Curcumin (diferuloylmethane) is a dietary polyphenol derived from the rhizomes of turmeric (Curcuma longa). For a long time, curcumin has been applied as an anti-inflammatory, 1) anti-oxidative, 2-4) and anti-carcinogenic 5) compound. The multiple therapeutic effects of curcumin result from its ability to modulate enzyme activities and gene expression. For example, curcumin has been shown to down-regulate the activities of several transcription factors, including NF-kappa B, AP-1, and Egr-1, as well as growth factor receptors such as EGFR and HER2. 6) Curcumin also inhibits the activities of COX2, LOX, iNOS, MMP-9, c-Jun N-terminal kinase, protein tyrosine kinases, and protein serine/threonine kinases. 6) Curcumin has been shown to repress expression of oncogenes such as c-fos, c-jun and c-myc, and suppress proliferation of tumour cells. [7][8][9] Finally, recent studies have demonstrated that curcumin can inhibit p300/CBP histone acetyltransferase activity both in vivo and in vitro. 10,11) p300/CBP transfers the acetyl group from an acetyl-CoA to conserved lysine residues in the histones, consequently, leading to transcription activity.12) Therefore, curcumin may modulate gene expression through inhibition of p300/CBP activities.Although the effects of curcumin on enzyme activities and gene expression have been studied in detail, only a few reports described its toxicity to embryos. The studies using rats as animal models have shown that orally administered curcumin has no toxic effects on fertility or pregnancy in the fed rats, and no malformations were observed in their offspring.13) In this report, we used zebrafish (Danio rerio) as model organisms to investigate the developmental toxicity of curcumin. Advantages of using zebrafish as model organisms include their small size (2-4 cm long), ease of breeding in the laboratory, light-induced fertilization, and sensitivity to environmental changes. Our results indicated that, unlike in rats, curcumin had embryotoxic and teratogenic effects on zebrafish embryos in a mM region. MATERIALS AND METHODS Collecting Fertilized Zebrafish EggsAdult zebrafish purchased from a local fish store were maintained in a laboratory under 28Ϯ1°C and a 14 h day/10 h night photoperiod.Fertilized eggs were collected within 30 min after natural mating, washed with sterile water, and placed in petri dishes.Curcumin Treatment and Embryos Observances Curcumin was purchased from Sigma Chemical (St. Louis, MO, U.S.A.), and dissolved in dimethyl sulfoxide (DMSO) to make a 25 mM stock solution. For embryo exposures, fertilized eggs were placed in 6-well petri dishes with ten embryos per well in 10 ml sterile water. Next, 30 ml of seriously diluted curcumin stock solutions was added to get final concentrations of 5, 7.5, 10, 12.5, and 15 mM. Thirty embryos were used for each of four replicates. The embryotoxic and teratogenic effects of resveratrol, quercetin, and rutin were also investigated in this study. Resveratrol, quercetin, and rutin were all purchased from Sigma Chemical (St. Louis, MO...

Bone regeneration procedures require alternative graft biomaterials to those for autogenous bone. Therefore, we developed a novel porcine graft using particle sizes of 250–500 μm and 500–1000 μm in rabbit calvarial bone defects and compared the graft properties with those of commercial hydroxyapatite (HA)/beta-tricalcium phosphate (β-TCP) over eight weeks. Surgery was performed in 20 adult male New Zealand white rabbits. During a standardized surgical procedure, four calvarial critical-size defects of 5 mm diameter and 3 mm depth were prepared. The defects were filled with HA/β-TCP, 250–500 μm or 500–1000 μm porcine graft, and control defects were not filled. The animals were grouped for sacrifice at 1, 2, 4, and 8 weeks post-surgery. Subsequently, sample blocks were prepared for micro-computed tomography (micro-CT) scanning and histological sectioning. Similar bone formations were observed in all three treatment groups, although the 250–500 μm porcine graft performed slightly better. Rabbit calvarial bone tissue positively responded to porcine grafts and commercial HA/β-TCP, structural analyses showed similar crystallinity and porosity of the porcine and HA/β-TCP grafts, which facilitated bone formation through osteoconduction. These porcine grafts can be considered as graft substitutes, although further development is required for clinical applications.

Axonal damage leads to the release of neurofilament light chain (NFL), which enters the CSF or blood. In this work, an assay kit for plasma NFL utilizing immunomagnetic reduction (IMR) was developed. Antibodies against NFL were immobilized on magnetic nanoparticles to develop an IMR NFL kit. The preclinical properties, such as the standard curve, limit of detection (LoD), and dynamic range, were characterized. Thirty-one normal controls (NC), fifty-two patients with Parkinson's disease (PD) or PD dementia (PDD) and thirty-one patients with Alzheimer's disease (AD) were enrolled in the study evaluating the plasma NFL assay using an IMR kit. T-tests and receiver operating characteristic (ROC) curve analysis were performed to investigate the capability for discrimination among the clinical groups according to plasma NFL levels. The LoD of the NFL assay using the IMR kit was found to be 0.18 fg/ml. The dynamic range of the NFL assay reached 1000 pg/ml. The NC group showed a plasma NFL level of 7.70 ± 4.00 pg/ml, which is significantly lower than that of the PD/PDD (15.85 ± 7.82 pg/ml, p < 0.001) and AD (19.24 ± 8.99 pg/ml, p < 0.001) groups. A significant difference in plasma NFL levels was determined between the PD and AD groups (p < 0.01). Through ROC curve analysis, the cutoff value of the plasma NFL concentration for differentiating NCs from dementia patients (AD and PD/PDD) was found to be 12.71 pg/ ml, with a clinical sensitivity and specificity of 73.5% and 90.3%, respectively. The AUC was 0.868. Furthermore, the cutoff value of the plasma NFL concentration for discriminating AD from PD/PDD was found to be 18.02 pg/ml, with a clinical sensitivity and specificity of 61.3% and 65.4%, respectively. The AUC was 0.630. An ultrasensitive assay for measuring plasma NFL utilizing IMR technology was developed. Clear differences in plasma NFL concentrations were observed among NCs and PD and AD patients. These results imply that the determination of plasma NFL is promising not only for screening dementia but also for differential diagnosis.

In this study, we propose a new solution based on Adaboost algorithm and Back Propagation Network (BPN) of Neural Network (NN) combining local and global features with cascade architecture to detect human faces. We use Modified Census Transform (MCT) feature that belong to texture features and is less sensitive to illumination for local feature calculation. By this approach, it is not necessary to preprocess each sub-window of the image. For classification, we use the structure of hierarchical feature to control the number of features. With only MCT, it is easy to misjudge faces, and therefore in this work we include the brightness information of global features to eliminate the false positive regions. As a result, the proposed approach can have Detection Rate (DR) of 99%, false positives of only 11, and detection speed of 27.92 Frame Per Second (FPS).