Search

In this study, we present lateral scanning white light interferometry (LS-WLI), where phase-shifting algorithms are applied to inspect the topography of a large field of view (FOV) with high-speed measurements. At a point, the interference signal must be acquired with a specific condition to adapt the phase-shifting algorithm. This means that all points have two points, of which the phase difference is π/2, when the number of points acquired in a phase period is multiple of 4, despite increasing the data points in a period. Consequently, stretching the fringe spacing in LS-WLI facilitates the application of phase-shift techniques, thereby enhancing stage speed, even with a fixed camera speed. Using the proposed method, we can successfully obtain a laterally expended topographic image as 5.25 mm × 1.25 mm, where the step height of the microstructure is 140 nm.

Graphdiyne (GDY), a new 2D material, has recently proven excellent performance in photodetector applications due to its direct bandgap and high mobility. Different from the zero-gap of graphene, these preeminent properties made GDY emerge as a rising star for solving the bottleneck of graphene-based inefficient heterojunction. Herein, a highly effective graphdiyne/molybdenum (GDY/MoS 2 ) type-II heterojunction in a charge separation is reported toward a high-performance photodetector. Characterized by robust electron repulsion of alkyne-rich skeleton, the GDY based junction facilitates the effective electron-hole pairs separation and transfer. This results in significant suppression of Auger recombination up to six times at the GDY/MoS 2 interface compared with the pristine materials owing to an ultrafast hot hole transfer from MoS 2 to GDY. GDY/MoS 2 device demonstrates notable photovoltaic behavior with a short-circuit current of -1.3 × 10 -5 A and a large open-circuit voltage of 0.23 V under visible irradiation. As a positive-charge-attracting magnet, under illumination, alkyne-rich framework induces positive photogating effect on the neighboring MoS 2 , further enhancing photocurrent. Consequently, the device exhibits broadband detection (453-1064 nm) with a maximum responsivity of 78.5 A W -1 and a high speed of 50 µs. Results open up a new promising strategy using GDY toward effective junction for future optoelectronic applications., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background and Aim: Although resting heart rate (RHR) is associated with prevalence and incidence of diabetes, whether it is associated with undiagnosed diabetes is still unclear. We aimed to investigate whether the RHR is associated with the prevalence of undiagnosed diabetes in a large Korean national dataset., Methods and Results: The Korean National Health and Nutrition Examination Survey data from 2008 to 2018 were used. After screening, 51,637 participants were included in this study. The odds ratios and 95% confidence intervals (CIs) for undiagnosed diabetes were calculated using multivariable-adjusted logistic regression analyses. Analyses showed that participants with a RHR of ≥90 bpm showed a 4.00- (95% CI: 2.77-5.77) and 3.21-times (95% CI: 2.01-5.14) higher prevalence of undiagnosed diabetes for men and women, respectively, than those with a RHR of <60 bpm. The linear dose-response analyses showed that each 10-bpm increment in RHR was associated with a 1.39- (95% CI: 1.32-1.48) and 1.28-times (95% CI: 1.19-1.37) higher prevalence of undiagnosed diabetes for men and women, respectively. In the stratified analyses, the positive association between RHR and the prevalence of undiagnosed diabetes was tended to be stronger among those who were younger (age: <40 years) and lean (BMI: <23 kg/m 2 )., Conclusions: Elevated RHR was significantly associated with a higher prevalence of undiagnosed diabetes in Korean men and women, independent of demographic, lifestyle, and medical factors. Accordingly, the value of RHR as a clinical indicator and health marker, especially in reducing the prevalence of undiagnosed diabetes, is suggestible., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

As semiconductor device architecture develops, from planar field-effect transistors (FET) to FinFET and gate-all-around (GAA), there is an increased need to measure 3D structure sidewalls precisely. Here, we present a 3-Dimensional Atomic Force Microscope (3D-AFM), a powerful 3D metrology tool to measure the sidewall roughness (SWR) of vertical and undercut structures. First, we measured three different dies repeatedly to calculate reproducibility in die level. Reproducible results were derived with a relative standard deviation under 2%. Second, we measured 13 different dies, including the center and edge of the wafer, to analyze SWR distribution in wafer level and reliable results were measured. All analysis was performed using a novel algorithm, including auto flattening, sidewall detection, and SWR calculation. In addition, SWR automatic analysis software was implemented to reduce analysis time and to provide standard analysis. The results suggest that our 3D-AFM, based on the tilted Z scanner, will enable an advanced methodology for automated 3D measurement and analysis., (© 2022. The Author(s).)

The purpose of this study was to analyse differences in leisure satisfaction among leisure activity participants according to the type of activity including differences by gender. The study subjects were 448 adult men and women who were participating in leisure activities in Seoul, Gyeonggi, Chungcheong, and Gangwon-do, Korea. Frequency analysis, confirmatory factor analysis, and latent mean analysis were applied to the data collected from the participants. First, the form, measurement, and intercept uniformity were verified to check that the study scale could be used equally with men and women. Second, it showed that leisure satisfaction was higher in sports activity of leisure activity patterns than hobbies, watching, socializing, tourism and games. It is concluded that infrastructure for sports should expand and that policy support is needed to increase leisure satisfaction in other leisure activities.

The 1D wire TaS 3 exhibits metallic behavior at room temperature but changes into a semiconductor below the Peierls transition temperature ( T p ), near 210 K. Using the 3ω method, we measured the thermal conductivity κ of TaS 3 as a function of temperature. Electrons dominate the heat conduction of a metal. The Wiedemann-Franz law states that the thermal conductivity κ of a metal is proportional to the electrical conductivity σ with a proportional coefficient of L 0 , known as the Lorenz number-that is, κ=σLoT. Our characterization of the thermal conductivity of metallic TaS 3 reveals that, at a given temperature T, the thermal conductivity κ is much higher than the value estimated in the Wiedemann-Franz (W-F) law. The thermal conductivity of metallic TaS 3 was approximately 12 times larger than predicted by W-F law, implying L=12L0. This result implies the possibility of an existing heat conduction path that the Sommerfeld theory cannot account for.

The purpose of this study was to investigate leisure satisfaction among outdoor sports participants in golf and yachting. Influence was also measured of recreation specialization on leisure satisfaction, and the effect of the relationship between leisure facilitation and leisure satisfaction on golf and yacht participation was investigated as well. Frequency, reliability, confirmatory, and correlation analysis, as well as structural equation modeling results, indicate that leisure facilitation had no influence on outdoor sports participants' recreation specialization. Leisure facilitation had a positive influence on leisure satisfaction among the golf and yachting participants, and their recreation specialization had a positive influence on their leisure satisfaction. The effects of the COVID-19 pandemic are addressed, specifically the constraints that the disease has imposed on outdoor sports and leisure, and strategies are presented for addressing these constraints and promoting outdoor sports participation.

Background: Systemic Clinic Outcome and Routine Evaluation (SCORE-15) is a compact scale that contains the most critical family function assessment tools including assessments of the strengths, adaptability, and communication among family members. It has been translated into other languages in the United States and Europe. This study aimed to verify the reliability and validity of SCORE-15 with a small research population and justify its applicability in Korea., Methods: SCORE-15 is a self-reporting family function measurement tool for each family member over the age of 11 years. This study used the Family Communication Scale (FCS) included in the Family Adaptability and Cohesion Evaluation Scales (FACES) IV package and FACES in FACES-III to verify the validity of the Korean-translated SCORE-15. Cronbach's α value was calculated to check the reliability of SCORE-15. Data were analyzed using STATA ver. 15.0 (Stata Corp., College Station, TX, USA)., Results: The study analyzed the correlation between FACES-III and SCORE-15 and FCS and SCORE-15 so that there was a significant static correlation in both comparisons (r=0.72 and r=0.81, respectively). Also, the research compared each subscale to analyze the correlation and the range was 0.47 to 0.95. The total SCORE-15 Cronbach's α value was 0.92 and those values of the subscales for family strengths, family communication, and family difficulty were 0.89, 0.73, and 0.87, respectively (P<0.001)., Conclusion: Our study was the first to validate the Korean SCORE-15, which can be used as an appropriate shortform indicator for evaluating family function and changes in detecting therapeutic improvements in Korea.

The spontaneous separation of a polymer thin film from a substrate is an innovative technology that will enable material recycling and reduce manufacturing cost in the film industry, and this can be applied in a wide range of applications, from optical films to wearable devices. Here, we present an unprecedented spontaneous strategy for separating transparent polymer films from substrates on the basis of microbubble generation using nanocapsules containing an evaporable material. The core-shell nanocapsules are prepared from poly(methyl methacrylate)-polyethyleneimine nanoparticles via the encapsulation of methylcyclohexane (MCH). A spherical nanostructure with a vaporizable core is obtained, with the heat-triggered gas release ability leading to the formation of microbubbles. Our separation method applied to transparent polymer films doped with a small amount of the nanocapsules encapsulating evaporable MCH enables spontaneous detachment of thin films from substrates via vacuum-assisted rapid vaporization of MCH over a short separation time, and clear detachment of the film is achieved with no deterioration of the inherent optical transparency and adhesive property compared to a pristine film.

With increasing demand for transparent conducting electrodes, graphene has attracted considerable attention, owing to its high electrical conductivity, high transmittance, low reflectance, flexibility, and tunable work function. Two faces of single-layer graphene are indistinguishable in its nature, and this idea has not been doubted even in multilayered graphene (MLG) because it is difficult to separately characterize the front (first-born) and the rear face (last-born) of MLG by using conventional analysis tools, such as Raman and ultraviolet spectroscopy, scanning probe microscopy, and sheet resistance. In this paper, we report the striking difference of the emission pattern and performance of transparent organic light-emitting diodes (OLEDs) depending on the adopted face of MLG and show the resolved chemical and physical states of both faces by using depth-selected absorption spectroscopy. Our results strongly support that the interface property between two different materials rules over the bulk property in the driving performance of OLEDs.

Background: Rice prolamin has been reported to possess antioxidative, anti-inflammatory and immune-promoting properties. This study is aimed to examine the protective effects of dietary rice prolamin extract (RPE) against dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in mice., Methods: BALB/c mice were fed diet supplemented with 0-0.1 % RPE for 6 weeks. For the last 2 weeks, 1 % or 0.2 % DNCB was applied repeatedly to the back skin of mice to induce AD-like lesions. Following AD induction, the severity of skin lesions was examined macroscopically and histologically. In addition, the serum levels of IgE, IgG1 and IgG2a were determined by ELISA, and the mRNA expression of IL-4 and IFN-γ in the skin was determined by real-time PCR., Results: Dietary RPE suppressed the clinical symptoms of DNCB-induced dermatitis as well as its associated histopathological changes such as epidermal hyperplasia and infiltration of mast cells and eosinophils in the dermis. RPE treatment also suppressed the DNCB-induced increase in transepidermal water loss. Dietary RPE inhibited the DNCB-induced enhancement of serum IgE and IgG1 levels, whereas it increased the serum IgG2a level in DNCB-treated mice. In addition, dietary RPE upregulated the IFN-γ mRNA expression and downregulated the IL-4 mRNA expression in the skin of DNCB-treated mice., Conclusions: The above results suggest that dietary RPE exerts a protective effect against DNCB-induced AD in mice via upregulation of Th1 immunity and that RPE may be useful for the treatment of AD.

PTEN is reversibly oxidized in various cells by exogenous hydrogen peroxide as well as by endogenous hydrogen peroxide generated when cells are stimulated with growth factors, cytokines and hormones. A gel mobility shift assay showed that oxidized PTEN migrated more rapidly than reduced PTEN on a non-reducing SDS-PAGE gel. Oxidized PTEN was reduced when treated with dithiothreitol. Supplementation of N-ethylmaleimide in the cell lysis buffer was critical for the apparent bands of oxidized and reduced PTEN. Formation of oxidized PTEN was abolished when the active site Cys(124) or nearby Cys(71) was replaced with Ser suggesting that Cys(124) and Cys(71) are involved in the formation of an intramolecular disulfide bond. These results show that the mobility shift assay is a convenient method to analyze the redox state of PTEN in cells., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We investigated the impact of rice prolamin extract (RPE) on lipopolysaccharide (LPS)-induced nuclear factor (NF)-κB signalling in intestinal epithelial cells and macrophages, and determined the therapeutic efficacy of RPE in acute murine colitis. The effect of RPE on LPS-induced NF-κB signalling and proinflammatory gene expression was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA). The in-vivo efficacy of RPE was assessed in mice with 3% dextran sulphate sodium (DSS)-induced colitis. Apoptotic and cellular proliferative activities were evaluated by immunostaining with cleaved caspase-3 and proliferating cell nuclear antigen (PCNA) antibodies. RPE inhibited LPS-induced expression of monocyte chemotactic protein (MCP)-1, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha and LPS-induced NF-κB signalling in intestinal epithelial cells and macrophages. RPE-fed, DSS-exposed mice showed less weight loss, longer colon length and lower histological score compared to control diet-fed, DSS-exposed mice. Immunostaining analysis revealed a significant decrease of cleaved caspase-3 positive cells in RPE-fed, DSS-exposed mice compared to DSS-exposed mice. Also, the number of PCNA-positive cells within intact colonic crypts decreased significantly in RPE-fed, DSS-exposed mice compared to control diet-fed, DSS-exposed mice. DSS-induced NF-κB signalling was inhibited by RPE. RPE ameliorates intestinal inflammation by inhibiting NF-κB activation and modulating intestinal apoptosis and cell proliferation in an acute murine colitis., (© 2014 British Society for Immunology.)

Purpose: The purpose of this study was to evaluate the functional outcomes of the over-tensioning technique compared with those of the standard tensioning technique in the transfer of extensor indicis proprius (EIP) to extensor pollicis longus (EPL) for the chronic rupture of the thumb extensor., Methods: Data were collected from patients who underwent tendon transfer using EIP between March 2003 and August 2011. 23 were treated with the standard tensioning technique and 25 patients (Group B) with the over-tensioning technique. While standard tension was maintained with the thumb in full extension and the wrist in 30° of flexion, over-tension was maintained with the thumb in full extension and the wrist in the neutral position. All patients were assessed for total range of motion, elevation and flexion deficit, the thumb grip and pinch strength, and the thumb and the index extension strength compared to the unaffected side, EIP-EPL evaluation as suggested by Lemmen et al. and Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH)., Results: Group A: total range of motion 115°, elevation deficit 2.0 cm, combined flexion deficit 1.0 cm, thumb extension strength 75%, thumb grip strength 91%, and pinch strength 87%. Functional outcomes were 13 excellent, 6 good, 3 fair, and 1 poor. Median DASH score was 21.3 points. Group B: total range of motion 125°, elevation deficit 1.0 cm, combined flexion deficit 1.5 cm, thumb extension strength 85%, thumb grip strength 88%, and pinch strength 83%. Functional outcomes were 16 excellent, 7 good, 2 fair, and 0 poor. Median DASH score was 19.8 points. There are significant differences in the range of motion, elevation deficit, and extension strength of thumb between the two groups (p=.001, p=.001, and p=.028, respectively)., Conclusion: While the functional outcomes of both groups were favorably acceptable in a majority of the patients, there were significant differences in aspects of range of motion, elevation deficit, and strength of the thumb between both groups., Level of Evidence: Case-control study, Level III., (Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

This study was designed to evaluate the efficacy of an orally administered aqueous extract of glutinous rice (GRE) to protect against acute gastric mucosal lesions induced by ethanol, indomethacin, and water immersion restraint stress in rats and to characterize the active substances responsible for the protection. GRE was shown to dose-dependently prevent the gastric lesions induced by the above ulcerogenic treatments at doses of 30 to 300 mg/kg. GRE treatment increased the gastric mucin content and partially blocked the ethanol-induced depletion of the gastric mucus layer. Also, it increased the nonprotein sulfhydryl concentration in the gastric mucosa. The gastroprotective action of GRE was markedly enhanced by co-treatment with 4-8 mg/kg tea extracts. The activity of GRE was completely lost by heat treatment at 80℃ for 3 min or treatment with 0.01% pepsin at 37℃ for 1 h. Protein extraction studies indicated that prolamins are involved in the gastroprotective activity of GRE. Our results suggest that glutinous rice proteins are useful for the prevention and treatment of gastritis and peptic ulcer.

Background: Black tea has been shown to elicit anti-oxidant, anti-carcinogenic, anti-inflammatory and anti-mutagenic properties. In this study, we investigated the impact of black tea extract (BTE) on lipopolysaccharide (LPS)-induced NF-κB signaling in bone marrow derived-macrophages (BMM) and determined the therapeutic efficacy of this extract on colon inflammation., Methods: The effect of BTE on LPS-induced NF-κB signaling and pro-inflammatory gene expression was evaluated by RT-PCR, Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA). The in vivo efficacy of BTE was assessed in mice with 3% dextran sulfate sodium (DSS)-induced colitis. The severity of colitis was measured by weight loss, colon length and histologic scores., Results: LPS-induced IL-12p40, IL-23p19, IL-6 and IL-1β mRNA expressions were inhibited by BTE. LPS-induced IκBα phosphorylation/degradation and nuclear translocation of NF-κB/p65 were blocked by BTE. BTE treatment blocked LPS-induced DNA-binding activity of NF-κB. BTE-fed, DSS-exposed mice showed the less weight loss, longer colon length and lower histologic score compared to control diet-fed, DSS-exposed mice. DSS-induced IκBα phosphorylation/degradation and phosphorylation of NF-κB/p65 were blocked by BTE. An increase of cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) in DSS-exposed mice was blocked by BTE., Conclusions: These results indicate that BTE attenuates colon inflammation through the blockage of NF-κB signaling and apoptosis in DSS-induced experimental colitis model.

Human PTEN (phosphatase and tensin homolog deleted on chromosome 10; a phosphatidylinositol 3-phosphatase) expressed in Saccharomyces cerevisiae was oxidized in a time- and H(2)O(2)-concentration-dependent manner. Oxidized hPTEN was reduced by cellular reductants as in human cells. The reduction rate of oxidized hPTEN was monitored in S. cerevisiae mutants in which the genes involved in redox homeostasis had been disrupted. Reduction of hPTEN was delayed in each of S. cerevisiae grx5Δ and ycp4Δ mutants. Expression of Grx5 and Ycp4 in each of the mutants rescued the reduction rate of oxidized hPTEN. Furthermore, an in vitro assay revealed that the human Grx5/GSH system efficiently catalyzed the reduction of oxidized hPTEN. These results suggest that the reduction of oxidized hPTEN is regulated by Grx5 and Ycp4., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Sidewall surface roughness is an important parameter in electronic device manufacture. At present, no high resolution technique exists to quantitatively characterize this property for undercut structures created by semiconductor processing techniques. We developed a three-dimensional atomic force microscope (3D-AFM) to measure the surface roughness of undercut sidewalls with nanometer precision. Decoupled from the positional scanner, the 3D-AFM probe had a variable tilt up to 40° off the normal. Nonorthogonal scans resolved the sidewall surface roughness, base width, and acute critical angle for undercut structures, including a metal overhang and the transmission line of a photonic device. Compatible with standard cantilevers, the 3D-AFM demonstrates great potential for characterizing the sidewalls of soft materials such as photoresist.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expressed in Saccharomyces cerevisiae was reversibly oxidized by hydrogen peroxide and reduced by cellular reductants. Reduction of hPTEN was delayed in each of S. cerevisiae gsh1Delta and gsh2Delta mutants. Expression of gamma-glutamylcysteine synthetase Gsh1 in the gsh1Delta mutant rescued regeneration rate of hPTEN. Oxidized hPTEN was reduced by glutathione in a concentration- and time-dependent manner. Glutathionylated PTEN was detected. Incubation of 293T cells with BSO and knockdown expression of GCLc in HeLa cells by siRNA resulted in the delay of reduction of oxidized PTEN. Also, in HeLa cells transfected with GCLc siRNA, stimulation with epidermal growth factor resulted in the increase of oxidized PTEN and phosphorylation of Akt. These results suggest that the reduction of oxidized hPTEN is mediated by glutathione., (Copyright 2010 Federation of European Biochemical Societies. All rights reserved.)

This study was to investigate factors underlying the age-related decrease in NO production in vascular endothelial cells. The age-related changes in NO production, the activity and expression level of eNOS, and eNOS binding proteins, were studied in HUVECs. NO production in HUVECs significantly decreased in an age-dependent manner. The potentiation of NO production by L-Arg was significantly suppressed by L-NIO (eNOS-specific inhibitor) in young HUVECs and was suppressed by 1400W (iNOS-specific inhibitor) in aged HUVECs. The aged HUVECs had lower eNOS protein levels than young cells. eNOS phosphorylation at Ser-1177 (active) decreased gradually from PDL 23 through 40, and eNOS phosphorylation at Thr-495 (inactive) increased in aged cells. Changes of intracellular eNOS binding proteins, such as caveolin-1, pAkt, and Hsp90, as well as interaction between eNOS and eNOS binding proteins, indicated decreasing enzyme activity in aged HUVECs. Aging might decrease the activity as well as expression level of eNOS in HUVECs. And the decrease in eNOS activity probably implicated to the alterations in the regulatory binding proteins. For further study, it needs to be confirmed that the age-related change in the intracellular distribution of eNOS and the relative contribution of eNOS and iNOS on vascular dysfunction in aged endothelial cells., (2010 Elsevier Ireland Ltd. All rights reserved.)

Overexpression of epidermal growth factor (EGF) and urokinase plasminogen activator receptor (uPAR) have been observed in human gastric cancers. However, the interaction between EGF and uPAR in gastric cancer has not been well elucidated. In this study, we investigated the effect of EGF on uPAR expression and the underlying signal pathways in human gastric cancer AGS cells. EGF induced uPAR mRNA expression in a time- and concentration-dependent manner. EGF also induced uPAR promoter activity. In addition, EGF induced the activation of extracellular signal regulated kinase-1/2 (ERK-1/2) and P38 mitogen-activated protein kinase (MAPK) but not the activation of c-Jun amino terminal kinase. A specific inhibitor of MEK-1 (an upstream effector of ERK-1/2) and a dominant negative MEK-1 were able to suppress the EGF-induced uPAR promoter activity. Site-directed mutagenesis and electrophoretic mobility shift assays demonstrated that the binding sites of transcription factors, activator protein-1 (AP-1) and nuclear factor (NF)-kappaB, are involved in the EGF-induced uPAR transcription. Suppression of the EGF-induced uPAR promoter activity by the AP-1 decoy oligonuclotide, as well as expression vectors encoding mutated-type NF-kappaB-inducting kinase and I-kappaB, confirmed that the activation of AP-1 and NF-kappaB are essential for the EGF-induced uPAR upregulation. The AGS cells pretreated with EGF showed a remarkably enhanced invasiveness and this effect was partially abrogated by uPAR neutralizing antibodies and by the inhibitors of ERK-1/2, AP-1, and NF-kappaB. The above results suggest that EGF induces uPAR expression via ERK-1/2, AP-1, and NF-kappaB signaling pathways and, in turn, stimulates cell invasiveness in human gastric cancer AGS cells.

Considering the importance of inflammation and apoptosis in neurodegenerative conditions, the potential suppressive effects of the Rg3, a by-product obtained during the steaming of red ginseng, may indicate that Rg3 could provide a beneficial therapeutic approach to treating or preventing neurodegenerative disease. We investigated the effect of Rg3 on Abeta42-mediated microglial activation and inflammation-mediated neurotoxicity in murine BV-2 microglial and Neuro-2a neuroblastoma cells, respectively. Rg3 effectively reduced inflammatory cytokine expression in Abeta42-treated BV-2, and inhibited the binding of NF-kappaB p65 to its DNA consensus sequences, and significantly reduced the expression of TNF-alpha in activated microglia. Pretreatment with Rg3 increased the survival rate of Neuro-2a exposed to TNF-alpha. These observations suggest that Rg3 reduced neurotoxicity by inhibiting chronic inflammation through the suppression of activated microglia. In addition, the expression of pro-inflammatory cytokines in BV-2 stimulated by Abeta42 was decreased but not eliminated by Rg3 when binding to the macrophage scavenger receptor type A (MSRA) was blocked with fucoidan. This implies that the inflammatory response may not be exclusively triggered via MSRA. More interestingly, iNOS was almost completely inhibited in the presence of Rg3 when MSRA binding was blocked with fucoidan. Moreover, Rg3 increased the expression of MSRA in BV-2 transfected with siRNA targeting MSRA mRNA, and this increased MSRA expression may play a role in the phagocytosis of Abeta42 peptides. Our results indicate that inhibition of the inflammatory repertoire of microglia, neuroprotection, and increased MSRA expression induced by Rg3 may at least partly explain its therapeutic effects in chronic neurodegenerative diseases.

There is a strong correlation between the overexpression of urokinase-type plasminogen activator receptor (uPAR) and gastric cancer invasion. This study examined the effect of phospholipid lysophosphatidic acid (LPA) on uPAR expression in human gastric cancer AGS cells and the underlying signal transduction pathways. Treating human gastric AGS cells with LPA induced the expression of uPAR mRNA and promoter activity in both a time- and dose-dependent manner. Small interfering RNA targeting for LPA receptors, dominant negative Rho-family GTPase (RhoA, Rac1, and Cdc42) and an expression vector encoding a mutated c-jun (TAM67) partially blocked the LPA-induced uPAR expression. Site-directed mutagenesis and electrophoretic mobility shift studies showed that the transcription factors activation protein-1 (AP-1) and nuclear factor (NF)-kappaB are essential for the LPA-induced uPAR transcription. In addition, AGS cells treated with LPA showed enhanced invasion, which was partially abrogated by the uPAR-neutralizing antibodies and inhibitors of Rho kinase, JNK, and NF-kappaB. This suggests that LPA induces uPAR expression through the LPA receptors, Rho-family GTPase, JNK, AP-1 and NF-kappaB signaling pathways, which in turn stimulates the cell invasiveness of human gastric cancer AGS cells.

Licochalcones have a variety of biological properties including anti-tumor, anti-parasitic and anti-bacterial activities. Recently, a new retrochalcone (licochalcone E, Lico-E) was isolated from the roots of Glycyrrhiza inflata (Chem. Pharm. Bull., 53, 2005, Yoon et al.) by cytotoxicity-guided fractionation. This study examined whether or not Lico-E-induced endothelial cell death occurs through apoptosis, and investigated molecular mechanisms involved in this process. Lico-E was found to suppress ECV304 cell growth and induce apoptosis. The induction of apoptosis by Lico-E was confirmed by the ladder-patterned DNA fragmentation, the presence of cleaved and condensed nuclear chromatin and the increased number of annexin V-positive cells. Lico-E could effectively inhibit the constitutive NF-kappaB activation, as revealed by the electrophoretic mobility shift assay and NF-kappaB-dependent luciferase reporter study. In addition, the Lico-E treatment caused a change in the Bax/Bcl-2 ratio that favored apoptosis. These results suggest that Lico-E induces endothelial cell apoptosis by modulating NF-kappaB and the Bcl-2 family.

Nuclear factor (NF)-kappaB regulates a central common signaling for immunity and cell survival. Artemisolide (ATM) was previously isolated as a NF-kappaB inhibitor from a plant of Artemisia asiatica. However, molecular basis of ATM on NF-kappaB activation remains to be defined. Here, we demonstrate that ATM is a typical inhibitor of IkappaB kinase beta (IKKbeta), resulting in inhibition of lipopolysaccharide (LPS)-induced NF-kappaB activation in RAW 264.7 macrophages. ATM inhibited the kinase activity of highly purified IKKbeta and also LPS-induced IKK activity in the cells. Moreover, the effect of ATM on IKKbeta activity was completely abolished by substitution of Cys-179 residue of IKKbeta to Ala residue, indicating direct targeting site of ATM. ATM could inhibit IkappaBalpha phosphorylation in LPS-activated RAW 264.7 cells and subsequently prevent NF-kappaB activation. Further, we demonstrate that ATM down-regulates NF-kappaB-dependent TNF-alpha expression. Taken together, this study provides a pharmacological potential of ATM in NF-kappaB-dependent inflammatory disorders.

The overexpression of urokinase-type plasminogen activator receptor (uPAR) is closely related to tumor cell invasion. Therefore, strategies for down-regulating uPAR expression may be of clinical utility. This study examined the effects of triptolide, which is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook F., on the induction of uPAR in human gastric cancer AGS cells. Triptolide inhibited the phorbol 12-myristate 13-acetate (PMA)-induced uPAR mRNA and protein expression in a dose-dependent manner, and reduced the uPAR transcriptional activity. The stability of the uPAR transcripts was not altered by the triptolide treatment. The signals involved in uPAR induction by PMA were investigated to determine the mechanisms for the triptolide-mediated regulation of uPAR. The inhibitors of extracellular signal-regulated kinases 1 and 2 (Erk-1/2, PD98059), c-Jun N-terminal kinases (JNK, SP600125) and nuclear factor-kappa B (NF-kappaB, Bay11-7082) inhibited the PMA-induced expression of uPAR, which suggests that PMA induces uPAR through multiple signals. Triptolide suppressed the PMA-induced activation of NF-kappaB but not Erk-1/2 and JNKI The inhibitory effect of triptolide on the activation of NF-kappaB was confirmed by an electrophoretic mobility shift assay and NF-kappaB dependent transcription studies. AGS cells treated with PMA showed a remarkably enhanced invasiveness, which was partially abrogated by triptolide and uPAR-neutralizing antibodies. This suggests that triptolide may exert at least part of its anti-invasive effect in gastric cancer by controlling the expression of uPAR through the suppression of NF-kappaB activation.

Monocyte chemotactic protein-1 (MCP-1) is a potent chemoattractant for monocytes and plays a key role in various inflammatory responses, including atherosclerosis. In this study, we examined the effect of (-)-epigallocatechin-3-gallate (EGCG), a major green tea catechin, on the expression of MCP-1 in human endothelial ECV304 cells. EGCG markedly inhibited the phorbol 12-myristate 13-acetate (PMA)-induced MCP-1 mRNA and protein levels in a dose-dependent manner. EGCG was also found to reduce the MCP-1 transcriptional activity. The upregulation of MCP-1 by PMA was significantly inhibited by blockade of P38 mitogen-activated protein kinase (MAPK) and NF-kappaB, but not by blockade of extracellular-signal-regulated kinase and c-Jun N-terminal kinase pathway. Furthermore, The PMA-induced p38 MAPK and NF-kappaB activation were obviously attenuated after pretreating ECV304 cells with EGCG. The conditioned media from the endothelial ECV304 cells treated with PMA could remarkably stimulate the migration of THP-1 monocytes and this effect was partially abrogated by MCP-1 neutralizing antibodies. Moreover, the media from the EGCG-pretreated ECV304 cells lost the stimulatory activity for THP-1 migration. These results suggest that EGCG may exert an anti-inflammatory effect in endothelial cells by controlling MCP-1 expression, at least in part, mediated through the suppression of p38 MAPK and NF-kappaB activation.

The gastric pathogen, helicobacter pylori (H. pylori), has been associated with the progression of gastric cancer. It was previously reported that H. pylori induced urokinase plasminogen activator receptor (uPAR) expression and stimulated cell invasiveness in human gastric cancer AGS cells. However, the precise mechanisms for how H. pylori upregulates uPAR are unclear. This study investigated the underlying signal pathways in H. pylori-induced uPAR in human gastric cancer AGS cells. The intracellular H2O2 content, as determined using H2O2-sensitive probe 2',7'-dichlorodihydrofluorescein, increased after the H. pylori treatment. N-acetyl cysteine (NAC), an antioxidant, prevented the H. pylori-induced production of H2O2 and uPAR expression. In addition, exogenous H2O2 was found to increase uPAR mRNA expression and its promoter activity. Site-directed mutagenesis of the potential NF-kappaB element in the uPAR promoter showed that the redox-sensitive transcription factor NF-kappaB was essential for H. pylori-induced uPAR expression. The expression of vectors encoding a mutated-type NF-kappaB-inducing kinase and I-kappaB, and a specific inhibitor of NF-kappaB (BAY11-7082) decreased the H. pylori-induced uPAR promoter activity. Chromatin immunoprecipitation and the electrophoretic mobility shift assay confirmed that H. pylori increased the DNA binding activity of NF-kappaB. With the aid of NAC and H2O2, it was determined that reactive oxygen species (ROS) is an upstream signaling molecule for activating the NF-kappaB induced by H. pylori. The enhanced AGS cell invasiveness by H. pylori was partially abrogated by an NAC and BAY11-7082 treatment. These results suggest that the ROS and NF-kappaB signaling pathway is important in H. pylori-induced uPAR expression and the increased cell invasiveness of human gastric cancer AGS cells.

Platelet-derived growth factor (PDGF) has been known to induce vascular endothelial growth factor (VEGF) expression in human vascular smooth muscle cells (hVSMCs). We previously reported that Erk-1/2 and AP-1 pathways are crucial in the PDGF-induced VEGF expression in hVSMCs . In this study, we investigated the effect of epigallocatechin-3-gallate (EGCG), the major green tea catechin, on the PDGF-induced VEGF expression in hVSMCs and the underlying mechanisms. EGCG were found to inhibit dose-dependently the VEGF expression and activation of PDGF receptor, Erk-1/2 and AP-1 induced by PDGF. In addition, cell free studies demonstrated that EGCG could directly inhibit the Erk-1/2 activity. Conditioned media from the hVSMCs treated with PDGF could remarkably stimulate the in vitro growth of human umbilical vein endothelial cells (HUVECs) but the media from the EGCG-pretreated hVSMCs lost its stimulatory activity for HUVEC proliferation. These results suggest that EGCG may exert the anti-angiogenic effect by inhibiting the PDGF-induced VEGF expression at multiple signaling levels.

Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) have been shown to communicate with each other via cytokine signaling during neovascularization. In this study, we investigated the effect of platelet-derived growth factor (PDGF), a cytokine released from tumors and ECs, on vascular endothelial growth factor (VEGF) expression in human VSMCs and underlying signal transduction pathways. PDGF induced VEGF expression in a time- and concentration-dependent manner. PDGF induced the activation of extra-cellular signal-regulated kinase-1/2 (ERK-1/2), but not the activation of c-jun amino terminal kinase (JNK) and P38 mitogen-activated protein kinase (MAPK). Specific inhibitor of mitogen-activated protein kinase kinase (MEK)-1 was found to suppress VEGF expression and promoter activity. The expression of vectors encoding a mutated-type MEK-1 decreased the VEGF promoter activity. Electrophoretic mobility shift assay revealed that PDGF dose-dependently increased the DNA binding activity of AP-1. Transient transfection studies using an AP-1 decoy oligonucleotide confirmed that the activation of AP-1 is involved in PDGF-induced VEGF upregulation. Conditioned media from the human VSMCs pretreated with PDGF could remarkably stimulate the in vitro growth of human umbilical vein endothelial cells and this effect was partially abrogated by VEGF neutralizing antibodies. The above results suggest that ERK-1/2 and AP-1 signaling pathways are involved in the PDGF-induced VEGF expression in human VSMCs and that these paracrine signaling pathways induce endothelial cell proliferation.

The gastric pathogen Helicobacter pylori (H. pylori) is suggested to be associated with gastric cancer progression. In this study, we investigated the effect of H. pylori on urokinase plasminogen activator receptor (uPAR) expression which has been known to correlate closely with gastric cancer invasion. H. pylori induced the uPAR expression in a time- and concentration-dependent manner. Specific inhibitors and inactive mutants of MEK-1 and JNK were found to suppress the H. pylori-induced uPAR expression and the uPAR promoter activity. Electrophoretic mobility shift assay and transient transfection study using an AP-1 decoy oligonucleotide confirmed that the activation of AP-1 is involved in the H. pylori-induced uPAR upregulation. The AGS cells treated with H. pylori showed a remarkably enhanced invasiveness, and this effect was partially abrogated by uPAR-neutralizing antibodies. These results suggest that H. pylori induces uPAR expression via Erk-1/2, JNK, and AP-1 signaling pathways and, in turn, stimulates the cell invasiveness in human gastric cancer AGS cells.

Overexpression of urokinase plasminogen activator receptor (uPAR) is known to correlate closely with tumor cell invasion and metastasis. In gastric cancer, however, the mechanism for induction of uPAR remains to be elucidated. In this study, to investigate the effect of reactive oxygen species (ROS) on uPAR expression and the underlying signal pathways in human gastric cancer AGS cells, phenazine methosulfate (PMS) and H2O2 were used as ROS generator. PMS and H2O2 induced the uPAR expression in time- and concentration-dependent manner. PMS and H2O2 also induced the activation of extracellular signal-regulated kinases (Erk)-1/2. A specific inhibitor of MEK-1 (PD980590) was found to suppress the PMS-induced uPAR expression and the uPAR promoter activity. Expression of vectors encoding a mutated-type MEK-1 resulted in decreases in the uPAR promoter activity. Electrophoretic mobility shift assay revealed that PMS increased time-dependently the DNA binding activity of AP-1. Transient transfection studies using AP-1 decoy confirmed that the activation of AP-1 is involved in PMS-induced uPAR upregulation. The AGS cells pretreated with PMS showed a remarkably enhanced invasiveness and this effect was partially abrogated by uPAR neutralizing antibodies. The above results suggest that ROS induces uPAR expression via Erk-1/2 and AP-1 signaling pathways and, in turn, stimulates the cell invasiveness in human gastric cancer AGS cells.

Recent studies have suggested that the expression of interleukin-8 (IL-8) directly correlates with the vascularity of human gastric carcinomas. In this study, the effect of IL-1beta on IL-8 expression in human gastric cancer TMK-1 cells and the underlying signal transduction pathways were investigated. IL-1beta induced the IL-8 expression in a time- and concentration-dependent manner. IL-1beta induced the activation of extracellular signal-regulated kinases-1/2 and P38 mitogen-activated protein kinase (MAPK), but not the activation of c-jun amino-terminal kinse and Akt. Specific inhibitors of MEK-1 (PD980590) and P38 MAPK (SB203580) were found to suppress the IL-8 expression and the IL-8 promoter activity. Expression of vectors encoding a mutated-type MEK-1 and P38 MAPK resulted in decrease in the IL-8 promoter activity. IL-1beta also induced the production of reactive oxygen species (ROS). N-acetyl cysteine (NAC) prevented the IL-1beta-induced ROS production and IL-8 expression. In addition, exogenous H2O2 could induce the IL-8 expression. Deletional and site-directed mutagenesis studies on the IL-8 promoter revealed that activator protein-1 (AP-1) and nuclear factor (NF)-kappaB sites were required for the IL-1beta-induced IL-8 transcription. Electrophoretic mobility shift assay confirmed that IL-1beta increased the DNA-binding activity of AP-1 and NF-kappaB. Inhibitor (PD980590, SB203580) and ROS scavenger (NAC) studies revealed that the upstream signalings for the transcription factors AP-1 and NF-kappaB were MAPK and ROS, respectively. Conditioned media from the TMK-1 cells pretreated with IL-1beta could remarkably stimulate the in vitro growth of HUVEC and this effect was partially abrogated by IL-8-neutralizing antibodies. The above results suggest that MAPK-AP-1 and ROS-NF-kappaB signaling pathways are involved in the IL-1beta-induced IL-8 expression and that these paracrine signaling pathways induce endothelial cell proliferation.

(-)-Epigallocatechin-3-gallate (EGCG), a main flavanol of green tea, potently suppressed the urokinase-type plasminogen activator (uPA) expression in human fibrosarcoma HT 1080 cells. EGCG induced not only the suppression of the uPA promoter activity but also the destabilization of uPA mRNA. EGCG inhibited the phosphorylation of extracellular signal-regulated kinases 1 and 2 (Erk-1/2) and P38 mitogen-activated protein kinase (MAPK), but not the phosphorylation of c-jun N-terminal kinase (JNK) and Akt. Specific inhibitors of Erk-1/2 (2'-amino-3'-methoxyflavone, PD98059) and P38 MAPK (pyridinylimidazole, SB203580) were found to suppress the uPA expression and the uPA promoter activity. However, the specific inhibitors did not affect the uPA mRNA stability. These results suggest that EGCG could regulate the uPA expression by at least two different mechanisms: EGCG may inhibit the Erk-1/2 and P38 MAPK, leading to suppression of the uPA promoter activity, and EGCG may destabilize the uPA mRNA in an Erk-1/2- and p38 MAPK-independent way.

Overexpression of matrix metalloproteinases (MMPs) has been known to correlate closely with tumor cell invasion and strategies to down-regulate their expression may ultimately be of clinical utility. In this study, we investigated the effects of (-)-epigallocatechin gallate (EGCG), a major green tea catechin, on the cell invasiveness and MMP-9 induction in human gastric cancer AGS cells. EGCG inhibited the phorbol 12-myristate 13-acetate (PMA)-induced cell invasiveness and MMP-9 expression in a dose-dependent manner. EGCG treatment was found to reduce the MMP-9 transcriptional activity. To further study the mechanisms for the EGCG-mediated regulation of MMP-9, the effects of EGCG on transcription factor AP-1 and mitogen-activated protein kinase (MAPK) activities were examined. The results showed that EGCG suppressed the PMA-induced AP-1 activation. EGCG also abrogated the PMA-induced activation of extracellular-regulated protein kinase (Erk) and c-jun N-terminal kinase (JNK), which are upstream modulators of AP-1. These results suggest that EGCG may exert at least part of its anti-invasive effect in gastric cancer by controlling MMP expression through the suppression of MAPK and AP-1 activation.

Silibinin, the flavonoid found in the milk thistle, has been shown to suppress cell growth and exhibit anti-cancer effects. Some flavonoids were reported to inhibit angiogenesis which is essential for tumor growth and metastasis. In this study, to clarify the underlying mechanisms for the anti-cancer effect of silibinin, we examined the effects of silibinin on human endothelial ECV304 cells. Silibinin was found to suppress the growth and induce the apoptosis of ECV304 cells. The induction of apoptosis by silibinin was confirmed by ladder-patterned DNA fragmentation, cleaved and condensed nuclear chromatin and DNA hypoploidy. Silibinin could effectively inhibit constitutive NF-kappaB activation as revealed by electrophoretic mobility shift assay and NF-kappaB-dependent luciferase reporter study. Consistent with this, silibinin treatment resulted in a significant decrease in the nuclear level of p65 subunit of NF-kappaB. In addition, silibinin treatment caused a change in the ratio of Bax/Bcl-2 in a manner that favors apoptosis. Silibinin also induced the cytochrome c release, activation of caspase-3 and caspase-9 and cleavage of PARP. These results suggest that silibinin may exert, at least partly, its anti-cancer effect by inhibiting angiogenesis through induction of endothelial apoptosis via modulation of NF-kappaB, Bcl-2 family and caspases.

Overexpression of urokinase plasminogen activator (uPA) is known to correlate closely with tumor cell invasion and metastasis. In gastric cancer, however, the mechanism for induction of uPA remains to be elucidated. In this study, we investigated the intracellular signaling for uPA expression in human gastric carcinoma cells (AGS, SNU-1, SNU-5, and SNU-638). SNU-638 cells which expressed a high level of uPA was found to be highly invasive on a matrigel, while AGS, SNU-1, and SNU-5 cells with low levels of uPA expression were only slightly invasive. SNU-638 cells showed a much higher P38 MAPK activity than the 3 other cell lines. However, there was no significant difference in the activities of P44/42 MAPK (Erk-1/2), JNK and Akt among the above cell lines. Treatment of SNU-638 cells with SB203580, a specific P38 MAPK inhibitor, reduced both the promoter activity and mRNA expression of uPA. Expression of a vector encoding a mutated-type P38alpha MAPK resulted in decrease in the uPA promoter activity in SNU-638 cells. These results suggest that P38 MAPK signaling pathway is important for uPA expression in gastric SNU-638 cells by enhancing the promoter activity of uPA.

The relation between transforming growth factor-beta (TGF-beta) and cyclooxygenase (COX) in hepatoma malignancy is not understood yet. To investigate regulation mechanism of endogenous TGF-beta on hepatoma, we established MH129F mouse hepatoma cell overexpressing the cytoplasmic domain of type II TGF-beta receptor (TRII). MH129F cell apoptosis was elevated almost 20% after 5 ng/ml TGF-beta1 treatment. However, soluble TRII-overexpressing cells (MH129F/TRIIs) did not show any change of growth pattern after TGF-beta1 treatment because MH129F/TRIIs cells blocked the growth inhibitory effect of TGF-beta1. In MH129F/TRIIs cells, expression of cycooxygenase-2 (COX-2) and bcl-2 was remarkably elevated, and then enhancement of COX-2 mediated induction of prostaglandin E(2) (PGE(2)) production up to 7-fold. Especially, vascular endothelial growth factor (VEGF) expression was regulated by COX-2 in MH129F/TRIIs cells, which were inhibited endogenous TGF-beta response. Implantation of 5x10(6) MH129F/TRIIs cells into nude mice showed the significantly enhanced tumor formation, and intensity of COX-2 expression was slightly higher in MH129F/TRIIs tumor section than control. Moreover, a strong antitumor response was observed in MH129F/TRIIs-bearing mice that were treated with a specific COX-2 inhibitor, celecoxib. Therefore, we suggest that COX-2 mediate the tumorigenicity of hepatoma cells blocking endogenous TGF-beta effect via VEGF regulation.

Purpose: The role of P38 mitogen-activated protein kinase (MAPK) in gastric cancer invasion has not yet been determined. In this study, we examined the effects of SB203580, a specific P38 MAPK inhibitor, on the in vitro invasion of gastric cancer and upon the molecules involved in this process., Materials and Methods: Human gastric cancer SNU-638 cells were maintained in RPMI 1640 supplemented with 10% FBS. BIOCOAT matrigel invasion chambers were used to examine in vitro invasiveness, zymography for gelatinase activity, CAT assay for uPA promoter activity and Western and Northern blotting to determine protein and mRNA levels, respectively., Results: Treatment of SNU-638 cells with SB203580, a specific P38 MAPK inhibitor, reduced in vitro invasiveness, dose-dependently. SB203580 treatment was found to decrease both mRNA expression and uPA promoter activity in gastric SNU-638 cells. In vitro invasion of SNU-638 cells was partially abrogated by uPA-neutralizing antibodies. The activities of MMPs were not significantly altered by SB203580., Conclusion: Our results suggest that P38 MAPK is a potential therapeutic target for inhibiting uPA-dependent gastric tumor invasiveness and metastasis.

We have previously shown that treatment with (-)-epigallocatechin-3-gallate (EGCG) inhibited vascularity and tumor growth in human colon cancer xenografts in nude mice (Jung et al: Br J Cancer 84, 2001). In this study, we examined whether endothelial cell death by EGCG is mediated by apoptosis and which molecular mechanisms are involved in this process. EGCG was found to suppress cell growth and induce apoptosis largely through mitochondrial depolarization, activation of caspase-3 and cleavage of DNA fragmentation factor-45 in human endothelial ECV 304 cells. The induction of apoptosis by EGCG was confirmed by cleaved and condensed nuclear chromatin and DNA hypoploidy. These results suggest that EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through inducing endothelial apoptosis.

IL-1beta increased the production of proenzyme of MMP-9 (pro-MMP-9) in a time- and dose-dependent manner in murine macrophage RAW 264.7 cells. However, the production of MMP-2 was not significantly changed by IL-1beta treatment. The intracellular H(2)O(2) content, as determined with H(2)O(2)-sensitive probe 2('),7(')-dichlorodihydrofluorescein, also increased after IL-1beta treatment (5ng/ml). In addition, exogenous H(2)O(2) (50 microM) was found to increase the production of pro-MMP-9. Transient transfection study using a MMP-9 promoter-reporter construct showed that IL-1beta enhanced the MMP-9 promoter activity. Electrophoretic mobility shift assay and site-directed mutagenesis study on the consensus binding site for NF-kappaB revealed that the activation of NF-kappaB is required for the IL-1beta-induced activation of MMP-9 promoter. N-acetylcysteine, an antioxidant, could abrogate the production of pro-MMP-9, H(2)O(2) generation, and activation of NF-kappaB and MMP-9 promoter. These results suggest that IL-1beta upregulates the MMP-9 expression via production of reactive oxygen species and activation of NF-kappaB in RAW 264.7 cells.

Tea catechins and other flavonoids have been shown to potentially protect against chronic cardiovascular diseases such as coronary heart disease and atherosclerosis. In this study, 6-month-old female Sprague-Dawley rats were fed green tea extract (50 mg/100 ml in drinking water) up to the age of 22 months, and the age-associated changes in Maillard-type fluorescence and carbonyl groups in the aortic and skin collagen were compared with those occurring in the water-fed control animals. Collagen-linked Maillard-type fluorescence was found to increase in both the aortic and skin tissues as animals aged. The age-associated increase in the fluorescence in the aortic collagen was remarkably inhibited by the green tea extract treatment, while that occurring in the skin collagen was not significantly inhibited by the treatment. The collagen carbonyl content also increased in both the aortic and skin tissues as animals aged. In contrast with the case of Maillard-type fluorescence, however, the age-associated increase in the carbonyl content was not inhibited by the green tea extract treatment either in the aortic or skin collagen. These results suggest that the inhibition of AGE formation in collagen is an important mechanism for the protective effects of tea catechins against cardiovascular diseases., ((c)2002 Elsevier Science.)

Catechins are key components of teas that have antiproliferative properties. We investigated the effects of green tea catechins on intracellular signalling and VEGF induction in vitro in serum-deprived HT29 human colon cancer cells and in vivo on the growth of HT29 cells in nude mice. In the in vitro studies, (-)-epigallocatechin gallate (EGCG), the most abundant catechin in green tea extract, inhibited Erk-1 and Erk-2 activation in a dose-dependent manner. However, other tea catechins such as (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) did not affect Erk-1 or 2 activation at a concentration of 30 microM. EGCG also inhibited the increase of VEGF expression and promoter activity induced by serum starvation. In the in vivo studies, athymic BALB/c nude mice were inoculated subcutaneously with HT29 cells and treated with daily intraperitoneal injections of EC (negative control) or EGCG at 1.5 mg day(-1)mouse(-1)starting 2 days after tumour cell inoculation. Treatment with EGCG inhibited tumour growth (58%), microvessel density (30%), and tumour cell proliferation (27%) and increased tumour cell apoptosis (1.9-fold) and endothelial cell apoptosis (3-fold) relative to the control condition (P< 0.05 for all comparisons). EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through blocking the induction of VEGF., (Copyright 2001 Cancer Research Campaign.)

DNA could readily associate with the aggregated forms of the beta-amyloid peptides beta(1-40) and beta(25-35), giving rise to a shift in the electrophoretic mobility of DNA. As a result, DNA was retained at the top of a 1% agarose gel. In contrast, the electrophoretic mobility of DNA was little influenced by the monomeric forms of beta(1-40) and beta(25-30). DNA from different sources such as lambda phage, Escherichia coli plasmid, and human gene showed similar results. However, the electrophoretic mobility of RNA was shifted by the monomeric beta(1-40) and beta(25-35) as well as by the aggregated beta(1-40) and beta(25-35). The association of DNA with the aggregated beta-amyloid peptides could occur at pH 4-9. The inhibitory action of hemin on beta-amyloid aggregation could be confirmed using the DNA mobility shift assay. These results indicate that the DNA mobility shift assay is useful for kinetic study of beta-amyloid aggregation as well as for testing of agents that might modulate beta-amyloid aggregation., (Copyright 2000 Academic Press.)

Seventy-eight patients (85 affected hips and 71 unaffected hips) with Legg-Calvé-Perthes disease were included in this study to evaluate the metaphyseal change in radiographs and magnetic resonance imaging (MRI) and to define the type of the metaphyseal cyst according to presence or absence of the epiphyseal involvement. The content of the metaphyseal cyst was evaluated by using T1,T2, proton, and gadolinium-enhanced T1-weighted MRI scans. Among 85 hips, there were no changes in 32 hips, marrow edema in 13 hips, false cyst with epiphyseal involvement in 28 hips, and true cyst without epiphyseal involvement in 12 hips. Granulation tissue was found in the false cysts and water-rich fibrotic tissue was found in the true cysts based on the MRI scans. The metaphyseal change in MRI scans was shown in 71% of groups 3 and 4 and in 35% of groups 1 and 2 according to the Catterall classification, and 52% of group A, 56% of group B, and 86% of group C according to the Herring classification. Of the 30 hips at the avascular stage, 33% showed metaphyseal cyst in MRI scans. Of the 53 hips at the fragmentation stage, 60% showed the metaphyseal cyst.