BV2 microglia under amyloid-ß42 (Aß42) exposure induced a reduction of Aß42 in the medium as well as an overexpression of the Aß-degrading enzyme neprilysin (NEP) in microglia. Cytokine array examinations of co-cultured media revealed elevated release of soluble intracellular adhesion molecule-1 (sICAM-1) from hUCB-MSCs. Administration of human recombinant ICAM-1 in BV2 cells and wild-type mice brains induced NEP expression in time- and dose-dependent manners. In co-culturing with BV2 cells under Aß42 exposure, knockdown of ICAM-1 expression on hUCB-MSCs by small interfering RNA (siRNA) abolished the induction of NEP in BV2 cells as well as reduction of added Aß42 in the co-cultured media. By contrast, siRNA-mediated inhibition of the sICAM-1 receptor, lymphocyte function-associated antigen-1 (LFA-1), on BV2 cells reduced NEP expression by ICAM-1 exposure. When hUCB-MSCs were transplanted into the hippocampus of a 10-month-old transgenic mouse model of Alzheimer's disease for 10, 20, or 40 days, NEP expression was increased in the mice brains. Moreover, Aß42 plaques in the hippocampus and other regions were decreased by active migration of hUCB-MSCs toward Aß deposits. These data suggest that hUCB-MSC-derived sICAM-1 decreases Aß plaques by inducing NEP expression in microglia through the sICAM-1/LFA-1 signaling pathway.

Effects of HB-EGF and epiregulin on wound healing of gingival cells in vitro.

OBJECTIVE: Gingival wound healing is important to periodontal disease and surgery. This in vitro study was conducted to assess the manner in which heparin-binding epidermal growth factor-like growth factor (HB-EGF) and epiregulin cooperatively participate in the wound-healing process in the gingival epithelial and fibroblast cells of the oral mucosa. MATERIAL AND METHODS: Gingival epithelium and fibroblast were separated from gingival tissue biopsies and prepared to primary cultures. The changes in the mRNA expression were evaluated via real-time PCR. The effects on cell proliferation, migration, and repopulation were evaluated in vitro. RESULTS: The different regulation of expressions of HB-EGF, epiregulin, and epidermal growth factor receptors was observed over time and with different gingival cell types. HB-EGF exerted a cell migration-inducing effect on both epithelial and fibroblast cells, whereas epiregulin did not. Both growth factors functioned as mitogens for epithelial cell proliferation, but not for fibroblast proliferation. HB-EGF strongly promoted epithelial cell repopulation and mildly promoted fibroblast repopulation, whereas epiregulin promoted only fibroblast repopulation. CONCLUSION: These results indicated that both growth factors might function importantly in the wound-healing process of human gingival tissue via the different regulation of the expression, cell migration, proliferation, and repopulation.

Td92, an outer membrane protein of Treponema denticola, induces osteoclastogenesis via prostaglandin E(2)-mediated RANKL/osteoprotegerin regulation.

BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease of the periodontium that causes significant alveolar bone loss. Osteoclasts are bone-resorbing multinucleated cells. Osteoblasts regulate osteoclast differentiation by expression of RANKL and osteoprotegerin (OPG). Td92 is a surface-exposed outer membrane protein of Treponema denticola, a periodontopathogen. Although it has been demonstrated that Td92 acts as a stimulator of various proinflammatory mediators, the role of Td92 in alveolar bone resorption remains unclear. Therefore, in this study, we investigated the role of Td92 in bone resorption. MATERIAL AND METHODS: Mouse bone marrow cells were co-cultured with calvariae-derived osteoblasts in the presence or absence of Td92. Osteoclast formation was assessed by TRAP staining. Expressions of RANKL, osteoprotegerin (OPG) and prostaglandin E(2) (PGE(2) ) in osteoblasts were estimated by ELISA. RESULTS: Td92 induced osteoclast formation in the co-cultures. In the osteoblasts, RANKL and PGE(2) expressions were up-regulated, whereas OPG expression was down-regulated by Td92. The addition of OPG inhibited Td92-induced osteoclast formation. The prostaglandin synthesis inhibitors NS398 and indomethacin were also shown to inhibit Td92-induced osteoclast formation. The effects of Td92 on the expressions of RANKL, OPG and PGE(2) in osteoblasts were blocked by NS398 or indomethacin. CONCLUSION: These results suggest that Td92 promotes osteoclast formation through the regulation of RANKL and OPG production via a PGE(2) -dependent mechanism.

Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes.

OBJECTIVE: Evodiamine (evo) has been shown to exert anti-inflammatory, antinociceptive and anticancer effects. In this study, we investigated the effects of evo alone and in combination with rosiglitazone (rosi) on in vitro adipocyte differentiation and in vivo obesity related to diabetes. METHODS: Adipocyte differentiation was investigated in vitro using 3T3-L1 and C3H10T1/2 cells. To determine the degree of differentiation, Oil Red O staining and reverse transcription-PCR were carried out. Four groups of db/db mice were treated intraperitoneally once per day with vehicle, evo, rosi and evo+rosi. The mice were killed after 14 days and the blood, liver and adipose tissue were analyzed. RESULTS: The presence of evo or evo combined with rosi during adipogenic induction has been shown to inhibit adipocyte differentiation to a significant degree, particularly at the commitment and early induction stages. The evo and evo+rosi groups of db/db mice evidenced significant reductions in body weight gain. The ratio of epididymal white adipocyte tissue weight to body weight of the evo group was also significantly reduced. It is important to note that in the evo+rosi treatment, blood glucose levels were reduced to a degree similar to that of the rosi group, and plasma insulin levels were reduced significantly better than that of rosi group. Furthermore, hepatic lesions associated with fat and glycogen deposition were morphologically improved in the evo and evo+rosi groups. CONCLUSION: The results of this study showed that evo exerts an inhibitory effect on in vitro adipocyte differentiation and in vivo obesity, and also an improvement effect on insulin resistance. These desirable effects of evo were noted even in the presence of rosi. These results indicate that evo improves the undesirable effects of rosi, including adipogenesis, body weight gain and hepatotoxicity, while preserving its desirable blood-glucose-lowering effect.

Effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro.

BACKGROUND AND OBJECTIVE: A growing amount of attention has been placed on periodontal regeneration and wound healing for periodontal therapy. This study was conducted in an effort to determine the effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro. MATERIAL AND METHODS: Human periodontal ligament cells were acquired from explant tissue of human healthy periodontal ligament. After the wounding of periodontal ligament cells, the change in expression of heparin-binding epidermal growth factor-like growth factor and epidermal growth factor receptors 1-4 mRNA was assessed. The effects of heparin-binding epidermal growth factor-like growth factor on periodontal ligament cell proliferation and repopulation were assessed in vitro via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and by photographing the injuries, respectively. Extracellular signal-regulated kinase (Erk)1/2, p38 and Akt phosphorylation was characterized via western blotting. RESULTS: Scratch wounding resulted in a significant up-regulation of heparin-binding epidermal growth factor-like growth factor mRNA expression, whereas wounding had no effect on the expression levels of epidermal growth factor receptors 1-4. Interestingly, no expression of epidermal growth factor receptors 2 and 4 was detectable prior to or after wounding. Heparin-binding epidermal growth factor-like growth factor treatment promoted the proliferation and repopulation of periodontal ligament cells. The scratch wounding also stimulated the phosphorylation of Erk1/2 and p38, but not of Akt, in periodontal ligament cells, and heparin-binding epidermal growth factor-like growth factor treatment applied after wounding amplified and extended the activations of Erk1/2 and p38, but not of Akt. Furthermore, Erk1/2 inhibition blocked the process of cell repopulation induced by heparin-binding epidermal growth factor-like growth factor, whereas the inhibition of p38 delayed the process. CONCLUSION: These results indicate that heparin-binding epidermal growth factor-like growth factor may constitute a critical factor in the wound healing of human periodontal ligament cells by a mechanism that requires the activation of Erk1/2 via specific interaction with epidermal growth factor receptor 1.