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Find video protocols related to scientific articles indexed in Pubmed.
Sc(OTf)3-mediated 1,3-dipolar cycloaddition-ring cleavage-rearrangement: a highly stereoselective access to Z-?-enaminonitriles.
Org. Biomol. Chem.
PUBLISHED: 11-07-2014
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A novel and highly stereoselective synthesis of Z-?-enaminonitriles from azides and ?,?-unsaturated nitriles is reported. The reaction proceeds via a 1,3-dipolar cycloaddition-ring cleavage-rearrangement cascade mediated by a catalytic amount of Sc(OTf)3. A plausible reaction mechanism for this process is depicted.
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Fluorinated Pickering Emulsions Impede Interfacial Transport and Form Rigid Interface for the Growth of Anchorage-Dependent Cells.
ACS Appl Mater Interfaces
PUBLISHED: 10-28-2014
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This study describes the design and synthesis of amphiphilic silica nanoparticles for the stabilization of aqueous drops in fluorinated oils for applications in droplet microfluidics. The success of droplet microfluidics has thus far relied on one type of surfactant for the stabilization of drops. However, surfactants are known to have two key limitations: (1) interdrop molecular transport leads to cross-contamination of droplet contents, and (2) the incompatibility with the growth of adherent mammalian cells as the liquid-liquid interface is too soft for cell adhesion. The use of nanoparticles as emulsifiers overcomes these two limitations. Particles are effective in mitigating undesirable interdrop molecular transport as they are irreversibly adsorbed to the liquid-liquid interface. They do not form micelles as surfactants do, and thus, a major pathway for interdrop transport is eliminated. In addition, particles at the droplet interface provide a rigid solid-like interface to which cells could adhere and spread, and are thus compatible with the proliferation of adherent mammalian cells such as fibroblasts and breast cancer cells. The particles described in this work can enable new applications for high-fidelity assays and for the culture of anchorage-dependent cells in droplet microfluidics, and they have the potential to become a competitive alternative to current surfactant systems for the stabilization of drops critical for the success of the technology.
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The association between prostate cancer and mood disorders: a nationwide population-based study in Taiwan.
Int Psychogeriatr
PUBLISHED: 10-23-2014
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ABSTRACT Background: This study identified possible risk factors for newly diagnosed mood disorders, including depressive and bipolar disorders, in prostate cancer patients. Methods: From 2000 to 2006, two cohorts were evaluated on the occurrence of mood disorder diagnosis and treatment. For the first cohort, data of patients diagnosed with prostate cancer was obtained from the Taiwan National Health Insurance (NHI) Research Database. As the second cohort, a cancer-free comparison group was matched for age, comorbidities, geographic region, and socioeconomic status. Results: Final analyses involved 12,872 men with prostate cancer and 12,872 matched patients. Increased incidence of both depressive (IRR 1.52, 95% CI 1.30-1.79, P <0.001) and bipolar disorder (IRR 1.84, 95% CI 1.25-2.74, P = 0.001) was observed among patients diagnosed with prostate cancer. Multivariate matched regression models show that cerebrovascular disease (CVD) and radiotherapy treatment could be independent risk factors for developing subsequent depressive and bipolar disorders. Conclusion: We observed that the risk of developing newly diagnosed depressive and bipolar disorders is higher among Taiwanese prostate cancer patients. Clinicians should be aware of the possibility of increased depressive and bipolar disorders among prostate cancer patients in Taiwan. A prospective study is necessary to confirm these findings.
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Numerical simulation and field test study of desulfurization wastewater evaporation treatment through flue gas.
Water Sci. Technol.
PUBLISHED: 10-18-2014
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Aimed at cost saving and pollution reduction, a novel desulfurization wastewater evaporation treatment system (DWETS) for handling wet flue gas desulfurization (WFGD) wastewater of a coal-fired power plant was studied. The system's advantages include simple process, and less investment and space. The feasibility of this system has been proven and the appropriate position and number of nozzles, the spray droplet size and flue gas temperature limitation have been obtained by computational fluid dynamics (CFD) simulation. The simulation results show that a longer duct, smaller diameter and higher flue gas temperature could help to increase the evaporation rate. The optimal DWETS design of Shangdu plant is 100 ?m droplet sprayed by two nozzles located at the long duct when the flue gas temperature is 130 °C. Field tests were carried out based on the simulation results. The effects of running DWETS on the downstream devices have been studied. The results show that DWETS has a positive impact on ash removal efficiency and does not have any negative impact on the electrostatic precipitator (ESP), flue gas heat exchanger and WFGD. The pH values of the slurry of WFGD slightly increase when the DWETS is running. The simulation and field test of the DWETS show that it is a feasible future technology for desulfurization wastewater treatment.
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Down-regulation of Slit-Robo Pathway Mediating Neuronal Cytoskeletal Remodeling Processes Facilitates the Antidepressive-like Activity of Gastrodia elata Blume.
J. Agric. Food Chem.
PUBLISHED: 10-16-2014
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Nowadays, depression is a serious psychological disorder that causes extreme economic loss and social problems. Previously, we discovered that the water extract of Gastrodia elata Blume (WGE) improved depressive-like behavior by influencing neurotransmitters in rats subjected to the forced swimming test. To elucidate possible mechanisms, in the present study, we performed a proteomics and bioinformatics analysis to identify the related pathways. Western blot-validated results indicated that the core protein network modulated by WGE administration was closely associated with down-regulation of the Slit-Robo pathway, which modulates neuronal cytoskeletal remodeling processes. Although Slit-Robo signaling has been well investigated in neuronal development, its relationship with depression is not fully understood. We provide a potential hint on the mechanism responsible for the antidepressive-like activity of WGE. In conclusion, we suggest that the Slit-Robo pathway and neuronal cytoskeleton remodeling are possibly one of the pathways associated with the antidepressive-like effects of WGE.
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When hepatoma rupture happens in situs inversus totalis: side matters.
Acta Clin Belg
PUBLISHED: 10-10-2014
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The authors reported a 73-year-old alcoholic man with previously-unrecognized situs inversus totalis suffering from left upper quadrant pain. Acute myocardial infarction was diagnosed and coronary angioplasty was performed immediately. However, the massive bleeding from the previously-unfound hepatomas caused hypovolemic shock and fatal outcome. Situs inversus totalis is a rare congenital anomaly with a complete mirror image of the thoracic and abdominal organs. Although being considered a benign entity, it would disturb diagnosis-making of the visceral diseases owing to the altered anatomy. To our knowledge, the coexistence of the coronary artery disease and ruptured hepatomas in situs inversus totalis, as in our patient, is never described. Recognition of any situs anomalies in time is the key to avoid misdiagnosis, inappropriate managements, and unwanted consequences.
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Anti-inflammatory and anti-proliferative effects of CBS3830 in arterialized vein grafts in rats.
Immunopharmacol Immunotoxicol
PUBLISHED: 09-10-2014
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Abstract Objective: To investigated whether CBS3830, a highly selectively inhibitor of p38MAPK, could ameliorate inflammation and intimal hyperplasia in arterialized vein grafts (AVGs).
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Anxiety and depressive disorders among patients with esophageal cancer in Taiwan: a nationwide population-based study.
Support Care Cancer
PUBLISHED: 09-02-2014
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The comorbidity of depression with anxiety disorders is associated with poorer treatment outcomes, worse quality of life, poorer adherence to treatment, and greater suicide risk in cancer patients.
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Relationships of COX2 and MMP12 genetic polymorphisms with chronic obstructive pulmonary disease risk: a meta-analysis.
Mol. Biol. Rep.
PUBLISHED: 08-28-2014
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We performed the present meta-analysis in an attempt to confirm the correlation of genetic polymorphisms in the COX2 and MMP12 genes with the susceptibility to chronic obstructive pulmonary disease (COPD). We searched English database such as PubMed, CISCOM, CINAHL, Web of Science, Google Scholar and several Chinese database for meta-analysis. There were no specific language restrictions. Two investigators systematically extracted relevant data within those included studies. Crude ORs with its corresponding 95 % CI were calculated. STATA 12.0 software was adopted for statistical analysis. The impact of COX2 and MMP12 genetic polymorphisms on the pathogenesis of COPD was investigated in the current study with a total of 10 case-control studies, which includes 1,751 COPD patients and 2,472 healthy subjects. Four common polymorphisms, including rs689466 G > A and rs20417 G > C in the COX2 gene, rs652438 A > G and rs2276109 A > G were evaluated in the MMP12 gene. Pooled OR of the present studies and results showed that the frequency of COX2 rs20417 polymorphism was prevalent in COPD patients than those of healthy subjects (C allele vs. G allele OR = 1.33, 95 % CI 1.06-1.67, P = 0.014; GC + CC vs. GG OR = 1.86, 95 % CI 1.07-3.24, P = 0.029; respectively). However, we found no significant correlation between COX2 rs689466 polymorphism and the risk of COPD (all P > 0.05). Furthermore, our meta-analysis illustrated that individuals with MMP12 rs652438 polymorphism had significantly increased risk of developing COPD (G allele vs. A allele OR = 1.62, 95 % CI 1.08-2.42, P = 0.020; AG + GG vs. AA OR = 2.14, 95 % CI 1.12-4.09, P = 0.021; respectively). Nevertheless, no positive relation was detected between MMP12 rs2276109 variant and the risk of COPD. Our meta-analysis indicates that COX2 and MMP12 genetic polymorphisms may be strongly implicated in the development of COPD, especially for the COX2 rs20417 and MMP12 rs652438 polymorphisms. Thus, COX2 and MMP12 genetic polymorphisms could potentially be utilized as helpful biomarkers for early diagnosis of COPD.
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Nanoparticle growth. Facet development during platinum nanocube growth.
Science
PUBLISHED: 08-23-2014
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An understanding of how facets of a nanocrystal develop is critical for controlling nanocrystal shape and designing novel functional materials. However, the atomic pathways of nanocrystal facet development are mostly unknown because of the lack of direct observation. We report the imaging of platinum nanocube growth in a liquid cell using transmission electron microscopy with high spatial and temporal resolution. The growth rates of all low index facets are similar until the {100} facets stop growth. The continuous growth of the rest facets leads to a nanocube. Our calculation shows that the much lower ligand mobility on the {100} facets is responsible for the arresting of {100} growing facets. These findings shed light on nanocrystal shape-control mechanisms and future design of nanomaterials.
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Star-shaped poly(L-lactide)-b-poly(lactobionamidoethyl methacrylate) with porphyrin core: synthesis, self-assembly, singlet oxygen research and recognition properties.
J Biomater Sci Polym Ed
PUBLISHED: 08-20-2014
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Star-shaped porphyrin-cored poly(L-lactide)-b-poly(lactobionamidoethyl methacrylate) block copolymers (SPPLA-b-PLAMA) were synthesized via RAFT of unprotected Lactobionamidoethyl methacrylate (LAMA) in 1-methyl-2-pyrrolidinone (NMP) solution at 70 °C. The structure of this as-synthesized SPPLA-b-PLAMA block copolymer was thoroughly studied by nuclear magnetic resonance spectroscopy, gel permeation chromatography (GPC), and Fourier transforms infrared. Moreover, under the irradiation, such SPPLA-b-PGAMA copolymer exhibits efficient singlet oxygen generation (0.17) and indicates high fluorescence quantum yields (0.20). Notably, with UV-vis investigation, SPPLA-b-PLAMA showed a very specific recognition with RCA120 lectin. This will not only provide potentially prophyrin-cored star-shaped SPPLA-b-PLAMA block copolymers for targeted photodynamic therapy, but also improve the physical, biodegradation, biocompatibility properties of PLA-based biomaterials.
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Synthesis and biological evaluation of novel aniline-derived asiatic acid derivatives as potential anticancer agents.
Eur J Med Chem
PUBLISHED: 08-12-2014
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Asiatic acid (AA) derivatives 4 and 5 modified at the C-11 and C-28 positions were designed and synthesized, their structures were confirmed using HRMS, (1)H NMR and (13)C NMR. In vitro antitumor activities of all compounds against MGC-803, NCI-H460, HepG2, Hela and 7404 cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The new compounds 5a-5t showed stronger anti-proliferative activity than AA, especially compound 5b was found to be the best inhibition activity on HepG2 cell line. In addition, the mechanism of compound 5b was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, flow cytometric, qRT-PCR (quantitative real-time PCR) and Western blot. Compound 5b induced the productions of ROS, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activations of caspase-9 and caspase-3 for causing cell apoptosis. Moreover, the cell cycle analysis showed that compound 5b mainly arrested HepG2 cells in G1 stage.
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One-pot stepwise approach to ?-enaminoketoesters through "masked" 1,3-aza-dipoles.
Org. Lett.
PUBLISHED: 07-23-2014
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t-BuOK-mediated rearrangement of 1,3-ketoesters with 2-(azidomethyl) aromatics in a two-step, one-pot telescoped sequence affords ?-enaminoketoesters in moderate to good yields. A novel pathway is proposed in which the umpolung of the azide is achieved from electrophilicity to nucleophilicity via deprotonation and undergoes nucleophilic attack onto the 1,3-ketoester.
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IL-18 genetic polymorphisms may contribute to the pathogenesis of tuberculosis among Asians: a meta-analysis of case-control studies.
Mol. Biol. Rep.
PUBLISHED: 06-16-2014
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This current meta-analysis of case-control studies was continued to investigate whether the genetic polymorphisms of IL-18 gene contribute to the occurrence and progression of tuberculosis (TB). We searched certain English and Chinese databases for relevant studies without language restrictions. Meta-analysis for the moment was performed with the adoption of the STATA statistical software. Crude OR and its corresponding 95 % confidence interval (95 % CI) were calculated as estimates of relative risk for UC under different genetic models. Seven case-control studies (TB patients = 1,325, healthy subjects = 1,778) were included for the following analysis. We evaluated two functional polymorphisms (rs1946518 C>A and rs187238 G>C). Pooled OR within the progression of statistical analysis indicated that the specific polymorphism of IL-18 rs1946518 C>A showed a closely relationship with the elevated susceptibility to TB under those three genetic models (allele model: OR 1.24, 95 % CI 1.11-1.38, P < 0.001; dominant model: OR 1.41, 95 % CI 1.21-1.65, P < 0.001; homozygous model: OR 1.46, 95 % CI 1.15-1.86, P = 0.002; respectively). However, we observed no statistical associations of the IL-18 rs187238 G>C polymorphism with the susceptibility to TB under any of the genetic models (all P > 0.05). Country-stratified analysis results detected that the variants of IL-18 may be strongly enrolled in the risk of TB among populations in China (allele model: OR 1.19, 95 % CI 1.06-1.33, P = 0.003; recessive model: OR 1.54, 95 % CI 1.00-2.36, P = 0.048; homozygous model: OR 1.59, 95 % CI 1.09-2.33, P = 0.016; respectively), but not among populations in Iran, Korea and India (all P > 0.05). Current results provide strong evidence that IL-18 mutations may be evidently related to the occurrence and development of TB, especially for the rs1946518 C>A polymorphism among populations in China.
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Monascin attenuates oxidative stress-mediated lung inflammation via peroxisome proliferator-activated receptor-gamma (PPAR-?) and nuclear factor-erythroid 2 related factor 2 (Nrf-2) modulation.
J. Agric. Food Chem.
PUBLISHED: 06-03-2014
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We speculated that peroxisome proliferator-activated receptor (PPAR)-? agonists may modulate the oxidative stress pathway to ameliorate the development of airway inflammation. The effect of Monascus-fermented metabolite monascin (MS) and rosiglitazone (Rosi) on oxidative stress-induced lung inflammation was evaluated. Luciferase assay and DNA binding activity assay were used to point out that MS may be a novel PPAR-? agonist and nuclear factor-erythroid 2 related factor 2 (Nrf-2) activator. We used hydrogen peroxide (H2O2) to induce inflammation in lung epithelial cells. MS and Rosi prevented H2O2-induced ROS generation in A549 epithelial cells through PPAR-? translocation, avoiding inflammatory mediator expression via inhibiting nuclear factor (NF)-?B translocation. The regulatory ability of MS was abolished by siRNA against PPAR-?. MS also elevated antioxidant enzyme expression via Nrf-2 activation. Both PPAR-? and Nrf-2 might have benefits against lung inflammation. MS regulated PPAR-? and Nrf-2 to improve lung oxidative inflammation.
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Sensitive birefringent temperature sensor based on a waveguide ring resonator.
Appl Opt
PUBLISHED: 05-03-2014
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A sensitive birefringent thermometer based on a SiO2 waveguide ring resonator is demonstrated in this paper. It can be used to fabricate a terahertz thermal detector. The temperature sensitivity is enhanced by the resonances of two polarization modes in the waveguide ring resonator. A high degree of common rejection exists for external influence. A linear temperature range from 6°C to 40°C has been detected with resolution of 0.025°C.
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Ce(OTf)?-catalyzed [3 + 2] cycloaddition of azides with nitroolefins: regioselective synthesis of 1,5-disubstituted 1,2,3-triazoles.
J. Org. Chem.
PUBLISHED: 04-25-2014
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The first example of rare earth metal-catalyzed [3 + 2] cycloaddition of organic azides with nitroolefins and subsequent elimination reaction is described. In the presence of a catalytic amount of Ce(OTf)3, both benzyl and phenyl azides react with a broad range of aryl nitroolefins containing a range of functionalities selectively producing 1,5-disubstituted 1,2,3-triazoles in good to excellent yields.
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A novel PPARgamma agonist monascin's potential application in diabetes prevention.
Food Funct
PUBLISHED: 04-23-2014
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Edible fungi of the Monascus species have been used as traditional Chinese medicine in eastern Asia for several centuries. Monascus-fermented products possess a number of functional secondary metabolites, including the anti-inflammatory pigments monascin and ankaflavin. Monascin has been shown to prevent or ameliorate several conditions, including hypercholesterolemia, hyperlipidemia, diabetes, and obesity. Recently, monascin has been shown to improve hyperglycemia, attenuate oxidative stress, inhibit insulin resistance, and suppress inflammatory cytokine production. In our recent study, we have found that monascin is a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist. The PPARgamma agonist activity had been investigated and its exerted benefits are inhibition of inflammation in methylglyoxal (MG)-treated rats, prevention of pancreas impairment causing advanced glycation endproducts (AGEs), promotion of insulin expression in vivo and in vitro, and attenuated carboxymethyllysine (CML)-induced hepatic stellate cell (HSC) activation in the past several years. Moreover, our studies also demonstrated that monascin also activated nuclear factor-erythroid 2-related factor 2 (Nrf2) in pancreatic RIN-m5F cell line thereby invading methylglyoxal induced pancreas dysfunction. In this review, we focus on the chemo-preventive properties of monascin against metabolic syndrome through PPARgamma and Nrf2 pathways.
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Single nucleotide polymorphism of RANKL and OPG genes may play a role in bone and joint injury in rheumatoid arthritis.
Clin. Exp. Rheumatol.
PUBLISHED: 04-07-2014
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This paper aims to investigate the influence of single-nucleotide polymorphisms (SNPs) in the receptor of activator of nuclear factor kappaB ligand (RANKL) gene (TNFSF11) and osteoprotegerin (OPG) gene (TNFRSF11B) on bone and joint injury in patients with rheumatoid arthritis (RA).
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Model studies with gold: a versatile oxidation and hydrogenation catalyst.
Acc. Chem. Res.
PUBLISHED: 03-19-2014
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Historically, scientists have considered gold an inert catalyst constituent. However, in recent decades, chemists have discovered that nanoscale gold shows exceptional activity for many chemical reactions. They have investigated model gold surfaces in order to obtain fundamental understanding of catalytic properties. In this Account, we present our current understanding of oxidation and hydrogenation reactions on the Au(111) single crystal as a planar representative of gold catalysts, revealing the interesting surface chemistry of gold. We begin by comparing two inverse reactions, alcohol oxidation and aldehyde hydrogenation, on a Au(111) surface. Beyond the expected different chemistry, we observe intriguing similarities since the same surface is employed. First, both molecular oxygen and hydrogen have high barriers to dissociation on Au(111), and frequently chemists study reactions here by using atomic O and H to populate the surfaces. Recombinative desorption features of oxygen and hydrogen are apparent at ?500 and ?110 K, lower than other transition metals. These results indicate that oxygen and hydrogen have low desorption activation energies and weakly chemisorb on the surface, likely leading to selective reactions. On the oxygen-precovered Au(111) surface, alcohols are selectively oxidized to aldehydes. Similarly, weakly bound hydrogen atoms on Au(111) also show chemoselective reactivity for hydrogenation of propionaldehyde and acetone. The second similarity is that the gold surface activates self-coupling of alcohol or aldehyde with oxygen or hydrogen, resulting in the formation of esters and ethers, respectively, in alcohol oxidation and aldehyde hydrogenation. During these two reactions, both alkoxy groups and alcohol-like species show up as intermediates, which likely play a key role in the formation of coupling products. In addition, the cross coupling reaction between alcohol and aldehyde occurs on both O- and H-modified surfaces, yielding the production of esters and ethers, respectively. Thus, we can tune the molecular structure of both esters and ethers by selecting the corresponding aldehyde and alcohol for the coupling reaction. These studies indicate that gold is a versatile active catalyst for various reactions, including oxidation and hydrogenation transformations. Despite the very different chemistry for these two reactions, we can establish an intrinsic relationship due to the distinct catalytic properties of gold. It can show activity for selective reactions on both O- and H-covered Au(111) and further induce the coupling reaction between surface reactants and adsorbed O/H to produce esters and ethers. This comparison demonstrates the unique surface chemistry of gold and enhances understanding of its catalytic properties.
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Treatment of metabolic syndrome with ankaflavin, a secondary metabolite isolated from the edible fungus Monascus spp.
Appl. Microbiol. Biotechnol.
PUBLISHED: 02-25-2014
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Edible fungi of the Monascus species have been used as traditional Chinese medicine in eastern Asia for several centuries. Monascus-fermented products possess a number of functional secondary metabolites, including anti-inflammatory pigments (such as monascin and ankaflavin [AK]), monacolins, and dimerumic acid. These secondary metabolites have anti-inflammatory, anti-oxidative, and anti-tumor activities. We found that AK positively regulates several transcription factors associated with the prevention of metabolic syndrome and other diseases, including peroxisome proliferator-activated receptor (PPAR)-gamma, PPAR-alpha, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). AK reduced hyperglycemia and enhanced pancreatic function via PPAR-gamma activation and increased lipid metabolism due to PPAR-alpha activation. The compound also exerted antioxidant effects via activation of Nrf2. These results suggest that AK belongs to the class of selective peroxisome proliferator-activated receptor modulators (SPPARMs), which are associated with a good safety profile when used in patients suffering from metabolic syndrome. Together with our studies to determine how AK production can be increased during Monascus fermentation, these data demonstrate the great potential of AK as a nutraceutical or therapeutic agent.
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Gene variation in IL10 and susceptibility to chronic hepatitis B.
J. Infect.
PUBLISHED: 02-20-2014
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To evaluate the correlation between IL-10 gene polymorphisms and hepatitis B infection.
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Synthesis and antitumor activities of novel ?-aminophosphonate derivatives containing an alizarin moiety.
Eur J Med Chem
PUBLISHED: 02-19-2014
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A series of novel ?-aminophosphonate derivatives containing an alizarin moiety (6-7) was designed and synthesized as antitumor agents. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay results indicated that most compounds exhibited moderate to high inhibitory activity against KB, NCI-H460, HepG 2, A549, MGC-803, Hct-116, CNE and Hela tumor cell lines. The action mechanism of representative compounds 7h, 7j and 7n were investigated by fluorescence staining assays, flow cytometric analysis and real-time polymerase chain reaction (PCR) assays, which indicated that these compounds induced apoptosis and involved G1 phase arrest by increasing the production of intracellular Ca(2+) and reactive oxygen species (ROS) and affecting associated enzymes and genes. The results demonstrated that these compounds may induce apoptosis through a mitochondrion-dependent pathway.
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Deranged NMDAergic cortico-subthalamic transmission underlies parkinsonian motor deficits.
J. Clin. Invest.
PUBLISHED: 02-13-2014
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Parkinson's disease (PD) is the most prevalent hypokinetic movement disorder, and symptomatic PD pathogenesis has been ascribed to imbalances between the direct and indirect pathways in the basal ganglia circuitry. Here, we applied glutamate receptor blockers to the subthalamic nucleus (STN) of parkinsonian rats and evaluated locomotor behaviors via single-unit and local-field recordings. Using this model, we found that inhibition of NMDAergic cortico-subthalamic transmission ameliorates parkinsonian motor deficits without eliciting any vivid turning behavior and abolishes electrophysiological abnormalities, including excessive subthalamic bursts, cortico-subthalamic synchronization, and in situ beta synchronization in both the motor cortex and STN. Premotor cortex stimulation revealed that cortico-subthalamic transmission is deranged in PD and directly responsible for the excessive stimulation-dependent bursts and time-locked spikes in the STN, explaining the genesis of PD-associated pathological bursts and synchronization, respectively. Moreover, application of a dopaminergic agent via a microinfusion cannula localized the therapeutic effect to the STN, without correcting striatal dopamine deficiency. Finally, optogenetic overactivation and synchronization of cortico-subthalamic transmission alone sufficiently and instantaneously induced parkinsonian-associated locomotor dysfunction in normal mice. In addition to the classic theory emphasizing the direct-indirect pathways, our data suggest that deranged cortico-subthalamic transmission via the NMDA receptor also plays a central role in the pathophysiology of parkinsonian motor deficits.
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A novel methodology for synthesis of dihydropyrazole derivatives as potential anticancer agents.
Org. Biomol. Chem.
PUBLISHED: 02-12-2014
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A novel, simple, and efficient method for the synthesis of 4,5-dihydropyrazole derivatives has been developed. The reaction proceeded through the base-induced isomerization of easily accessible propargyl alcohols followed by cyclization of ?,?-unsaturated hydrazones. Furthermore, selected compounds 3ab and 3ac exhibited good activities against Bel-7404 (human hepatoma cancer), HepG2 (human liver cancer), NCI-H460 (human lung cancer) and SKOV3 (human ovarian cancer) cell lines with IC50 in the range of 22-46 ?mol L(-1).
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Improvement in pH sensitivity of low-temperature polycrystalline-silicon thin-film transistor sensors using H2 sintering.
Sensors (Basel)
PUBLISHED: 02-10-2014
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In this article, we report an improvement in the pH sensitivity of low-temperature polycrystalline-silicon (poly-Si) thin-film transistor (TFT) sensors using an H2 sintering process. The low-temperature polycrystalline-silicon (LTPS) TFT sensor with H2 sintering exhibited a high sensitivity than that without H2 sintering. This result may be due to the resulting increase in the number of Si-OH2(+) and Si-O(-) bonds due to the incorporation of H in the gate oxide to reduce the dangling silicon bonds and hence create the surface active sites and the resulting increase in the number of chemical reactions at these surface active sites. Moreover, the LTPS TFT sensor device not only offers low cost and a simple fabrication processes, but the technique also can be extended to integrate the sensor into other systems.
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Copper-mediated cross-coupling-cyclization-oxidation: a one-pot reaction to construct polysubstituted pyrroles.
Chem. Commun. (Camb.)
PUBLISHED: 02-01-2014
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A novel and efficient procedure for the synthesis of polysubstituted pyrroles has been developed in this work. The polysubsituted pyrroles were synthesized directly from terminal alkenes, amines and ?-keto esters through cross-coupling-cyclization-oxidation in the presence of a catalytic amount of cuprous chloride. This method provides a one-pot synthesis route from terminal alkenes to polysubstituted pyrroles for the first time and opens a new area in cuprous catalysis.
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Safety and mutagenicity evaluation of red mold dioscorea fermented from Monascus purpureus NTU 568.
Food Chem. Toxicol.
PUBLISHED: 01-21-2014
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Monascus-fermented products, including red mold rice and red mold dioscorea, have been developed as functional foods with many health benefits. We performed safety and mutagenic evaluations on red mold dioscorea powder (RMDP) fermented from Monascus purpureus NTU 568. The results of Ames test using Salmonella typhimurium strains TA97a, TA98, TA100, TA102, and TA1535 showed that RMDP (?5 mg/plate) was not mutagenic. The mammalian chromosomal aberration test showed that the number of Chinese hamster ovary cells with abnormal chromosomes was <3% after RMDP treatment (maximum concentration: 5 mg/mL). Imprinting control region mice were used to estimate the genotoxicity of RMDP. Compared with the control, high-dose RMDP administration (2000 mg/kg) did not show significant differences in the number of reticulocytes or the occurrence of micronucleated reticulocytes. A 28-day oral toxicity assay in Sprague-Dawley rats was performed to investigate the no observed adverse effect level of RMDP. Compared with the control, high-dose RMDP administration (2000 mg/kg) caused no toxicological responses such as mortality, variation in body weight, or toxicopathologic lesions. Thus, RMDP from M. purpureus NTU 568 shows no significant mutagenic or toxic effects.
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Synthesis and antitumor activities of novel dipeptide derivatives derived from dehydroabietic acid.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-20-2014
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A series of dipeptide derivatives from dehydroabietic acid were designed and synthesized as novel antitumor agents. The antitumor activities screening indicated that many compounds showed moderate to high levels of inhibition activities against NCI-H460, HepG2, SK-OV-3, BEL-7404, HeLa and HCT-116 cancer cell lines and that some displayed more potent inhibitory activities than commercial anticancer drug 5-fluorouracil. The mechanism of representative compound 7b was studied by AO/EB staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which exhibited that the compound could induce apoptosis in HeLa cells. Further investigation showed that compound 7b induced apoptosis of HeLa cells through a mitochondrial pathway.
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Effects of chemical and low-temperature treatments and adaption on the responses of virulence factor genes and outer membrane proteins in Escherichia coli O157:H7.
J Microbiol Immunol Infect
PUBLISHED: 01-14-2014
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In the years after the discovery of this pathogen, Escherichia coli O157:H7 has become increasingly prominent, and outbreaks have been reported in many areas.
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Resistive switching behavior in Lu2O3 thin film for advanced flexible memory applications.
Nanoscale Res Lett
PUBLISHED: 01-03-2014
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In this article, the resistive switching (RS) behaviors in Lu2O3 thin film for advanced flexible nonvolatile memory applications are investigated. Amorphous Lu2O3 thin films with a thickness of 20 nm were deposited at room temperature by radio-frequency magnetron sputtering on flexible polyethylene terephthalate substrate. The structural and morphological changes of the Lu2O3 thin film were characterized by x-ray diffraction, atomic force microscopy, and x-ray photoelectron spectroscopy analyses. The Ru/Lu2O3/ITO flexible memory device shows promising RS behavior with low-voltage operation and small distribution of switching parameters. The dominant switching current conduction mechanism in the Lu2O3 thin film was determined as bulk-controlled space-charge-limited-current with activation energy of traps of 0.33 eV. The oxygen vacancies assisted filament conduction model was described for RS behavior in Lu2O3 thin film. The memory reliability characteristics of switching endurance, data retention, good flexibility, and mechanical endurance show promising applications in future advanced memory.
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Gastroesophageal reflux disease and risk for bipolar disorder: a nationwide population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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Studies have shown that chronic inflammation may play a vital role in the pathophysiology of both gastroesophageal reflux disease (GERD) and bipolar disorder. Among patients with GERD, the risk of bipolar disorder has not been well characterized.
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Rheumatoid arthritis and the risk of bipolar disorder: a nationwide population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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Studies have suggested that chronic inflammation plays an essential role in the pathophysiology of both rheumatoid arthritis (RA) and bipolar disorder. The most common clinical features associated with RA are anxiety and depression. The risk of bipolar disorder among patients with RA has not been characterized adequately.
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Risk of psychiatric disorders following polycystic ovary syndrome: a nationwide population-based cohort study.
PLoS ONE
PUBLISHED: 01-01-2014
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Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A higher prevalence of psychiatric comorbidities, including depressive disorder, anxiety disorder, and bipolar disorder has been proved in patients with PCOS. However, a clear temporal causal relationship between PCOS and psychiatric disorders has not been well established.
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Risk of depressive disorder following non-alcoholic cirrhosis: a nationwide population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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To evaluate the risk of depressive disorders among non-alcoholic patients by using the Taiwan National Health Insurance Research Database (NHIRD).
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Samarium(III)-Catalyzed C(sp(3))-H Bond Activation: Synthesis of Indolizines via C-C and C-N Coupling between 2-Alkylazaarenes and Propargylic Alcohols.
Org. Lett.
PUBLISHED: 12-20-2013
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A new rare earth metal and samarium-catalyzed C(sp(3))-H bond activation is reported in which 2-alkylazaarenes and propargylic alcohols were converted to indolizines. This process operates under mild conditions and solvent-free conditions. A broad scope of coupling partners has been established, and a likely mechanism has also been suggested.
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Association study of glucocorticoid receptor genetic polymorphisms with efficacy of glucocorticoids in systemic lupus erythematosus: a prospective cohort study.
Autoimmunity
PUBLISHED: 10-24-2013
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The response to glucocorticoids (GCs) for patients with systemic lupus erythematosus (SLE) is characterized by wide interindividual variability, with a significant number of patients who have no response. We analyzed whether genetic polymorphisms within glucocorticoid receptor (GR) gene are related to variability in the efficacy of GCs in Chinese population with SLE. A cohort of 220 patients with SLE was studied. These patients were treated with GCs (prednisone) for 12 weeks. The efficacy of GCs was measured with the scores on SLE disease activity index (SLEDAI). Patients were classified into two groups (sensitive and insensitive) according to their response to GCs. Polymorphisms of GR gene were genotyped by using multiplex SNaPshot method. A total of 212 patients (96.4%) were included in the final data analyses. Of these patients, 110 patients were considered sensitive to GCs, and 102 patients were considered insensitive to GCs. Eighteen tag single nucleotide polymorphisms (SNPs) of GR gene were selected. Significant associations were seen for rs4912905 (dominant model: crude OR?=?0.410, 95%CI?=?0.233-0.722, p?=?0.002; adjusted OR?=?0.419, 95%CI?=?0.233-0.754, p?=?0.004), rs17100234 (dominant model: crude OR?=?0.521, 95%CI?=?0.282-0.963, p?=?0.038; adjusted OR?=?0.520, 95%CI?=?0.279-0.970, p?=?0.040) and rs7701443 (recessive model: crude OR?=?2.736, 95%CI?=?1.183-6.331, p?=?0.019; adjusted OR?=?2.639, 95%CI?=?1.116-6.239, p?=?0.027) in GR gene, but not for other polymorphisms (p?>?0.05). The results of the present study suggest that GR genetic polymorphisms may play a major role in the efficacy of GCs in Chinese population with SLE.
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Monacolin K and monascin attenuated pancreas impairment and hyperglycemia induced by advanced glycation endproducts in BALB/c mice.
Food Funct
PUBLISHED: 10-23-2013
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Several lines of evidence have implicated high levels of advanced glycation endproducts (AGEs) in diabetes. Pancreas impairment caused by AGEs has been found in recent studies. Monascin (MS) and monacolin K (MK) are active compounds identified from Monascus-fermented products, which have been reported to inhibit inflammation and improve insulin resistance. In order to confirm the protective effects of MS and MK on pancreatic function, BALB/c mice were treated with AGEs via intraperitoneal injection for 22 weeks to induce hyperglycemia, and the pancreas-protecting mechanism of MS and MK from AGE-induced damage was investigated. We found that the expression of pancreatic and duodenal homeobox-1 (PDX-1) and glucose transporter 2 (GLUT2) was recovered by MS or MK administration to AGE-treated mice. In addition, MS strongly improved performance in the oral glucose tolerance test (OGTT) and the insulin tolerance test (ITT), suggesting that MS sensitized to insulin in AGE-treated mice. Both MS and MK elevated pancreatic insulin expression when compared to the AGE-treated group, suggesting that MS and MK attenuated AGE-induced pancreatic dysfunction. Histopathology studies showed that intraperitoneal injection of AGEs did not result in pancreas damage. These findings confirm that the potential mechanism of AGEs on pancreatic dysfunction involves the induction of inflammation and the suppression of PDX-1 and GLUT2 expression. Taken together, MS and MK may be developed as an anti-diabetic agent in the future.
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Association of XPC Gene Polymorphisms with Susceptibility to Prostate Cancer: Evidence from 3,936 Subjects.
Genet Test Mol Biomarkers
PUBLISHED: 10-05-2013
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Aim: Polymorphisms of xeroderma pigmentosum complementation group C (XPC) are thought to have significant effects on prostate cancer (PCa) risk. The aim of our study was to evaluate the impact of XPC gene polymorphisms on PCa risk by using a meta-analysis. Methods: Data were collected from the following electronic databases: PubMed, EMBASE, Elsevier Science Direct, Cochrane Library, and CNKI, with the last report up to April 30, 2013. Odds ratios with 95% confidence intervals were used to assess the strength of the association. Results: A total of five separate case-control studies (1966 cases and 1970 controls) were included in this meta-analysis. Meta-analysis was performed for the rs2228001 and PAT+/-polymorphisms. We did not detect a significant association between rs2228001 polymorphism and PCa (p>0.05). Similar results were found in stratification analyses by ethnicity and tumor stage. We detected a significant association of PAT+/-polymorphism with PCa (p<0.05). In stratification analysis, we did not detect a significant association of PAT+/-polymorphism with risk of bone metastasis in PCa patients (p>0.05). Conclusion: These analyses suggest that XPC gene PAT+/-polymorphism, but not rs2228001, likely contributes to susceptibility to PCa.
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Synthesis and antitumor activities of novel rhein ?-aminophosphonates conjugates.
Bioorg. Med. Chem. Lett.
PUBLISHED: 08-29-2013
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Several rhein ?-aminophosphonates conjugates (5a-5q) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially, compound 5i exhibited the strongest cytotoxicity against Hct-116 cells (IC50 was 5.32?M). All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The mechanism of compound 5i was preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound 5i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis showed that these compound 5i mainly arrested Hct-116 cells in G1 stage. The effects of 5i on the activation of caspases expression indicated that 5i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 5i to DNA were investigated by methods (UV-vis, fluorescence, CD spectroscopy and FRET-melting) in compare with that of rhein. Results indicated that 5i showed moderate ability to interact ct-DNA.
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Inhibition of Th2 cytokine production in T cells by monascin via PPAR-? activation.
J. Agric. Food Chem.
PUBLISHED: 08-14-2013
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Yellow pigment monascin (MS) is a secondary metabolite isolated from Monascus -fermented products and has numerous physiological activities. However, the potential use of MS for immunomodulation remains unclear. We showed that MS and the synthetic peroxisome proliferator-activated receptor (PPAR)-? ligand rosiglitazone (RG) significantly inhibited the production of Th2 cytokines, including IL-4, IL-5, and IL-13, in PMA/ionomycin-activated mouse EL-4 T cells. Moreover, we showed that this was due to cellular PPAR-? translocation. These results indicate that MS and RG promote PPAR-?-DNA interactions and suggest that the regulatory effects of MS and RG on Th2 cytokine production could be abolished with PPAR-? antagonist treatment. MS and RG also suppressed Th2 transcription factor translocation (e.g., GATA-3 and nuclear factor of activated T cells) by preventing the phosphorylation of protein kinase C and signal transducer and activator of transcription 6.
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Enhanced anti-obesity activities of red mold dioscorea when fermented using deep ocean water as the culture water.
Mar Drugs
PUBLISHED: 08-09-2013
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Deep ocean water (DOW) has, in previous studies, been found to be a novel anti-obesity drink and useful in raising Monascus-produced monascin and ankaflavin levels. This may resolve the limited anti-obesity ability of red mold dioscorea (RMD) known as the Monascus purpureus-fermented Disocorea batatas. This study aims to compare the anti-obesity effect of DOW-cultured RMD (DOW-RMD) and ultra-pure water-cultured RMD (UPW-RMD) in rats fed on a high fat diet. Moreover, the effect of ions composition of DOW and DOW-influenced functional metabolites change of RMD on the differentiation and lipogenesis regulation were investigated using 3T3-L1 pre-adipocytes. In the animal test, compared to UPW-RMD, DOW-RMD possessed better ability to inhibit increases in weight gain, and better feed efficiency, body-fat pad and cross-sectional area of adipocytes. In the cell test, the anti-obesity abilities of DOW-RMD in inhibiting PPAR? and C/EBP? expression in differentiation and lipoprotein lipase activity in lipogenesis were contributed to by the DOW-increased monascin and ankaflavin levels and the ions of DOW, respectively.
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Relationship between interleukin-6 polymorphism and susceptibility to chronic hepatitis B virus infection.
World J. Gastroenterol.
PUBLISHED: 08-05-2013
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To identify the relationship between tag single nucleotide polymorphisms (tag SNPs) of interleukin-6 (IL-6) gene and susceptibility to chronic hepatitis B virus (HBV) infection in a Han Chinese population.
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Real-time and label-free detection of the prostate-specific antigen in human serum by a polycrystalline silicon nanowire field-effect transistor biosensor.
Anal. Chem.
PUBLISHED: 07-30-2013
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In this research, we used a polycrystalline silicon nanowire field-effect transistor (poly-Si NWFET) as a biosensor that employs the sidewall spacer technique instead of an expensive electron beam lithography method. When compared with commercial semiconductor processes, the sidewall spacer technique has the advantages of simplicity and low cost. In this study, we employed a novel poly-Si NWFET device for real-time, label-free, and ultrahigh-sensitivity detection of prostate-specific antigen (PSA) in human serum. Since serum proteome is very complex containing high levels of salts and other interfering compounds, we hereby developed a standard operating procedure for real-sample pretreatment to keep a proper pH value and ionic strength of the desalted serum and also utilized Tween 20 to serve as the passivation agent by surface modification on the NWFET to reduce nonspecific binding for medical diagnostic applications. We first modified 3-aminopropyltriethoxysilane on the surface of a poly-Si nanowire device followed by glutaraldehyde functionalization, and the PSA antibodies were immobilized on the aldehyde terminal. While PSA was prepared in the buffers to maintain an appropriate pH value and ionic strength, the results indicated that the sensor could detect trace PSA at less than 5 fg/mL in a microfluidic channel. The novel poly-Si NWFET is developed as a diagnostic platform for monitoring prostate cancer and predicting the risk of early biochemical relapse.
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Synthesis and antitumor activity evaluation of maleopimaric acid N-aryl imide atropisomers.
Bioorg. Med. Chem. Lett.
PUBLISHED: 07-25-2013
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Maleopimaric acid N-aryl imides (2) and methyl maleopimaric acid N-aryl imides (3) were designed and synthesized. Their atropisomers (A and B) were separated into their enantiomeric pure forms and the anti-proliferative activity was tested against NCI, A549, Hep G-2, MGC-803 and Hct-116 cell lines, respectively. A significant difference in the level of cytotoxicity was observed between R and S conformers. Atropisomers A with an R configuration exhibited significant toxicity (the IC50 values ranging from 7.51 to 32.1?M). Further experiments proved that antitumor activity of 2A was achieved through the induction of cell apoptosis by G1 cell-cycle arrest.
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Impact of environmental factors on efficacy of glucocorticoids in Chinese population with systemic lupus erythematosus.
Inflammation
PUBLISHED: 07-11-2013
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Although glucocorticoids (GCs) are effective in inducing remission in systemic lupus erythematosus (SLE) patients, there is a significant variation in response to therapeutic GCs, and some patients do not achieve full remission. The aim of this study was to explore the impact of environmental factors on the efficacy of GCs in a Chinese population with SLE. This was a prospective cohort study, and a total of 260 SLE patients treated with GCs (prednisone) were followed up for 12 weeks. The efficacy of GCs was measured with the scores on SLE disease activity index. Environmental factors were collected using a questionnaire. Single-variable analysis and multivariate logistic regression analysis were used to discriminate the impact of environmental factors on the efficacy of GCs. Two hundred forty-seven patients (95.00 %) completed the 12-week follow-up. Among these patients, 131 (53.04 %) were classified into sensitive group and 116 (46.96 %) were classified into insensitive group. Results from logistic analysis showed that the following environmental factors were significantly associated with decreased efficacy of GCs: high salt intake (OR = 3.464, 95%CI = 1.481-8.102, P = 0.004), introverted personality (OR = 3.550, 95%CI = 1.901-6.628, P < 0.0001), experience with negative life events (OR = 5.526, 95%CI = 1.612-18.946, P = 0.007), and history of allergy (OR = 2.966, 95%CI = 1.312-6.704, P = 0.009). These results indicate that environmental factors, including salt intake, personality, experience with negative life events, and history of allergy, may play an important role in the efficacy of GCs in the Chinese population with SLE.
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Peroxisome proliferator-activated receptor-? activators monascin and rosiglitazone attenuate carboxymethyllysine-induced fibrosis in hepatic stellate cells through regulating the oxidative stress pathway but independent of the receptor for advanced glycat
J. Agric. Food Chem.
PUBLISHED: 07-05-2013
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Advanced glycation end products (AGEs) signaling through its receptors (RAGE) results in an increase in reactive oxygen species (ROS) and is thought to contribute to hepatic fibrosis via hyperglycemia. Carboxymethyllysine (CML) is a key AGE, with highly reactive dicarbonyl metabolites. We investigated the inhibitory effect of Monascus -fermented metabolite monascin and rosiglitazone on CML-induced RAGE signaling in hepatic stellate cells (HSCs) and its resulting antihepatic fibrosis activity. We found that monascin and rosiglitazone upregulated peroxisome proliferator-activated receptor-? (PPAR-?) to attenuate ?-smooth muscle actin (SMA) and ROS generation in CML-treated HSCs in a RAGE activation-independent pathway. Therefore, monascin may delay or inhibit the progression of liver fibrosis through the activation of PPAR-? and might prove to be a major antifibrotic mechanism to prevent liver disease.
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Treatment of Cytomegalovirus infection after renal transplantation: experience from a single center in China.
Ann. Transplant.
PUBLISHED: 06-25-2013
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We compared the efficacy and safety of 2 different treatments of CMV infection, including asymptomatic CMV replication and CMV disease.
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Suppression of dimerumic acid on hepatic fibrosis caused from carboxymethyl-lysine (CML) by attenuating oxidative stress depends on Nrf2 activation in hepatic stellate cells (HSCs).
Food Chem. Toxicol.
PUBLISHED: 06-21-2013
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Hyperglycemia facilitates the formation of advanced glycation end-products (AGEs) in type-2 diabetes. Evidence indicates that carboxymethyl-lysine (CML) is highly prevalent in diabetes, resulting in hepatic fibrosis. The current study was designed to evaluate the effects of dimerumic acid (DMA) identified from Monascus-fermented products on receptor for AGEs (RAGE) signal and hepatic stellate cells (HSCs) activation by CML treatment. We found that DMA (50?M) eliminated collagen generation, mRNA expressions of ?-smooth muscle actin (?-SMA), platelet-derived growth factor-? receptor (PDGF-?R), and procollagen 1a1 (proCol-1a1) in CML (100?g/ml)-treated HSCs, and these effects were similar to allyl isothiocyanate (AITC; 50?M). In addition, the suppression of ?-SMA, PDGF-?R, proCol-1a1 by DMA were abolished while nuclear factor-erythroid 2-related factor 2 (Nrf2) silence in CML-treated HSCs. These findings suggested that DMA and AITC increased Nrf2 and glutamate-cysteine ligase (GCL) activities thereby inhibiting oxidative stress caused by CML and showing anti-fibrogentic effect in HSCs.
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Monascin and AITC Attenuate Methylglyoxal-Induced PPAR? Phosphorylation and Degradation through Inhibition of the Oxidative Stress/PKC Pathway Depending on Nrf2 Activation.
J. Agric. Food Chem.
PUBLISHED: 06-13-2013
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Abnormal cellular accumulation of the dicarbonyl metabolite methylglyoxal (MG) results in cell damage, inflammation, and oxidative stress. It is also associated with increased protein linkage to form advanced glycation end products (AGEs) or induce DNA strand breaks. The association between peroxisome proliferator-activated receptor-? (PPAR?) and nuclear factor-erythroid 2-related factor 2 (Nrf2) is unclear. This study investigated Nrf2 activator protection against PPAR? phosphorylation and degradation to maintain pancreatic function. MG was used at a noncytotoxic concentration (200 ?M) to induce protein kinase C (PKC) and PPAR? phosphorylation in pancreatic RINm5F cells. For in vivo studies, MG (60 mg/kg bw) was intraperitoneally (IP) injected into Balb/C mice for 28 d to induce pancreas damage, at which point we investigated the effect of monascin protection (PPAR? and Nrf2 activator), rosiglitazone (PPAR? activator), allyl isothiocyanate (AITC; Nrf2 activator), or N-acetylcysteine (NAC) on pancreatic function. The in vitro and in vivo results indicated that MG leads to marked PPAR? phosphorylation (serine 82); this effect led to reduction in pancreatic and duodenal homeobox-1 (PDX-1), glucokinase (GCK), and insulin expression. However, monascin and rosiglitazone may protect PPAR? degradation by elevating PDX-1, GCK, and as a result, insulin expression. Monascin and AITC can attenuate PKC activation to suppress PPAR? phosphorylation caused by oxidative stress through the Nrf2 pathway. Similarly, the N-acetylcysteine (NAC) antioxidant also improved oxidative stress and pancreatic function. This study examined whether MG caused impairment of PDX-1, GCK, and insulin through PPAR? phosphorylation and degradation. MG and AGE accumulation improved on Nrf2 activation, thereby protecting against pancreas damage. Taken together, PPAR? activation maintained pancreatic PDX-1, GCK, and insulin expression levels to regulate blood glucose levels.
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Monascin improves diabetes and dyslipidemia by regulating PPAR? and inhibiting lipogenesis in fructose-rich diet-induced C57BL/6 mice.
Food Funct
PUBLISHED: 05-14-2013
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Monascin (MS) is a yellow compound isolated from Monascus-fermented products that has pancreatic protective, anti-inflammatory, anti-oxidative, and hypolipidemic activity. We recently found that MS also acts as a peroxisome proliferator-activated receptor-gamma (PPAR?) agonist, thereby promoting insulin sensitivity in C2C12 cells. However, the attenuation of hyperglycemia by MS treatment in vivo remains uncertain. In the present study, both MS and pioglitazone significantly down-regulated blood glucose and hyperinsulinemia in fructose-rich diet (FRD)-induced C57BL/6 mice (8 weeks). In addition, inhibitions of inflammatory factor production, serum dyslipidemia, and hepatic fatty acid accumulation by MS and pioglitazone were attenuated by GW9662 (PPAR? antagonist). These results were mediated by MS-suppressing FRD-elevated lipogenic transcription factors, including sterol regulatory element-binding protein-1c (SREBP-1c), carbohydrate response element-binding protein (ChREBP), PPAR? coactivator-1? (PGC-1?), and PPAR? coactivator-1? (PGC-1?). Taken together, de novo lipogenesis results in hyperlipidemia and hyperglycemia by fructose induction thereby leading to diabetes development; we found that MS may inhibit lipogenesis in FRD-induced mice. These findings suggest that MS acts as an antidiabetic agent and thus may have therapeutic potential for prevention of diabetes.
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Synthesis and antitumor activities of novel ?-aminophosphonates dehydroabietic acid derivatives.
Bioorg. Med. Chem. Lett.
PUBLISHED: 05-07-2013
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A series of novel ?-aminophosphonate derivatives containing DHA structure were designed and synthesized as antitumor agents. In vitro antitumor activities of these compounds against the NCI-H460 (human lung cancer cell), A549 (human lung adenocarcinoma cell), HepG2 (human liver cancer cell) and SKOV3 (human ovarian cancer cell) human cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The pharmacological screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-FU. The action mechanism of representative compound 7c was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound can induce cell apoptosis in NCI-H460 cells. Cell cycle analysis showed that compound 7c mainly arrested NCI-H460 cells in G1 stage.
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Synthesis and antitumor activities of novel thiourea ?-aminophosphonates from dehydroabietic acid.
Eur J Med Chem
PUBLISHED: 05-03-2013
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A series of novel thiourea ?-aminophosphonate derivatives containing DHA structure was designed and synthesized as antitumor agents. Their inhibitory activities against the NCI-H460 (lung), A549 (lung adenocarcinoma), HepG2 (liver) and SKOV3 (ovarian) human cancer cell lines were estimated using MTT assay in vitro. The screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-fluorouracil. The mechanism of compound 5f was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which indicated that the compound can induce cell apoptosis in A549 cells.
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The first palladium-catalyzed 1,4-addition of terminal alkenes to acrylate esters.
Chem. Commun. (Camb.)
PUBLISHED: 05-02-2013
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A novel and efficient procedure for the synthesis of ?,?-alkenyl esters with complete E-stereochemistry by the 1,4-addition of alkenes to acrylate esters in the presence of a catalytic amount of palladium chloride has been developed. This method provides a rapid and efficient access to substituted ?,?-alkenyl esters.
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Association of TGF-?1 +869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis.
Mol. Biol. Rep.
PUBLISHED: 04-29-2013
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Many case-control studies have investigated the role of TGF-?1 gene +869C/T promoter polymorphism in autoimmune diseases, but the results are inconsistent. To clarify this point, we performed a meta-analysis based on all available studies in Pubmed, Elsevier Science Direct, Google Searching, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. Crude odds ratios (ORs) with 95% confidence intervals were calculated to estimate the strength of the association. A fixed or random effects model was used on the basis of heterogeneity. A total of 21 papers including 2,693 cases and 3,036 controls were considered in the current meta-analysis. These studies encompass two ankylosing spondylitis (AS), eight rheumatoid arthritis (RA), four systemic lupus erythematosus (SLE), and seven systemic sclerosis (SSc). The results showed that TGF-?1 +869C/T promoter polymorphism were associated with susceptibility to RA (CC vs. TT: OR=0.65, 95% CI=0.48-0.88, P=0.005; CC vs. CT+TT: OR=0.56, 95% CI=0.45-0.69, P=0.000; C vs. T: OR=0.81, 95% CI=0.71-0.93, P=0.003). When stratified by race, significant association was observed only in Asian population. However, we failed to reveal the association between this gene promoter polymorphism and AS, SLE, and SSc. Therefore, this meta-analysis suggests a possible association between TGF-?1 +869C/T promoter polymorphism and RA, especially in Asian population.
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Adsorption of lead(II) by silica/cell composites from aqueous solution: kinetic, equilibrium, and thermodynamics studies.
Water Environ. Res.
PUBLISHED: 03-12-2013
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Silica/cell composites were prepared for the adsorption of lead ions, Pb(II), from aqueous solution in a batch system. The silica/cell composites possessed micropores, high surface area, and abundant functional groups. Adsorption performance was investigated by analyzing the effects of such factors as the initial pH, contact time with different initial concentration, and initial Pb(II) concentration at different temperature. The kinetic data were fitted to pseudo-second-order and intraparticle diffusion kinetic models. The results were better fitted by the pseudo-second-order kinetic model. Intraparticle diffusion increased with an increase of initial concentration and the sorption process was controlled by film diffusion. The Langmuir isotherm model was fitted to the experimental data significantly better than Freundlich and Dubinin-Radushkevich isotherm models. The maximum adsorption capacity was 97.10 mg g(-1), according to the Langmuir isotherm model. Thermodynamics parameters confirmed the spontaneous, endothermic, and entropy-gained nature within the studied temperature range (from 298 to 318 K). The composites could be effectively desorbed by the 2.0 mol L(-1) HNO3 solution and would be a potential adsorbent.
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Prevalence of systemic lupus erythematosus and risk factors in rural areas of Anhui Province.
Rheumatol. Int.
PUBLISHED: 03-08-2013
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Systemic lupus erythematosus (SLE) is a severe complex rheumatic disease, but good estimate of its prevalence and risk factors is lacking in China. The aim of the study was to explore the prevalence of SLE and risk factors in rural areas of Anhui Province of China. Eleven counties were randomly selected in Anhui Province, and then, 15 % of the villages in selected counties were randomly sampled as study sites. Patients with SLE were identified through two phases. Based on the cases identified, a population-based case-control study was designed to examine risk factors associated with SLE. A total of 1,253,832 individuals and identified 471 SLE cases were surveyed. Crude and age-standardized prevalence were estimated at 37.56 and 36.03 per 100,000 persons, respectively. Gender difference in the prevalence of SLE was significant (P = 4.62 × 10(-76)), and the age-standardized prevalence was 6.17 for males and 67.78 for females per 100,000 persons. The distribution of SLE prevalence was significant by age group (P = 1.78 × 10(-53)), and the peak prevalence was observed at 40-50 years. Multiple environmental factors were associated with SLE, including birth conditions, sweet food, cooking oil, taste, fruit consumption, sunlight exposure, quality of sleep, physical activities, drinking water, residence, negative life events, hepatitis B vaccine, age of menarche, and age at birth of first child (P < 0.05). Our large population-based epidemiological survey estimated the prevalence of SLE at 37.56 per 100,000 persons. Multiple environmental factors were associated with the development of SLE.
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Anti-inflammatory Properties of Yellow and Orange Pigments from Monascus purpureus NTU 568.
J. Agric. Food Chem.
PUBLISHED: 03-08-2013
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The Monascus species has been used in foods for thousands of years in China. In this study, 10 azaphilone pigments, including four yellow and six orange pigments, were isolated from the fermented rice and dioscorea of Monascus purpureus NTU 568. By employing lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells, we determined the inhibitory activities of these pigments on nitric oxide (NO) production. As a result, four orange pigments, monaphilols A-D, showed the highest activities (IC50 = 1.0-3.8 ?M), compared with the other two orange pigments, monascorubrin (IC50 > 40 ?M) and rubropunctatin (IC50 = 21.2 ?M), and the four yellow pigments ankaflavin (IC50 = 21.8 ?M), monascin (IC50 = 29.1 ?M), monaphilone A (IC50 = 19.3 ?M), and monaphilone B (IC50 = 22.6 ?M). Using Western blot and ELISA kits, we found that treatments with 30 ?M of the yellow pigments and 5 ?M of the orange pigments could down-regulate the protein expression of inducible nitric oxide synthase (iNOS) and suppress the production of tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and interleukin-6 (IL-6). We also used two animal experiments to evaluate the anti-inflammatory effects of these pigments. In a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema model, eight of these pigments (0.5 mg/ear) could prevent ear edema against TPA administrations on the ears of BALB/c mice. In an LPS-injection mice model, several of these pigments (10 mg/kg) could inhibit the NO, TNF-?, IL-1?, and IL-6 levels in the plasma of BALB/c mice. As concluded from the in vitro and in vivo studies, six azaphilonoid pigments, namely, ankaflavin, monaphilone A, and monaphilols A-D, showed high potential to be developed into chemopreventive foods or drugs against inflammation-associated diseases.
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A novel natural Nrf2 activator with PPAR?-agonist (monascin) attenuates the toxicity of methylglyoxal and hyperglycemia.
Toxicol. Appl. Pharmacol.
PUBLISHED: 03-07-2013
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Methylglyoxal (MG) is a toxic-glucose metabolite and a major precursor of advanced glycation endproducts (AGEs). MG has been reported to result in inflammation by activating receptor for AGEs (RAGE). We recently found that Monascus-fermented metabolite monascin acts as a novel natural peroxisome proliferator-activated receptor-? (PPAR?) agonist that improves insulin sensitivity. We investigated the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats treated with oral administration of monascin or rosiglitazone. Monascin (a novel PPAR? agonist) activated nuclear factor-erythroid 2-related factor 2 (Nrf2) and down-regulated hyperinsulinmia in oral glucose tolerance test (OGTT). Monascin was able to elevate glyoxalase-1 expression via activation of hepatic Nrf2, hence, resulting in MG metabolism to d-lactic acid and protected from AGEs production in MG-treated rats. Rosiglitazone did not activate Nrf2 nor glyoxalase expression to lower serum and hepatic AGEs levels. Monascin acts as a novel natural Nrf2 activator with PPAR?-agonist activity were confirmed by Nrf2 and PPAR? reporter assays in Hep G2 cells. These findings suggest that monascin acts as an anti-diabetic and anti-oxidative stress agent to a greater degree than rosiglitazone and thus may have therapeutic potential for the prevention of diabetes.
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Monascin and ankaflavin act as natural AMPK activators with PPAR? agonist activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed C57BL/6 mice.
Food Chem. Toxicol.
PUBLISHED: 03-05-2013
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Yellow pigments monascin (MS) and ankaflavin (AK) are secondary metabolites derived from Monascus-fermented products. The hypolipidemic and anti-inflammatory effects of MS and AK indicate that they have potential on preventing or curing nonalcoholic fatty liver disease (NAFLD). Oleic acid (OA) and high-fat diet were used to induce steatosis in FL83B hepatocytes and NAFLD in mice, respectively. We found that both MS and AK prevented fatty acid accumulation in hepatocytes by inhibiting fatty acid uptake, lipogenesis, and promoting fatty acid beta-oxidation mediated by activating peroxisome proliferator-activated receptor (PPAR)-? and AMP-activated kinase (AMPK). Furthermore, MS and AK significantly attenuated high-fat diet-induced elevation of total cholesterol (TC), triaceylglycerol (TG), free fatty acid (FFA), and low density lipoprotein-cholesterol (LDL-C) in plasma. MS and AK promoted AMPK phosphorylation, suppressed the steatosis-related mRNA expression and inflammatory cytokines secretion, as well as upregulated farnesoid X receptor (FXR), peroxisome proliferator-activated receptor gamma co-activator (PGC)-1?, and PPAR? expression to induce fatty acid oxidation in the liver of mice. We provided evidence that MS and AK act as PPAR? agonists to upregulate AMPK activity and attenuate NAFLD. MS and AK may be supplied in food supplements or developed as functional foods to reduce the risk of diabetes and obesity.
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Model studies of heterogeneous catalytic hydrogenation reactions with gold.
Chem Soc Rev
PUBLISHED: 03-01-2013
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Supported gold nanoparticles have recently been shown to possess intriguing catalytic activity for hydrogenation reactions, particularly for selective hydrogenation reactions. However, fundamental studies that can provide insight into the reaction mechanisms responsible for this activity have been largely lacking. In this tutorial review, we highlight several recent model experiments and theoretical calculations on a well-structured gold surface that provide some insights. In addition to the behavior of hydrogen on a model gold surface, we review the reactivity of hydrogen on a model gold surface in regards to NO2 reduction, chemoselective C=O bond hydrogenation, ether formation, and O-H bond dissociation in water and alcohols. Those studies indicate that atomic hydrogen has a weak interaction with gold surfaces which likely plays a key role in the unique hydrogenative chemistry of classical gold catalysts.
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p38 MAPK inhibitor, CBS3830 limits vascular remodelling in arterialised vein grafts.
Heart Lung Circ
PUBLISHED: 02-21-2013
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Following bypass surgery vein grafts undergo a remodelling process that can lead to restenosis and ultimately vein graft failure. Signalling through mitogen activated protein kinases (MAPKs) is a key mechanism involved in vein graft failure. Here, we investigated whether CBS3830 (c-a-i-r biosciences GmbH, Tübingen, Germany), a new highly selectively inhibitor of p38 MAPK, has a significant effect on inhibiting intimal, medial and adventitial hyperplasia.
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High-? GdTixOy sensing membrane-based electrolyte-insulator-semiconductor with magnetic nanoparticles as enzyme carriers for protein contamination-free glucose biosensing.
Biosens Bioelectron
PUBLISHED: 02-19-2013
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This paper reports an electrolyte-insulator-semiconductor (EIS) device featuring a novel high-? GdTixOy sensing membrane for high-performance pH sensing and glucose biosensing. The effect of the annealing temperature (700, 800, or 900°C) on the sensing properties of the GdTixOy membranes was investigated. The GdTixOy EIS device annealed at 900°C exhibited the greatest pH sensing performance, including the highest sensitivity (62.12mV/pH), the smallest hysteresis voltage (5mV), and the lowest drift rate (0.4mV/h), presumably because of its well-crystallized GdTixOy structure. To overcome the problems typically encountered during the practical application of biosensors (e.g., protein adsorption; preservation of enzymatic activity), we employed Fe3O4-based magnetic nanoparticles (MNPs) as enzyme carriers. The adsorption of serum protein on the unmodified sensing membrane led to poor EIS-based pH sensing (r(2)=0.71); the performance was greatly improved, however, after attaching the MNPs to the sensing membrane, thereby blocking protein adsorption significantly (by 98%) and allowing excellent pH sensing (r(2)=0.99). Moreover, we prepared a hybrid configuration of the proposed GdTixOy membrane-EIS, with magnetically attached glucose oxidase-immobilized MNPs, for glucose biosensing. The use of MNPs as enzyme carriers effectively preserved the enzymatic activity of glucose oxidase, with 45.3% of the original enzymatic activity retained after 120h of storage at 4°C (compared with complete loss of the free enzymes activity under the same storage conditions). In addition, the proposed biosensor exhibited superior detection sensitivity of 11.03mV/mM relative to that (8.17mV/mM) obtained using the conventional enzyme immobilization method. Finally, we established the accuracy of the proposed method for blood glucose measurement; gratifyingly, blood glucose detection was comparable with the high-sensitivity glucose quantification obtained using a commercial glucose assay kit.
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Single nucleotide polymorphisms rs2120131, rs4935047, and rs7095891 in the MBL2 gene show no association with susceptibility to chronic hepatitis B in a Chinese Han population.
J. Med. Virol.
PUBLISHED: 02-19-2013
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Thus far, many studies have evaluated the correlation between MBL2 gene polymorphisms and hepatitis B infection. Tag single nucleotide polymorphisms (SNPs) were used to investigate the relationship between MBL2 gene polymorphisms and susceptibility to chronic hepatitis B virus (HBV) infection by comparing 996 chronic HBV infection cases to 301 acute infection controls. There was no significant correlation between rs2120131, rs4935047, and rs7095891 and chronic HBV infection. This suggested that the new SNPs within MBL2 were not associated with susceptibility to chronic hepatitis B in a Chinese Han population.
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Atom-economical chemoselective synthesis of 1,4-enynes from terminal alkenes and propargylic alcohols catalyzed by Cu(OTf)2.
J. Org. Chem.
PUBLISHED: 02-13-2013
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A novel and efficient Cu(OTf)2-catalyzed sp(3)-sp(2) C-C bond formation reaction through the direct coupling of propargylic alcohols with terminal alkenes has been realized under mild conditions. The reaction is tolerant to air and is atom-economical, in accordance with the concept of modern green chemistry. The present protocol provides an attractive approach to a diverse range of 1,4-enynes in high to excellent yields.
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Monascus-fermented yellow pigments monascin and ankaflavin showed antiobesity effect via the suppression of differentiation and lipogenesis in obese rats fed a high-fat diet.
J. Agric. Food Chem.
PUBLISHED: 02-08-2013
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Monascus-fermented monascin and ankaflavin are found to strongly inhibit differentiation and lipogenesis and stimulate lipolysis effects in a 3T3-L1 preadipocyte model, but the in vivo regulation mechanism is unclear. This study uses obese rats caused by a high-fat diet to examine the effects of daily monascin and ankaflavin feeding (8 weeks) on antiobesity effects and modulation of differentiation, lipogenesis, and lipid absorption. The results show that monascin and ankaflavin had a significant antiobesity effect, which should result from the modulation of monascin and ankaflavin on the inhibition of differentiation by inhibiting CCAT/enhancer-binding protein ? (C/EBP?) expression (36.4% and 48.3%) and its downstream peroxisome proliferator-activated receptor ? (PPAR?) (55.6% and 64.5%) and CCAT/enhancer-binding protein ? (C/EBP?) expressions (25.2% and 33.2%) and the inhibition of lipogenesis by increasing lipase activity (14.0% and 10.7%) and decreasing heparin releasable lipoprotein lipase (HR-LPL) activity (34.8% and 30.5%). Furthermore, monascin and ankaflavin are the first agents found to suppress Niemann-Pick C1 Like 1 (NPC1L1) protein expression (73.6% and 26.1%) associated with small intestine tissue lipid absorption. Importantly, monascin and ankaflavin are not like monacolin K, which increases creatine phosphokinase (CPK) activity, known as a rhabdomyolysis indicator.
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Synthesis, cytotoxicity, DNA binding and apoptosis of rhein-phosphonate derivatives as antitumor agents.
Int J Mol Sci
PUBLISHED: 01-31-2013
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Several rhein-phosphonate derivatives (5a-c) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially compounds 5b exhibited the strongest cytotoxicity against HepG-2 and Spca-2 cells (IC50 was 8.82 and 9.01 µM), respectively. All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. Further experiments proved that 5b could disturb the cell cycle in HepG-2 cells and induce apoptosis. In addition, the binding properties of a model conjugate 5b to DNA were investigated by methods (UV-Vis, fluorescence, CD spectroscopy). Results indicated that 5b showed moderate ability to interact ct-DNA.
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Effects of monascin on anti-inflammation mediated by Nrf2 activation in advanced glycation end product-treated THP-1 monocytes and methylglyoxal-treated wistar rats.
J. Agric. Food Chem.
PUBLISHED: 01-31-2013
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Hyperglycemia is associated with advanced glycation end products (AGEs). This study was designed to evaluate the inhibitory effects of monascin on receptor for advanced glycation end product (RAGE) signal and THP-1 monocyte inflammation after treatment with S100b, a specific ligand of RAGE. Monascin inhibited cytokine production by S100b-treated THP-1 monocytes via up-regulation of nuclear factor-erythroid 2-related factor-2 (Nrf2) and alleviated p47phox translocation to the membrane. Methylglyoxal (MG, 600 mg/kg bw) was used to induce diabetes in Wistar rats. Inhibitions of RAGE and p47phox by monascin were confirmed by peripheral blood mononuclear cells (PBMCs) of MG-induced rats. Silymarin (SM) was used as a positive control group. It was found that monascin promoted heme oxygenase-1 (HO-1) expression mediated by Nrf2. Suppressions of AGEs, tumor necrosis factor-? (TNF-?), and interleukin-1? (IL-?) in serum of MG-induced rats were attenuated in the monascin administration group treated with retinoic acid (RA). RA treatment resulted in Nrf2 inactivation by increasing RA receptor-? (RAR?) activity, suggesting that RA acts as an inhibitor of Nrf2. The results showed that monascin exerted anti-inflammatory and antioxidative effects mediated by Nrf2 to prevent the development of diseases such as type 2 diabetes caused by inflammation.
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Dimerumic acid attenuates receptor for advanced glycation endproducts signal to inhibit inflammation and diabetes mediated by Nrf2 activation and promotes methylglyoxal metabolism into d-lactic acid.
Free Radic. Biol. Med.
PUBLISHED: 01-29-2013
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This study was designed to evaluate the effects of dimerumic acid (DMA) on receptor for advanced glycation endproducts (RAGE) signal activation and THP-1 monocyte inflammation treated with S100b, a specific ligand of RAGE. We found that DMA inhibited inflammatory cytokine production via upregulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and alleviated oxidative stress through attenuation of p47phox translocation to the membrane of S100b-treated THP-1 monocytes. We found that DMA activated Nrf2 mediated by the p38 kinase pathway in THP-1 monocytes. However, anti-inflammatory activity of DMA was attenuated by Nrf2 siRNA treatment. In an animal model, methylglyoxal (MG; 200mg/kg bw) was chosen to induce diabetes in Balb/C mice (6 weeks) in this work. The in vivo verification of anti-inflammation in peripheral blood mononuclear cells by DMA treatment was confirmed by tumor necrosis factor-? and interleukin-1? measurements. Oral glucose tolerance test, insulin tolerance test, hyperinsulinemia, and hyperglycemia were improved in MG-treated mice by DMA treatment and these effects were greater than those of silymarin and N-acetylcysteine. Furthermore, DMA increased hepatic glyoxalase mRNA and glutathione mediated by Nrf2 activation to metabolize MG into d-lactic acid, thereby reducing serum and hepatic AGE levels and suppressing inflammatory factor generation in MG-treated mice. However, DMA did not exert the antiglycation activity in MG-bovine serum albumin incubation. Taken together, the results indicate that DMA is a novel antioxidant and Nrf2 activator that lowers AGE levels and may prove to be an effective treatment for diabetes.
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