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Donor-doped SrTiO 3 is a promising material for use as an alternative anode to solve stability problems due to carbon coking or Ni coarsening etc. of conventional Ni-cermet anodes. Electro-catalytic Ni nanoparticles can be produced in La and Ni co-doped SrTiO 3 or La 0.2 Sr 0.8 Ti 0.9 Ni 0.1 O 3-δ (LSTN) anode when it is exposed to a reducing atmosphere. In this work, we study the effects of Gd 0.2 Ce 0.8 O 2−δ (GDC) either as an anode interlayer (between anode and electrolyte) or as a composite phase in an anode composed of La and Ni co-doped SrTiO 3 (La 0.2 Sr 0.8 Ti 0.9 Ni 0.1 O 3- δ , LSTN). The electrochemical performance (i.e., impedance spectra and power density) of electrolyte-supported cells in which scandia-stabilized zirconia (ScSZ) is used as an electrolyte and LSTN or LSTN-GDC is used as the anode, are examined and compared at 800 ° C in H 2 and CH 4 fuels. LSTN anode was stable and had improved performance in both H 2 and CH 4 fuels when GDC was composited and also used as an anode interlayer. A significant reduction of anodic polarization resistance in CH 4 gas is clearly demonstrated.

Perovskite oxides have potential for use as alternative anode materials in solid oxide fuel cells (SOFCs) due to stability in anode atmosphere; donor-doped SrTiO3 (e.g., La0.2Sr0.8TiO3−δ) is a good candidate for this purpose. Electro-catalytic nanoparticles can be produced in oxide anodes by the ex-solution method, e.g., by incorporating Ni into a perovskite oxide in air, then reducing the oxide in H2 atmosphere. In this study, we varied the temperature (1100, 1250 °C) and atmosphere (air, H2) of La0.2Sr0.8Ti0.9Ni0.1O3−δ (LSTN) anode firing to control the degree of Ni ex-solution and microstructure. LSTN fired at 1250 °C in H2 showed the best anodic performance for scandia-stabilized zirconia (ScSZ) electrolyte-supported cells in H2 and CH4 fuels due to the favorable microstructure and Ni ex-solution.

In our previous study, Hizikia fusiformis extract (HFE) has gastroprotective effects in animal model for gastric ulcer. The purpose of this study was to investigate whether HFE had similar gastro-protective effects in human subjects. A randomized, double-blind, placebo-controlled trial was conducted. To fulfill this purpose, a group of subjects with erosive gastritis were orally supplemented with the HFE or placebo for 4 weeks and efficacy and safety were measured. Primary outcome (number of erosions, endoscopic score and estimated cure rates of erosions) and the secondary outcomes (estimated improvement rates of erosions, subjects’ symptom questionnaires and blood profiles) before and after the 4-week intervention period were compared. The HFE supplementation showed a significant reduction in number of erosions compared with placebo group. In subjects whose endoscopic score were 4 points (erosions more than 6) at baseline, HFE supplementation resulted in a significant decrease of number of erosions compared with placebo group. High sensitive-C reactive protein (hs-CRP) levels showed a tendency to decrease in HFE-supplemented group. Finally, blood parameters and clinical findings for organ toxicity remained within the normal range. These results suggest that HFE may have therapeutic potential in subjects with erosive gastritis.

Scope In this study, we focus on the effects of n-3 polyunsaturated fatty acids (PUFAs) on tunicamycin-, streptozotocin-, or high fat diet (HFD)-induced β-cell damage and dysfunction. Materials and methods Pretreatment with n-3 PUFAs protected RINm5F cells and mouse islets against tunicamycin-induced β-cell damage through suppression of ER stress and apoptosis induction. This protective effect of n-3 PUFAs on β-cells was further demonstrated by the normalization of insulin secretion in response to glucose in tunicamycin-treated islets. In multiple low-dose streptozotocin-induced diabetes models, fat-1 mice, which endogenously synthesize n-3 PUFAs from n-6 PUFAs, were fully resistant to the development of diabetes, with normal islet morphology, high insulin immunoreactivity, and decreased apoptotic cells. In HFD-induced diabetes models, fat-1 mice also exhibited improved glucose tolerance and functional β-cell mass. In both diabetes models, we observed an attenuation of ER stress in fat-1 mice. Interestingly, n-3 PUFAs attenuated the nuclear translocation of lipogenic transcription factors sterol regulatory element-binding protein-1 (SREBP-1) and C/EBPβ, induced by tunicamycin or HFD, suggesting that n-3 PUFAs suppress ER stress via modulation of SREBP-1 and C/EBPβ. Conclusion Together, these results suggest that n-3 PUFAs block ER stress, thus protecting β cells against diabetogenic insult; therefore, dietary supplementation of n-3 PUFAs has therapeutic potential for the preservation of functional β-cell mass.

It is suggested that n-3 polyunsaturated fatty acids (PUFAs) can be used in the preventive or therapeutic management of rheumatoid arthritis (RA); however, controversial results have been reported. Here, we examined the effects of a decrease in the n-6/n-3 PUFA ratio on RA using fat-1 transgenic mice. First, we tested whether fat-1 expression modulated signaling pathways in fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor α (TNF-α). TNF-α activated p38 mitogen-activated protein kinase and increased phosphorylation of the signal transducer and activator of transcription 3 in wild type (WT) FLSs but not in fat-1 FLSs. Arthritis was induced by injection of K/BxN serum. Based on clinical scores, ankle thickness and pathological severity, we showed that WT mice developed clinically overt arthritis, whereas fat-1 mice showed attenuated arthritis. Moreover, fat-1 mice exhibited down-regulated local and systemic levels of inflammatory cytokines. Lastly, bone marrow-derived macrophages (BMMs) of WT mice differentiated into tartrate-resistant acid phosphatase-positive multinucleated osteoclasts, whereas the osteoclastogenenic process was suppressed in BMMs of fat-1 mice. The endogenous conversion of n-6 to n-3 PUFAs via fat-1 plays a key role in attenuation of RA; therefore, dietary supplementation of n-3 PUFAs may have therapeutic potential for the management of RA.

Aim Mixed grain, which contributes to lowered glycaemic responses, has been shown to be effective in dietary management of patients with impaired glucose tolerance or diabetes. Methods The present study determined the postprandial blood glucose response of 20 healthy volunteers to mixed grains containing giant embryonic rice (MG-GER) or giant embryonic brown rice (MG-GEBR) compared with white rice (WR) in a randomised crossover design. Plasma glucose and serum insulin at 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes were measured, and glycaemic index (GI) and incremental area under the curve (iAUC) were calculated. Results The GIs for WR, MG-GER and MG-GEBR were 86.75 ± 5.78, 76.09 ± 7.01 and 69.33 ± 6.54, respectively. The 120-minute iAUCs after administration of MG-GER or MG-GEBR were significantly lower than that of WR. In addition, the MG-GEBR diet group had a significantly lower C-peptide concentration at the 120-minute time point when compared to the WR group. Conclusions These results suggest that consumption of MG-GER or MG-GEBR instead of WR is more effective to reduce postprandial glucose levels without increasing insulin secretion.

Background & aims Kochujang, a traditional fermented red pepper paste, is known for its hypocholesterolemic effect; however, these studies used non-commercial preparations of kochujang. In this study, we examined whether commercially-made kochujang in which Aspergillus oryzae (also known as koji) was used as a microorganism for fermentation has the same cholesterol-lowering effects. Methods Hyperlipidemic subjects (based upon criteria of 110 ∼ 190 mg/dL LDL cholesterol or 200 ∼ 260 mg/dL total cholesterol) who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 30 subjects were randomly divided into either the kochujang (n = 15) or placebo (n = 15) group. All subjects ingested either the kochujang pill (34.5 g/d) or a placebo three times daily during meals for 12 weeks. Outcomes included measurements of efficacy (total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride) and safety (adverse events, laboratory tests, electrocardiogram, and vital signs). Results In the kochujang-supplemented group, subjects' total cholesterol level significantly decreased (from 215.5 ± 16.1 mg/dL to 194.5 ± 25.4 mg/dL, p = 0.001). LDL-C cholesterol levels were also decreased by kochujang supplementation (from 133.6 ± 14.8 mg/dL to 113.5 ± 23.1 mg/dL); however no significant difference was seen between groups (p = 0.074). There were no statistically significant differences in HDL-cholesterol and triglyceride levels between the supplemented and non-supplemented groups. None of the subjects complained of any adverse effects. Conclusions These results indicate that A. oryzae-fermented kochujang elicits a significant hypocholesterolemic effect and might be useful for improving blood cholesterol levels in subjects at high risk for cardiovascular disease. Clinical trial registration NCT01865370.

Previously, powdered persimmon leaves have been reported to have glucose- and lipid-lowering effects in diabetic (db/db) mice. As persimmon leaf is commonly consumed as tea, an aqueous extract of persimmon leaves (PLE) was prepared and its anti-diabetic efficacy was investigated. In the present study, PLE was tested for its inhibitory activity on α-glucosidase in vitro. An oral maltose tolerance test was performed in diabetic mice. Next, the acute effect of PLE was examined in streptozotocin-induced diabetic mice. Last, the long-term effect of PLE supplementation was assessed in db/db after eight weeks. An oral glucose tolerance test, biochemical parameters, as well as histological analyses of liver and pancreas were evaluated at the end of the study. PLE inhibited α-glucosidase activity and increased antioxidant capacity. Streptozotocin-induced diabetic mice pre-treated with PLE displayed hypoglycemic activity. Daily oral supplementation with PLE for eight weeks reduced body weight gain without affecting food intake, enhanced the glucose tolerance during the oral glucose tolerance test (OGTT), improved blood lipid parameters, suppressed fat accumulation in the liver and maintained islet structure in db/db mice. Further mechanistic study showed that PLE protected pancreatic islets from glucotoxicity. In conclusion, the results of the present study indicated that PLE exhibits considerable anti-diabetic effects through α-glucosidase inhibition and through the maintenance of functional β-cells. These results provided a rationale for the use of persimmon leaf tea for the maintenance of normal blood glucose levels in diabetic patients.

An advanced centrifugal microsystem is developed which has capability of automatic and programmed chemical reagent loading and reactions to screen the colloidal nanocrystal synthesis in a high-throughput manner. As a proof of concept, triplicate synthetic reactions for water-soluble multi-color CdS nanocrystals are executed under ten different conditions on a chip. The proposed disk-shaped microdevice contains a top layer for distributing the reagents through zig-zag continuous channels and a bottom layer for 30 functional units, each of which is composed of a reaction chamber and three reservoirs connected with a control, a precursor, and a basic solution, respectively. All the reservoirs are linked to the main channel via different microfluidic channel dimension, and the main channel is directed to the reaction chamber. Through rotational speed control, the three solutions are sequentially loaded to the reaction chamber with precise volume, and the multiplex CdS nanocrystals synthesis is processed. By tuning the concentration of sulfur in a control solution, multi-color CdS nanocrystals are produced from green to red depending on the molar ratios of Cd2+ to S2−.

We have proposed a novel rotary microdevice in which multiplex anisotropic metallic nanoparticles (NPs) can be synthesized under diverse conditions in a high-throughput manner. In this study, by tuning the concentration of ascorbic acid (AA) as a control solution, the shape evolution from hexagon to tripod of gold nanoparticles (Au NPs) was achieved.

A catalyst of Ag with alumina has been widely used for the decomposition of odorous ammonia. In order to meet cost effectiveness, copper was added with five different doping ratios of Ag/Cu in this work, and NH3 decomposition was examined at 150–400 °C. Experimental results show that the catalyst doped with only Cu shows very weak potential to oxidize NH3 despite its excellent selectivity for nitrogen molecules than NO or N2O at temperatures over 300 °C. Analysis by X-ray photoelectron spectroscopy indicates that Ag0 is the major chemical functionality that determines the decomposition rate of NH3 at low temperature, e.g., 200 °C, while Ag+ and Ag2+ are efficient at higher temperatures. Among the five segregated copper functionalities, only Cu 2pa/2 appeared to be favorable for the activity of Ag particles. It was found from the experimental results that Ag/Cu = 1:9 could provide a cost-effective combination for the low temperature regime.

With the growth of the wearable electronics industry, structural modifications of sensing materials have been widely attempted to improve the sensitivity of sensors. Herein, we demonstrate patterned graphene strain sensors, which can monitor small-scale motions by using the simple, scalable, and solution-processable method. The electrical properties of the sensors are easily tuned via repetition of the layer-by-layer assembly, leading to increment of thickness of the conducting layers. In contrast to nonpatterned sensors, the patterned sensors show enhanced sensitivity and the ability to distinguish subtle motions, such as similar phonations and 81 beats per minute of pulse rate.

Sirtuin (Sirt)6 has been implicated in negative regulation of inflammation and lipid metabolism, although its function in the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains to be defined. To explore the role of hepatocyte Sirt6 in NASH development, we generated hepatocyte-specific Sirt6-knockout (KO) mice that were fed a high-fat and high-fructose (HFHF) diet for 16 wk. HFHF-fed KO mice had increased hepatic steatosis and inflammation and aggravated glucose intolerance and insulin resistance compared with wild-type mice. HFHF-induced liver fibrosis and oxidative stress and related gene expression were significantly elevated in KO mice. In the livers of KO mice, nuclear factor erythroid 2-related factor 2 (Nrf2) was down-regulated; conversely, BTB domain and CNC homolog 1 (Bach1), a nuclear repressor of Nrf2, were up-regulated. We discovered that Sirt6, which interacts with Bach1 under basal condition, induces its detachment from the antioxidant response element (ARE) region of heme oxygenase 1 promoter. Furthermore, we found that Sirt6 promotes Nrf2 binding to ARE in response to oxidative stimuli, which leads to the expression of phase II/antioxidant enzymes. Finally, we showed that HFHF-induced steatosis, inflammation, and fibrosis were ameliorated by adenoviral Sirt6 overexpression. Sirt6 may be a useful therapeutic target for amelioration of NASH by curbing inflammation and oxidative stress.-Ka, S.-O, Bang, I. H., Bae, E. J., Park, B.-H. Hepatocyte-specific sirtuin 6 deletion predisposes to nonalcoholic steatohepatitis by up-regulation of Bach1, an Nrf2 repressor.

Recently, the roles of FAM83H in tumorigenesis have been interested and increased expression of FAM83H and MYC in hepatocellular carcinoma (HCC) have been reported. Therefore, we investigated the expression and role of FAM83H in 163 human HCCs and further investigated the relationship between FAM83H and oncogene MYC. The expression of FAM83H is elevated in liver cancer cells, and nuclear expression of FAM83H predicted shorter survival of HCC patients. In HLE and HepG2 HCC cells, knock-down of FAM83H inhibited proliferation and invasive activity of HCC cells. FAM83H induced expression of cyclin-D1, cyclin-E1, snail and MMP2 and inhibited the expression of P53 and P27. In hepatic tumor cells derived from Tet-O-MYC mice, the expression of mRNA and protein of FAM83H were dependent on MYC expression. Moreover, a chromatin immunoprecipitation assay demonstrated that MYC binds to the promotor of FAM83H and that MYC promotes the transcription of FAM83H, which was supported by the results of a dual-luciferase reporter assay. In conclusion, we present an oncogenic role of FAM83H in liver cancer, which is closely associated with the oncogene MYC. In addition, our results suggest FAM83H expression as a poor prognostic indicator of HCC patients.

Inflammation is an important factor in the development of insulin resistance. SIRT1, a class 3 histone/protein deacetylase, has anti-inflammatory functions. Myeloid-specific deletion ofSirt1promotes macrophage infiltration into insulin-sensitive organs and aggravates tissue inflammation. In this study, we investigated how SIRT1 in macrophages alters tissue inflammation in the pancreas as well as liver and adipose tissue, and further explored the role of SIRT1 in locomotion of macrophages. Myeloid-specificSirt1-deleted mice (mS1KO) and WT littermates were fed a 60% calorie high-fat diet (HFD) for 16 weeks. Tissue inflammation and metabolic phenotypes were compared. Bone marrow macrophages (BMMs) from WT or mS1KO mice were used inin vitrochemotaxis assays and macrophage polarization studies. mS1KO mice fed a HFD exhibited glucose intolerance, reduced insulin secretion, and insulin sensitivity with a slight decrease in body weight. Consistent with these results, pancreatic islets of mS1KO mice fed a HFD displayed decreased mass with profound apoptotic cell damage and increased macrophage infiltration and inflammation. Liver and adipose tissues from mS1KO HFD mice also showed greater accumulation of macrophages and tissue inflammation. Results fromin vitroexperiments indicated that deletion of myeloidSirt1stimulated proinflammatory M1-like polarization of BMMs and augmented the adipocyte-mediated macrophage chemotaxis. The latter effect was accompanied by increased expression and acetylation of focal adhesion kinase, as well as nuclear factor kappa B. Our results indicate that myeloid SIRT1 plays a crucial role in macrophage polarization and chemotaxis, and thus regulates the development of HFD-induced pancreatic inflammation and insulin secretion, and metabolic derangements in liver and adipose tissue.

The development of esophageal squamous carcinomas (ESC) results from numerous genetic alterations. Our previous study demonstrated that p63 is highly expressed in human ESC cells and stimulates their growth; however, the mechanism by which p63 regulates ESC cell adhesion and invasion remains unclear. In the present study, we further elucidated the underlying molecular mechanisms by which p63 regulates metastasis in ESC cells. Knockdown of p63 significantly diminished the invasion of ESC cell lines TE-8 and TE-12, whereas overexpression of p63 significantly increased the migration rates of BE3 and OE33 cells. The mRNA and protein levels of vimentin, twist, SUSD2, and uPA were significantly decreased in p63-knockdown ESC cells, while overexpression of p63 induced an increase in vimentin, SUSD2, and uPA. In addition, knockdown of p63 in ESC cells significantly reduced levels of β-catenin and c-Myc, while overexpression of p63 increased β-catenin, but reduced p-β-catenin level. Therefore, p63 regulates the migration and invasion of ESC cells through activation of the β-catenin/c-Myc pathway. Our results suggest that targeting p63 may constitute a potential therapeutic strategy for ESC.

Electro-catalytic nanoparticles can be produced in oxide anodes for solid oxide fuel cell (SOFC) by an ex-solution method, i.e., by incorporating metals into a perovskite oxide phase in air followed by the reduction of the perovskite oxide. In this study, we used a Ni ex-solution method with a La and Ni co-doped SrTiO 3 (La 0.2 Sr 0.8 Ti 1 − x Ni x O 3 − δ , x = 0–0.2) anode for SOFC. The parameters and mechanisms of the Ni ex-solution were investigated by varying the ex-solution temperature (800–1300 °C) and time (3–24 h). The degrees of Ni ex-solution and Ti reduction were dependent on time and temperature. Ni ex-solution reaction was relatively faster than Ti reduction which required a higher temperature or a longer time. XRD analysis was used to observe the changes in the lattice parameter of La 0.2 Sr 0.8 Ti 1 − x Ni x O 3 − δ after the ex-solution process. The electrochemical performance of an electrolyte (Sc-stabilized zirconia)-supported cell with the La 0.2 Sr 0.8 Ti 1 − x Ni x O 3 − δ anode with x = 0.1 showed that the total cell resistance is high, due mostly to the anode resistance. The maximum power density at 800 °C is also relatively low, ~ 150 mW/cm 2 , due to the thick (~ 300 μm) electrolyte and the low level of anodic performance.

Stresses, such as exposure to ultraviolet radiation and those associated with aging, are known to cause premature cellular senescence that is characterized by growth arrest and morphological and gene expression changes. This study was designed to investigate the protective effect of Sirtuin1 (SIRT1) on the UVB-induced premature senescence. Under in vitro experimental conditions, exposure to a subcytotoxic dose of UVB enhanced human skin fibroblasts senescence, as characterized by increased β-galactosidase activity and increased levels of senescence-associated proteins. However, adenovirus-mediated SIRT1 overexpression significantly protected fibroblasts from UVB-induced cellular deterioration. Exposure to UVB-induced cell senescence was associated with oxidative stress and p38 mitogen-activated protein kinase activation. Molecular analysis demonstrated that deacetylation of Forkhead box O3α (FOXO3α) by SIRT1 changed the transcriptional activity of FOXO3α and increased resistance to the oxidative stress. In addition, SIRT1 suppressed UVB-induced p53 acetylation and its transcriptional activity, which directly affected the cell cycle arrest induced by UVB. Further study demonstrated that SIRT1 activation inhibited cell senescence in the skin of the HR1 hairless mouse exposed to UVB. The study identifies a new role for SIRT1 in the UVB-induced senescence of skin fibroblats and provides a potential target for skin protection through molecuar insights into the mechanisms responsible for UVB-induced photoaging.

Metal-supported solid oxide fuel cell (MS-SOFC) is promising for use at intermediate temperature range (500-700°C) since metal could provide the good thermal conductivity and the mechanical strength in addition to the low cost. The MS-SOFCs are often fabricated by co-firing in reducing atmosphere to avoid metal oxidation. However, the inter-diffusion between Fe/Cr in stainless steel (STS) and Ni in the conventional cermet anode is detrimental to the electrochemical performance of the cell. In this study, a multi-layered cell consisting of a yttria-stabilized zirconia (YSZ) electrolyte, and a porous anode layer, and a ferritic STS support, was fabricated using tape casting and co-firing process. The cell with alternative anode was compared with that with conventional anode in terms of microstructure, Cr poisoning, and thus anodic performance. It was found that the use of diffusion barrier layer (DBL) reduces the reaction between conventional Ni-cermet anode and STS and provides a stable performance. The performance can be further enhanced with an alternative anode.

CK2a has diverse effects on the tumorigenesis owing to its kinase activity, which phosphorylates various proteins involved in tumorigenesis. We, therefore, investigated the expression and role of CK2a in the phosphorylation of deleted in breast cancer 1 (DBC1) in gastric carcinomas. We used 187 gastric carcinomas and human gastric cancer cells to investigate the roles and relationship between CK2a and DBC1 in gastric carcinomas. Positive expression of CK2a and phospho-DBC1 predicted shorter overall survival and relapse-free survival by univariate analysis. Especially, CK2a expression was an independent prognostic indicator for gastric carcinoma patients. In gastric carcinoma cells, CK2a was bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2a was evidenced by co-immunoprecipitation of CK2a and DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. Inhibition of both CK2a and DBC1 decreased proliferation and invasive activity of cancer cells. Decreased migration and invasive activity was associated with a downregulation of MMP2, MMP9 and the epithelial–mesenchymal transition. A mutation at the phosphorylation site of DBC1 also downregulated the signals related with the epithelial–mesenchymal transition. Our study demonstrated that CK2a is an independent prognostic indicator for gastric carcinoma patients and is involved in tumorigenesis by regulating the phosphorylation of DBC1. In addition, the blocking of CK2a and DBC1 inhibited the proliferation and invasive potential of gastric cancer cells. Therefore, our study suggests that CK2a–DBC1 pathway might be a new therapeutic target for the treatment of gastric carcinoma.

Objective Insulin-like growth factor binding protein 3 (IGFBP-3) is known to interfere with the NF-κB signaling pathway, and it effectively promotes apoptosis in tumor cells by a variety of mechanisms. NF-κB activation and apoptosis resistance of fibroblast-like synoviocytes (FLS) play pivotal roles in rheumatoid arthritis (RA). This study was undertaken to evaluate whether IGFBP-3 has antiarthritic effects. Methods To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 complementary DNA (AdIGFBP-3) or IGFBP-3 mutant that is devoid of IGF binding affinity but retains IGFBP-3 receptor binding ability (AdmtIGFBP-3). The regulatory roles of IGFBP-3 in inflammation and bone destruction were investigated in mice with collagen-induced arthritis (CIA). Results IGFBP-3 levels were significantly higher in patients with RA than in those with osteoarthritis (OA) and were notably higher in patients with active RA. AdIGFBP-3 suppressed NF-κB activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor α (TNFα) in RA FLS. AdIGFBP-3 sensitized RA FLS to TNFα-induced apoptosis in vitro and also significantly increased apoptosis in an in vivo model of Matrigel implants engrafted into immunodeficient mice. AdIGFBP-3–injected mice with CIA had attenuated arthritis severity and reduced radiologic and pathologic abnormalities. Moreover, AdIGFBP-3 down-regulated local and systemic levels of NF-κB–targeted proinflammatory cytokines. Of note, RA FLS and mice with CIA treated with AdmtIGFBP-3 exhibited similar effects as those treated with AdIGFBP-3. Conclusion Our results suggest that both the inflammatory response and bone destruction are reduced with blockage of NF-κB activation and induction of apoptosis in RA FLS by IGFBP-3. Therefore, IGFBP-3 may have therapeutic potential in RA.

The Hippo pathway is often dysregulated in many carcinomas, which results in various stages of tumor progression. Ursolic acid (UA), a natural compound that exists in many herbal plants, is known to obstruct cancer progression and exerts anti-carcinogenic effect on a number of human cancers. In this study, we aimed to examine the biological mechanisms of action of UA through the Hippo pathway in gastric cancer cells. MTT assay showed a decreased viability of gastric cancer cells after treatment with UA. Following treatment with UA, colony numbers and the sizes of gastric cancer cells were significantly diminished and apoptosis was observed in SNU484 and SNU638 cells. The invasion and migration rates of gastric cancer cells were suppressed by UA in a dose-dependent manner. To further determine the gene expression patterns that are related to the effects of UA, a microarray analysis was performed. Gene ontology analysis revealed that several genes, such as the Hippo pathway upstream target gene, ras association domain family (RASSF1), and its downstream target genes (MST1, MST2, and LATS1) were significantly upregulated by UA, while the expression of YAP1 gene, together with oncogenes (FOXM1, KRAS, and BATF), were significantly decreased. Similar to the gene expression profiling results, the protein levels of RASSF1, MST1, MST2, LATS1, and p-YAP were increased, whereas those of CTGF were decreased by UA in gastric cancer cells. The p-YAP expression induced in gastric cancer cells by UA was reversed with RASSF1 silencing. In addition, the protein levels in the Hippo pathway were increased in the UA-treated xenograft tumor tissues as compared with that in the control tumor tissues, thus, UA significantly inhibited the tumorigenesis of gastric cancer in vivo in xenograft animals. Collectively, UA diminishes the proliferation and metastasis of gastric cancer via the regulation of Hippo pathway through Rassf1, which suggests that UA can be used as a potential chemopreventive and therapeutic agent for gastric cancer.

Estrogen withdrawal in post-menopausal women leads to overactivation of osteoclasts, which contributes to the development of osteoporosis. Inflammatory cytokines are known as one of mechanisms of osteoclast activation after estrogen deficiency. SPA0355 is a thiourea derivative that has been investigated for its antioxidant and anti-inflammatory activities. However, its efficacy in bone resorption has not been previously investigated. The aim of this study was to investigate the impact of SPA0355 on the development of osteoporosis and to explore its mode of action. In vitro experiments showed that SPA0355 inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages. This effect appears to be independent of estrogen receptor activation as ICI 180,782 failed to abrogate its effects on osteoclasts. Further signaling studies revealed that SPA0355 suppressed activation of the MAPKs, Akt, and NF-κB pathways. SPA0355 also increased osteoblastic differentiation, as evidenced by its effects on alkaline phosphatase activity and mineralization nodule formation. Intraperitoneal administration of SPA0355 to ovariectomized mice prevented bone loss, as verified by three-dimensional images and bone morphometric parameters derived from µCT analysis. Noticeably, SPA0355 did not show hepatotoxicity and nephrotoxicity and also had little effect on hematological parameters. Taken together, the results indicate that SPA0355 may protect against bone loss in ovariectomized mice by stimulation of osteoblast differentiation and by inhibition of osteoclast resorption. Therefore, SPA0355 is a safe and potential candidate for management of postmenopausal osteoporosis.

Since the emergence of lab-on-a-chip technology, a variety of chemical and biochemical assays were successfully implemented on microdevice platforms. Among the chip-based applications, genetic analysis based on the polymerase chain reaction (PCR) has been extensively developed in order to accomplish the goal of cheap, rapid, high-throughput, and point-of-care DNA testing. We are summarizing here several formats of the miniaturized PCR systems including the integration of units for sample pretreatment and downstream analytical detection. The various sections cover (a) miniaturized PCR systems, (b) integrated sample pretreatment-PCR microsystems, (c) integrated PCR-detection microsystems, and (d) integrated sample pretreatment-PCR-detection microsystems. Respective microdevices were successfully introduced recently in the form of a fully integrated microsystem for genetic analysis with sample-in-answer-out capability. Contains 120 references.

Background context There is no comparative study of the in vitro and in vivo osteogenic potential of iliac bone chips (autogenous iliac cancellous bone chips) compared with bone dusts generated during the decortication process with a high-speed burr in spine fracture or fusion surgery. Purpose To compare the osteogenic potential of three sizes of bone dusts with iliac bone chips and to determine whether bone dusts can be used as a bone graft substitute. Study design In vitro and in vivo study. Methods Bone chips were harvested from the posterior superior iliac spine and bone dusts from the vertebrae of 15 patients who underwent spinal fracture surgery. Bone dust was divided into three groups: small (3 mm), middle (4 mm), and large (5 mm) according to the size of the burr tip. A comparison was made using a cell proliferation assay, alkaline phosphatase (ALP) activity, the degree of mineralization in an in vitro model, and radiographic and histologic studies (the change of absorbable area and tissue density) after implantation of the various materials into back muscles of nude mice. Results Although all three bone dust groups were less active with regard to cell proliferation, ALP activity, and the degree of mineralization, than were bone chips, they still exhibited osteogenic potential. Furthermore, there was no significant difference among the three bone dust groups. The three bone dust groups did show greater absorbable area and change of the tissue density than did the iliac bone chip group. Again, there was no significant difference among the three bone dust groups in this regard. Histologically, specimens from the bone dust groups had a higher osteoclast cell number than specimens from the iliac bone chip group. Conclusions The osteogenic potential of bone dusts is lower than that of iliac bone chips, and the absorption speed of bone dusts in vivo is faster than that of iliac bone chips. The increased resorption speed appeared to result from an increase in osteoclast cell number. Therefore, caution needs to be used when surgeons employ bone dust as a bone graft substitute.

Conventional Ni-cermet anodes show problems for the stability due to carbon coking or Ni coarsening etc.. Perovskite oxides are good candidates as an alternative anode. Electro-catalytic nanoparticles such as Ni can be produced using exsolution method or produced in oxide anodes after exposure to reducing atmosphere. In this study, we have used LSTN (La0.2Sr0.8Ti1-xNixO3-ä) as an alternative anode and investigated its electrochemical performance. Impedance spectra and power measurement of the cell with the exsolution anodes have shown the improved performance of LSTN anode in hydrogen and methane fuel.

Metabolic syndrome is characterized by insulin resistance, dyslipidemia and hypertension. These metabolic changes contribute to the development of obesity-induced kidney injury. AMP-activated protein kinase (AMPK) is a ubiquitous enzyme that is involved in the cellular metabolic response to metabolic stress. Metformin, an AMPK activator, has been reported to exert a protective effect against non-alcoholic steatohepatitis. However, little is known about its role in the pathogenesis of obesity-induced renal injury. The aim of this study was to investigate the effects of metformin on high-fat diet (HFD)-induced kidney injury. Obesity was induced by HFD (60% of total calories from fat, 20% protein and 20% carbohydrates) in 6-week-old C57BL/6 mice. Mice were fed HFD plus 0.5% metformin. The effects of metformin on HFD-induced renal injury were evaluated by determining metabolic parameters, serum adipokine levels and renal AMPK/acetyl-CoA carboxylase (ACC) activities, as well as a histological examination. HFD induced metabolic derangement, systemic insulin resistance and glomerular mesangial matrix expansion. The administration of metformin reduced HFD-induced metabolic derangement and renal injury. The administration of metformin reduced the HFD-induced increase in adipokine expression and macrophage infiltration. Moreover, renal AMPK activity, which was decreased by HFD, was recovered following the administration of metformin; in addition, fatty acid oxidation was increased by the inhibition of ACC. These results indicate that metformin exerts beneficial effects on obesity-induced renal injury by regulating systemic inflammation, insulin resistance and the renal AMPK/ACC pathway. The clinical application of metformin to obese or early diabetic patients may be helpful in preventing obesity- or diabetes-related kidney disease.

The purpose of this study was to examine the reliability of posturography using a newly developed automatic balance calibration system (I Balance S (CyberMedic Co., Korea)). Twenty-three patients who volunteered participated in this study. Mean center of gravity (COG) sway velocity, total distance, maximum velocity (MV), average movement degree (AMD), maximum excursion (ME) and directional control (DC) were measured by I Balance S. Overall stability index and overall directional control score were measured by Biodex Balance System (Biodex Medical Systems Inc., New York, USA). For the accurate measurement, the COG was automatically calibrated to zero before each measurement by I Balance S. Each subject was tested twice by examiner A and once by examiner B. The intraclass correlation coefficients (ICC) were calculated to assess the inter-rater and intra-rater reliability. Inter-rater reliabilities were higher with the I Balance S (ICC, 0.80-0.91) than with the Biodex Balance System (ICC, 0.71-0.82). Intra-rater reliabilities were similar between the I Balance S (ICC, 0.88-0.94) and the Biodex Balance System SD (ICC, 0.90-0.91). I Balance S using an automatic balance calibration system is a reliable posturography method for performing balance assessments.

The purpose of this study was to evaluate the effect of newly developed balance training system (I balance S®) in chronic hemiplegic patients. Thirty chronic (more than 6 months) hemiplegic patients who were capable of standing without assistive devices participated in this study. The study started with “pre-evaluation” such as Berg balance test (BBT), 10 m walking test (10mWT) and Functional reach test (FRT). After pre-evaluations, balance training was applied for 4 weeks. And then, three phases of post-evaluation were performed, just after (post 1), 1 week (post 2), and 4 weeks (post 3) after treatment. All subjects showed a significant improvement in BBT (52.19±3.87 (pre), 53.12±3.14 (post 1), 53.38±2.99 (post 2), 53.65±2.90 (post 3)), 10m WT (9.93±2.36 sec, 9.56±2.53 sec, 9.30±2.25 sec, 9.16±2.62 sec, respectively) and FRT (19.33±4.99 cm, 21.55±4.57 cm, 21.98±4.69 cm, 21.83±4.84 cm, respectively) after training compared to the status before training. The hemiplegic patients trained by I balance S® showed a significant improvement in BBT, 10mWT and FRT after training. In addition, this effect lasted for 4 weeks. Therefore, newly developed balance training system (I balance S®) is considered to be a useful tool for balance training of chronic hemiplegic patients.

Obesity is considered a clinical risk sign for Legg-Calve-Perthes disease (LCPD). Leptin is primarily secreted by adipocytes, and it regulates adipose tissue mass and body weight. Furthermore, obesity is clearly associated with increased leptin levels. We investigated the roles of leptin and the soluble leptin receptor (sOB-R) in LCPD. This matched case-control study included 38 male and 3 female patients with LCPD, and an equal number of age-(range was 4-12) and sex-matched control patients with healthy fractures. Serum leptin and sOB-R levels were quantified with ELISA. The free leptin index (FLI) was defined as the ratio of leptin to sOB-R levels. Serum leptin levels, sOB-R, and FLI were compared between groups. The relationship between leptin, disease severity, and treatment outcomes were analyzed in the LCPD group. There were no significant differences between groups in terms of age, sex, and body mass index (BMI) percentile. Mean leptin levels (p = 0.042), sOB-R levels (p = 0.003), and FLI (p = 0.013) differed significantly between groups. In the LCPD group, the serum leptin levels, sOB-R levels, and FLI differed significantly between the lateral pillar and Stulberg classification groups (p

Objective Sirtuin 6 (SIRT-6) is an NAD+-dependent deacetylase and mono-ADP-ribosyltransferase. It is known to interfere with the NF-κB signaling pathway and thereby has an antiinflammatory function. Due to the central role of NF-κB in rheumatoid arthritis (RA) development, we undertook this study to test our hypothesis that SIRT-6 could have antiarthritic effects. Methods An adenovirus containing SIRT-6 complementary DNA (Ad-SIRT6) was used to deliver SIRT-6 to human RA fibroblast-like synoviocytes in vitro as well as to mice with collagen-induced arthritis (CIA) in vivo via bilateral intraarticular injections into the ankle joints. Results In vitro experiments demonstrated that SIRT-6 overexpression suppressed NF-κB target gene expression induced by tumor necrosis factor α. SIRT-6 overexpression inhibited osteoclast differentiation induced by macrophage colony-stimulating factor and RANKL in bone marrow–derived macrophages. Mice with CIA had an increased incidence of disease and developed arthritis in the hind paws. In contrast, mice injected with Ad-SIRT6 showed attenuated severity of arthritis based on clinical scores, hind paw thickness, and radiographic and pathologic findings. Moreover, the injection of Ad-SIRT6 down-regulated local and systemic levels of proinflammatory cytokines. After induction of CIA, mice injected with Ad-SIRT6 showed significantly decreased arthritis severity, from the onset of clinical signs to the end of the study. Conclusion These results suggest that blocking the NF-κB pathway by SIRT-6 in rheumatoid joints reduces both the inflammatory response and tissue destruction. Therefore, the development of an immunoregulatory strategy based on SIRT-6 may have therapeutic potential for the treatment of RA.

The filtration performance of filter media fabricated by foam coating technology is highly dependent upon their pore sizes. Therefore, we investigated the effect of the mixing ratio of combined coating components (PTFE emulsion, a foam stabilizer, a foaming agent, and a thickener) and operating parameters (feed rate of coating solution, air flow rate, mixing speed, and cooling temperature) on the bubble size distribution of generated foams in a foam generator. The mean bubble size and bubble size distributions were observed through microscopic observations with an optical microscope. We found that viscosity was the most critical parameter in preparing a coating solution, and the entire series of operating parameters as mentioned above influenced the bubble size in a foamed solution. The bubble size decreased with an increasing ratio of thickening agent up to 1.8%, mixing speed, and with decreasing solution feed rate, and cooling temperature. Furthermore, we had a minimum bubble size for the condition of air flow rate at 200 mL/min. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 2062–2067, 2013

STUDY DESIGN In vitro and in vivo study. OBJECTIVE To evaluate the role of recombinant human bone morphogenetic protein-2 (rhBMP2) on breast cancer cell (MDA-MB-231 cells) growth. SUMMARY OF BACKGROUND DATA Bone morphogenetic proteins (BMPs) are expressed in a variety of human carcinoma cell lines and are known to promote tumor invasion and metastasis. However, their roles in tumor progression have not been fully clarified. In addition, there is no in vivo study regarding the inhibitory effect of BMP2 on breast cancer cell proliferation. METHOD Cell proliferation was determined by BrdU incorporation assay and flow cytometry. BMP2 signal transduction pathways were estimated on Western blot. Fifteen animals were divided into 2 groups; 1 (control = 5) was breast cancer cells alone, while the other (experiment = 5) was rhBMP2 + breast cancer cells. Cancer cells were injected into 2 sites (subcutaneous and femur) of nude mice with or without BMP2. Tumor size was determined by direct measurements for subcutaneous tumor formation and by femur radiographs. Histological and immunohistochemical analyses were performed. RESULTS RhBMP2 inhibited the proliferation of MDA-MB-231 cells in vitro. Inhibition was associated with changes in both the Smad and Wnt signaling pathways and was ultimately mediated through effects on various cell cycle proteins. Furthermore, rhBMP2 inhibited the growth of MDA-MB-231 cells injected both subcutaneously and intrafemorally. CONCLUSION In this model using human breast adenocarcinoma cell line, rhBMP2 has no stimulatory effect of tumor growth. Therefore, we can provide the basic science data to support the utilization in the management of patients with spine tumor in the future.

The prevention and management of type 2 diabetes mellitus has become a major global public health challenge. Decursin, an active compound of Angelica gigas Nakai roots, was recently reported to have a glucose-lowering activity. However, the antidiabetic effect of Angelica gigas Nakai extract (AGNE) has not yet been investigated. We evaluated the effects of AGNE on glucose homeostasis in type 2 diabetic mice and investigated the underlying mechanism by which AGNE acts. Male C57BL/KsJ-db/db mice were treated with either AGNE (10 mg/kg, 20 mg/kg, and 40 mg/kg) or metformin (100 mg/kg) for 8 weeks. AGNE supplementation (20 and 40 mg/kg) significantly decreased fasting glucose and insulin levels, decreased the areas under the curve of glucose in oral glucose tolerance and insulin tolerance tests, and improved homeostatic model assessment-insulin resistant (HOMA-IR) scores. AGNE also ameliorated hepatic steatosis, hyperlipidemia, and hypercholesterolemia. Mechanistic studies suggested that the glucose-lowering effect of AGNE was mediated by the activation of AMP activated protein kinase, Akt, and glycogen synthase kinase-3[Formula: see text]. AGNE can potentially improve hyperglycemia and hepatic steatosis in patients with type 2 diabetes.

Sirtuin 6 (Sirt6), a chromatin associated class III deacetylase, controls whole-body energy homeostasis and has a critical role in glucose-stimulated insulin secretion (GSIS) in pancreatic β cells. However, its underlying molecular mechanism remains poorly understood. To gain further insights, we studied the pathway by which Sirt6 regulates GSIS utilizing mice lacking Sirt6 in their β cells (βS6KO). Further, we overexpressed wild type or deacetylase-inactive mutant Sirt6 in isolated islets as well as in MIN6 cells. We confirmed that βS6KO mice developed glucose intolerance with severely impaired GSIS. Gene expression analysis of knockout islets and overexpression studies demonstrated that Sirt6 deacetylates forkhead box protein O1 (FoxO1) to trigger its nuclear export and releases its transcriptional repression of key glucose sensing genes such as Pdx1 and Glut2. Ectopic overexpression of Sirt6 in knockout islets resulted in rescue of the defective insulin secretion and restoration of the expression of Pdx1 and Glut2. These results show that Sirt6 in pancreatic β cells deacetylates FoxO1 and subsequently increases the expression of Pdx1 and Glut2 to maintain the glucose-sensing ability of pancreatic β cells and systemic glucose tolerance.

Constipation affects up to 20% of the world's population. The aim of this study was to investigate whether supplementation with Ficus carica paste could be used to treat constipation in Korean subjects with functional constipation.We conducted a randomized, double-blind, placebo-controlled trial. Subjects with functional constipation were orally supplemented with either F. carica paste (n=40) or placebo (n=40) for 8 weeks. We measured the efficacy and safety of F. carica paste. Primary outcomes (colon transit time) and secondary outcomes (questionnaire related to defecation) were compared before and after the 8-week intervention period.F. carica paste supplementation was associated with a significant reduction in colon transit time and a significant improvement in stool type and abdominal discomfort compared with the placebo. Blood parameters and clinical findings for organ toxicity remained within normal ranges.These results suggest that F. carica paste may have beneficial effects in subjects suffering from constipation.背景和目的：便秘影响到世界人口的20%。这项研究目的是探讨无花果酱是 否可以用于韩国功能性便秘患者的治疗。方法与研究设计：我们进行了一项 随机、双盲与安慰剂对照试验。功能性便秘患者摄入无花果酱（n=40）或安 慰剂（n=40）8 周。测定无花果酱的疗效和安全性并且比较8 周前后干预的主 要疗效（结肠转运时间）和次要疗效（涉及到排便的调查问卷）。结果：与 安慰剂组比较，无花果酱能显著减少结肠转运时间，改善粪便类型和腹部不 适。血液和器官毒性的临床参数均保持在正常范围以内。结论：这些结果表 明无花果酱可能对便秘患者产生有益的影响。.

Existing studies report a negative association between health literacy and hospital/emergency room use. Despite substantial research on this topic among older Americans, little is known about the link between health literacy and healthcare services use among older Koreans. This study investigates this link, using a sample of 596 adults, 65 and older, from Korea's three largest cities. Andersen's behavior model guided the study. Findings revealed that participants with higher health literacy were significantly less likely to use emergent health services. Enhanced health literacy will likely promote better health outcomes for older Koreans and reduce Korea's healthcare costs.

Despite that recombinant human bone morphogenetic protein-2 (rhBMP-2) has been reported as a stimulatory effecter of cancer cell growth because of its characteristic like morphogen, the biological functions of rhBMP-2 in human esophageal cancer cells are unknown. The purpose of this study was to investigate whether rhBMP-2 has an inhibitory effect on the growth of human esophageal squamous carcinoma cells (ESCC). RhBMP-2 significantly inhibited proliferation of ESCC cells in a dose-dependent manner in the MTT assay. Cell cycle arrest at the G1 phase was induced 24 h after rhBMP2 treatment. RhBMP-2 also reduced cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK 6 activities, and stimulated p-Smad1/5/8, p53, and p21 levels at 12 h. In contrast, rhBMP-2 diminished poly (ADP-ribose) polymerase (PARP) protein expression levels and activated cleaved PARP, cleaved caspase-7, and cleaved-caspase 9 levels in ESCC cells. In addition, rhBMP-2 increased MST1, MOB1, and p-YAP protein levels and the RASSF1 binds Mst1 more upon treatment with rhBMP2. The induced p-YAP expression in TE-8 and TE-12 cells by rhBMP-2 was reversed by the RASSF1 knockdown. In vivo study, rhBMP-2 decreased tumor volume following subcutaneous implantation and showed higher radiologic score (less bony destruction) after femoral implantation compared to those in a control group. These results suggest that rhBMP-2 inhibits rather than activates proliferation of human esophageal cancer cells which is mediated through activating the hippo signaling pathway.