Urinary concentration of transforming growth factor-&bgr;-inducible gene-h3(&bgr;ig-h3) in patients with Type 2 diabetes mellitus

Cha, D. R.,Kim, I. S.,Kang, Y. S.,Han, S. Y.,Han, K. H.,Shin, C.,Ji, Y. H.,Kim, N. H. Blackwell Science Ltd 2005 Diabetic medicine Vol.22 No.1

<P>Abstract</P><P>Aims </P><P>The expression of TGF&bgr;-inducible gene h3(&bgr;ig-h3) has been used to assess the biological activity of TGF&bgr; in the kidney. In this study, we investigated whether the urinary concentration of &bgr;ig-h3 is associated with diabetic nephropathy in patients with Type 2 diabetes mellitus. We also evaluated the relationship between the urinary concentration of &bgr;ig-3 and proteinuria and microalbuminuria (AER) in a normal healthy population and in Type 2 diabetes patients.</P><P>Methods </P><P>Four hundred and seventy-nine Type 2 diabetic patients without non-diabetic kidney diseases and 528 healthy control subjects were enrolled. The study subjects were divided into five groups: a non-diabetic healthy control group with normal ACR (<I>n</I> = 443), a non-diabetic healthy control group with microalbuminuria (<I>n</I> = 85), a normoalbuminuric diabetic group (<I>n</I> = 198), a microalbuminuric diabetic group (<I>n</I> = 155) and an overt proteinuria group (<I>n</I> = 126). Urinary levels of &bgr;ig-h3 were measured by enzyme-linked immunosorbent assay.</P><P>Results </P><P>(i) Urinary excretion of &bgr;ig-h3 was significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage (25.02 ± 8.84 vs. 18.67 ± 6.56, <I>P</I> = 0.03). In diabetic patients, urinary &bgr;ig-h3 levels increased significantly as diabetic nephropathy advanced (25.02 ± 8.84 vs. 34.06 ± 24.55 vs. 169.63 ± 57.33, <I>P</I> < 0.001). (ii) Proteinuria was found to be significantly correlated with urinary &bgr;ig-h3 (healthy control; <I>r</I> = 0.137, <I>P</I> = 0.019, diabetic patients; <I>r</I> = 0.604, <I>P</I> < 0.001). ACR was also found to be significantly related with urinary &bgr;ig-h3 in diabetic patients (<I>r =</I> 0.383, <I>P</I> = 0.006). (iii) In diabetic patients, urinary &bgr;ig-h3 was significantly related with systolic and diastolic blood pressure (systolic blood pressure: <I>r</I> = 0.436, <I>P</I> = 0.024; diastolic blood pressure, <I>r</I> = 0.365, <I>P</I> = 0.042), total cholesterol and HbA<SUB>1c</SUB> (cholesterol: <I>r</I> = 0.169, <I>P</I> = 0.03, HbA<SUB>1c</SUB>; <I>r</I> = 0.387, <I>P</I> = 0.044). Logistic regression analyses showed that urinary &bgr;ig-h3 was associated with a significant increase in the risk of microalbuminuria and proteinuria in diabetic patients.</P><P>Conclusions </P><P>Longitudinal monitoring of urinary &bgr;ig-h3 may improve the likelihood of detecting diabetic nephropathy at an earlier stage and &bgr;ig-h3 could be a sensitive marker of diabetic kidney disease progression.</P>

Exendin-4 induction of cyclin D1 expression in INS-1 beta-cells: involvement of cAMP-responsive element.

Kim, M-J,Kang, J-H,Park, Y G,Ryu, G R,Ko, S H,Jeong, I-K,Koh, K-H,Rhie, D-J,Yoon, S H,Hahn, S J,Kim, M-S,Jo, Y-H Journal of Endocrinology, Ltd. [etc.] 2006 The Journal of endocrinology Vol.188 No.3

<P>Glucagon-like peptide-1 (GLP-1) and its analog exendin-4 (EX) have been considered as a growth factor implicated in pancreatic islet mass increase and beta-cell proliferation. This study aimed to investigate the effect of EX on cyclin D1 expression, a key regulator of the cell cycle, in the pancreatic beta-cell line INS-1. We demonstrated that EX significantly increased cyclin D1 mRNA and subsequently its protein levels. Although EX induced phosphorylation of Raf-1 and extracellular-signal-regulated kinase (ERK), both PD98059 and exogenous ERK1 had no effect on the cyclin D1 induction by EX. Instead, the cAMP-elevating agent forskolin induced cyclin D1 expression remarkably and this response was inhibited by pretreatment with H-89, a protein kinase A (PKA) inhibitor. Promoter analyses revealed that the cAMP-responsive element (CRE) site (at position -48; 5'-TAACGTCA-3') of cyclin D1 gene was required for both basal and EX-induced activation of the cyclin D1 promoter, which was confirmed by site-directed mutagenesis study. For EX to activate the cyclin D1 promoter effectively, CRE-binding protein (CREB) should be phosphorylated and bound to the putative CRE site, according to the results of electrophoretic mobility shift and chromatin immunoprecipitation assays. Lastly, a transfection assay employing constitutively active or dominant-negative CREB expression plasmids clearly demonstrated that CREB was largely involved in both basal and EX-induced cyclin D1 promoter activities. Taken together, EX-induced cyclin D1 expression is largely dependent on the cAMP/PKA signaling pathway, and EX increases the level of phosphorylated CREB and more potently trans-activates cyclin D1 gene through binding of the CREB to the putative CRE site, implicating a potential mechanism underlying beta-cell proliferation by EX.</P>

3D crustal velocity structure beneath the broadband seismic array in the Gyeongju area of Korea by receiver function analyses

Lee, D.H.,Lee, J.M.,Cho, H.M.,Kang, T.S. Elsevier Scientific Publishing Co 2016 Tectonophysics Vol.689 No.-

<P>A temporary seismic array was in operation between October 2010 and March 2013 in the Gyeongju area of Korea. Teleseismic records of the seismic array appropriate for receiver function analysis were collected, and selected seismograms were split into five groups based on epicenters-the Banda-Molucca, Sumatra, Iran, Aleutian, and Vanuatu groups. ID velocity structures beneath each seismic station were estimated by inverting the stacked receiver functions for possible groups. The inversion was done by applying a genetic algorithm, whereas surface wave dispersion data were used as constraints to avoid non-uniqueness in the inversion. The composite velocity structure was constructed by averaging the velocity structures weighted by the number of receiver functions used in stacking. The uncertainty analysis for the velocity structures showed that the average of 95% confidence intervals was +/- 0.1 km/s. The 3D velocity structure was modeled through interpolation of 1D composite velocity structures. Moho depths were determined in each composite velocity structure based on the AK135-F S-wave velocity model, and the depths were similar to the H-kappa analysis results. The deepest Moho depth in the study area was found to be 31.9 km, and the shallowest, was 25.9 km. The Moho discontinuity dips in a southwestward direction beneath the area. A low velocity layer was also detected between 4 and 14 km depth. Adaldtic intrusions and/or a high geothermal gradient appear to be the causes of this low velocity layer. The 3D velocity structure can be used to reliably assess seismic hazards in this area. (C) 2016 Elsevier B.V. All rights reserved.</P>

Nondegenerate n-type doping phenomenon on molybdenum disulfide (MoS₂) by zinc oxide (ZnO)

Kang, D.H.,Hong, S.T.,Oh, A.,Kim, S.H.,Yu, H.Y.,Park, J.H. Pergamon Press 2016 Materials research bulletin Vol.82 No.-

<P>In this paper, we have demonstrated nondegenerate n-type doping phenomenon of MoS2 by ZnO. The ZnO doping effects were systematically investigated by Raman spectroscopy and electrical/optical measurements (I-D-V-G with/without exposure to 520, 655, 785, and 850 nm laser sources). The ZnO doping improved the performance parameters of MoS2-based electronics (Ion up arrow, mu(FE)up arrow, n up arrow) owing to reduction of the effective barrier height between the source and the MoS2 channel. We also monitored the effects of ZnO doping during exposure to air; reduction in Delta V-TH of about 75% was observed after 156 h. In addition, the optoelectronic performance of the MoS2 photodetector was enhanced due to the reduction of the recombination rate of photogenerated carriers caused by ZnO doping. In our results, the highest photoresponsivity (about 3.18 x 10(3) A/W) and detectivity (5.94 x 10(12) Jones) of the ZnO-doped photodetector were observed for 520 nm laser exposure. (C) 2016 Elsevier Ltd. All rights reserved.</P>

Ethanol extract of Prunus mume fruit attenuates hydrogen peroxide-induced oxidative stress and apoptosis involving Nrf2/HO-1 activation in C2C12 myoblasts

Kang, J.S.,Kim, D.J.,Kim, G.Y.,Cha, H.J.,Kim, S.,Kim, H.S.,Park, C.,Hwang, H.J.,Kim, B.W.,Kim, C.M.,Choi, Y.H. Sociedade Brasileira de Farmacognosia 2016 Revista brasileira de farmacognosia Vol.26 No.2

<P>The fruit of the Prunus mume (Siebold) Siebold & Zucc., Rosaceae (Korean name: Maesil) has long been used as a health food or valuable medicinal material in traditional herb medicine in Southeast Asian countries. In this study, we determined the potential therapeutic efficacy of the ethanol extract of P. mume fruits (EEPM) against H2O2-induced oxidative stress and apoptosis in the murine skeletal muscle myoblast cell line C2C12, and sought to understand the associated molecular mechanisms. The results indicated that exposure of C2C12 cells to H2O2 caused a reduction in cell viability by increasing the generation of intracellular reactive oxygen species and by disrupting mitochondrial membrane permeability, leading to DNA damage and apoptosis. However, pretreatment of the cells with EEPM before H2O2 exposure effectively attenuated these changes, suggesting that EEPM prevented H2O2-induced mitochondria-dependent apoptosis. Furthermore, the increased ex-pression and phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and up-regulation of heme oxygenase-1 (HO-1), a phase II antioxidant enzyme, were detected in EEPM-treated C2C12 cells. We also found that zinc protoporphyrin IX, an HO-1 inhibitor, attenuated the protective effects of EEPM against H2O2-induced reactive oxygen species accumulation and cytotoxicity. Therefore, these results indicate that the activation of the Nrf2/HO-1 pathway might be involved in the protection of EEPM against H2O2-induced cellular oxidative damage. In conclusion, these results show that EEPM contributes to the prevention of oxidative damage and could be used as a nutritional agent for oxidative stress-related diseases. (C) 2016 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda. All rights reserved.</P>

Potential roles of D-serine and serine racemase in experimental temporal lobe epilepsy

Ryu, H.J.,Kim, J.-E.,Yeo, S.-I.,Kim, D.-S.,Kwon, O.-S.,Choi, S.Y.,Kang, T.-C. Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of neuroscience research Vol.88 No.11

<P>To confirm the roles of D-serinergic gliotransmission in epilepsy, we investigated the relationship between spatiotemporally specific glial responses and the D-serine/serine racemase system in mesial temporal structures following status epilepticus (SE). In control animals, D-serine and serine racemase immunoreactivities were detected mainly in astrocytes. After SE, D-serine and serine racemase immunoreactivities were increased in astrocytes. Double-immunofluorescence study revealed that up-regulation of serine racemase immunoreactivity was relevant not to D-serine immunoreactivity but to nestin or vimentin immunoreactivity. Neither D-serine nor serine racemase was found in naïve or reactive microglia. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor subunit 1 (pNR1-Ser896) immunoreactivity in the hippocampus was increased compared with controls. Increased D-serine immunoreactivity showed direct correlation with the phosphorylation of Ser896 of NR1. Given the findings of our previous study, these findings suggest that D-serine and serine racemase in astrocytes may play roles in neuronal hyperexcitability via a cooperative activation of NMDA receptors. Furthermore, serine racemase may be involved in migration and differentiation of immature astrocytes, which is relevant to reactive astrogliosis. © 2010 Wiley-Liss, Inc.</P>

Gibberellin secreting rhizobacterium, Pseudomonas putida H-2-3 modulates the hormonal and stress physiology of soybean to improve the plant growth under saline and drought conditions

Kang, S.M.,Radhakrishnan, R.,Khan, A.L.,Kim, M.J.,Park, J.M.,Kim, B.R.,Shin, D.H.,Lee, I.J. Gauthier-Villars ; Elsevier Science Ltd 2014 Vol. No.

The physiological changes in tolerant soybean plants under salt and drought stress conditions with Pseudomonas putida H-2-3 were investigated. A bacterial isolate H-2-3 was isolated from soil and identified as Pseudomonas putida H-2-3 by 16S rDNA sequences. The treatment of P. putida H-2-3 significantly increased the length, fresh and dry weight of shoot and chlorophyll content in gibberellins (GAs) deficient mutant Waito-c rice seedlings over the control, it might be the presence of GA<SUB>1</SUB>, GA<SUB>4,</SUB> GA<SUB>9</SUB> and GA<SUB>20.</SUB> The soybean plant growth was retarded in salt (120 mM sodium chloride) and drought (15% polyethylene glycol) stress conditions at 10 days treatments, while P. putida H-2-3 effectively enhanced the shoot length and fresh weight of plants suffered at salt and drought stress. The chlorophyll content was lower in abiotic stress conditions and bacterial inoculant P. putida H-2-3 mitigated the stress effects by an evidence of higher quantity of chlorophyll content in plants exposed to salt and drought. The stress hormonal analysis revealed that individual treatment of P. putida H-2-3, salt and drought significantly enhanced the abscisic acid and salicylic acid content than their control. P. putida H-2-3 applied to salt and drought stressed plants showed a lower level of abscisic acid and salicylic acid and a higher level of jasmonic acid content. Under stress condition induced by salt and drought in plants expressed higher level of total polyphenol, superoxide dismutase and radical scavenging activity and no significant changes in flavonoids. The bio-inoculant, P. putida H-2-3 modulated those antioxidants by declining superoxide dismutase, flavonoids and radical scavenging activity. P. putida H-2-3 induced tolerance against abiotic stress was confirmed by a reduction of Na content in abiotic stressed plants. The results suggest that P. putida H-2-3 application reprograms the chlorophyll, stress hormones and antioxidants expression in abiotic stress affected soybean plant and improves their growth under stress environment.

Weak version of restriction estimates for spheres and paraboloids in finite fields

Kang, H.,Koh, D. Academic Press 2014 Journal of mathematical analysis and applications Vol.419 No.2

We study L<SUP>p</SUP>-L<SUP>r</SUP> restriction estimates for algebraic varieties in d-dimensional vector spaces over finite fields. Unlike the Euclidean case, if the dimension d is even, then it is conjectured that the L<SUP>(2d+2)/(d+3)</SUP>-L<SUP>2</SUP> Stein-Tomas restriction result can be improved to the L<SUP>(2d+4)/(d+4)</SUP>-L<SUP>2</SUP> estimate for both spheres and paraboloids in finite fields. In this paper we show that the conjectured L<SUP>p</SUP>-L<SUP>2</SUP> restriction estimate holds in the specific case when test functions under consideration are restricted to d-coordinate functions or homogeneous functions of degree zero. To deduce our result, we use the connection between the restriction phenomena for our varieties in d dimensions and those for homogeneous varieties in (d+1) dimensions.

Rebamipide abolishes Helicobacter pylori CagA-induced phospholipase D1 expression via inhibition of NFκB and suppresses invasion of gastric cancer cells

Kang, D W,Hwang, W C,Park, M H,Ko, G-H,Ha, W-S,Kim, K-S,Lee, Y-C,Choi, K-Y,Min, D S Macmillan Publishers Limited 2013 Oncogene Vol.32 No.30

Infection with cagA-positive Helicobacter pylori is a risk factor for the development of severe gastritis and gastric cancer (GC). CagA protein is injected into gastric epithelial cells and deregulates a variety of cellular signaling molecules. Phospholipase D (PLD) is elevated in many different types of human cancers and has been implicated as a critical factor in inflammation and carcinogenesis. In this study, we show that infection with cagA-positive H. pylori in GC cells significantly induces PLD1 expression via CagA-dependent activation of nuclear factor κB (NFκB). Interestingly, the level of PLD1 protein and IκBα phosphorylation is aberrantly upregulated in H. pylori-infected human GC tissues. Infection with cagA-positive H. pylori and expression of CagA enhanced the binding of NFκB to the PLD1 promoter, and two functional NFκB-binding sites were identified within the PLD1 promoter. Rebamipide, a mucosal-protective antiulcer agent, abolished H. pylori cagA-induced PLD1 expression via inhibition of binding of NFκB to the PLD1 promoter, and also inhibited PLD activity. Moreover, rebamipide suppressed H. pylori-induced matrix metalloproteinase-9, interleukin-8 and activation-induced cytidine deaminase expression as well as invasion of GC cells through downregulation of PLD1. Our data suggest that H. pylori cagA targets PLD1 for invasion of GC cells, and rebamipide might contribute to the antitumorigenic effect of GC cells via inhibition of the H. pylori cagA-NFκB-PLD1 signaling pathway.

Photocatalytic H2 production on trititanate nanotubes coupled with CdS and platinum nanoparticles under visible light: revisiting H2 production and material durability

Park, H.,Ou, H. H.,Kim, M.,Kang, U.,Han, D.,Hoffmann, M. Royal Society of Chemistry 2017 Faraday discussions Vol.198 No.-

<P>The photocatalytic production of molecular hydrogen (H-2) on ternary composites of Pt, CdS, and sodium trititanate nanotubes (NaxH2-xTi3O7, TNTs) is examined in an aqueous 2-propanol (IPA) solution (typically 5 vol%) at a circum-neutral pH under visible light (lambda > 420 nm). The H-2 production rates are dependent on the Pt-loading level, and the optimum production rate in the Pt/CdS/TNTs is approximately six times higher than that in Pt/CdS/TiO2. A D2O solution containing 5 vol% IPA leads only to the production of D-2 molecules, whereas increasing the IPA amount to 30 vol% leads to the production of DH molecules. This indicates that the Pt/CdS/TNTs composites enable H-2 production via true water splitting under our typical experimental conditions. X-ray photoelectron spectroscopy (XPS) analyses of the as-synthesized Pt/CdS/TNTs and those used for 6 and 12 h show that metallic Pt on the CdS/TNTs is less susceptible to oxidation than Pt on CdS/TiO2. In addition, photocorrosion of CdS (i.e., sulfate formation) is significantly inhibited during the photocatalytic H-2 production reactions in the Pt/CdS/TNTs because of the efficient charge transfer via the TNTs framework. The Pt/CdS/TNTs samples are thermally more stable than Pt/CdS/TiO2 and CdS/TNTs, effectively inhibiting the formation of CdO during the thermal synthesis. Detailed surface characterizations of the as-synthesized ternary composites are performed using Xray diffraction, transmission electron microscopy, energy dispersive spectroscopy, and XPS.</P>