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Background: The osteogenic capabilities and biodegradability of octacalcium phosphate (OCP) composites make them unique. Despite the excellent characteristics of OCP, their use is limited due to handling difficulties. In this study, we aimed to evaluate and compare three types of OCPs (cemented OCP (C-OCP), C-OCP with collagen (OCP/Col), and synthetic OCP (S-OCP) with alginate (OCP/Alg)) versus commercially available β-tricalcium phosphate (β-TCP) regarding their potential to accelerate bone formation in defective rat tibias. Methods: The specimens with OCP composite were manufactured into 5 ​mm cubes and inserted into the segmental defects of rat tibias fixed with an external fixator. In addition, 3 ​mm-hole defects in rat tibias were evaluated to compare the graft material properties in different clinical situations. Serial X-ray studies were evaluated weekly and the tibias were harvested at postoperative 6 weeks or 8 weeks for radiologic evaluation. Histological and histomorphometric analyses were performed to evaluate the acceleration of bone formation. Results: In the critical-defect model, OCP/Alg showed bone bridges between segmentally resected bone ends that were comparable to those of β-TCP. However, differences were observed in the residual graft materials. Most β-TCP was maintained until 8 weeks postoperatively; however, OCP/Alg was more biodegradable. In addition calcification in the β-TCP occurred at the directly contacted area between graft particles and bony ingrowth was observed in the region adjacent resected surface of tibia. In contrast, no direct bony ingrowth was observed in OCP-based materials, but osteogenesis induced from resected surface of tibia was more active. In the hole-defect model, OCP/Col accelerated bone formation. β-TCP and OCP/Alg showed similar patterns with relatively higher biodegradability. In histology, among the OCP-based materials, directly contacted new bone was formed only in OCP/Alg group. The new bone formation in the periphery area of graft materials was much more active in the OCP-based materials, and the newly formed bone showed a thicker trabecular and more mature appearance than the β-TCP group. Conclusions: In this study, OCP/Alg was equivalent to β-TCP in the acceleration of bone formation with better biodegradability appropriate for clinical situations in different circumstances. Our OCP/Col composite showed fast degradation, which makes it unsuitable for use in mechanical stress conditions in clinical orthopedic settings. The Translational Potential of this Article: In our research, we compared our various manufactured OCP composites to commercially available β-TCP in critical-defect rat tibia model. OCP/Col showed acceleration in hole-defect model as previous studies in dental field but in our critical-sized defect model it resorbed fast without acceleration of bony union. OCP/Alg showed matched results compared to β-TCP and relatively fast resorption so we showed market value in special clinical indication depending on treatment strategy. This is the first OCP composite study in orthopaedics with animal critical-sized tibia bone study and further study should be considered for clinical application based on this study.

Tissue-specific transcriptional activity is silenced in mitotic cells. Here the authors reveal a general phosphorylation-dependent mechanism of recognition for the anaphase-promoting complex (APC) substrates, and show that the APC targets ID2 during the establishment of post-mitotic transcription.

Obesity can be associated with an increased risk of metabolic complications. Here, the authors show that adipocyte-specific ablation of the phosphatase PHLPP2 improves glucose homeostasis in high-fat diet fed obese mice, and that this may be due at least in part to PHLPP2 dephosphorylation of HSL.

Abstract Aims/Introduction Natural killer (NK) cells are cytotoxic lymphocytes critical to human immunity. Previous studies showed correlations between NK cell function and blood glucose concentrations. The purpose of the present study was to assess the NK cell activity and various metabolic parameters in people with type 2 diabetes, prediabetes and normal glucose tolerance. Materials and Methods A total of 49 participants were enrolled in the study. Anthropometric and biochemical parameters including age, sex, body mass index, smoking status, blood pressure, fasting plasma glucose, C‐peptide, insulin, glycated hemoglobin, total cholesterol, triglyceride, high‐density lipoprotein cholesterol and low‐density lipoprotein cholesterol were assessed. The 75 g oral glucose tolerance test was carried out for 2‐h postload glucose level. Homeostatic model assessment was calculated for insulin resistance and β‐cell function. NK cell activity was measured by detecting the circulating interferon‐gamma level secreted from NK cells. Results NK cell activity was lower in patients with type 2 diabetes (768.01 ± 650.35) compared with those with prediabetes (2,396.08 ± 653.76, P

BackgroundRecently, the triglyceride glucose (TyG) index has been considered a surrogate marker of insulin resistance which is a well-known pathogenic factor in nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated the relationship between the TyG index and NAFLD. Thus, we investigated the relationship between the TyG index and NAFLD and the effectiveness of the TyG index compared with the homeostasis model assessment of insulin resistance (HOMA-IR) in identifying NAFLD in Korean adults.MethodsParticipants of 4,986 who underwent ultrasonography in a health promotion center were enrolled. The TyG index was calculated as ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2], and HOMA-IR was estimated. NAFLD was diagnosed by ultrasonography.ResultsSignificant differences were observed in metabolic parameters among the quartiles of the TyG index. The prevalence of NAFLD significantly increased with increment in the TyG index. After adjusting for multiple risk factors, a logistic regression analysis was performed. When the highest and lowest quartiles of the TyG index and HOMA-IR were compared, the odds ratios for the prevalence of NAFLD were 2.94 and 1.93 (95% confidence interval, 2.32 to 3.72 and 1.43 to 2.61; both P for trend

BackgroundGenetic variations in calpain-10 and adiponectin gene are known to influence insulin secretion and resistance in type 2 diabetes mellitus. Recently, several single nucleotide polymorphisms (SNPs) in calpain-10 and adiponectin gene have been reported to be associated with type 2 diabetes and various metabolic derangements. We investigated the associations between specific calpain-10 and adiponectin gene polymorphisms and Korean type 2 diabetes patients.MethodsOverall, 249 type 2 diabetes patients and 131 non-diabetic control subjects were enrolled in this study. All the subjects were genotyped for SNP-43 and -63 of calpain-10 gene and G276T and T45G frequencies of the adiponectin gene. The clinical characteristics and measure of glucose metabolism were compared within these genotypes.ResultsAmong calpain-10 polymorphisms, SNP-63 T/T were more frequent in diabetes patients, and single SNP-63 increases the susceptibility to type 2 diabetes. However, SNP-43 in calpain-10 and T45G and intron G276T in adiponectin gene were not significantly associated with diabetes, insulin resistance, nor insulin secretion.ConclusionVariations in calpain-10, SNP-63 seems to increase the susceptibility to type 2 diabetes in Koreans while SNP-43 and adiponectin SNP-45, -276 are not associated with impaired glucose metabolism.

Abstract Background The triglyceride glucose (TyG) index has been suggested as a simple surrogate marker of insulin resistance. However, there are limited data regarding the association between the TyG index and arterial stiffness in adults. Therefore, we evaluated the relationship between the TyG index and arterial stiffness as measured based on brachial ankle pulse wave velocity (baPWV) in Korean adults. Methods A total of 3587 subjects were enrolled in this study. Anthropometric and cardiovascular risk factors were measured. The TyG index was calculated as ln[fasting triglycerides(mg/dl) × fasting glucose(mg/dl)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. Arterial stiffness was determined by measuring baPWV. Results The subjects were stratified into four groups based on the TyG index. There were significant differences in cardiovascular parameters among the groups; the mean baPWV increased significantly with increasing TyG index. According to the logistic regression analysis after adjusting for multiple risk factors, the odds ratio (95% CI) for increased baPWV (> 75th percentile) for the highest and lowest quartiles of the TyG index was 2.92 (1.92–4.44) in men and 1.84 (1.15–2.96) in women, and the odds ratio for increased baPWV for the highest and lowest quartiles of the HOMA-IR was 1.80 (1.17–2.78) in men and 1.46 (1.06–2.47) in women, respectively. Conclusion The TyG index is more independently associated with increased arterial stiffness than HOMA-IR in Korean adults.

Although benign nerve sheath tumors have been described, primary tracheal schwannomas are extremely rare. We report a case of primary tracheal schwannoma, a rare benign nerve sheath tumor in a 58-year-old man with atypical symptoms of chronic cough, sputum and dyspnea for 2 months. Chest computerized tomography showed a 1.7 cm polypoid lesion in posterior wall of mid trachea. The results of bronchoscopic biopsy and immuno-histo-chemical studies were consistent with schwannoma. A surgical treatment of tumor resection and tracheal reconstruction by end-to-end anastomosis was performed.

We demonstrate a passively mode-locked fiber laser using aqueous DNA solution as a saturable absorber (SA), with broadband pulse laser emission from 1 to 1.5 µm. The mode-locked laser with erbium-doped fiber as the gain material has a center wavelength of 1563 nm, a 3 dB bandwidth of 3.9 nm, and a pulse width of 822 fs, whereas the laser with ytterbium-doped fiber as the gain material and an identical DNA aqueous SA has a center wavelength of 1037 nm, a 3 dB bandwidth of 5.04 nm, and a pulse width of 250 ps. The proposed laser, which is simple and cost effective to fabricate, exhibits excellent long-term stability as well as thermal stability during high-power operation. This mode-locked laser scheme with a liquid-phase DNA component has the potential to provide in-depth understanding of the optical nonlinearity and usefulness of DNA.

Summary: Id helix-loop-helix (HLH) proteins (Id1–4) bind E protein bHLH transcription factors, preventing them from forming active transcription complexes that drive changes in cell states. Id proteins are primarily expressed during development to inhibit differentiation, but they become re-expressed in adult tissues in diseases of the vasculature and cancer. We show that the genetic loss of Id1/Id3 reduces ocular neovascularization in mouse models of wet age-related macular degeneration (AMD) and retinopathy of prematurity (ROP). An in silico screen identifies AGX51, a small-molecule Id antagonist. AGX51 inhibits the Id1-E47 interaction, leading to ubiquitin-mediated degradation of Ids, cell growth arrest, and reduced viability. AGX51 is well-tolerated in mice and phenocopies the genetic loss of Id expression in AMD and ROP models by inhibiting retinal neovascularization. Thus, AGX51 is a first-in-class compound that antagonizes an interaction formerly considered undruggable and that may have utility in the management of multiple diseases. : Wojnarowicz et al., describe the identification, by an in silico screen, and characterization of a small molecule, AGX51, that targets Id proteins. AGX51 treatment of cells lead to Id protein degradation, cell cycle arrest, and reduced cell viability. AGX51 inhibited pathologic ocular neovascularization in mouse models, phenocopying genetic Id loss. Keywords: Id proteins, protein-protein interactions, macular degeneration, retinopathy of prematurity, angiogenesis

Many studies have demonstrated that an alteration in hemorheological properties is closely correlated with diabetic microcirculatory diseases. However, most of these studies have been limited to animal studies or used a small number of clinical samples, due to a lack of effective point-of-care (POC) devices to measure such properties within clinical environments. Owing to recent developments in microfluidic technology, several hemorheological POC devices have been designed that allow for the possibility of conducting extensive clinical studies using hemorheological measurements. Here, we reviewed recent clinical studies of diabetic kidney disease (DKD) associated with hemorheological parameters. We found that RBC deformability alone did not show a significant difference according to the degree of DKD, whereas critical shear stress (CSS) was found to be closely related to the ratio of albumin to creatinine and glomerular filtration rate. We also reviewed studies that alteration of hemorheological properties are associated with the development of DKD, which showed that CSS could be considered as a potential index to diagnose other diabetic complications as well as DKD.

Objective: To investigate the triglyceride-glucose (TyG) index association with coronary artery calcification (CAC) progression in adult Koreans.Research Design and Methods: Various cardiovascular risk factors and anthropometric profiles were assessed in 1,175 subjects who previously had a CAC evaluation at least twice by multidetector computed tomography in a health care center. The TyG index was determined using ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). The CAC progression was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACSs) of subjects with detectable CAC at baseline.Results: CAC progression was seen in 312 subjects (27%) during 4.2 years follow-up. On the basis of the TyG index, subjects were stratified into three groups. Follow-up CACS and incidence of CAC progression were markedly elevated with rising TyG index tertile. Logistic regression analysis adjusted for various risk factors revealed an odds ratio for CAC progression of 1.82 (95% CI 1.20-2.77; P ≤ 0.01) when the highest and lowest TyG index tertiles were compared.Conclusions: The TyG index is an independent predictor of CAC progression. [ABSTRACT FROM AUTHOR]

We propose and experimentally demonstrate a Brillouin optical correlation domain analysis system adopting time-domain data processing and differential measurement for simultaneous interrogation of multiple sensing points. Continuous probe and pulsed pump waves are simultaneously frequency-modulated by a MHz-order sinusoidal RF wave so that multiple correlation peaks are sequentially generated according to the propagation of the pump along a fiber under test (FUT). The Brillouin gain spectrum of each correlation peak is obtained and interrogated by moving window averaging of the probe wave with a span of the period of the RF modulation, leading to the simultaneous monitoring of the multiple sensing points. In experiments, 148 correlation peaks are concurrently interrogated with a spatial resolution less than 3 cm along a 1530 m FUT. [ABSTRACT FROM AUTHOR]

An all-fiber type, CW, linearly polarized thulium-doped fiber laser is reported. Highly linear polarization was achieved by a special management of fiber Bragg gratings, which performs as the laser cavity reflectors. The laser generated 28 W signal output at 1949 nm with a slope efficiency of 47.3%. The polarization extinction ratio of the laser was measured to be around 20 dB. The beam quality of the laser was near diffraction-limited, with M² of 1.1. The laser's output features make it to be a potential light source for some important applications such as for pumping holmium-doped solid state lasers. [ABSTRACT FROM AUTHOR]

Dental light-cured resins can undergo different degrees of polymerization when applied in vivo. When polymerization is incomplete, toxic monomers may be released into the oral cavity. The present study assessed the cytotoxicity of different materials, using sample preparation methods that mirror clinical conditions. Composite and bonding resins were used and divided into four groups according to sample preparation method: uncured; directly cured samples, which were cured after being placed on solidified agar; post-cured samples were polymerized before being placed on agar; and "removed unreacted layer" samples had their oxygen-inhibition layer removed after polymerization. Cytotoxicity was evaluated using an agar diffusion test, MTT assay, and confocal microscopy. Uncured samples were the most cytotoxic, while removed unreacted layer samples were the least cytotoxic (p < 0.05). In the MTT assay, cell viability increased significantly in every group as the concentration of the extracts decreased (p < 0.05). Extracts from post-cured and removed unreacted layer samples of bonding resin were less toxic than post-cured and removed unreacted layer samples of composite resin. Removal of the oxygen-inhibition layer resulted in the lowest cytotoxicity. Clinicians should remove unreacted monomers on the resin surface immediately after restoring teeth with light-curing resin to improve the restoration biocompatibility. [ABSTRACT FROM AUTHOR]

Thisstudy reports a synthetic polymer functionalized with catecholgroups as dental adhesives. We hypothesize that a catechol-functionalizedpolymer functions as a dental adhesive for wet dentin surfaces, potentiallyeliminating the complications associated with saliva contamination.We prepared a random copolymer containing catechol and methoxyethylgroups in the side chains. The mechanical and adhesive propertiesof the polymer to dentin surface in the presence of water and salivarycomponents were determined. It was found that the new polymer combinedwith an Fe3+additive improved bond strength of a commercialdental adhesive to artificial saliva contaminated dentin surface ascompared to a control sample without the polymer. Histological analysisof the bonding structures showed no leakage pattern, probably dueto the formation of Fe–catechol complexes, which reinforcethe bonding structures. Cytotoxicity test showed that the polymersdid not inhibit human gingival fibroblast cells proliferation. Resultsfrom this study suggest a potential to reduce failure of dental restorationsdue to saliva contamination using catechol-functionalized polymersas dental adhesives. [ABSTRACT FROM AUTHOR]

B23/nucleophosmin is a multifunctional protein that participates in cell survival signaling by shuttling between the nucleolus/nucleoplasm and nucleus/ cytoplasm. In this paper, we report a novel neuroprotective function of B23 through regulation of the SIAH1- glyceraldehyde-3-phosphate dehydrogenase (GAPDH) death cascade. B23 physiologically bound to both SIAH1 and GAPDH, disrupting the SIAH1-GAPDH complex in the nucleus in response to nitrosative stress. S-nitrosylation of B23 at cysteine 275 by trans-nitrosytation from GAPDH dramatically reduced the interaction between SIAH1 and GAPDH. S-nitrosylation of B23 enhanced B23-SIAH1 binding and mediated the neuroprotective actions of B23 by abrogating the E3 ligase activity of SIAH1. In mice, overexpression of B23 notably inhibited N-methyi-D-aspartate-mediated neurotoxicity, whereas expression of the C275S mutant, which is defective in binding to SIAH1, did not prevent neurotoxicity. Thus, B23 regulates neuronal survival by preventing SIAH1-GAPDH death signaling under stress-induced conditions in the brain. [ABSTRACT FROM AUTHOR]

Dental implant failure often occurs due to oral bacterial infection. The aim of this study was to demonstrate that antibiotic efficacy could be enhanced with modified titanium. First, the titanium was modified by anodization and heat-treatment. Then, a biomimetic coating process was completed in two steps. Surface characterization was performed with scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. Release of antibiotic was evaluated by UV/VIS spectrometry, and the antibacterial effect was evaluated on Streptococcus mutans. After the second coating step, we observed a thick homogeneous apatite layer that contained the antibiotic, cefalotin. The titanium formed a rutile phase after the heat treatment, and a carbonated apatite phase appeared after biomimetic coating. We found that the modified titanium increased the loading of cefalotin onto the hydroxyapatite coated surface. The results suggested that modified titanium coated with a cefalotin using biomimetic coating method might be useful for preventing local post-surgical implant infections. [ABSTRACT FROM AUTHOR]

B23/NPM is a major nucleolar phosphoprotein that has a critical role in cell proliferation and cell death. Here, we show that it forms a complex with Akt on growth factor (GF) stimulation in both the cytoplasm and the nucleus, for which Akt activation is indispensable. The C terminus of B23 (239-294 residues) potently binds pleckstrin homology (PH) domain of Akt. Akt binding to B23 protects it from proteolytic degradation by caspase-3, leading to the up-regulation of cell survival, Interestingly, unsumoylated B23 K263R, but not wild-type 823, strongly interacts with Akt in the nucleoplasm in the absence of GFs. Furthermore, we show that Akt2, but not other isoforms, specifically regulates B23 sumoylation and protein stability. Also, nuclear Akt regulates the cell cycle progression activity of B23. Therefore, our findings support that nuclear Akt binds and stabilizes B23 in the nucleoplasm, and regulates its activities in cell survival and cell cycle. [ABSTRACT FROM AUTHOR]