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Sample records for berberine bridge enzyme

  1. The family of berberine bridge enzyme-like enzymes: A treasure-trove of oxidative reactions.

    Science.gov (United States)

    Daniel, Bastian; Konrad, Barbara; Toplak, Marina; Lahham, Majd; Messenlehner, Julia; Winkler, Andreas; Macheroux, Peter

    2017-10-15

    Biological oxidations form the basis of life on earth by utilizing organic compounds as electron donors to drive the generation of metabolic energy carriers, such as ATP. Oxidative reactions are also important for the biosynthesis of complex compounds, i.e. natural products such as alkaloids that provide vital benefits for organisms in all kingdoms of life. The vitamin B 2 -derived cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) enable an astonishingly diverse array of oxidative reactions that is based on the versatility of the redox-active isoalloxazine ring. The family of FAD-linked oxidases can be divided into subgroups depending on specific sequence features in an otherwise very similar structural context. The sub-family of berberine bridge enzyme (BBE)-like enzymes has recently attracted a lot of attention due to the challenging chemistry catalyzed by its members and the unique and unusual bi-covalent attachment of the FAD cofactor. This family is the focus of the present review highlighting recent advancements into the structural and functional aspects of members from bacteria, fungi and plants. In view of the unprecedented reaction catalyzed by the family's namesake, BBE from the California poppy, recent studies have provided further insights into nature's treasure chest of oxidative reactions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Structure of a Berberine Bridge Enzyme-Like Enzyme with an Active Site Specific to the Plant Family Brassicaceae

    DEFF Research Database (Denmark)

    Daniel, Bastian; Wallner, Silvia; Steiner, Barbara

    2016-01-01

    Berberine bridge enzyme-like (BBE-like) proteins form a multigene family (pfam 08031), which is present in plants, fungi and bacteria. They adopt the vanillyl alcohol-oxidase fold and predominantly show bi-covalent tethering of the FAD cofactor to a cysteine and histidine residue, respectively....... The Arabidopsis thaliana genome was recently shown to contain genes coding for 28 BBE-like proteins, while featuring four distinct active site compositions. We determined the structure of a member of the AtBBE-like protein family (termed AtBBE-like 28), which has an active site composition that has not been...... be exploited for catalysis. The structure also indicates a shift of the position of the isoalloxazine ring in comparison to other members of the BBE-like family. The dioxygen surrogate chloride was found near the C(4a) position of the isoalloxazine ring in the oxygen pocket, pointing to a rapid reoxidation...

  3. Berberine

    Science.gov (United States)

    ... barberry, goldenseal, goldthread, Oregon grape, phellodendron, and tree tumeric. People take berberine for heart failure. Some people ... caused by radiation in patients being treated for cancer. Low blood platelet counts (thrombocytopenia). Blood platelets are ...

  4. [Effects of berberine on the recovery of rat liver xenobiotic-metabolizing enzymes after partial hepatectomy].

    Science.gov (United States)

    Zverinsky, I V; Zverinskaya, H G; Sutsko, I P; Telegin, P G; Shlyahtun, A G

    2015-01-01

    We have studied the effect of berberine on the recovery processes of liver xenobiotic-metabolizing function during its compensatory growth after 70% partial hepatectomy. It was found the hepatic ability to metabolize foreign substances are not restored up to day 8. Administration of berberine (10 mg/kg intraperitoneally) for 6 days led to normalization of both cytochrome P450-dependent and flavin-containing monooxygenases. It is suggested that in the biotransformation of berberine involved not only cytochrome P450, but also flavin-containing monooxygenases.

  5. Structure of a Berberine Bridge Enzyme-Like Enzyme with an Active Site Specific to the Plant Family Brassicaceae

    Czech Academy of Sciences Publication Activity Database

    Daniel, B.; Wallner, S.; Steiner, B.; Oberdorfer, G.; Kumar, P.; van der Graaff, E.; Roitsch, Thomas; Sensen, Ch. W.; Gruber, K.

    2016-01-01

    Roč. 11, č. 6 (2016), e0156892 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : Covalently attached fad * flavoproteins * arabidopsis * metabolism * identification * oxidation * mutagenesis * alkaloids * software * protein s Subject RIV: CE - Biochemistry Impact factor: 2.806, year: 2016

  6. Herbicidal Spectrum, Absorption and Transportation, and Physiological Effect on Bidens pilosa of the Natural Alkaloid Berberine.

    Science.gov (United States)

    Wu, Jiao; Ma, Jing-Jing; Liu, Bo; Huang, Lun; Sang, Xiao-Qing; Zhou, Li-Juan

    2017-08-02

    Berberine is a natural herbicidal alkaloid from Coptis chinensis Franch. Here we characterized its herbicidal spectrum and absorption and transportation in the plant, along with the possible mechanism. Berberine showed no effect on the germination of the 10 tested plants. The IC 50 values of berberine on the primary root length and fresh weight of the 10 tested plants ranged from 2.91 to 9.79 mg L -1 and 5.76 to 35.07 mg L -1 , respectively. Berberine showed a similar herbicidal effect on Bidens pilosa as the commercial naturally derived herbicide cinmethylin. HPLC and fluorescence analysis revealed that berberine was mainly absorbed by B. pilosa root and transported through vascular bundle acropetally. Enzyme activity studies, GC-MS analysis, and SEM and TEM observations indicated that berberine might first function on the cell membrane indicated by variation of the IUFA percent and then cause POD, PPO, and SOD activity changes and cellular structure deformity, which was eventually expressed as the decrease of cell adaptation ability and abnormal cell function and may even result in cell death. Environmental safety evaluation tests revealed that berberine was low in toxicity to Brachydanio rerio. These indicate that berberine has the potential to be a bioherbicide and/or a lead molecule for new herbicides.

  7. Engineering and introduction of de novo disulphide bridges in organophosphorus hydrolase enzyme for thermostability improvement.

    Science.gov (United States)

    Farnoosh, Gholamreza; Khajeh, Khosro; Latifi, Ali Mohammad; Aghamollaei, Hossein

    2016-12-01

    The organophosphorus hydrolase (OPH) has been used to degrade organophosphorus chemicals, as one of the most frequently used decontamination methods. Under chemical and thermal denaturing conditions, the enzyme has been shown to unfold. To utilize this enzyme in various applications, the thermal stability is of importance. The engineering of de novo disulphide bridges has been explored as a means to increase the thermal stability of enzymes in the rational method of protein engineering. In this study, Disulphide by Design software, homology modelling and molecular dynamics simulations were used to select appropriate amino acid pairs for the introduction of disulphide bridge to improve protein thermostability. The thermostability of the wild-type and three selected mutant enzymes were evaluated by half-life, delta G inactivation (ΔGi) and structural studies (fluorescence and far-UV CD analysis). Data analysis showed that half-life of A204C/T234C and T128C/E153C mutants were increased up to 4 and 24 min, respectively; however, for the G74C/A78C mutant, the half-life was decreased up to 9 min. For the T128C/E124C mutant, both thermal stability and Catalytic efficiency (kcat) were also increased. The half-life and ΔGi results were correlated to the obtained information from structural studies by circular dichroism (CD) spectrometry and extrinsic fluorescence experiments; as rigidity increased in A204C/T2234C and T128C/E153C mutants, half-life and ΔGi also increased. For G74C/A78C mutant, these parameters decreased due to its higher flexibility. The results were submitted a strong evidence for the possibility to improve the thermostability of OPH enzyme by introducing a disulphide bridge after bioinformatics design, even though this design would not be always successful.

  8. Fluorescence of berberine in microheterogeneous systems

    Energy Technology Data Exchange (ETDEWEB)

    Colina, Ariel N.; Díaz, Marta S.; Gutiérrez, María Isela, E-mail: isela@unpata.edu.ar

    2013-12-15

    Spectral properties of the alkaloid berberine were studied in micellar solution and microemulsions based on anionic sodium dodecyl sulfate, cationic cetyltrimethylammonium bromide and nonionic Triton X-100 surfactants. Absorption and fluorescence emission spectra were determined. For screening the influence of type and concentration of micelles on the fluorescence of berberine a 3{sup 2} full factorial design was used. Higher responses were obtained when berberine was dissolved in sodium dodecyl sulfate micelles 0.01 M. Comparative results of fluorescence quantum yields (Φ{sub f}) reveal that the highest values (Φ{sub f}≥0.01) were observed in microemulsions. In the microheterogeneous systems investigated the most probable location of berberine is the micellar interfacial region. -- Highlights: • Spectroscopic propereies of berberine in microheterogeneous media were investigated. • Berberine shows enhanced fluorescence in SDS micelles as compared to water • Berberine is probably located in the interface of the microheterogeneous systems.

  9. Fluorescence of berberine in microheterogeneous systems

    International Nuclear Information System (INIS)

    Colina, Ariel N.; Díaz, Marta S.; Gutiérrez, María Isela

    2013-01-01

    Spectral properties of the alkaloid berberine were studied in micellar solution and microemulsions based on anionic sodium dodecyl sulfate, cationic cetyltrimethylammonium bromide and nonionic Triton X-100 surfactants. Absorption and fluorescence emission spectra were determined. For screening the influence of type and concentration of micelles on the fluorescence of berberine a 3 2 full factorial design was used. Higher responses were obtained when berberine was dissolved in sodium dodecyl sulfate micelles 0.01 M. Comparative results of fluorescence quantum yields (Φ f ) reveal that the highest values (Φ f ≥0.01) were observed in microemulsions. In the microheterogeneous systems investigated the most probable location of berberine is the micellar interfacial region. -- Highlights: • Spectroscopic propereies of berberine in microheterogeneous media were investigated. • Berberine shows enhanced fluorescence in SDS micelles as compared to water • Berberine is probably located in the interface of the microheterogeneous systems

  10. Berberine inhibits hepatic gluconeogenesis via the LKB1-AMPK-TORC2 signaling pathway in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Jiang, Shu-Jun; Dong, Hui; Li, Jing-Bin; Xu, Li-Jun; Zou, Xin; Wang, Kai-Fu; Lu, Fu-Er; Yi, Ping

    2015-07-07

    To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model. The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups (n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine (156 mg/kg per day) (berberine group) or metformin (184 mg/kg per day) (metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR) (0.5 mg/kg per day) (AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested. The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator (TORC)2 was observed by immunohistochemical staining. Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Berberine upregulated protein expression of liver kinase (LK)B1, AMP-activated protein kinase (AMPK) and phosphorylated AMPK (p-AMPK). The level of phophorylated TORC2 (p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2

  11. Bridges

    NARCIS (Netherlands)

    Zant, W.

    2017-01-01

    We estimate to what extent bridges in Mozambique lead to transport cost reductions and attribute these reductions to key determinants, in particular road distance, road quality and crossing borders. For identification we exploit the introduction of a road bridge over the Zambezi river, in August

  12. Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

    Directory of Open Access Journals (Sweden)

    Doaa A. Ghareeb

    2015-01-01

    Full Text Available Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL. The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE and amyloid beta precursor protein (AβPP. These changes were significantly correlated with decreased insulin degrading enzyme (IDE and beta-amyloid40 (Aβ40 and increased beta-amyloid42 (Aβ42 in the hippocampal region. Daily administration of berberine (50 mg/kg for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.

  13. Toxicology effects of Berberis vulgaris (barberry and its active constituent, berberine: a review

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    Seyede Zohre Kamrani Rad

    2017-05-01

    Full Text Available Berberis vulgaris and berberine, its main component, traditionally have been used for treatment of various disorders. The pharmacological properties of them have been investigated using different in vivo and in vitro models. In spite of beneficial effects of B. vulgaris on different cell lines, there are documents have revealed negative impacts of it on animal and human. In this regards, the determination of its toxicity in a scientific view is necessary. In current report, we provide classified information about the toxicity of B. vulgaris and berberine in different conditions consist of acute, sub-acute, sub-chronic and chronic state. Besides, it discusses the cytotoxicity, genotoxicity, mutagenicity, and carcinogenicity of B. vulgaris and berberine as well as developmental toxicity and clinical studies. Data from the present study indicate that their toxicity is depending on the route and duration of administration. According to present study, they could induce GI upset and ulceration, immunotoxicity, phototoxicity, neurotoxicity, cardiotoxicity and jaundice in a dose dependent manner. They should be used with caution in pregnancy, neonatal and G6PD deficiency. Besides, consideration should be taken in co-administration of berberine with drugs that are metabolized with CYP enzymes due their inhibitory effects on these enzymes. Furthermore, they evoke cytotoxicity on both normal and cancer cell line which is time and concentration dependent.

  14. Enzyme

    Science.gov (United States)

    Enzymes are complex proteins that cause a specific chemical change in all parts of the body. For ... use them. Blood clotting is another example of enzymes at work. Enzymes are needed for all body ...

  15. Berberine exposure triggers developmental effects on planarian regeneration.

    Science.gov (United States)

    Balestrini, Linda; Isolani, Maria Emilia; Pietra, Daniele; Borghini, Alice; Bianucci, Anna Maria; Deri, Paolo; Batistoni, Renata

    2014-05-09

    The mechanisms of action underlying the pharmacological properties of the natural alkaloid berberine still need investigation. Planarian regeneration is instrumental in deciphering developmental responses following drug exposure. Here we report the effects of berberine on regeneration in the planarian Dugesia japonica. Our findings demonstrate that this compound perturbs the regenerative pattern. By real-time PCR screening for the effects of berberine exposure on gene expression, we identified alterations in the transcriptional profile of genes representative of different tissues, as well as of genes involved in extracellular matrix (ECM) remodeling. Although berberine does not influence cell proliferation/apoptosis, our experiments prove that this compound causes abnormal regeneration of the planarian visual system. Potential berberine-induced cytotoxic effects were noticed in the intestine. Although we were unable to detect abnormalities in other structures, our findings, sustained by RNAi-based investigations, support the possibility that berberine effects are critically linked to anomalous ECM remodeling in treated planarians.

  16. Role of berberine in Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Cai Z

    2016-10-01

    Full Text Available Zhiyou Cai,1,* Chuanling Wang,1,* Wenming Yang2 1Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, Hubei Province, 2Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, People’s Republic of China *These authors contributed equally to this work Abstract: Berberine, an important protoberberine isoquinoline alkaloid, has several pharmacological activities, including antimicrobial, glucose- and cholesterol-lowering, antitumoral, and immunomodulatory properties. Substantial studies suggest that berberine may be beneficial to Alzheimer’s disease (AD by limiting the pathogenesis of extracellular amyloid plaques and intracellular neurofibrillary tangles. Increasing evidence has indicated that berberine exerts a protective role in atherosclerosis related to lipid- and glucose-lowering properties, implicating that berberine has the potential to inhibit these risk factors for AD. This review also attempts to discuss the pharmacological basis through which berberine may retard oxidative stress and neuroinflammation to exhibit its protective role in AD. Accordingly, berberine might be considered a potential therapeutic approach to prevent or delay the process of AD. However, more detailed investigations along with a safety assessment of berberine are warranted to clarify the role of berberine in limiting these risk factors and AD-related pathologies. Keywords: berberine, amyloid, tau, oxidative stress, neuroinflammation, risk factors

  17. A rigidifying salt-bridge favors the activity of thermophilic enzyme at high temperatures at the expense of low-temperature activity.

    Science.gov (United States)

    Lam, Sonia Y; Yeung, Rachel C Y; Yu, Tsz-Ha; Sze, Kong-Hung; Wong, Kam-Bo

    2011-03-01

    Thermophilic enzymes are often less active than their mesophilic homologues at low temperatures. One hypothesis to explain this observation is that the extra stabilizing interactions increase the rigidity of thermophilic enzymes and hence reduce their activity. Here we employed a thermophilic acylphosphatase from Pyrococcus horikoshii and its homologous mesophilic acylphosphatase from human as a model to study how local rigidity of an active-site residue affects the enzymatic activity. Acylphosphatases have a unique structural feature that its conserved active-site arginine residue forms a salt-bridge with the C-terminal carboxyl group only in thermophilic acylphosphatases, but not in mesophilic acylphosphatases. We perturbed the local rigidity of this active-site residue by removing the salt-bridge in the thermophilic acylphosphatase and by introducing the salt-bridge in the mesophilic homologue. The mutagenesis design was confirmed by x-ray crystallography. Removing the salt-bridge in the thermophilic enzyme lowered the activation energy that decreased the activation enthalpy and entropy. Conversely, the introduction of the salt-bridge to the mesophilic homologue increased the activation energy and resulted in increases in both activation enthalpy and entropy. Revealed by molecular dynamics simulations, the unrestrained arginine residue can populate more rotamer conformations, and the loss of this conformational freedom upon the formation of transition state justified the observed reduction in activation entropy. Our results support the conclusion that restricting the active-site flexibility entropically favors the enzymatic activity at high temperatures. However, the accompanying enthalpy-entropy compensation leads to a stronger temperature-dependency of the enzymatic activity, which explains the less active nature of the thermophilic enzymes at low temperatures.

  18. A rigidifying salt-bridge favors the activity of thermophilic enzyme at high temperatures at the expense of low-temperature activity.

    Directory of Open Access Journals (Sweden)

    Sonia Y Lam

    2011-03-01

    Full Text Available Thermophilic enzymes are often less active than their mesophilic homologues at low temperatures. One hypothesis to explain this observation is that the extra stabilizing interactions increase the rigidity of thermophilic enzymes and hence reduce their activity. Here we employed a thermophilic acylphosphatase from Pyrococcus horikoshii and its homologous mesophilic acylphosphatase from human as a model to study how local rigidity of an active-site residue affects the enzymatic activity.Acylphosphatases have a unique structural feature that its conserved active-site arginine residue forms a salt-bridge with the C-terminal carboxyl group only in thermophilic acylphosphatases, but not in mesophilic acylphosphatases. We perturbed the local rigidity of this active-site residue by removing the salt-bridge in the thermophilic acylphosphatase and by introducing the salt-bridge in the mesophilic homologue. The mutagenesis design was confirmed by x-ray crystallography. Removing the salt-bridge in the thermophilic enzyme lowered the activation energy that decreased the activation enthalpy and entropy. Conversely, the introduction of the salt-bridge to the mesophilic homologue increased the activation energy and resulted in increases in both activation enthalpy and entropy. Revealed by molecular dynamics simulations, the unrestrained arginine residue can populate more rotamer conformations, and the loss of this conformational freedom upon the formation of transition state justified the observed reduction in activation entropy.Our results support the conclusion that restricting the active-site flexibility entropically favors the enzymatic activity at high temperatures. However, the accompanying enthalpy-entropy compensation leads to a stronger temperature-dependency of the enzymatic activity, which explains the less active nature of the thermophilic enzymes at low temperatures.

  19. Antibacterial activity and mechanism of berberine against Streptococcus agalactiae.

    Science.gov (United States)

    Peng, Lianci; Kang, Shuai; Yin, Zhongqiong; Jia, Renyong; Song, Xu; Li, Li; Li, Zhengwen; Zou, Yuanfeng; Liang, Xiaoxia; Li, Lixia; He, Changliang; Ye, Gang; Yin, Lizi; Shi, Fei; Lv, Cheng; Jing, Bo

    2015-01-01

    The antibacterial activity and mechanism of berberine against Streptococcus agalactiae were investigated in this study by analyzing the growth, morphology and protein of the S. agalactiae cells treated with berberine. The antibacterial susceptibility test result indicated minimum inhibition concentration (MIC) of berberine against Streptococcus agalactiae was 78 μg/mL and the time-kill curves showed the correlation of concentration-time. After the bacteria was exposed to 78 μg/mL berberine, the fragmentary cell membrane and cells unequal division were observed by the transmission electron microscopy (TEM), indicating the bacterial cells were severely damaged. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) study demonstrated that berberine could damage bacterial cells through destroying cellular proteins. Meanwhile, Fluorescence microscope revealed that berberine could affect the synthesis of DNA. In conclusion, these results strongly suggested that berberine may damage the structure of bacterial cell membrane and inhibit synthesis of protein and DNA, which cause Streptococcus agalactiae bacteria to die eventually.

  20. Combination of upflow anaerobic sludge blanket (UASB) and membrane bioreactor (MBR) for berberine reduction from wastewater and the effects of berberine on bacterial community dynamics.

    Science.gov (United States)

    Qiu, Guanglei; Song, Yonghui; Zeng, Ping; Duan, Liang; Xiao, Shuhu

    2013-02-15

    Berberine is a broad-spectrum antibiotic extensively used in personal medication. The production of berberine results in the generation of wastewater containing concentrated residual berberine. However, few related studies up to date focus on berberine removal from wastewaters. In this study, a lab-scale upflow anaerobic sludge blanket (UASB)-membrane bioreactor (MBR) process was developed for berberine removal from synthetic wastewater. The performance of the UASB-MBR system on berberine, COD and NH(4)(+)--N removal was investigated at different berberine loadings. And the effects of berberine on bacterial communities were evaluated using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Results showed that, as the increase of berberine loadings, UASB performance was affected remarkably, whereas, efficient and stable performance of MBR ensured the overall removal rates of berberine, COD and NH(4)(+)--N consistently reached up to 99%, 98% and 98%, respectively. Significant shifts of bacterial community structures were detected in both UASB and MBR, especially in the initial operations. Along with the increase of berberine loadings, high antibiotic resisting species and some functional species, i.e. Acinetobacter sp., Clostridium sp., Propionibacterium sp., and Sphingomonas sp. in UASB, as well as Sphingomonas sp., Methylocystis sp., Hydrogenophaga sp. and Flavobacterium sp. in MBR were enriched in succession. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism

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    Qian Zhang

    2011-01-01

    Full Text Available Berberine is known to improve glucose and lipid metabolism disorders, but the mechanism is still under investigation. In this paper, we explored the effects of berberine on the weight, glucose levels, lipid metabolism, and serum insulin of KKAy mice and investigated its possible glucose and lipid-regulating mechanism. We randomly divided KKAy mice into two groups: berberine group (treated with 250 mg/kg/d berberine and control group. Fasting blood glucose (FBG, weight, total cholesterol (TC, triglyceride (TG, high-density lipoprotein-cholesterol (HDL-c, low-density lipoprotein-cholesterol (LDL-c, and fasting serum insulin were measured in both groups. The oral glucose tolerance test (OGTT was performed. RT2 PCR array gene expression analysis was performed using skeletal muscle of KKAy mice. Our data demonstrated that berberine significantly decreased FBG, area under the curve (AUC, fasting serum insulin (FINS, homeostasis model assessment insulin resistance (HOMA-IR index, TC, and TG, compared with those of control group. RT2 profiler PCR array analysis showed that berberine upregulated the expression of glucose transporter 4 (GLUT4, mitogen-activated protein kinase 14 (MAPK14, MAPK8(c-jun N-terminal kinase, JNK, peroxisome proliferator-activated receptor α (PPARα, uncoupling protein 2 (UCP2, and hepatic nuclear factor 4α(HNF4α, whereas it downregulated the expression of PPARγ, CCAAT/enhancer-binding protein (CEBP, PPARγ coactivator 1α(PGC 1α, and resistin. These results suggest that berberine moderates glucose and lipid metabolism through a multipathway mechanism that includes AMP-activated protein kinase-(AMPK- p38 MAPK-GLUT4, JNK pathway, and PPARα pathway.

  2. Response of Escherichia coli to Prolonged Berberine Exposure.

    Science.gov (United States)

    Budeyri Gokgoz, Nilay; Avci, Fatma Gizem; Yoneten, Kubra Karaosmanoglu; Alaybeyoglu, Begum; Ozkirimli, Elif; Sayar, Nihat Alpagu; Kazan, Dilek; Sariyar Akbulut, Berna

    2017-07-01

    Berberine is a plant-derived alkaloid possessing antimicrobial activity; unfortunately, its efflux through multidrug resistance pumps reduces its efficacy. Cellular life span of Escherichia coli is generally shorter with prolonged berberine exposure; nevertheless, about 30% of the cells still remain robust following this treatment. To elucidate its mechanism of action and to identify proteins that could be involved in development of antimicrobial resistance, protein profiles of E. coli cells treated with berberine for 4.5 and 8 hours were compared with control cells. A total of 42 proteins were differentially expressed in cells treated with berberine for 8 hours when compared to control cells. In both 4.5 and 8 hours of berberine-treated cells, carbohydrate and peptide uptake regimens remained unchanged, although amino acid maintenance regimen switched from transport to synthesis. Defect in cell division persisted and this condition was confirmed by images obtained from scanning electron microscopy. Universal stress proteins were not involved in stress response. The significant increase in the abundance of elongation factors could suggest the involvement of these proteins in protection by exhibiting chaperone activities. Furthermore, the involvement of the outer membrane protein OmpW could receive special attention as a protein involved in response to antimicrobial agents, since the expression of only this porin protein was upregulated after 8 hours of exposure.

  3. Enzyme-assisted growth of nacreous CaCO3/polymer hybrid nanolaminates via the formation of mineral bridges

    Science.gov (United States)

    Yeom, Bongjun; Char, Kookheon

    2016-06-01

    Laminated nanostructures in nacre have been adopted as models in the fabrication of strong, tough synthetic nanocomposites. However, the utilization of CaCO3 biominerals in these composites is limited by the complexity of the synthesis method for nanosized biominerals. In this study, we use the enzymatic reaction of urease to generate a nanoscale CaCO3 thin film to prepare CaCO3/polymer hybrid nanolaminates. Additional layers of CaCO3 thin film are consecutively grown over the base CaCO3 layer with the intercalation of organic layers. The morphology and crystallinity of the added CaCO3 layers depend strongly on the thickness of the organic layer coated on the underlying CaCO3 layer. When the organic layer is less than 20 nm thick, the amorphous CaCO3 layer is spontaneously transformed into crystalline calcite layer during the growth process. We also observe crystalline continuity between adjacent CaCO3 layers through interconnecting mineral bridges. The formation of these mineral bridges is crucial to the epitaxial growth of CaCO3 layers, similar to the formation of natural nacre.

  4. Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, Shatrunajay [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi ‐110062 (India); Sharma, Ankita [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Pandey, Vivek Kumar [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Academy of Scientific and Innovative Research (India); Raisuddin, Sheikh [Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi ‐110062 (India); Kakkar, Poonam, E-mail: kakkarp59@gmail.com [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Academy of Scientific and Innovative Research (India)

    2016-01-15

    Post-translational modifications i.e. phosphorylation and acetylation are pivotal requirements for proper functioning of eukaryotic proteins. The current study aimed to decode the impact of acetylation/deacetylation of non-histone targets i.e. FoxO1/3a and p53 of sirtuins (NAD{sup +} dependent enzymes with lysine deacetylase activity) in berberine treated human hepatoma cells. Berberine (100 μM) inhibited sirtuins significantly (P < 0.05) at transcriptional level as well as at translational level. Combination of nicotinamide (sirtuin inhibitor) with berberine potentiated sirtuins inhibition and increased the expression of FoxO1/3a and phosphorylation of p53 tumor suppressor protein. As sirtuins deacetylate non-histone targets including FoxO1/3a and p53, berberine increased the acetylation load of FoxO1/3a and p53 proteins. Acetylated FoxO and p53 proteins transcriptionally activate BH3-only proteins Bim and PUMA (3.89 and 3.87 fold respectively, P<0.001), which are known as direct activator of pro-apoptotic Bcl-2 family protein Bax that culminated into mitochondria mediated activation of apoptotic cascade. Bim/PUMA knock-down showed no changes in sirtuins' expression while cytotoxicity induced by berberine and nicotinamide was curtailed up to 28.3% (P < 0.001) and it restored pro/anti apoptotic protein ratio in HepG2 cells. Sirtuins inhibition was accompanied by decline in NAD{sup +}/NADH ratio, ATP generation, enhanced ROS production and decreased mitochondrial membrane potential. TEM analysis confirmed mitochondrial deterioration and cell damage. SRT-1720 (1–10 μM), a SIRT-1 activator, when pre-treated with berberine (25 μM), reversed sirtuins expression comparable to control and significantly restored the cell viability (P < 0.05). Thus, our findings suggest that berberine mediated sirtuins inhibition resulting into FoxO1/3a and p53 acetylation followed by BH3-only protein Bim/PUMA activation may in part be responsible for mitochondria

  5. Berberine promotes glucose consumption independently of AMP-activated protein kinase activation.

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    Miao Xu

    Full Text Available Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1 inhibition of AMPK activity by Compound C, (2 suppression of AMPKα expression by siRNA, and (3 blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.

  6. A new triple system DNA-Nanosilver-Berberine for cancer therapy

    Science.gov (United States)

    Grebinyk, Anna; Yashchuk, Valeriy; Bashmakova, Nataliya; Gryn, Dmytro; Hagemann, Tobias; Naumenko, Antonina; Kutsevol, Nataliya; Dandekar, Thomas; Frohme, Marcus

    2018-03-01

    The isoquinoline quaternary alkaloid Berberine possesses a variety of pharmacological properties that suggests its promising application for an anticancer delivery system design utilizing its ability to intercalate DNA. In the current work, we have investigated the effects of Berberine on the human T cell leukemia cell line in vitro. Fluorescent microscopy of leukemic cells revealed Berberine nuclear localization. The results showed that Berberine inhibited leukemic cell growth in a time- and dose-dependent manner, that was associated with reactive oxygen species production intensification and caspase 3/7 activity increase with followed apoptosis induction. Berberine was used as a toxic and phototoxic agent for triple system synthesis along with DNA as a carrier and nanosilver as a plasmonic accelerator of Berberine electronic transitions and high energy emission absorbent centers. The proposed method allows to obtain the complex of DNA with Berberine molecules and silver nanoparticles. The optical properties of free components as well as their various combinations, including the final triple system DNA-Nanosilver-Berberine, were investigated. Obtained results support the possibility to use the triple system DNA-Nanosilver-Berberine as an alternative therapeutic agent for cancer treatment.

  7. Enzyme-like catalysis via ternary complex mechanism: alkoxy-bridged dinuclear cobalt complex mediates chemoselective O-esterification over N-amidation.

    Science.gov (United States)

    Hayashi, Yukiko; Santoro, Stefano; Azuma, Yuki; Himo, Fahmi; Ohshima, Takashi; Mashima, Kazushi

    2013-04-24

    Hydroxy group-selective acylation in the presence of more nucleophilic amines was achieved using acetates of first-row late transition metals, such as Mn, Fe, Co, Cu, and Zn. Among them, cobalt(II) acetate was the best catalyst in terms of reactivity and selectivity. The combination of an octanuclear cobalt carboxylate cluster [Co4(OCOR)6O]2 (2a: R = CF3, 2b: R = CH3, 2c: R = (t)Bu) with nitrogen-containing ligands, such as 2,2'-bipyridine, provided an efficient catalytic system for transesterification, in which an alkoxide-bridged dinuclear complex, Co2(OCO(t)Bu)2(bpy)2(μ2-OCH2-C6H4-4-CH3)2 (10), was successfully isolated as a key intermediate. Kinetic studies and density functional theory calculations revealed Michaelis-Menten behavior of the complex 10 through an ordered ternary complex mechanism similar to dinuclear metallo-enzymes, suggesting the formation of alkoxides followed by coordination of the ester.

  8. The role of phytohormone on the production of berberine in the calli ...

    African Journals Online (AJOL)

    The role of phytohormone on the production of berberine in the calli cultures of an endangered medicinal plant, turmeric ( Coscinium fenestratum l. ) ... The presence of berberine was first checked by preparative thin layer chromatography (TLC) and then confirmed by High Pressure Liquid chromatography (HPLC) and mass ...

  9. The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment.

    Science.gov (United States)

    An, Yuan; Sun, Zhuangzhuang; Zhang, Yajuan; Liu, Bin; Guan, Yuanyuan; Lu, Meisong

    2014-03-01

    Previous studies have indicated that berberine is an effective insulin sensitizer with comparable activity to metformin (Diabetes 2006, 55, 2256). Reduced insulin sensitivity is reportedly a factor adversely affecting the outcome of IVF in patients with polycystic ovary syndrome (PCOS) (Human Reproduction 2006, 21, 1416). Our objective was to evaluate the clinical, metabolic and endocrine effects of berberine vs metformin in PCOS women scheduled for IVF treatment and to explore the potential benefits to the IVF process. We performed a prospective study in 150 infertile women with PCOS undergoing IVF treatment. Patients were randomized to receive berberine, metformin or placebo tablets for 3 months before ovarian stimulation. The clinical, endocrine, metabolic parameters and the outcome of IVF. Compared with placebo, greater reductions in total testosterone, free androgen index, fasting glucose, fasting insulin and HOMA-IR, and increases in SHBG, were observed in the berberine and metformin groups. Three months of treatment with berberine or metformin before the IVF cycle increased the pregnancy rate and reduced the incidence of severe ovarian hyperstimulation syndrome. Furthermore, treatment with berberine, in comparison with metformin, was associated with decreases in BMI, lipid parameters and total FSH requirement, and an increase in live birth rate with fewer gastrointestinal adverse events. Berberine and metformin treatments prior to IVF improved the pregnancy outcome by normalizing the clinical, endocrine and metabolic parameters in PCOS women. Berberine has a more pronounced therapeutic effect and achieved more live births with fewer side effects than metformin. © 2013 John Wiley & Sons Ltd.

  10. On the Mechanism of Berberine-INF55 (5-Nitro-2-phenylindole) Hybrid Antibacterials.

    Science.gov (United States)

    Dolla, Naveen K; Chen, Chao; Larkins-Ford, Jonah; Rajamuthiah, Rajmohan; Jagadeesan, Sakthimala; Conery, Annie L; Ausubel, Frederick M; Mylonakis, Eleftherios; Bremner, John B; Lewis, Kim; Kelso, Michael J

    Berberine-INF55 hybrids are a promising class of antibacterials that combine berberine and the NorA multidrug resistance pump inhibitor INF55 (5-nitro-2-phenylindole) together in one molecule via a chemically stable linkage. Previous studies demonstrated the potential of these compounds for countering efflux-mediated antibacterial drug resistance but they didn't establish whether the compounds function as originally intended, i.e. with the berberine moiety providing antibacterial activity and the attached INF55 component independently blocking multidrug resistance pumps, thereby enhancing the activity of berberine by reducing its efflux. We hypothesised that if the proposed mechanism is correct, then hybrids carrying more potent INF55 pump inhibitor structures should show enhanced antibacterial effects relative to those bearing weaker inhibitors. Two INF55 analogues showing graded reductions in NorA inhibitory activity compared with INF55 were identified and their corresponding berberine-INF55 hybrids carrying equivalent INF55 inhibitor structures synthesised. Multiple assays comparing the antibacterial effects of the hybrids and their corresponding berberine-INF55 analogue combinations showed that the three hybrids all show very similar activities, leading us to conclude that the antibacterial mechanism(s) of berberine-INF55 hybrids is different from berberine-INF55 combinations.

  11. Myocardial Bridge

    Science.gov (United States)

    ... Center > Myocardial Bridge Menu Topics Topics FAQs Myocardial Bridge En español Your heart is made of muscle, ... surface of the heart. What is a myocardial bridge? A myocardial bridge is a band of heart ...

  12. Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents.

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    Jiaolin Bao

    Full Text Available Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU, camptothecin (CPT, and paclitaxel (TAX. The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer.

  13. Interaction of Herbal Compounds with Biological Targets: A Case Study with Berberine

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    Xiao-Wu Chen

    2012-01-01

    Full Text Available Berberine is one of the main alkaloids found in the Chinese herb Huang lian (Rhizoma Coptidis, which has been reported to have multiple pharmacological activities. This study aimed to analyze the molecular targets of berberine based on literature data followed by a pathway analysis using the PANTHER program. PANTHER analysis of berberine targets showed that the most classes of molecular functions include receptor binding, kinase activity, protein binding, transcription activity, DNA binding, and kinase regulator activity. Based on the biological process classification of in vitro berberine targets, those targets related to signal transduction, intracellular signalling cascade, cell surface receptor-linked signal transduction, cell motion, cell cycle control, immunity system process, and protein metabolic process are most frequently involved. In addition, berberine was found to interact with a mixture of biological pathways, such as Alzheimer’s disease-presenilin and -secretase pathways, angiogenesis, apoptosis signalling pathway, FAS signalling pathway, Hungtington disease, inflammation mediated by chemokine and cytokine signalling pathways, interleukin signalling pathway, and p53 pathways. We also explored the possible mechanism of action for the anti-diabetic effect of berberine. Further studies are warranted to elucidate the mechanisms of action of berberine using systems biology approach.

  14. Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

    Science.gov (United States)

    Chu, Ming; Zhang, Ming-Bo; Liu, Yan-Chen; Kang, Jia-Rui; Chu, Zheng-Yun; Yin, Kai-Lin; Ding, Ling-Yu; Ding, Ran; Xiao, Rong-Xin; Yin, Yi-Nan; Liu, Xiao-Yan; Wang, Yue-Dan

    2016-04-01

    Berberine is an isoquinoline alkaloid widely used in the treatment of microbial infections. Recent studies have shown that berberine can enhance the inhibitory efficacy of antibiotics against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA). However, the underlying mechanisms are poorly understood. Here, we demonstrated that sub-minimum inhibitory concentrations (MICs) of berberine exhibited no bactericidal activity against MRSA, but affected MRSA biofilm development in a dose dependent manner within the concentration ranging from 1 to 64 μg/mL. Further study indicated that berberine inhibited MRSA amyloid fibrils formation, which consist of phenol-soluble modulins (PSMs). Molecular dynamics simulation revealed that berberine could bind with the phenyl ring of Phe19 in PSMα2 through hydrophobic interaction. Collectively, berberine can inhibit MRSA biofilm formation via affecting PSMs’ aggregation into amyloid fibrils, and thereby enhance bactericidal activity of antibiotics. These findings will provide new insights into the multiple pharmacological properties of berberine in the treatment of microbial-generated amyloid involved diseases.

  15. Impacts of berberine on the growth, migration and radiosensitivity of breast cancer cells

    International Nuclear Information System (INIS)

    Zhao Chaoqian; Xu Jiaying; Jiao Yang; Hu Xudong; Che Jun; Fan Saijun

    2012-01-01

    Objective: To study the impacts of berberine on the growth, migration and radiosensitivity in human breast cancer cells. Methods: MTT assay was used to evaluate cell growth.In vitro scratch migration assay was used to determine cell migration. Annexin V assay was used to detect cell apoptosis. The distribution of cell cycle was evaluated by flow cytometry assay. Colony formation assay was used to detect the influence of berberine on cell radiosensitivity. Western blot assay was employed to measure protein expression. Results: Berberine inhibited cell growth and migration in two human breast cancer cell lines, MCF-7 and MDA-MB-231, in a dose-and time-dependent manner. Furthermore, berberine resulted in a cell cycle G 0 /G 1 arrest. Compared with control, the early apoptosis in MDA-MB-231 and MCF-7 cells treated with 40 pμmol/L of berberine was as high as 86.6% and 66.6% (t=8.79, 10.32, P<0.01), respectively. Berberine caused a dose-dependent increase in Bax and Caspase-3 protein expressions, but did not change Cyclin D1 protein expression, while suppressed the expressions of Cyclin B1 and Bcl-2 protein. As analyzed with multi-target click model fitting curves, the SER D0 of berberine-treated cells were 1.12 and 1.22 for MDA-MB-231 and MCF-7 cells respectively at the dose D 0 of X-rays. Conclusions: The berberine inhibited the growth and migration of breast cancer cells via apoptosis induction and cell cycle arrest. Moreover, berberine increases cell sensitivity to X-ray irradiation. (authors)

  16. Update on Berberine in Nonalcoholic Fatty Liver Disease

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    Yang Liu

    2013-01-01

    Full Text Available Berberine (BBR, an active ingredient from nature plants, has demonstrated multiple biological activities and pharmacological effects in a series of metabolic diseases including nonalcoholic fatty liver disease (NAFLD. The recent literature points out that BBR may be a potential drug for NAFLD in both experimental models and clinical trials. This review highlights important discoveries of BBR in this increasing disease and addresses the relevant targets of BBR on NAFLD which links to insulin pathway, adenosine monophosphate-activated protein kinase (AMPK signaling, gut environment, hepatic lipid transportation, among others. Developing nuanced understanding of the mechanisms will help to optimize more targeted and effective clinical application of BBR for NAFLD.

  17. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Yu, Hyeon-Hee; Kim, Kang-Ju; Cha, Jeong-Dan; Kim, Hae-Kyoung; Lee, Young-Eun; Choi, Na-Young; You, Yong-Ouk

    2005-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) bacteria have been responsible for substantial morbidity and mortality in hospitals because they usually have multidrug resistance. Some natural products are candidates as new antibiotic substances. In the present study, we investigated the antimicrobial activity of berberine, the main antibacterial substance of Coptidis rhizoma (Coptis chinensis Franch) and Phellodendri cortex (Phellodendron amurense Ruprecht), against clinical isolates of MRSA, and the effects of berberine on the adhesion to MRSA and intracellular invasion into human gingival fibroblasts (HGFs). Berberine showed antimicrobial activity against all tested strains of MRSA. Minimum inhibition concentrations (MICs) of berberine against MRSA ranged from 32 to 128 microg/mL. Ninety percent inhibition of MRSA was obtained with 64 microg/mL or less of berberine. In the checkerboard dilution test, berberine markedly lowered the MICs of ampicillin and oxacillin against MRSA. An additive effect was found between berberine and ampicillin, and a synergistic effect was found between berberine and oxacillin against MRSA. In the presence of 1-50 microg/mL berberine, MRSA adhesion and intracellular invasion were notably decreased compared with the vehicle-treated control group. These results suggest that berberine may have antimicrobial activity and the potential to restore the effectiveness of beta-lactam antibiotics against MRSA, and inhibit the MRSA adhesion and intracellular invasion in HGFs.

  18. Antibacterial activity of berberine-NorA pump inhibitor hybrids with a methylene ether linking group.

    Science.gov (United States)

    Samosorn, Siritron; Tanwirat, Bongkot; Muhamad, Nussara; Casadei, Gabriele; Tomkiewicz, Danuta; Lewis, Kim; Suksamrarn, Apichart; Prammananan, Therdsak; Gornall, Karina C; Beck, Jennifer L; Bremner, John B

    2009-06-01

    Conjugation of the NorA substrate berberine and the NorA inhibitor 5-nitro-2-phenyl-1H-indole via a methylene ether linking group gave the 13-substituted berberine-NorA inhibitor hybrid, 3. A series of simpler arylmethyl ether hybrid structures were also synthesized. The hybrid 3 showed excellent antibacterial activity (MIC Staphylococcus aureus, 1.7 microM), which was over 382-fold more active than the parent antibacterial berberine, against this bacterium. This compound was also shown to block the NorA efflux pump in S. aureus.

  19. Inhibition of CYP1 by berberine, palmatine, and jatrorrhizine: Selectivity, kinetic characterization, and molecular modeling

    International Nuclear Information System (INIS)

    Lo, Sheng-Nan; Chang, Yu-Ping; Tsai, Keng-Chang; Chang, Chia-Yu; Wu, Tian-Shung; Ueng, Yune-Fang

    2013-01-01

    Cytochrome P450 (P450, CYP) 1 family plays a primary role in the detoxification and bioactivation of polycyclic aromatic hydrocarbons. Human CYP1A1, CYP1A2, and CYP1B1 exhibit differential substrate specificity and tissue distribution. Berberine, palmatine, and jatrorrhizine are protoberberine alkaloids present in several medicinal herbs, such as Coptis chinensis (Huang-Lian) and goldenseal. These protoberberines inhibited CYP1A1.1- and CYP1B1.1-catalyzed 7-ethoxyresorufin O-deethylation (EROD) activities, whereas CYP1A2.1 activity was barely affected. Kinetic analysis revealed that berberine noncompetitively inhibited EROD activities of CYP1A1.1 and CYP1B1.1, whereas palmatine and jatrorrhizine caused either competitive or mixed type of inhibition. Among protoberberines, berberine caused the most potent and selective inhibitory effect on CYP1B1.1 with the least K i value of 44 ± 16 nM. Berberine also potently inhibited CYP1B1.1 activities toward 7-ethoxycoumarin and 7-methoxyresorufin, whereas the inhibition of benzo(a)pyrene hydroxylation activity was less pronounced. Berberine inhibited the polymorphic variants, CYP1B1.3 (V432L) and CYP1B1.4 (N453S), with IC 50 values comparable to that for CYP1B1.1 inhibition. Berberine-mediated inhibition was abolished by a mutation of Asn228 to Thr in CYP1B1.1, whereas the inhibition was enhanced by a reversal mutation of Thr223 to Asn in CYP1A2.1. This result in conjugation with the molecular modeling revealed the crucial role of hydrogen-bonding interaction of Asn228 on CYP1B1.1 with the methoxy moiety of berberine. These findings demonstrate that berberine causes a selective CYP1B1-inhibition, in which Asn228 appears to be crucial. The inhibitory effects of berberine on CYP1B1 activities toward structurally diverse substrates can be different. - Highlights: • Berberine preferentially inhibited CYP1B1 activity. • Berberine caused similar inhibitory effects on CYP1B1.1, CYP1B1.3 and CYP1B1.4. • Asn228 in CYP1B1 was an

  20. Inhibition of CYP1 by berberine, palmatine, and jatrorrhizine: Selectivity, kinetic characterization, and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Sheng-Nan [National Research Institute of Chinese Medicine, Taipei 112, Taiwan, ROC (China); Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan, ROC (China); Chang, Yu-Ping; Tsai, Keng-Chang [National Research Institute of Chinese Medicine, Taipei 112, Taiwan, ROC (China); Chang, Chia-Yu [National Research Institute of Chinese Medicine, Taipei 112, Taiwan, ROC (China); Institute of Medical Sciences, Taipei Medical University, Taipei 101, Taiwan, ROC (China); Wu, Tian-Shung [Department of Chemistry, National Chung-Kung University, Tainan 701, Taiwan, ROC (China); Ueng, Yune-Fang, E-mail: ueng@nricm.edu.tw [National Research Institute of Chinese Medicine, Taipei 112, Taiwan, ROC (China); Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan, ROC (China); Institute of Medical Sciences, Taipei Medical University, Taipei 101, Taiwan, ROC (China)

    2013-11-01

    Cytochrome P450 (P450, CYP) 1 family plays a primary role in the detoxification and bioactivation of polycyclic aromatic hydrocarbons. Human CYP1A1, CYP1A2, and CYP1B1 exhibit differential substrate specificity and tissue distribution. Berberine, palmatine, and jatrorrhizine are protoberberine alkaloids present in several medicinal herbs, such as Coptis chinensis (Huang-Lian) and goldenseal. These protoberberines inhibited CYP1A1.1- and CYP1B1.1-catalyzed 7-ethoxyresorufin O-deethylation (EROD) activities, whereas CYP1A2.1 activity was barely affected. Kinetic analysis revealed that berberine noncompetitively inhibited EROD activities of CYP1A1.1 and CYP1B1.1, whereas palmatine and jatrorrhizine caused either competitive or mixed type of inhibition. Among protoberberines, berberine caused the most potent and selective inhibitory effect on CYP1B1.1 with the least K{sub i} value of 44 ± 16 nM. Berberine also potently inhibited CYP1B1.1 activities toward 7-ethoxycoumarin and 7-methoxyresorufin, whereas the inhibition of benzo(a)pyrene hydroxylation activity was less pronounced. Berberine inhibited the polymorphic variants, CYP1B1.3 (V432L) and CYP1B1.4 (N453S), with IC{sub 50} values comparable to that for CYP1B1.1 inhibition. Berberine-mediated inhibition was abolished by a mutation of Asn228 to Thr in CYP1B1.1, whereas the inhibition was enhanced by a reversal mutation of Thr223 to Asn in CYP1A2.1. This result in conjugation with the molecular modeling revealed the crucial role of hydrogen-bonding interaction of Asn228 on CYP1B1.1 with the methoxy moiety of berberine. These findings demonstrate that berberine causes a selective CYP1B1-inhibition, in which Asn228 appears to be crucial. The inhibitory effects of berberine on CYP1B1 activities toward structurally diverse substrates can be different. - Highlights: • Berberine preferentially inhibited CYP1B1 activity. • Berberine caused similar inhibitory effects on CYP1B1.1, CYP1B1.3 and CYP1B1.4. • Asn228 in CYP

  1. Potential Benefits of Berberine in the Management of Perimenopausal Syndrome

    Directory of Open Access Journals (Sweden)

    Cristiana Caliceti

    2015-01-01

    Full Text Available Cardiovascular diseases are one of the leading causes of morbidity and mortality in women after menopause and 56% of all causes of death in Western European countries. Nowadays, with increasing life span, women spend approximately one-third of their life-time in postmenopausal state; therefore, the development of new strategies to improve the prevention and treatment of menopause-associated pathologies is important topic in clinical practice. The studies to assess the safety of hormone replacement therapy in women with estrogen deficiency have not been conclusive due to the relative contraindications; therefore, hormone replacement therapy is prescribed only in selected cases and for a limited time. For this reason, today women are encouraged to use naturally available compounds to prevent or to attenuate menopausal symptoms and correlated pathologies, with fewer side effects. Among these compounds, berberine, an isoquinoline alkaloid derived from plants of the generis Berberis, has been recognized as being capable of decreasing oxidative stress, LDL, triglycerides, and insulin resistance and of improving the mood. This review describes the cellular and clinical effects associated with the use of berberine, which suggest that this molecule could be an effective natural supplement to ensure a smooth peri- and postmenopausal transition.

  2. Percutaneous penetration of 3H-Huangbai extracts and H3-berberine

    International Nuclear Information System (INIS)

    Jin Xipeng; Yu Xiaozhong; Zhang Nianbao; Kuang Jianwen

    1992-01-01

    The percutaneous penetration of 3 H-huangbai extracts and 3 H-berberine through excised guinea pig and human shins was studied using the static diffusion cell technique. The data were treated with mathematical model of skin absorption. The results showed that huangbai extracts and berberine could penetrate the guinea pig and human skins at (above) dose of 8.38 μg/cm 2 and 14.32 μg/cm 2 , respectively. The amount and rate of penetration increased linearly with the time of exposure and dose. The permeability of berberine through guinea pig and human skins in two vehicles (water and glycol) was lower than that of huangbai extracts. When Huangbai extracts and berberine were applied in glycol solution, the vehicle greatly enhanced the penetration of the two penetrant. The lag time of two penetrant through human skin was longer than that through guinea pig skin

  3. Percutaneous penetration of [sup 3]H-Huangbai extracts and H[sup 3]-berberine

    Energy Technology Data Exchange (ETDEWEB)

    Xipeng, Jin; Xiaozhong, Yu [School of Public Health, Shanghai Medical Univ. (China); Nianbao, Zhang; Jianwen, Kuang [Shanghai Inst. of Nuclear Research Acdemic Sinica (China)

    1992-02-01

    The percutaneous penetration of [sup 3]H-huangbai extracts and [sup 3]H-berberine through excised guinea pig and human shins was studied using the static diffusion cell technique. The data were treated with mathematical model of skin absorption. The results showed that huangbai extracts and berberine could penetrate the guinea pig and human skins at (above) dose of 8.38 [mu]g/cm[sup 2] and 14.32 [mu]g/cm[sup 2], respectively. The amount and rate of penetration increased linearly with the time of exposure and dose. The permeability of berberine through guinea pig and human skins in two vehicles (water and glycol) was lower than that of huangbai extracts. When Huangbai extracts and berberine were applied in glycol solution, the vehicle greatly enhanced the penetration of the two penetrant. The lag time of two penetrant through human skin was longer than that through guinea pig skin.

  4. Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson's disease.

    Science.gov (United States)

    Kim, Mia; Cho, Ki-Ho; Shin, Mal-Soon; Lee, Jae-Min; Cho, Han-Sam; Kim, Chang-Ju; Shin, Dong-Hoon; Yang, Hyeon Jeong

    2014-04-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of nigral dopaminergic neurons and a reduction in striatal dopaminergic fibers, which result in tremors, rigidity, bradykinesia and gait disturbance. In addition to motor dysfunction, dementia is a widely recognized symptom of patients with PD. Berberine, an isoquinoline alkaloid isolated from Berberis vulgaris L., is known to exert anxiolytic, analgesic, anti-inflammatory, antipsychotic, antidepressant and anti-amnesic effects. In the present study, we investigated the effects of berberine on short-term memory in relation to dopamine depletion and hippocampal neurogenesis using a mouse model of PD, induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P) treatment. Mice in the berberine-treated groups were orally administered berberine once a day for a total of 5 weeks. Our results revealed that the injection of MPTP/P induced dopaminergic neuronal death in the substantia nigra and fiber loss in the striatum. This resulted in impaired motor balance and coordination, as assessed by the beam walking test. We further demonstrated that MPTP/P-induced apoptosis in the hippocampus deteriorated short-term memory, as shown by the step-down avoidance task. By contrast, neurogenesis in the hippocampal dentate gyrus, which is a compensatory adaptive response to excessive apoptosis, was increased upon PD induction. However, treatment with berberine enhanced motor balance and coordination by preventing dopaminergic neuronal damage. Treatment with berberine also improved short-term memory by inhibiting apoptosis in the hippocampus. Berberine demonstrated maximal potency at 50 mg/kg. Based on these data, treatment with berberine may serve as a potential therapeutic strategy for the alleviation of memory impairment and motor dysfunction in patients with PD.

  5. Anti-Inflammatory Effects of Berberine Hydrochloride in an LPS-Induced Murine Model of Mastitis

    Directory of Open Access Journals (Sweden)

    Xichun Wang

    2018-01-01

    Full Text Available Berberine hydrochloride is an isoquinoline type alkaloid extracted from Berberidaceae, Rutaceae, and other plants. Previous reports have shown that berberine hydrochloride has anti-inflammatory properties. However, the underlying molecular mechanisms remain unclear. In this study, a lipopolysaccharide- (LPS- induced murine model of mastitis was established to explore the anti-inflammatory action of berberine hydrochloride. Sixty mice that had been lactating for 5–7 days were randomly divided into six groups, including control, LPS, three berberine hydrochloride treatment groups (5, 10, and 20 mg/kg, and a dexamethasone (DEX (5 mg/kg group. Berberine hydrochloride was administered intraperitoneally 1 h before and 12 h after LPS-induced mastitis, and all mice were sacrificed 24 h after LPS induction. The pathological and histopathological changes of the mammary glands were observed. The concentrations and mRNA expressions of TNF-α, IL-1β, and IL-6 were measured by ELISA and qRT-PCR. The activation of TLR4 and NF-κB signaling pathways was analyzed by Western blot. Results indicated that berberine hydrochloride significantly attenuated neutrophil infiltration and dose-dependently decreased the secretion and mRNA expressions of TNF-α, IL-1β, and IL-6 within a certain range. Furthermore, berberine hydrochloride suppressed LPS-induced TLR4 and NF-κB p65 activation and the phosphorylation of I-κB. Berberine hydrochloride can provide mice robust protection from LPS-induced mastitis, potentially via the TLR4 and NF-κB pathway.

  6. Anti-Inflammatory Effects of Berberine Hydrochloride in an LPS-Induced Murine Model of Mastitis

    Science.gov (United States)

    Feng, Shibin; Ding, Nana; He, Yanting; Li, Cheng; Li, Manman; Ding, Xuedong; Ding, Hongyan; Li, Jinchun

    2018-01-01

    Berberine hydrochloride is an isoquinoline type alkaloid extracted from Berberidaceae, Rutaceae, and other plants. Previous reports have shown that berberine hydrochloride has anti-inflammatory properties. However, the underlying molecular mechanisms remain unclear. In this study, a lipopolysaccharide- (LPS-) induced murine model of mastitis was established to explore the anti-inflammatory action of berberine hydrochloride. Sixty mice that had been lactating for 5–7 days were randomly divided into six groups, including control, LPS, three berberine hydrochloride treatment groups (5, 10, and 20 mg/kg), and a dexamethasone (DEX) (5 mg/kg) group. Berberine hydrochloride was administered intraperitoneally 1 h before and 12 h after LPS-induced mastitis, and all mice were sacrificed 24 h after LPS induction. The pathological and histopathological changes of the mammary glands were observed. The concentrations and mRNA expressions of TNF-α, IL-1β, and IL-6 were measured by ELISA and qRT-PCR. The activation of TLR4 and NF-κB signaling pathways was analyzed by Western blot. Results indicated that berberine hydrochloride significantly attenuated neutrophil infiltration and dose-dependently decreased the secretion and mRNA expressions of TNF-α, IL-1β, and IL-6 within a certain range. Furthermore, berberine hydrochloride suppressed LPS-induced TLR4 and NF-κB p65 activation and the phosphorylation of I-κB. Berberine hydrochloride can provide mice robust protection from LPS-induced mastitis, potentially via the TLR4 and NF-κB pathway.

  7. Berberine, a genotoxic alkaloid, induces ATM-Chk1 mediated G2 arrest in prostate cancer cells

    International Nuclear Information System (INIS)

    Wang Yu; Liu Qiao; Liu Zhaojian; Li Boxuan; Sun Zhaoliang; Zhou Haibin; Zhang Xiyu; Gong Yaoqin; Shao Changshun

    2012-01-01

    Berberine has been shown to possess anti-tumor activity against a wide spectrum of cancer cells. It inhibits cancer cell proliferation by inducing cell cycle arrest, at G1 and/or G2/M, and apoptosis. While it has been documented that berberine induces G1 arrest by activating the p53-p21 cascade, it remains unclear what mechanism underlies the berberine-induced G2/M arrest, which is p53-independent. In this study, we tested the anti-proliferative effect of berberine on murine prostate cancer cell line RM-1 and characterized the underlying mechanisms. Berberine dose-dependently induced DNA double-strand breaks and apoptosis. At low concentrations, berberine was observed to induce G1 arrest, concomitant with the activation of p53-p21 cascade. Upon exposure to berberine at a higher concentration (50 μM) for 24 h, cells exhibited G2/M arrest. Pharmacological inhibition of ATM by KU55933, or Chk1 by UCN-01, could efficiently abrogate the G2/M arrest in berberine-treated cells. Downregulation of Chk1 by RNA interference also abolished the G2/M arrest caused by berberine, confirming the role of Chk1 in the pathway leading to G2/M arrest. Abrogation of G2/M arrest by ATM inhibition forced more cells to undergo apoptosis in response to berberine treatment. Chk1 inhibition by UCN-01, on the other hand, rendered cells more sensitive to berberine only when p53 was inhibited. Our results suggest that combined administration of berberine and caffeine, or other ATM inhibitor, may accelerate the killing of cancer cells.

  8. Berberine, a genotoxic alkaloid, induces ATM-Chk1 mediated G2 arrest in prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yu; Liu Qiao; Liu Zhaojian; Li Boxuan; Sun Zhaoliang; Zhou Haibin; Zhang Xiyu; Gong Yaoqin [Ministry of Education Key Laboratory of Experimental Teratology and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan (China); Shao Changshun, E-mail: changshun.shao@gmail.com [Ministry of Education Key Laboratory of Experimental Teratology and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan (China)

    2012-06-01

    Berberine has been shown to possess anti-tumor activity against a wide spectrum of cancer cells. It inhibits cancer cell proliferation by inducing cell cycle arrest, at G1 and/or G2/M, and apoptosis. While it has been documented that berberine induces G1 arrest by activating the p53-p21 cascade, it remains unclear what mechanism underlies the berberine-induced G2/M arrest, which is p53-independent. In this study, we tested the anti-proliferative effect of berberine on murine prostate cancer cell line RM-1 and characterized the underlying mechanisms. Berberine dose-dependently induced DNA double-strand breaks and apoptosis. At low concentrations, berberine was observed to induce G1 arrest, concomitant with the activation of p53-p21 cascade. Upon exposure to berberine at a higher concentration (50 {mu}M) for 24 h, cells exhibited G2/M arrest. Pharmacological inhibition of ATM by KU55933, or Chk1 by UCN-01, could efficiently abrogate the G2/M arrest in berberine-treated cells. Downregulation of Chk1 by RNA interference also abolished the G2/M arrest caused by berberine, confirming the role of Chk1 in the pathway leading to G2/M arrest. Abrogation of G2/M arrest by ATM inhibition forced more cells to undergo apoptosis in response to berberine treatment. Chk1 inhibition by UCN-01, on the other hand, rendered cells more sensitive to berberine only when p53 was inhibited. Our results suggest that combined administration of berberine and caffeine, or other ATM inhibitor, may accelerate the killing of cancer cells.

  9. Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts

    International Nuclear Information System (INIS)

    Tsang, Chi Man; Cheung, Yuk Chun; Lui, Vivian Wai-Yan; Yip, Yim Ling; Zhang, Guitao; Lin, Victor Weitao; Cheung, Kenneth Chat-Pan; Feng, Yibin; Tsao, Sai Wah

    2013-01-01

    Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC

  10. Railroad Bridges

    Data.gov (United States)

    Department of Homeland Security — Bridges-Rail in the United States According to The National Bridge Inspection Standards published in the Code of Federal Regulations (23 CFR 650.3), a bridge isA...

  11. Berberine Enhances the Antibacterial Activity of Selected Antibiotics against Coagulase-Negative Staphylococcus Strains in Vitro

    Directory of Open Access Journals (Sweden)

    Robert D. Wojtyczka

    2014-05-01

    Full Text Available Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

  12. Metformin and berberine prevent olanzapine-induced weight gain in rats.

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    Yueshan Hu

    Full Text Available Olanzapine is a first line medication for the treatment of schizophrenia, but it is also one of the atypical antipsychotics carrying the highest risk of weight gain. Metformin was reported to produce significant attenuation of antipsychotic-induced weight gain in patients, while the study of preventing olanzapine-induced weight gain in an animal model is absent. Berberine, an herbal alkaloid, was shown in our previous studies to prevent fat accumulation in vitro and in vivo. Utilizing a well-replicated rat model of olanzapine-induced weight gain, here we demonstrated that two weeks of metformin or berberine treatment significantly prevented the olanzapine-induced weight gain and white fat accumulation. Neither metformin nor berberine treatment demonstrated a significant inhibition of olanzapine-increased food intake. But interestingly, a significant loss of brown adipose tissue caused by olanzapine treatment was prevented by the addition of metformin or berberine. Our gene expression analysis also demonstrated that the weight gain prevention efficacy of metformin or berberine treatment was associated with changes in the expression of multiple key genes controlling energy expenditure. This study not only demonstrates a significant preventive efficacy of metformin and berberine treatment on olanzapine-induced weight gain in rats, but also suggests a potential mechanism of action for preventing olanzapine-reduced energy expenditure.

  13. Berberine enhances the antibacterial activity of selected antibiotics against coagulase-negative Staphylococcus strains in vitro.

    Science.gov (United States)

    Wojtyczka, Robert D; Dziedzic, Arkadiusz; Kępa, Małgorzata; Kubina, Robert; Kabała-Dzik, Agata; Mularz, Tomasz; Idzik, Danuta

    2014-05-22

    Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC) of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

  14. Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide

    International Nuclear Information System (INIS)

    Lin, Tseng-Hsi; Kuo, Hsing-Chun; Chou, Fen-Pi; Lu, Fung-Jou

    2008-01-01

    Arsenic trioxide (As 2 O 3 ) exhibits promising anticarcinogenic activity in acute promyelocytic leukemic patients and induces apoptosis in various tumor cells in vitro. Here, we investigated the effect of the natural alkaloid berberine on As 2 O 3 -mediated inhibition of cancer cell migration using rat and human glioma cell lines. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the viability of rat C6 and human U-87 glioma cells after treatment with As 2 O 3 or berberine, and after co-treatment with As 2 O 3 and berberine. The wound scratch and Boyden chamber assays were applied to determine the effect of As 2 O 3 and berberine on the migration capacity and invasiveness of glioma cancer cells. Zymography and Western blot analyses provided information on the effect of As 2 O 3 and berberine on the intracellular translocation and activation of protein kinase C (PKC), and some PKC-related downstream factors. Most assays were performed three times, independently, and data were analyzed using ANOVA. The cell viability studies demonstrated that berberine enhances As 2 O 3 -mediated inhibition of glioma cell growth after 24 h incubation. Untreated control cells formed a confluent layer, the formation of which was inhibited upon incubation with 5 μM As 2 O 3 . The latter effect was even more pronounced in the presence of 10 μM berberine. The As 2 O 3 -mediated reduction in motility and invasion of glioma cells was enhanced upon co-treatment with berberine. Furthermore, it has been reported that PKC isoforms influence the morphology of the actin cytoskeleton, as well as the activation of metalloproteases MT1-MMP and MMP-2, reported to be involved in cancer cell migration. Treatment of glioma cells with As 2 O 3 and berberine significantly decreased the activation of PKC α and ε and led to actin cytoskeleton rearrangements. The levels of two downstream transcription factors, myc and jun, and MT1-MMP and MMP-2 were also

  15. Antimicrobial activity of berberine--a constituent of Mahonia aquifolium.

    Science.gov (United States)

    Cernáková, M; Kostálová, D

    2002-01-01

    The antimicrobial activity of the protoberberine alkaloid, berberine, isolated from Mahonia aquifolium, was evaluated against 17 microorganisms including two Gram-negative bacteria--Pseudomonas aeruginosa and Escherichia coli (both resistant and sensitive), two Gram-positive bacteria--Bacillus subtilis and Staphylococcus aureus, Zoogloea ramigera, six filamentous fungi--Penicilium chrysogenum, Aspergillus niger, Aureobasidium pullulans (black and white strain), Trichoderma viride (original green strain and brown mutant), Fusarium nivale, Mycrosporum gypseum and two yeasts--Candida albicans and Saccharomyces cerevisiae. The IC50, minimum inhibitory concentration (MIC), minimum microbicidal concentration (MMC) and minimum microbistatic concentration (MMS) varied considerably depending on the microorganism tested, the sensitivity decreasing as follows: S. aureus > P. aeruginosa S (sensitive) > E. coli S > P. aeruginosa R (resistant) > E. coli R > B. subtilis > Z. ramigera > C. albicans > S. cerevisiae > A. pullulans B (black) > A. pullulans W (white) > T. viride Br (brown) > M. gypseum > A. niger > F. nivale > P. chrysogenum > T. viride G (green).

  16. Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis.

    Science.gov (United States)

    Wang, Zhigang; Chen, Zhe; Chen, Tao; Yi, Tao; Zheng, Zhou; Fan, Hong; Chen, Zebin

    2017-02-01

    Berberine, one of the active alkaloids from Rhizoma Coptidis, has been indicated to have anti-inflammatory and immunosuppressive properties. The aim of this study was to determine the role of berberine on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) and its potential mechanisms. Berberine treatment significantly reduced footpad swelling, inflammatory cells infiltration, anti-OVA IgG levels, IgE concentration in serum, and the tetramer + CD8 + cells. In homogenized footpad tissue, the production of Th1-mediated cytokines including IFN-γ, TNF-α, and IL-2 were suppressed following the administration of berberine. Detailed studies revealed that berberine prevented differentiation into Th1 cells in the OVA-primed lymphocytes, resulting from suppressing the expression of T-bet and secretion of IFN-γ but not IL-4. Concanavalin A stimulation assay and MTT assay also indicated inhibiting effect of berberine treatment on IFN-γ production and decreased cytotoxicity in lymphocytes proliferation, respectively. Additionally, berberine obviously decreased the cell apoptosis and enzymatic activity of caspase-3, which was further confirmed by the facts that berberine clearly lowered Bax/Bcl-2 ratio and expression of cleaved caspase-3 protein. On correlation analysis, the percentage of apoptotic cells showed a significant positive relationship with IFN-γ/IL-4 ratio of supernatant from footpad tissue in berberine-treated DTH mice. These results demonstrated that berberine attenuated Th1-mediated inflammation in OVA-induced DTH by curbing Th1 response and inhibiting cell apoptosis, suggesting a therapeutic potential for berberine for the treatment of type IV hypersensitivity.

  17. Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

    International Nuclear Information System (INIS)

    Li Guanghui; Zhang Yaping; Tang Jinliang; Chen Zhengtang; Hu Yide; Wei Hong; Li Dezhi; Hao Ping; Wang Donglin

    2010-01-01

    Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-α, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-α, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

  18. Pharmacokinetic Comparison of Berberine in Rat Plasma after Oral Administration of Berberine Hydrochloride in Normal and Post Inflammation Irritable Bowel Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Zipeng Gong

    2014-01-01

    Full Text Available In the present study, post inflammation irritable bowel syndrome (PI-IBS rats were firstly established by intracolonic instillation of acetic acid with restraint stress. Then the pharmacokinetics of berberine in the rat plasma were compared after oral administration of berberine hydrochloride (25 mg/kg to normal rats and PI-IBS rats. Quantification of berberine in the rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. Compared with the normal group, area under the plasma concentration vs. time curve from zero to last sampling time (AUC0–t and total body clearance (CL/F in the model group significantly increased or decreased, (2039.49 ± 492.24 vs. 2763.43 ± 203.14; 4999.34 ± 1198.79 vs. 3270.57 ± 58.32 respectively. The results indicated that the pharmacokinetic process of berberine could be altered in PI-IBS pathological conditions.

  19. Investigation on intermolecular interaction between berberine and β-cyclodextrin by 2D UV-Vis asynchronous spectra.

    Science.gov (United States)

    He, Anqi; Kang, Xiaoyan; Xu, Yizhuang; Noda, Isao; Ozaki, Yukihiro; Wu, Jinguang

    2017-10-05

    The interaction between berberine chloride and β-cyclodextrin (β-CyD) is investigated via 2D asynchronous UV-Vis spectrum. The occurrence of cross peaks around (420nm, 420nm) in 2D asynchronous spectrum reveals that specific intermolecular interaction indeed exists between berberine chloride and β-CyD. In spite of the difficulty caused by overlapping of cross peaks, we manage to confirm that the 420nm band of berberine undergoes a red-shift, and its bandwidth decreases under the interaction with β-CyD. The red-shift of the 420nm band that can be assigned to n-π* transition indicates the environment of berberine becomes more hydrophobic. The above spectral behavior is helpful in understanding why the solubility of berberine is enhanced by β-CyD. Copyright © 2017. Published by Elsevier B.V.

  20. Berberine-induced pigment dispersion in Bufo melanostictus melanophores by stimulation of beta-2 adrenergic receptors.

    Science.gov (United States)

    Ali, Sharique A; Naaz, Ishrat; Choudhary, Ram Kumar

    2014-02-01

    Reduced production of melanin by decreased or the absence of melanocytes leads to various hypopigmentation disorders, and the development of melanogenetic agents for photoprotection and hypopigmentation disorders is one of the top priority areas of research. Hence, the present study was carried out to elucidate the ability of berberine, a principal active ingredient present in the roots of the herb Berberis vulgaris to stimulate pigment dispersion in the isolated skin melanophores of the toad Bufo melanostictus. In the present study, mean melanophore size index of the isolated skin melanophores of B. melanostictus was assayed after treating with various concentrations of berberine. A marked melanin dispersion response leading to skin darkening was observed in the isolated melanophores of toad in response to berberine, which was found to be mediated through beta-2 adrenergic receptors. The physiologically significant dose-related melanin dispersion effects of berberine per se were found to be completely abolished by propranolol, which is a specific beta-2 adrenergic receptor blocker. These per se melanin dispersal effects were also found to be markedly potentiated by isoprenaline, which is a specific beta-adrenoceptor agonist. The results indicate that berberine causes a tremendous, dose-dependent, physiologically significant pigment dispersing in the isolated skin melanophores of B. melanostictus.

  1. Binding of the 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs to tRNA(phe..

    Directory of Open Access Journals (Sweden)

    Anirban Basu

    Full Text Available BACKGROUND: Three new analogs of berberine with aryl/ arylalkyl amino carbonyl methyl substituent at the 9-position of the isoquinoline chromophore along with berberrubine were studied for their binding to tRNA(phe by wide variety of biophysical techniques like spectrophotometry, spectrofluorimetry, circular dichroism, thermal melting, viscosity and isothermal titration calorimetry. METHODOLOGY/ PRINCIPAL FINDINGS: Scatchard binding isotherms revealed that the cooperative binding mode of berberine was propagated in the analogs also. Thermal melting studies showed that all the 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs stabilized the tRNA(phe more in comparison to berberine. Circular dichroism studies showed that these analogs perturbed the structure of tRNA(phe more in comparison to berberine. Ferrocyanide quenching studies and viscosity results proved the intercalative binding mode of these analogs into the helical organization of tRNA(phe. The binding was entropy driven for the analogs in sharp contrast to the enthalpy driven binding of berberine. The introduction of the aryl/arylalkyl amino carbonyl methyl substituent at the 9-position thus switched the enthalpy driven binding of berberine to entropy dominated binding. Salt and temperature dependent calorimetric studies established the involvement of multiple weak noncovalent interactions in the binding process. CONCLUSIONS/ SIGNIFICANCE: The results showed that 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs exhibited almost ten folds higher binding affinity to tRNA(phe compared to berberine whereas the binding of berberrubine was dramatically reduced by about twenty fold in comparison to berberine. The spacer length of the substitution at the 9-position of the isoquinoline chromophore appears to be critical in modulating the binding affinities towards tRNA(phe.

  2. Bridging Anticoagulation

    Science.gov (United States)

    ... clinical centers in the United States, Canada, and Brazil. A more detailed description of the study is ... Your Personal Message Send Message Share on Social Media Bridging Anticoagulation The BRIDGE Study Investigators Circulation. 2012; ...

  3. Berberine as a promising safe anti-cancer agent - is there a role for mitochondria?

    Science.gov (United States)

    Diogo, Catia V; Machado, Nuno G; Barbosa, Inês A; Serafim, Teresa L; Burgeiro, Ana; Oliveira, Paulo J

    2011-06-01

    Metabolic regulation is largely dependent on mitochondria, which play an important role in energy homeostasis. Imbalance between energy intake and expenditure leads to mitochondrial dysfunction, characterized by a reduced ratio of energy production (ATP production) to respiration. Due to the role of mitochondrial factors/events in several apoptotic pathways, the possibility of targeting that organelle in the tumor cell, leading to its elimination is very attractive, although the safety issue is problematic. Berberine, a benzyl-tetra isoquinoline alkaloid extracted from plants of the Berberidaceae family, has been extensively used for many centuries, especially in the traditional Chinese and Native American medicine. Several evidences suggest that berberine possesses several therapeutic uses, including anti-tumoral activity. The present review supplies evidence that berberine is a safe anti-cancer agent, exerting several effects on mitochondria, including inhibition of mitochondrial Complex I and interaction with the adenine nucleotide translocator which can explain several of the described effects on tumor cells.

  4. Berberine as a chemical and pharmacokinetic marker of the butanol-extracted Food Allergy Herbal Formula-2.

    Science.gov (United States)

    Yang, Nan; Srivastava, Kamal; Song, Ying; Liu, Changda; Cho, Sool; Chen, Yujuan; Li, Xiu-Min

    2017-04-01

    Food Allergy Herbal Formula-2 (FAHF-2) provided protection against peanut anaphylaxis in a murine model and induced beneficial immune-modulation in humans. Butanol-refined FAHF-2, B-FAHF-2, retained safety and efficacy in the peanut allergic murine model at only 1/5 of FAHF-2 dosage. One compound, berberine, was isolated and identified in vitro as a bioactive component present in FAHF-2 and B-FAHF-2. The aim of this study was to investigate berberine as a chemical and pharmacokinetic marker of B-FAHF-2. The consistency of constituents between B-FAHF-2 and FAHF-2 was tested. Peanut allergic C3H/HeJ mice were orally administered with 1mg of berberine or B-FAHF-2 containing an equivalent amount of berberine, and the ability to protect against peanut anaphylaxis and pharmacokinetic parameters were determined. Human intestinal epithelial cells (Caco-2) were cultured with berberine with or without the nine individual herbal constituents in B-FAHF-2, and the absorbed berberine levels were determined. Berberine is one of the major components in B-FAHF-2 and FAHF-2 formula. In a peanut allergic mouse model, B-FAHF-2, but not berberine, protected mice from anaphylaxis reactions. Pharmacokinetic profiles showed that the C max of B-FAHF-2 fed mice was 289.30±185.40ng/mL; whereas berberine alone showed very low bioavailability with C max value of 35.13±47.90ng/mL. Caco-2 cells influx assay showed that 7 of 9 herbal constituents in B-FAHF-2 increased berberine absorption at rates ranging from 18 to 205%. B-FAHF-2 remarkably increased the bioavailability of berberine. Berberine can be used as chemical and pharmacokinetic marker of B-FAHF-2. Other herbal components in B-FAHF-2 may facilitate the absorption of berberine. Copyright © 2017. Published by Elsevier B.V.

  5. Digital gene expression analysis of Microsporum canis exposed to berberine chloride.

    Directory of Open Access Journals (Sweden)

    Chen-Wen Xiao

    Full Text Available Berberine, a natural isoquinoline alkaloid of many medicinal herbs, has an active function against a variety of microbial infections including Microsporum canis (M. canis. However, the underlying mechanisms are poorly understood. To study the effect of berberine chloride on M. canis infection, a Digital Gene Expression (DGE tag profiling was constructed and a transcriptome analysis of the M. canis cellular responses upon berberine treatment was performed. Illumina/Hisseq sequencing technique was used to generate the data of gene expression profile, and the following enrichment analysis of Gene Ontology (GO and Pathway function were conducted based on the data of transcriptome. The results of DGE showed that there were 8476945, 14256722, 7708575, 5669955, 6565513 and 9303468 tags respectively, which was obtained from M. canis incubated with berberine or control DMSO. 8,783 genes were totally mapped, and 1,890 genes have shown significant changes between the two groups. 1,030 genes were up-regulated and 860 genes were down-regulated (P<0.05 in berberine treated group compared to the control group. Besides, twenty-three GO terms were identified by Gene Ontology functional enrichment analysis, such as calcium-transporting ATPase activity, 2-oxoglutarate metabolic process, valine catabolic process, peroxisome and unfolded protein binding. Pathway significant enrichment analysis indicated 6 signaling pathways that are significant, including steroid biosynthesis, steroid hormone biosynthesis, Parkinson's disease, 2,4-Dichlorobenzoate degradation, and tropane, piperidine and Isoquinoline alkaloid biosynthesis. Among these, eleven selected genes were further verified by qRT-PCR. Our findings provide a comprehensive view on the gene expression profile of M. canis upon berberine treatment, and shed light on its complicated effects on M. canis.

  6. Protoscolecidal Effect of Berberis vulgaris Root Extract and Its Main Compound, Berberine in Cystic Echinococcosis.

    Directory of Open Access Journals (Sweden)

    Hossein Mahmoudvand

    2014-12-01

    Full Text Available Cystic echinococcosis (CE, a zoonotic parasitic infection caused by the metacestode (larvae stage of dog tapeworm Echinococcus granulosus and recognized as a major economic and public health concern in the world. This study aimed to investigate the in vitro scolicidal effect of methanolic extract of Berberis vulgaris L. roots and its main compound, berberine against protoscoleces of hydatid cysts.For this purpose, protoscoleces were aseptically aspirated from sheep livers having hydatid cysts. Various concentrations of the methanolic extract (0.25-2 mg/ml and berberine (0.062- 0.5 mg/ml were used for 5 to 30 min. Viability of protoscoleces was confirmed by eosin exclusive test.In the present study, all of the various concentrations of the B. vulgaris methanolic extract (0.25, 0.5, 1 and 2 mg/ml and berberine (0.062, 0.125, 0.25 and 0.5 mg/ml revealed significant (P<0.05 scolicidal effects against protoscoleces of E. granulosus in a dose-dependent manner. Both berberine and methanolic extract exhibited 100% inhibition against protoscoleces of E. granulosus at the concentration of 2.0 and 0.5 mg/ml after 10 min incubation, respectively.According to the results, both B. vulgaris methanolic extract and berberine alone demonstrated high scolicidal activities against protoscoleces of hydatid cysts in low concentration and short exposure time on in vitro model. However, in vivo efficacy of B. vulgaris and berberine also requires to be evaluated using an animal model with hydatid infection.

  7. Berberine slows cell growth in autosomal dominant polycystic kidney disease cells

    International Nuclear Information System (INIS)

    Bonon, Anna; Mangolini, Alessandra; Pinton, Paolo; Senno, Laura del; Aguiari, Gianluca

    2013-01-01

    Highlights: •Berberine at appropriate doses slows cell proliferation in ADPKD cystic cells. •Reduction of cell growth by berberine occurs by inhibition of ERK and p70-S6 kinase. •Higher doses of berberine cause an overall cytotoxic effect. •Berberine overdose induces apoptotic bodies formation and DNA fragmentation. •Antiproliferative properties of this drug make it a new candidate for ADPKD therapy. -- Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary monogenic disorder characterized by development and enlargement of kidney cysts that lead to loss of renal function. It is caused by mutations in two genes (PKD1 and PKD2) encoding for polycystin-1 and polycystin-2 proteins which regulate different signals including cAMP, mTOR and EGFR pathways. Abnormal activation of these signals following PC1 or PC2 loss of function causes an increased cell proliferation which is a typical hallmark of this disease. Despite the promising findings obtained in animal models with targeted inhibitors able to reduce cystic cell growth, currently, no specific approved therapy for ADPKD is available. Therefore, the research of new more effective molecules could be crucial for the treatment of this severe pathology. In this regard, we have studied the effect of berberine, an isoquinoline quaternary alkaloid, on cell proliferation and apoptosis in human and mouse ADPKD cystic cell lines. Berberine treatment slows cell proliferation of ADPKD cystic cells in a dose-dependent manner and at high doses (100 μg/mL) it induces cell death in cystic cells as well as in normal kidney tubule cells. However, at 10 μg/mL, berberine reduces cell growth in ADPKD cystic cells only enhancing G 0 /G 1 phase of cell cycle and inhibiting ERK and p70-S6 kinases. Our results indicate that berberine shows a selected antiproliferative activity in cellular models for ADPKD, suggesting that this molecule and similar natural compounds could open new opportunities

  8. Berberine slows cell growth in autosomal dominant polycystic kidney disease cells

    Energy Technology Data Exchange (ETDEWEB)

    Bonon, Anna; Mangolini, Alessandra [Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara (Italy); Pinton, Paolo [Department of Morphology, Surgery and Experimental Medicine, Section of General Pathology, University of Ferrara, 44121 Ferrara (Italy); Senno, Laura del [Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara (Italy); Aguiari, Gianluca, E-mail: dsn@unife.it [Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara (Italy)

    2013-11-22

    Highlights: •Berberine at appropriate doses slows cell proliferation in ADPKD cystic cells. •Reduction of cell growth by berberine occurs by inhibition of ERK and p70-S6 kinase. •Higher doses of berberine cause an overall cytotoxic effect. •Berberine overdose induces apoptotic bodies formation and DNA fragmentation. •Antiproliferative properties of this drug make it a new candidate for ADPKD therapy. -- Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary monogenic disorder characterized by development and enlargement of kidney cysts that lead to loss of renal function. It is caused by mutations in two genes (PKD1 and PKD2) encoding for polycystin-1 and polycystin-2 proteins which regulate different signals including cAMP, mTOR and EGFR pathways. Abnormal activation of these signals following PC1 or PC2 loss of function causes an increased cell proliferation which is a typical hallmark of this disease. Despite the promising findings obtained in animal models with targeted inhibitors able to reduce cystic cell growth, currently, no specific approved therapy for ADPKD is available. Therefore, the research of new more effective molecules could be crucial for the treatment of this severe pathology. In this regard, we have studied the effect of berberine, an isoquinoline quaternary alkaloid, on cell proliferation and apoptosis in human and mouse ADPKD cystic cell lines. Berberine treatment slows cell proliferation of ADPKD cystic cells in a dose-dependent manner and at high doses (100 μg/mL) it induces cell death in cystic cells as well as in normal kidney tubule cells. However, at 10 μg/mL, berberine reduces cell growth in ADPKD cystic cells only enhancing G{sub 0}/G{sub 1} phase of cell cycle and inhibiting ERK and p70-S6 kinases. Our results indicate that berberine shows a selected antiproliferative activity in cellular models for ADPKD, suggesting that this molecule and similar natural compounds could open new

  9. [Adsorption characteristics of proteins on membrane surface and effect of protein solution environment on permeation behavior of berberine].

    Science.gov (United States)

    Li, Yi-Qun; Xu, Li; Zhu, Hua-Xu; Tang, Zhi-Shu; Li, Bo; Pan, Yong-Lan; Yao, Wei-Wei; Fu, Ting-Ming; Guo, Li-Wei

    2017-10-01

    In order to explore the adsorption characteristics of proteins on the membrane surface and the effect of protein solution environment on the permeation behavior of berberine, berberine and proteins were used as the research object to prepare simulated solution. Low field NMR, static adsorption experiment and membrane separation experiment were used to study the interaction between the proteins and ceramic membrane or between the proteins and berberine. The static adsorption capacity of proteins, membrane relative flux, rejection rate of proteins, transmittance rate of berberine and the adsorption rate of proteins and berberine were used as the evaluation index. Meanwhile, the membrane resistance distribution, the particle size distribution and the scanning electron microscope (SEM) were determined to investigate the adsorption characteristics of proteins on ceramic membrane and the effect on membrane separation process of berberine. The results showed that the ceramic membrane could adsorb the proteins and the adsorption model was consistent with Langmuir adsorption model. In simulating the membrane separation process, proteins were the main factor to cause membrane fouling. However, when the concentration of proteins was 1 g•L⁻¹, the proteins had no significant effect on membrane separation process of berberine. Copyright© by the Chinese Pharmaceutical Association.

  10. In Vitro Inhibitory Effect of Berberis vulgaris (Berberidaceae) and Its Main Component, Berberine against Different Leishmania Species.

    Science.gov (United States)

    Mahmoudvand, Hossein; Sharififar, Fariba; Sharifi, Iraj; Ezatpour, Behrouz; Fasihi Harandi, Majid; Makki, Mahsa Sadat; Zia-Ali, Naser; Jahanbakhsh, Sareh

    2014-03-01

    Leishmaniasis has been identified as a major public health problem in tropical and sub-tropical countries. The present study was aimed to investigate antileishmanial effects of various extracts of Berberis vulgaris also its active compoenent, berberine against Leishmania tropica and L. infantum species on in vitro experiments. In this study in vitro antileishmanial activity of various extracts of B. vulgaris also its active compoenent, berberine against promastigote and amastigote stages of L. tropica and L. infantum was evaluated, using MTT assay and in a macrophage model, respectively. Furthermore, infectivity rate and cytotoxicity effects of B. vulgaris and berberine in murine macrophage cells were investigated. The findings of optical density (OD) and IC50 indicated that B. vulgaris particulary berberine significantly (P<0.05) inhibited the growth rate of promastigote stage of L.tropica and L.infantum in comparison to meglumine antimoniate (MA). In addition, B. vulgaris and berberine significantly (P<0.05) decreased the mean number of amastigotes in each macrophage as compared with positive control. In the evaluation of cytotoxicity effects, it could be observed that berberine as compared with B. vulgaris exhibited more cytotoxicity against murine macrophages. Results also showed that when parasites were pre-incubated with B. vulgaris their ability to infect murine macrophages was significantly decreased. B.vulgaris particularly berberine exhibited potent in vitro leishmanicidal effects against L. tropica and L.infantum. Further works are required to evaluate the antileishmanial effects of B.vulgaris on Leishmania species using clinical settings.

  11. Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines.

    Science.gov (United States)

    Park, S H; Sung, J H; Kim, E J; Chung, N

    2015-02-01

    Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.

  12. Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines

    International Nuclear Information System (INIS)

    Park, S.H.; Sung, J.H.; Kim, E.J.; Chung, N.

    2014-01-01

    Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC 50 ), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy

  13. Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

    International Nuclear Information System (INIS)

    Choi, You-Jin; Lee, Kang-Yo; Jung, Seung-Hwan; Kim, Hyung Sik; Shim, Gayong; Kim, Mi-Gyeong; Oh, Yu-Kyoung; Oh, Seon-Hee; Jun, Dae Won; Lee, Byung-Hoon

    2017-01-01

    Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation. Activation of AMPK by berberine or transduction with adenoviral vectors encoding constitutively active AMPK in HepG2 and mouse primary hepatocytes increased the expression and membrane translocation of CD36, resulting in enhanced fatty acid uptake and lipid accumulation as determined by BODIPY-C16 and Nile red fluorescence, respectively. Activation of AMPK by berberine induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and subsequently induced CCAAT/enhancer-binding protein β (C/EBPβ) binding to the C/EBP-response element in the CD36 promoter in hepatocytes. In addition, hepatic CD36 expression and triglyceride levels were increased in normal diet-fed mice treated with berberine, but completely prevented when hepatic CD36 was silenced with adenovirus containing CD36-specific shRNA. Taken together, prolonged activation of AMPK by berberine increased CD36 expression in hepatocytes, resulting in fatty acid uptake via processes linked to hepatocellular lipid accumulation and fatty liver. - Highlights: • Berberine increases the expression and membrane translocation of CD36 in hepatocytes. • The increase of CD36 results in enhanced fatty acid uptake and lipid accumulation. • Berberine-induced fatty liver is mediated by AMPK-ERK-C/EBPβ pathway. • CD36-specific shRNA inhibited berberine-induced lipid accumulation in liver.

  14. Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, You-Jin; Lee, Kang-Yo; Jung, Seung-Hwan [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Hyung Sik [School of Pharmacy, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Shim, Gayong; Kim, Mi-Gyeong; Oh, Yu-Kyoung [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Oh, Seon-Hee [The Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju 501-759 (Korea, Republic of); Jun, Dae Won [Internal Medicine, Hanyang University School of Medicine, Seoul 133-791 (Korea, Republic of); Lee, Byung-Hoon, E-mail: lee@snu.ac.kr [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2017-02-01

    Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation. Activation of AMPK by berberine or transduction with adenoviral vectors encoding constitutively active AMPK in HepG2 and mouse primary hepatocytes increased the expression and membrane translocation of CD36, resulting in enhanced fatty acid uptake and lipid accumulation as determined by BODIPY-C16 and Nile red fluorescence, respectively. Activation of AMPK by berberine induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and subsequently induced CCAAT/enhancer-binding protein β (C/EBPβ) binding to the C/EBP-response element in the CD36 promoter in hepatocytes. In addition, hepatic CD36 expression and triglyceride levels were increased in normal diet-fed mice treated with berberine, but completely prevented when hepatic CD36 was silenced with adenovirus containing CD36-specific shRNA. Taken together, prolonged activation of AMPK by berberine increased CD36 expression in hepatocytes, resulting in fatty acid uptake via processes linked to hepatocellular lipid accumulation and fatty liver. - Highlights: • Berberine increases the expression and membrane translocation of CD36 in hepatocytes. • The increase of CD36 results in enhanced fatty acid uptake and lipid accumulation. • Berberine-induced fatty liver is mediated by AMPK-ERK-C/EBPβ pathway. • CD36-specific shRNA inhibited berberine-induced lipid accumulation in liver.

  15. Berberine blocks the relapse of Clostridium difficile infection in C57BL/6 mice after standard vancomycin treatment.

    Science.gov (United States)

    Lv, Zhi; Peng, Guoli; Liu, Weihua; Xu, Hufeng; Su, JianRong

    2015-07-01

    Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Dual-Targeting of AR and Akt Pathways by Berberine in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2014-08-01

    underlying the downregulation of full-length and splice variants of AR by the phytochemical berberine (BBR). We concluded that BBR inhibits the...46-54. [34] Narizhneva NV, Tararova ND, Ryabokon P, Shy- shynova I, Prokvolit A, Komarov PG, Purmal AA, Gudkov AV, Gurova KV. Small molecule screen

  17. Delayed luminescence to monitor programmed cell death induced by berberine on thyroid cancer cells

    Science.gov (United States)

    Scordino, Agata; Campisi, Agata; Grasso, Rosaria; Bonfanti, Roberta; Gulino, Marisa; Iauk, Liliana; Parenti, Rosalba; Musumeci, Francesco

    2014-11-01

    Correlation between apoptosis and UVA-induced ultraweak photon emission delayed luminescence (DL) from tumor thyroid cell lines was investigated. In particular, the effects of berberine, an alkaloid that has been reported to have anticancer activities, on two cancer cell lines were studied. The FTC-133 and 8305C cell lines, as representative of follicular and anaplastic thyroid human cancer, respectively, were chosen. The results show that berberine is able to arrest cell cycle and activate apoptotic pathway as shown in both cell lines by deoxyribonucleic acid fragmentation, caspase-3 cleavage, p53 and p27 protein overexpression. In parallel, changes in DL spectral components after berberine treatment support the hypothesis that DL from human cells originates mainly from mitochondria, since berberine acts especially at the mitochondrial level. The decrease of DL blue component for both cell lines could be related to the decrease of intra-mitochondrial nicotinamide adenine dinucleotide and may be a hallmark of induced apoptosis. In contrast, the response in the red spectral range is different for the two cell lines and may be ascribed to a different iron homeostasis.

  18. Myocardial Bridging

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan

    2016-02-01

    Full Text Available Abstract Myocardial bridging is rare. Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. The anatomic features of the bridges vary significantly. Alterations of the endothelial morphology and the vasoactive agents impact on the progression of atherosclerosis of myocardial bridging. Patients may present with chest pain, myocardial infarction, arrhythmia and even sudden death. Patients who respond poorly to the medical treatment with β-blockers warrant a surgical intervention. Myotomy is a preferred surgical procedure for the symptomatic patients. Coronary stent deployment has been in limited use due to the unsatisfactory long-term results.

  19. The Ameliorating Effect of Berberine-Rich Fraction against Gossypol-Induced Testicular Inflammation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Samar R. Saleh

    2018-01-01

    Full Text Available This study was aimed at evaluating the efficacy of berberine-rich fraction (BF as a protective and/or a therapeutic agent against inflammation and oxidative stress during male infertility. Sexually mature Sprague-Dawley male rats were divided into five groups treated with either corn oil, BF (100 mg/kg BW, orally, daily for 30 days, gossypol acetate (5 mg/kg BW, i.p. eight times for 16 days, BF alone for 14 days then coadministered with gossypol acetate for the next 16 days (protected group, or gossypol acetate for 16 days then treated with BF for 30 days (treated group. All animals completed the experimental period (46 days without obtaining any treatments in the gap period. Sperm parameters, oxidative index, and inflammatory markers were measured. Gossypol injection significantly decreased the semen quality and testosterone level that resulted from the elevation of testicular reactive oxygen and nitrogen species (TBARS and NO, TNF-α, TNF-α-converting enzyme, and interleukins (IL-1β, IL-6, and IL-18 by 230, 180, 12.5, 97.9, and 300%, respectively, while interleukin-12 and tissue inhibitors of metalloproteinases-3 were significantly decreased by 59 and 66%, respectively. BF (protected and treated groups significantly improved the semen quality, oxidative stress, and inflammation associated with male infertility. It is suitable to use more advanced studies to validate these findings.

  20. Berberine ameliorates collagen-induced arthritis in rats by suppressing Th17 cell responses via inducing cortistatin in the gut.

    Science.gov (United States)

    Yue, Mengfan; Xia, Yufeng; Shi, Can; Guan, Chunge; Li, Yunfan; Liu, Rui; Wei, Zhifeng; Dai, Yue

    2017-09-01

    Berberine, an isoquinoline alkaloid, has been reported to ameliorate various autoimmune diseases including rheumatoid arthritis by oral administration. However, its mechanism remains mysterious due to an extremely low bioavailability. The fact that berberine readily accumulates in the gut, the largest endocrine organ in the body, attracted us to explore its anti-arthritic mechanism in view of the induction of intestinal immunosuppressive neuropeptides. In this study, berberine (200 mg·kg -1 , i.g.) was shown to ameliorate collagen-induced arthritis in rats, which was manifested by the reduction of clinical signs and joint destruction, as well as marked down-regulation of Th17 cell frequency and interleukin-17 level in blood. In contrast, an intravenous injection of berberine failed to affect arthritis in rats, implying that its anti-arthritic effect was gut-dependent. Further studies revealed that oral berberine selectively elevated the levels of cortistatin, of five gut-derived neuropeptides tested, in the intestines and sera of arthrititic rats. Antagonists of ghrelin/growth hormone secretagogue receptor 1 (a subtype of cortistatin receptor) almost completely abolished the ameliorative effect of berberine on arthritis and Th17 cell responses in rats. In vitro, berberine showed a moderate ability to promote the expression of cortistatin in nerve cells, which was strengthened when the nerve cells were cocultured with enteroendocrine cells to induce an autocrine/paracrine environment. In summary, oral berberine exerted anti-arthritic effect through inhibiting the Th17 cell response, which was closely associated with the induction of cortistatin generation from gut through augmenting autocrine/paracrine action between enteric nerve cells and endocrine cells. © 2017 Federation of European Biochemical Societies.

  1. Berberine enhances radiosensitivity of esophageal squamous cancer by targeting HIF-1α in vitro and in vivo

    OpenAIRE

    Yang, Xi; Yang, Baixia; Cai, Jing; Zhang, Chi; Zhang, Qu; Xu, Liping; Qin, Qin; Zhu, Hongcheng; Ma, Jianxin; Tao, Guangzhou; Cheng, Hongyan; Sun, Xinchen

    2013-01-01

    Radiation therapy is an important treatment approach for esophageal squamous cell carcinoma (ESCC). However, how to promote radiation sensitivity in ESCC remains a challenge. This study aimed to evaluate the effects of berberine, a common used Chinese medicine, on the radiosensitivity of ESCC. ECSS cell line ECA109 and TE13 were subjected to hypoxia and/or ionizing radiation (IR), in the presence or absence of berberine treatment. Cell growth and survival, and apoptosis were evaluated. In add...

  2. Synergistic inhibitory effect of berberine and d-limonene on human gastric carcinoma cell line MGC803.

    Science.gov (United States)

    Zhang, Xiu-Zhen; Wang, Ling; Liu, Dong-Wu; Tang, Guang-Yan; Zhang, Hong-Yu

    2014-09-01

    This study aims at evaluating the anticancer effects of berberine hydrochloride (berberine) and d-limonene, alone and in combination, on human gastric carcinoma cell line MGC803 to determine whether berberine and d-limonene work synergistically and elucidate their mechanisms. MGC803 cells were treated with berberine and d-limonene, alone and in combination, for 24-48 h. The inhibitory effects of these drugs on growth were determined by MTT assay. The combination index and drug reduction index were calculated with the Chou-Talalay method based on the median-effect principle. Flow cytometry and laser scanning confocal microscopy were employed to evaluate the effects of both drugs on cell-cycle perturbation and apoptosis, generation of reactive oxygen species (ROS), mitochondrial membrane potential, and expression of Bcl-2 and caspase-3 in MGC803 cells. Berberine or d-limonene alone can inhibit the growth of MGC803 cells in a dose- and time-dependent manner. Berberine and d-limonene at a combination ratio of 1:4 exhibited a synergistic effect on anti-MGC803 cells. The two drugs distinctly induced intracellular ROS generation, reduced the mitochondrial transmembrane potential (ΔΨm), enhanced the expression of caspase-3, and decreased the expression of Bcl-2. The combination of berberine and d-limonene showed more remarkable effects compared with drugs used singly in MGC803 cells. The combination of berberine and d-limonene exerted synergistic anticancer effects on MGC803 cells by cell-cycle arrest, ROS production, and apoptosis induction through the mitochondria-mediated intrinsic pathway.

  3. Assessment of berberine as a multi-target antimicrobial: a multi-omics study for drug discovery and repositioning.

    Science.gov (United States)

    Karaosmanoglu, Kubra; Sayar, Nihat Alpagu; Kurnaz, Isil Aksan; Akbulut, Berna Sariyar

    2014-01-01

    Postgenomics drug development is undergoing major transformation in the age of multi-omics studies and drug repositioning. Rather than applications solely in personalized medicine, omics science thus additionally offers a better understanding of a broader range of drug targets and drug repositioning. Berberine is an isoquinoline alkaloid found in many medicinal plants. We report here a whole genome microarray study in tandem with proteomics techniques for mining the plethora of targets that are putatively involved in the antimicrobial activity of berberine against Escherichia coli. We found DNA replication/repair and transcription to be triggered by berberine, indicating that nucleic acids, in general, are among its targets. Our combined transcriptomics and proteomics multi-omics findings underscore that, in the presence of berberine, cell wall or cell membrane transport and motility-related functions are also specifically regulated. We further report a general decline in metabolism, as seen by repression of genes in carbohydrate and amino acid metabolism, energy production, and conversion. An involvement of multidrug efflux pumps, as well as reduced membrane permeability for developing resistance against berberine in E. coli was noted. Collectively, these findings offer original and significant leads for omics-guided drug discovery and future repositioning approaches in the postgenomics era, using berberine as a multi-omics case study.

  4. Synthesis and Cytotoxicity Evaluation of 13-n-Alkyl Berberine and Palmatine Analogues as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2012-09-01

    Full Text Available By introducing long carbon-chain alkyl groups at the C-13 position of berberine and palmatine, 13-n-hexyl/13-n-octyl berberine and palmatine chloride analogues 4ad were synthesized and examined by MTT assays for cytotoxic activity in seven human cancer cell lines (7701QGY, SMMC7721, HepG2, CEM, CEM/VCR, KIII, Lewis, yielding IC50 values of 0.02 ± 0.01–13.58 ± 2.84 μM. 13-n-Octyl palmatine (compound 4d gave the most potent inhibitor activity, with an IC50 of 0.02 ± 0.01 μM for SMMC7721. In all cases, the 13-n-alkyl berberine and palmatine analogues 4ad were more cytotoxic than berberine and palmatine. In addition, compounds 4ad also exhibited more potent cytotoxicity than berberine and palmatine in mice with S180 sarcoma xenografted in vivo. The primary screening results indicated that the 13-n-hexyl/13-n-octyl berberine and palmatine analogues might be valuable source for new potent anticancer drug candidates.

  5. Effects of Berberine on Amelioration of Hyperglycemia and Oxidative Stress in High Glucose and High Fat Diet-Induced Diabetic Hamsters In Vivo

    Directory of Open Access Journals (Sweden)

    Cong Liu

    2015-01-01

    Full Text Available This study investigated the effects of berberine on amelioration of hyperglycemia and hyperlipidemia and the mechanism involved in high glucose and high fat diet-induced diabetic hamsters. Golden hamsters fed with high glucose and high fat diet were medicated with metformin, simvastatin, and low or high dose of berberine (50 and 100 mg·kg−1 for 6 weeks. The results showed that the body weights were significantly lower in berberine-treated groups than control group. Histological analyses revealed that the treatment of berberine inhibited hepatic fat accumulation. Berberine significantly reduced plasma total cholesterol, triglyceride, free fatty acid, low density lipoprotein cholesterol, malondialdehyde, thiobarbituric acid-reactive substance, and 8-isoprostane level but significantly increased plasma superoxide dismutase activity. Glucose and insulin levels were significantly reduced in metformin and berberine-treated groups. Glucose tolerance tests documented that berberine-treated mice were more glucose tolerant. Berberine treatment increased expression of skeletal muscle glucose transporter 4 mRNA and significantly decreased liver low density lipoprotein receptor mRNA expression. The study suggested that berberine was effective in lowering blood glucose and lipids levels, reducing the body weight, and alleviating the oxidative stress in diabetic hamsters, which might be beneficial in reducing the cardiovascular risk factors in diabetes.

  6. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension.

    Science.gov (United States)

    Lan, Jiarong; Zhao, Yanyun; Dong, Feixia; Yan, Ziyou; Zheng, Wenjie; Fan, Jinping; Sun, Guoli

    2015-02-23

    Berberine, extracted from Coptis Root and Phellodendron Chinese, has been frequently used for the adjuvant treatment of type 2 diabetes mellitus, hyperlipidemia, and hypertension in China. Safety and efficacy studies in terms of evidence-based medical practice have become more prevalent in application to Chinese Herbal Medicine. It is necessary to assess the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipidemia and hypertension by conducting a systematic review and meta-analysis of available clinical data. We searched the English databases PubMed, ScienceDirect, Cochrane library, EMbase, etc., and Chinese databases including China biomedical literature database (CBM), Chinese Technology Journal Full-text Database, Chinese journal full text database (CNKI), and Wanfang digital periodical full text database. Relevant studies were selected based on the inclusion and exclusion criteria. Meta-analysis was performed with RevMan5.0 software after data extraction and the quality of studies assessment. Twenty-seven randomized controlled clinical trials were included with 2569 patients. There are seven subgroups in our meta-analysis: berberine versus placebo or berberine with intensive lifestyle intervention versus intensive lifestyle intervention alone; berberine combined with oral hypoglycemic versus hypoglycemic alone; berberine versus oral hypoglycemic; berberine combined with oral lipid lowering drugs versus lipid lowering drugs alone; berberine versus oral lipid lowering drugs; berberine combined with oral hypotensor versus hypotensive medications; berberine versus oral hypotensive medications. In the treatment of type 2 diabetes mellitus, we found that berberine with lifestyle intervention tended to lower the level of FPG, PPG and HbA1c than lifestyle intervention alone or placebo; the same as berberine combined with oral hypoglycaemics to the same hypoglycaemics; but there was no statistical significance between berberine and

  7. Bridge Management Systems

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle

    In this paper bridge management systems are discussed with special emphasis on management systems for reinforced concrete bridges. Management systems for prestressed concrete bridges, steel bridges, or composite bridges can be developed in a similar way....

  8. Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Sahibzada MUK

    2018-02-01

    Full Text Available Muhammad Umar Khayam Sahibzada,1,2 Abdul Sadiq,2 Hani S Faidah,3 Muhammad Khurram,4 Muhammad Usman Amin,4 Abdul Haseeb,5,6 Maria Kakar4 1Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan; 2Department of Pharmacy, University of Malakand, Chakdara, Pakistan; 3Department of Microbiology, Faculty of Medicine, Umm Al Qura University, Makkah, Saudi Arabia; 4Department of Pharmacy, Abasyn University, Peshawar, Pakistan; 5Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Science, Universiti Sains Malaysia, Peneng, Malaysia; 6Department of Clinical Pharmacy, College of Pharmacy, Umm Al Qura University, Makkah, Saudi Arabia Background: Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN and anti-solvent precipitation with a syringe pump (APSP were used to address the problems of solubility, dissolution rate and bioavailability of berberine. Methods: Semi-crystalline nanoparticles (NPs of 90–110 nm diameter for APSP and 65–75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC and X-ray powder diffractometry (XRD. Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity. Results: The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form. Conclusion: Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram

  9. Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.

    LENUS (Irish Health Repository)

    Alzamora, Rodrigo

    2011-01-01

    Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl(-) secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl(-) secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC(50) 80 ± 8 μM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K(+) current by 88%, suggesting inhibition of KCNQ1 K(+) channels. Berberine did not affect either apical Cl(-) conductance or basolateral Na(+)-K(+)-ATPase activity. Berberine stimulated p38 MAPK, PKCα and PKA, but had no effect on p42\\/p44 MAPK and PKCδ. However, berberine pre-treatment prevented stimulation of p42\\/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl(-) secretion was partially blocked by HBDDE (∼65%), an inhibitor of PKCα and to a smaller extent by inhibition of p38 MAPK with SB202190 (∼15%). Berberine treatment induced an increase in association between PKCα and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl(-) secretion through inhibition of basolateral KCNQ1 channels responsible for K(+) recycling via a PKCα-dependent pathway.

  10. Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.

    LENUS (Irish Health Repository)

    Alzamora, Rodrigo

    2012-02-01

    Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl(-) secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl(-) secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC(50) 80 +\\/- 8 muM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K(+) current by 88%, suggesting inhibition of KCNQ1 K(+) channels. Berberine did not affect either apical Cl(-) conductance or basolateral Na(+)-K(+)-ATPase activity. Berberine stimulated p38 MAPK, PKCalpha and PKA, but had no effect on p42\\/p44 MAPK and PKCdelta. However, berberine pre-treatment prevented stimulation of p42\\/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl(-) secretion was partially blocked by HBDDE ( approximately 65%), an inhibitor of PKCalpha and to a smaller extent by inhibition of p38 MAPK with SB202190 ( approximately 15%). Berberine treatment induced an increase in association between PKCalpha and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl(-) secretion through inhibition of basolateral KCNQ1 channels responsible for K(+) recycling via a PKCalpha-dependent pathway.

  11. Berberine-INF55 (5-Nitro-2-Phenylindole) Hybrid Antimicrobials: Effects of Varying the Relative Orientation of the Berberine and INF55 Components ▿

    Science.gov (United States)

    Tomkiewicz, Danuta; Casadei, Gabriele; Larkins-Ford, Jonah; Moy, Terence I.; Garner, James; Bremner, John B.; Ausubel, Frederick M.; Lewis, Kim; Kelso, Michael J.

    2010-01-01

    Hybrid antimicrobials containing an antibacterial linked to a multidrug resistance (MDR) pump inhibitor make up a promising new class of agents for countering efflux-mediated bacterial drug resistance. This study explores the effects of varying the relative orientation of the antibacterial and efflux pump inhibitor components in three isomeric hybrids (SS14, SS14-M, and SS14-P) which link the antibacterial alkaloid and known substrate for the NorA MDR pump berberine to different positions on INF55 (5-nitro-2-phenylindole), an inhibitor of NorA. The MICs for all three hybrids against wild-type, NorA-knockout, and NorA-overexpressing Staphylococcus aureus cells were found to be similar (9.4 to 40.2 μM), indicating that these compounds are not effectively effluxed by NorA. The three hybrids were also found to have similar curing effects in a Caenorhabditis elegans live infection model. Each hybrid was shown to accumulate in S. aureus cells to a greater extent than either berberine or berberine in the presence of INF55, and the uptake kinetics of SS14 were found to differ from those of SS14-M and SS14-P. The effects on the uptake and efflux of the NorA substrate ethidium bromide into S. aureus cells in the presence or absence of the hybrids were used to confirm MDR inhibition by the hybrids. MDR-inhibitory activity was confirmed for SS14-M and SS14-P but not for SS14. Molecular dynamics simulations revealed that SS14 prefers to adopt a conformation that is not prevalent in either SS14-M or SS14-P, which may explain why some properties of SS14 diverge from those of its two isomers. In summary, subtle repositioning of the pump-blocking INF55 moiety in berberine-INF55 hybrids was found to have a minimal effect on their antibacterial activities but to significantly alter their effects on MDR pumps. PMID:20498327

  12. Comparison of Helicobacter pylori Urease Inhibition by Rhizoma Coptidis, Cortex Phellodendri and Berberine: Mechanisms of Interaction with the Sulfhydryl Group.

    Science.gov (United States)

    Li, Cailan; Xie, Jianhui; Chen, Xiaoying; Mo, Zhizhun; Wu, Wen; Liang, Yeer; Su, Zuqing; Li, Qian; Li, Yucui; Su, Ziren; Yang, Xiaobo

    2016-03-01

    Rhizoma Coptidis, Cortex Phellodendri, and berberine were reported to inhibit Helicobacter pylori. However, the underlying mechanism remained elusive. Urease plays a vital role in H. pylori colonization and virulence. In this work, aqueous extracts of Rhizoma Coptidis, Cortex Phellodendri of different origins, and purified berberine were investigated against H. pylori urease and jack bean urease to elucidate the inhibitory capacity, kinetics, and mechanism. Results showed that berberine was the major chemical component in Rhizoma Coptidis and Cortex Phellodendri, and the content of berberine in Rhizoma Coptidis was higher than in Cortex Phellodendri. The IC50 values of Rhizoma Coptidis were significantly lower than those Cortex Phellodendri and purified berberine, of which Coptis chinensis was shown to be the most active concentration- and time-dependent urease inhibitor. The Lineweaver-Burk plot analysis indicated that the inhibition pattern of C. chinensis against urease was noncompetitive for both H. pylori urease and jack bean urease. Thiol protectors (L-cysteine, glutathione, and dithiothreithol) significantly protected urease from the loss of enzymatic activity, while fluoride and boric acid showed weaker protection, indicating the active-site sulfhydryl group was possibly responsible for its inhibition. Furthermore, the urease inhibition proved to be reversible since C. chinensis-blocked urease could be reactivated by glutathione. The results suggested that the anti-urease activity of Rhizoma Coptidis was superior to that of Cortex Phellodendri and berberine, which was believed to be more likely to correlate to the content of total alkaloids rather than berberine monomer. The concentration- and time-dependent, reversible, and noncompetitive inhibition against urease by C. chinensis might be attributed to its interaction with the sulfhydryl group of the active site of urease. Georg Thieme Verlag KG Stuttgart · New York.

  13. In Vitro Inhibitory Effect of Berberis vulgaris (Berberidaceae and Its Main Component, Berberine against Different Leishmania Species.

    Directory of Open Access Journals (Sweden)

    Hossein Mahmoudvand

    2014-03-01

    Full Text Available Leishmaniasis has been identified as a major public health problem in tropical and sub-tropical countries. The present study was aimed to investigate antileishmanial effects of various extracts of Berberis vulgaris also its active compoenent, berberine against Leishmania tropica and L. infantum species on in vitro experiments.In this study in vitro antileishmanial activity of various extracts of B. vulgaris also its active compoenent, berberine against promastigote and amastigote stages of L. tropica and L. infantum was evaluated, using MTT assay and in a macrophage model, respectively. Furthermore, infectivity rate and cytotoxicity effects of B. vulgaris and berberine in murine macrophage cells were investigated.The findings of optical density (OD and IC50 indicated that B. vulgaris particulary berberine significantly (P<0.05 inhibited the growth rate of promastigote stage of L.tropica and L.infantum in comparison to meglumine antimoniate (MA. In addition, B. vulgaris and berberine significantly (P<0.05 decreased the mean number of amastigotes in each macrophage as compared with positive control. In the evaluation of cytotoxicity effects, it could be observed that berberine as compared with B. vulgaris exhibited more cytotoxicity against murine macrophages. Results also showed that when parasites were pre-incubated with B. vulgaris their ability to infect murine macrophages was significantly decreased.B.vulgaris particularly berberine exhibited potent in vitro leishmanicidal effects against L. tropica and L.infantum. Further works are required to evaluate the antileishmanial effects of B.vulgaris on Leishmania species using clinical settings.

  14. Berberine attenuates CCN2-induced IL-1β expression and prevents cartilage degradation in a rat model of osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shan-Chi [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Lee, Hsiang-Ping [Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan (China); Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan (China); Hung, Chun-Yin [Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan (China); Tsai, Chun-Hao [Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan (China); Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan (China); Li, Te-Mao [School of Chinese Medicine, China Medical University, Taichung, Taiwan (China); Tang, Chih-Hsin, E-mail: chtang@mail.cmu.edu.tw [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan (China)

    2015-11-15

    Connective tissue growth factor (CTGF; also known as CCN2) is an inflammatory mediator that is abundantly expressed in osteoarthritis (OA). Interleukin-1β (IL-1β) plays a pivotal role in OA pathogenesis. Berberine exhibits an anti-inflammatory effect, but the mechanisms by which it modulates CCN2-induced IL-1β expression in OA synovial fibroblasts (OASFs) remain unknown. We showed that CCN2-induced IL-1β expression is mediated by the activation of α{sub v}β{sub 3}/α{sub v}β{sub 5} integrin-dependent reactive oxygen species (ROS) generation, and subsequent activation of apoptosis signal-regulating kinase 1 (ASK1), p38/JNK, and nuclear factor-κB (NF-κB) signaling pathways. This IL-1β expression in OASFs is attenuated by N-acetylcysteine (NAC), inhibitors of ASK1, p38, or JNK, or treatment with berberine. Furthermore, berberine also reverses cartilage damage in an experimental model of collagenase-induced OA (CIOA). We observed that CCN2 increased IL-1β expression via α{sub v}β{sub 3}/α{sub v}β{sub 5} integrins, ROS, and ASK1, p38/JNK, and NF-κB signaling pathways. Berberine was found to inhibit these signaling components in OASFs in vitro and prevent cartilage degradation in vivo. We suggest a novel therapeutic strategy of using berberine for managing OA. - Highlights: • CCN2 induce IL-1β production via αvβ3/αvβ5 integrin, ROS, ASK1, p38/JNK, and NF-κB. • Berberine attenuates CCN2-induced IL-1β expression in vitro and in OA rat model. • Berberine as natural drug of choice for anti-inflammatory effect to ameliorates OA.

  15. Dual-Targeting of AR and Akt Pathways by Berberine in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2016-10-01

    more effective treatments. Preliminary studies conducted in our lab have shown that a berberine (BBR), a plant -derived isoquinoline alkaloid...mice was measured weekly. At the end of experiment, animals were sacrificed by CO2 inhalation. The genitourinary bloc (GU bloc), consisting of the...phosphorylation by PDK1 and mTORC2 (7), in the Pten-null model. The experimental design is similar to that described above. Vehicle (10% 1- methyl

  16. National Bridge Inventory (NBI) Bridges

    Data.gov (United States)

    Department of Homeland Security — The NBI is a collection of information (database) describing the more than 600,000 of the Nation's bridges located on public roads, including Interstate Highways,...

  17. Role of berberine in ameliorating Schistosoma mansoni-induced hepatic injury in mice

    Directory of Open Access Journals (Sweden)

    Mohamed A Dkhi

    2014-01-01

    Full Text Available BACKGROUND: Schistosomiasis is caused by helminth parasites of the genus Schistosoma. Berberine chloride (BER, an isoquinoline alkaloid, has been used in vivo for its antiparasitic, antioxidant and hepatoprotective properties. In this study, the protective effect of BER and praziquantel has been compared for the extent of schistosomiasis-induced oxidative stress in hepatic tissue of mice. RESULTS: S. mansoni was able to induce inflammation and injury to the liver, evidenced (i by an increase in inflammatory cellular infiltrations, dilated sinusoids and vacuolated hepatocytes, (ii by decreased levels of alanine and aspartate aminotransferases and increased levels of alkaline phosphatase, γ-glutamyl transferase in the liver homogenate, (iii by increased production of nitric oxide and thiobarbituric acid reactive substances, and (iv by lowered glutathione levels and decreased activities of catalase and superoxide dismutase, respectively. All these infection-induced parameters were significantly altered during BER treatment. In particular, berberine counteracted the S. mansoni-induced loss of glutathione and the activities of catalase and superoxide dismutase. CONCLUSION: Based on these results, it is concluded that berberine could ameliorate pre-existing liver damage and oxidative stress conditions due to schistosomiasis.

  18. Spectroscopic investigation on the sonodynamic damage to proteins in the presence of berberine in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xin [School of Pharmaceutical Sciences, Liaoning University, Shenyang 110036 (China); He Lingling, E-mail: helingling76@163.co [College of Applied Chemistry, Shenyang University of Chemical Technology, Shenyang 110142 (China); Liu Bin [School of Pharmaceutical Sciences, Liaoning University, Shenyang 110036 (China); Wang Jun [Department of Chemistry, Liaoning University, Shenyang 110036 (China)

    2011-07-15

    In this paper, bovine serum albumin (BSA) was selected as a target molecule, and the sonodynamic damage to proteins in the presence of berberine (BER) and its mechanism were studied by means of absorption and fluorescence spectra. The results of hyperchromic effect of absorption spectra, and quenching of intrinsic fluorescence spectra indicated that the ultrasound-induced BSA molecules damage was enhanced by BER. The damage degree of BSA molecules increased with the increase in ultrasonic irradiation time and BER concentration. The results of synchronous fluorescence and three-dimensional fluorescence spectra confirmed that the synergistic effects of ultrasound and BER induced the damage of BSA molecules. The results of oxidation-extraction photometry with several reactive oxygen species (ROS) scavengers indicated that the damage of BSA molecules could be mainly due to the generation of ROS, and {sup 1}O{sub 2} was the major mediator of the ultrasound-induced BSA molecules damage in the presence of BER. - Highlights: {yields} Sonodynamic activity of berberine and its mechanism is first reported. {yields} Ultrasound-induced BSA molecules damage is enhanced by berberine. {yields} Damage of BSA molecules is mainly due to the generation of ROS.

  19. The Potential Mechanisms of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Xiaopeng Zhu

    2016-10-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a globally observed metabolic disease with high prevalence both in adults and children. However, there is no efficient medication available yet. Increased evidence indicates that berberine (BBR, a natural plant product, has beneficial effects on NAFLD, though the mechanisms are not completely known. In this review, we briefly summarize the pathogenesis of NAFLD and factors that influence the progression of NAFLD, and focus on the potential mechanisms of BBR in the treatment of NAFLD. Increase of insulin sensitivity, regulation of adenosine monophosphate-activated protein kinase (AMPK pathway, improvement of mitochondrial function, alleviation of oxidative stress, LDLR mRNA stabilization, and regulation of gut microenvironment are the major targets of BBR in the treatment of NAFLD. Additionally, reduction of proprotein convertase subtilisin/kexin 9 (PCSK9 expression and DNA methylation are also involved in pharmacological mechanisms of berberine in the treatment of NAFLD. The immunologic mechanism of BBR in the treatment of NAFLD, development of berberine derivative, drug combinations, delivery routes, and drug dose can be considered in the future research.

  20. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

    International Nuclear Information System (INIS)

    Liu Zhaojian; Liu Qiao; Xu Bing; Wu Jingjing; Guo Chun; Zhu Faliang; Yang Qiaozi; Gao Guimin; Gong Yaoqin; Shao Changshun

    2009-01-01

    Alkaloid berberine is widely used for the treatment of diarrhea and other diseases. Many laboratory studies showed that it exhibits anti-proliferative activity against a wide spectrum of cancer cells in culture. In this report we studied the mechanisms underlying the inhibitory effects of berberine on human osteosarcoma cells and on normal osteoblasts. The inhibition was largely attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53-deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes. However, the G2/M arrest could be induced by berberine regardless of the status of p53. Interestingly, DNA double-strand breaks, as measured by the phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells in a dose-dependent manner. Thus, one major mechanism by which berberine exerts its growth-inhibitory effect is to inflict genomic lesions on cells, which in turn trigger the activation of p53 and the p53-dependent cellular responses including cell cycle arrest and apoptosis

  1. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Liu Zhaojian; Liu Qiao; Xu Bing; Wu Jingjing [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Guo Chun; Zhu Faliang [Institute of Immunology, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Yang Qiaozi [Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States); Gao Guimin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Gong Yaoqin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China)], E-mail: yxg8@sdu.edu.cn; Shao Changshun [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States)], E-mail: shao@biology.rutgers.edu

    2009-03-09

    Alkaloid berberine is widely used for the treatment of diarrhea and other diseases. Many laboratory studies showed that it exhibits anti-proliferative activity against a wide spectrum of cancer cells in culture. In this report we studied the mechanisms underlying the inhibitory effects of berberine on human osteosarcoma cells and on normal osteoblasts. The inhibition was largely attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53-deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes. However, the G2/M arrest could be induced by berberine regardless of the status of p53. Interestingly, DNA double-strand breaks, as measured by the phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells in a dose-dependent manner. Thus, one major mechanism by which berberine exerts its growth-inhibitory effect is to inflict genomic lesions on cells, which in turn trigger the activation of p53 and the p53-dependent cellular responses including cell cycle arrest and apoptosis.

  2. Activation of IGF-1/IGFBP-3 signaling by berberine improves intestinal mucosal barrier of rats with acute endotoxemia.

    Science.gov (United States)

    He, Yan; Yuan, Xiaoming; Zhou, Guangrong; Feng, Aiwen

    2018-01-01

    Insulin-like growth factor I (IGF-I) and binding protein 3 (IGFBP-3) play a role in the maintenance of gut mucosal barrier function. Nevertheless, IGF-I/IGFBP-3 and tight junction protein (TJP) expression in small intestinal mucosa are often impaired during endotoxemia. In this model of acute endotoxemia, the regulatory effect of berberine on IGF-I/IGFBP-3 and TJP expression in ileal mucosa was evaluated. The findings revealed systemic injection of lipopolysaccharide (LPS) suppressed mRNA and protein expression of IGF-I and IGFBP-3, but berberine ameliorated their production. LPS injection inhibited occludin and claudin-1 protein generation, and this inhibitory effect of LPS was abolished by berberine. Inhibition of IGF-I/IGFBP-3 signaling by AG1024 or siRNAs reduced berberine-induced occludin and claudin-1 production. Additionally, GW9662 was found to repress berberine-induced IGF-I/IGFBP-3 expression, indicating of a cross-link between PPARγ and IGF-I/IGFBP-3 axis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Bridged graphite oxide materials

    Science.gov (United States)

    Herrera-Alonso, Margarita (Inventor); McAllister, Michael J. (Inventor); Aksay, Ilhan A. (Inventor); Prud'homme, Robert K. (Inventor)

    2010-01-01

    Bridged graphite oxide material comprising graphite sheets bridged by at least one diamine bridging group. The bridged graphite oxide material may be incorporated in polymer composites or used in adsorption media.

  4. [The effect of berberine administration of evaluation of the functional state of rat liver after ligation of common bile duct].

    Science.gov (United States)

    Zverinskiĭ, I V; Mel'nichenko, N G; Poplavskiĭ, V A; Sut'ko, I P; Telegin, P G; Shliakhtun, A G

    2013-01-01

    On the eighth day after ligation of the common bile duct in rats a significant increase in the serum content of total lipids, cholesterol bilirubin and ALT, alkaline phosphatase, and gamma-glutamyltransferase was observed. In the microsomal fraction there was a marked decrease in the content and activity of microsomal monooxygenases. Introperitoneal injection of berberine (10 mg/kg) for 6 days caused a partial normalization of permeability of hepatocytes plasma membranes and activity microsomal flavin-containing monooxygenases. It is suggested that berberine is a substrate and inducer of flavin-containing monooxygenases. Membrane-stabilizing effect of berberine is probably realized at the level of inhibition of prooxidant status of liver cells.

  5. Effect of Berberine on PPARα/NO Activation in High Glucose- and Insulin-Induced Cardiomyocyte Hypertrophy

    Directory of Open Access Journals (Sweden)

    Mingfeng Wang

    2013-01-01

    Full Text Available Rhizoma coptidis, the root of Coptis chinensis Franch, has been used in China as a folk medicine in the treatment of diabetes for thousands of years. Berberine, one of the active ingredients of Rhizoma coptidis, has been reported to improve symptoms of diabetes and to treat experimental cardiac hypertrophy, respectively. The objective of this study was to evaluate the potential effect of berberine on cardiomyocyte hypertrophy in diabetes and its possible influence on peroxisome proliferator-activated receptor-α (PPARα/nitric oxide (NO signaling pathway. The cardiomyocyte hypertrophy induced by high glucose (25.5 mmol/L and insulin (0.1 μmol/L (HGI was characterized in rat primary cardiomyocyte by measuring the cell surface area, protein content, and atrial natriuretic factor mRNA expression level. Protein and mRNA expression were measured by western blot and real-time RT-PCR, respectively. The enzymatic activity of NO synthase (NOS was measured using a spectrophotometric assay, and NO concentration was measured using the Griess assay. HGI significantly induced cardiomyocyte hypertrophy and decreased the expression of PPARα and endothelial NOS at the mRNA and protein levels, which occurred in parallel with declining NOS activity and NO concentration. The effect of HGI was inhibited by berberine (0.1 to 100 μmol/L, fenofibrate (0.3 μmol/L, or L-arginine (100 μmol/L. MK886 (0.3 μmol/L, a selective PPARα antagonist, could abolish the effects of berberine and fenofibrate. NG-nitro-L-arginine-methyl ester (100 μmol/L, a NOS inhibitor, could block the effects of L-arginine, but only partially blocked the effects of berberine. These results suggest that berberine can blunt HGI-induced cardiomyocyte hypertrophy in vitro, through the activation of the PPARα/NO signaling pathway.

  6. [In situ thin layer chromatography-fourier transform-surface-enhanced Raman spectrum study on ingredients of berberine].

    Science.gov (United States)

    Wang, Yuan; Guo, Zhan-sheng; Wang, Ying-feng; Wang, Song-ying; Ren, Gui-fen; Zhang, Xiang-lan; Han, Xiu-lan

    2002-10-01

    Surface Enhanced Raman Scattering (SERS) combined with Thin Layer Chromatography (TLC) has been used for studying characteristic spectrum of molecules in situ in micrograms samples. There are very few report for applying the SERS-TCL method in the study of the effective ingredients of Chinese traditional herbs. Coptis Chinensis France is an often-used clinic Chinese traditional medicine. Its main effective components include berberine and so on, which have antibiotic very wide and also have curative effect on improving the functions of heart vascular cycles. Therefore the concentrations of berberine are very important for the quality control of the medicine. In this work, the ethanol extract of Coptis Chinensis France was first separated by TLC, the SERS was then measure directly after dropping silver gel on the separated spots. The method can be used for the finger print analysis of the berberine. 3 microL of alcohol extract of Coptis Chinensis France with total alkaloids concentration of 1.0 mg.mL was placed on silicon GF254 TLC plate. The sample was separated by developing solvent of n bulanol-Acitic acid-H2O (7:2:1 V/V). The positions of berberine in the sample were confirmed by the standard alkaloid solutions. The Rf values for berberine are 0.29. The silver gel was used as surface enhanced substrate and placed on the separated berberine spots. FT-SERS was measured directly by a Nicolet FT-Raman 910 spectrometer. Berberine belong to isoquinoline alkaloids. His structure can be found in reference. The date of spectrum of berberine can be seen that the band at 1,396 cm-1 due to Ar-OCH3 deformation vibrations was greatly enhanced, indicating that the molecule was absorbed on silver gel strongly through lone-pair electron in Ar-OCH3. The ring stretching mode occurring around 1,548 cm-1 represents isoquinoline ring in the molecule. The band at 727 cm-1 due to CH (ring) deformation vibrations was also enhanced.

  7. Pancreatic Enzymes

    Science.gov (United States)

    ... Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Pancreatic enzymes Home Facing Pancreatic Cancer Living with Pancreatic Cancer ... and see a registered dietitian. What are pancreatic enzymes? Pancreatic enzymes help break down fats, proteins and ...

  8. Building Bridges

    DEFF Research Database (Denmark)

    The report Building Bridges adresses the questions why, how and for whom academic audience research has public value, from the different points of view of the four working groups in the COST Action IS0906 Transforming Audiences, Transforming Societies – “New Media Genres, Media Literacy and Trust...... in the Media”, “Audience Interactivity and Participation”, “The Role of Media and ICT Use for Evolving Social Relationships” and “Audience Transformations and Social Integration”. Building Bridges is the result of an ongoing dialogue between the Action and non-academic stakeholders in the field of audience......, Brian O’Neill, Andra Siibak, Sascha Trültzsch-Wijnen, Nicoletta Vittadini, Igor Vobič and Frauke Zeller. Stakeholder feedback from: Michelle Arlotta (DeAgostini), Andreea M. Costache (Association of Consumers of Audiovisual Media in Catalonia/TAC), Francesco Diasio (AMARC Europe), Marius Dragomir (Open...

  9. Mathematical bridges

    CERN Document Server

    Andreescu, Titu; Tetiva, Marian

    2017-01-01

    Building bridges between classical results and contemporary nonstandard problems, Mathematical Bridges embraces important topics in analysis and algebra from a problem-solving perspective. Blending old and new techniques, tactics and strategies used in solving challenging mathematical problems, readers will discover numerous genuine mathematical gems throughout that will heighten their appreciation of the inherent beauty of mathematics. Most of the problems are original to the authors and are intertwined in a well-motivated exposition driven by representative examples. The book is structured to assist the reader in formulating and proving conjectures, as well as devising solutions to important mathematical problems by making connections between various concepts and ideas from different areas of mathematics. Instructors and educators teaching problem-solving courses or organizing mathematics clubs, as well as motivated mathematics students from high school juniors to college seniors, will find Mathematical Bri...

  10. Metabolomics Profiling to Investigate the Pharmacologic Mechanisms of Berberine for the Treatment of High-Fat Diet-Induced Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Jian Li

    2015-01-01

    Full Text Available Objective. Berberine has been used to treat nonalcoholic steatohepatitis (NASH, which has been addressed in many studies. In this study, we investigated the molecular pharmacology mechanisms of berberine using metabolomic techniques. Methods. Sprague-Dawley rats were randomly divided into three groups (10 rats in each group: (i normal control group; (ii high-fat diet- (HFD- induced NASH model group; and (iii HFD berberine-treated group (i.d. 200 mg/kg. The handling procedure lasted eight weeks. Then, UPLC-Q-TOF/MS techniques coupled with histopathology and biochemical analyses were adopted to explore the mechanisms of berberine on the protective effects against NASH. Key Findings. (i According to conventional test results, berberine treatment plays a fighting role in HFD-induced NASH due to its beneficial effects against insulin resistance, inflammation, and lipid metabolism. (ii Based on UPLC-Q-TOF/MS techniques, metabolic profiles that involved sphingomyelin (SM, phosphatidylcholine (PC, lysophosphatidylcholine (LysoPC, 13-hydroperoxy-9, 11-octadecadienoic acid (13-HpODE, eicosatrienoic acid, docosatrienoic acid, and eicosenoic acid could provide potential metabolic biomarkers to address the pharmacological mechanisms of berberine. Conclusions. The parts of molecular pharmacological mechanisms of berberine for NASH treatment are related to the regulation of metabolic disruption involving phospholipid and unsaturated fatty acids in rats with NASH.

  11. Growth performance, innate immune responses and disease resistance of fingerling blunt snout bream, Megalobrama amblycephala adapted to different berberine-dietary feeding modes.

    Science.gov (United States)

    Xu, Wei-Na; Chen, Dan-Hong; Chen, Qing-Qing; Liu, Wen-Bin

    2017-09-01

    A 8-week feeding trial was conducted to evaluate the effect of different berberine-dietary feeding modes on growth, non-specific immune responses and disease resistance of blunt snout bream, Megalobrama amblycephala. Fish (average initial weight 4.70 ± 0.02 g) were fed two fat levels (5% and 10%) diets in three berberine-feeding modes (supplementing 50 mg/kg berberine continuously, two-week or four-week intervals) with four replicates, respectively. Then, fish were challenged by Aeromonas hydrophila and mortality was recorded for the next 96 h after feeding trial. The results showed that different feeding modes of berberine significantly influenced growth, innate immunity and antioxidant capability of fish. Fish fed normal diet with 50 mg/kg berberine at two-week interval mode reflected remarkably (P complement component 3 (C3) and complement component 4 (C4) concentrations were significantly (P feeding modes. Based on fish healthy improvement and feeding cost saving, blunt snout bream fed normal diet with 50 mg/kg berberine at two-week interval or fed high-fat diet with berberine at two-week or four-week intervals were optimal feeding mode, respectively. Copyright © 2017. Published by Elsevier Ltd.

  12. Berberine improves insulin resistance induced by high fat diet in rats

    International Nuclear Information System (INIS)

    Zhou Libin; Yang Ying; Shang Wenbin; Li Fengying; Tang Jinfeng; Wang Xiao; Liu Shangquan; Yuan Guoyue; Chen Mingdao

    2005-01-01

    Objective: To observe the effect of berberine on insulin resistance induced by high fat diet in rats. Methods: Normal male SD rats (8 weeks old) were divided into two groups taking either normal chow (NC, n=9) or high fat diet (HF, n=20). After fourteen weeks, HF rats were divided into two groups. Ten rats continued to take high fat diet. Another ten rats took additional berberine gavage (HF+B, 150mg/kg weight once a day). Six weeks later, oral glucose tolerance test and insulin tolerance test were performed for estimating insulin sensitivity. Results: The body weight, liver weight and epididyaml fat pads weight of HF group were significantly higher than those of HF+B group and NC group (all P<0.01). Fasting plasma glucose, insulin and plasma glucose, insulin 2h after taking glucose in HF+B rats were significantly lower than those in HF rats (all P<0.01). Plasma glucose and insulin levels at all time points in HF rats were significantly higher than those in NC rats. Homa-IR of HF group was markedly higher than that of HF+B group (P<0.01). The glucose-lowering effects after the administration of insuin (0.5u/kg intrapenitoneally) at all time points in HF+B rats were stronger than those in HF rats with 23% and 7% reduction at 15min respectively. Conclusion: Long term high fat diet resulted in insulin resistance. Berberine was able to reverse insulin resistance through promoting peripheral tissue up taking of glucose and decreasing insulin, which would be quite ideal for the intervention of IGT. (authors)

  13. Stability-Indicating Validated HPLC Method for Analysis of Berberine Hydrochloride and Trimethoprim in Pharmaceutical Dosage Form

    Directory of Open Access Journals (Sweden)

    Jing-Chun Wang

    2013-01-01

    Full Text Available A stability-indicating HPLC method was developed and validated for the determination of berberine hydrochloride and trimethoprim in pharmaceutical dosage form in the presence of degradation products. The proposed RP-HPLC method utilizes an Agilent TC-C18, 4.6 mm × 250 mm, 5 μm, column using a mobile phase consisting of acetonitrile-50 mM potassium dihydrogen phosphate (30 : 70, v/v, pH adjusted to 3 with orthophosphoric acid at a flow rate of 1.0 mL/min and UV detection at 271 nm. The linearity of berberine hydrochloride and trimethoprim was in the range of 2 to 60 μg/mL (r=0.9996 and 1 to 30 μg/mL (r=0.9995, respectively. Repeatability and intermediate precisions were also determined with percentage relative standard deviation (% RSD less than 2.0%. The limits of detection were found to be 9.8 ng/mL for berberine hydrochloride and 2.5 ng/mL for trimethoprim. The mean recoveries for berberine hydrochloride and trimethoprim were 99.8 and 98.8%, respectively. The stability of the two drugs was determined under different conditions and the proposed method has shown effective separation for their degradation products. And the proposed assays method can thus be considered stability-indicating.

  14. Antifungal, Antileishmanial, and Cytotoxicity Activities of Various Extracts of Berberis vulgaris (Berberidaceae) and Its Active Principle Berberine.

    Science.gov (United States)

    Mahmoudvand, Hossein; Ayatollahi Mousavi, Seyyed Amin; Sepahvand, Asghar; Sharififar, Fariba; Ezatpour, Behrouz; Gorohi, Fatemeh; Saedi Dezaki, Ebrahim; Jahanbakhsh, Sareh

    2014-01-01

    In this study, in vitro antidermatophytic activity against Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis, and Microsporum gypseum was studied by disk diffusion test and assessment of minimum inhibitory concentration (MIC) using CLSI broth macrodilution method (M38-A2). Moreover, antileishmanial and cytotoxicity activity of B. vulgaris and berberine against promastigotes of Leishmania major and Leishmania tropica were evaluated by colorimetric MTT assay. The findings indicated that the various extracts of B. vulgaris particularly berberine showed high potential antidermatophytic against pathogenic dermatophytes tested with MIC values varying from 0.125 to >4 mg/mL. The results revealed that B. vulgaris extracts as well as berberine were effective in inhibiting L. major and L. tropica promastigotes growth in a dose-dependent manner with IC50 (50% inhibitory concentration) values varying from 2.1 to 26.6  μ g/mL. Moreover, it could be observed that berberine as compared with B. vulgaris exhibited more cytotoxicity against murine macrophages with CC50 (cytotoxicity concentration for 50% of cells) values varying from 27.3 to 362.6  μ g/mL. Results of this investigation were the first step in the search for new antidermatophytic and antileishmanial drugs. However, further works are required to evaluate exact effect of these extracts in animal models as well as volunteer human subjects.

  15. Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial.

    Science.gov (United States)

    Li, Yan; Ma, Hongli; Zhang, Yuehui; Kuang, Hongying; Ng, Ernest Hung Yu; Hou, Lihui; Wu, Xiaoke

    2013-07-18

    Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on pelvic scanning. Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease. Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated. In this paper, we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS. This is a multicenter, randomized, placebo-controlled and double-blind trial. A total of 120 patients will be enrolled in this study and will be randomized into two groups. Berberine or placebo will be taken orally for 12 weeks. The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp. We postulate that women with PCOS will have improved insulin resistance following berberine administration. This study is registered at ClinicalTrials.gov, NCT01138930.

  16. Fabrication of Novel Hydrogel with Berberine-Enriched Carboxymethylcellulose and Hyaluronic Acid as an Anti-Inflammatory Barrier Membrane

    Directory of Open Access Journals (Sweden)

    Yu-Chih Huang

    2016-01-01

    Full Text Available An antiadhesion barrier membrane is an important biomaterial for protecting tissue from postsurgical complications. However, there is room to improve these membranes. Recently, carboxymethylcellulose (CMC incorporated with hyaluronic acid (HA as an antiadhesion barrier membrane and drug delivery system has been reported to provide excellent tissue regeneration and biocompatibility. The aim of this study was to fabricate a novel hydrogel membrane composed of berberine-enriched CMC prepared from bark of the P. amurense tree and HA (PE-CMC/HA. In vitro anti-inflammatory properties were evaluated to determine possible clinical applications. The PE-CMC/HA membranes were fabricated by mixing PE-CMC and HA as a base with the addition of polyvinyl alcohol to form a film. Tensile strength and ultramorphology of the membrane were evaluated using a universal testing machine and scanning electron microscope, respectively. Berberine content of the membrane was confirmed using a UV-Vis spectrophotometer at a wavelength of 260 nm. Anti-inflammatory property of the membrane was measured using a Griess reaction assay. Our results showed that fabricated PE-CMC/HA releases berberine at a concentration of 660 μg/ml while optimal plasticity was obtained at a 30 : 70 PE-CMC/HA ratio. The berberine-enriched PE-CMC/HA had an inhibited 60% of inflammation stimulated by LPS. These results suggest that the PE-CMC/HA membrane fabricated in this study is a useful anti-inflammatory berberine release system.

  17. Bridge resource program.

    Science.gov (United States)

    2013-09-01

    The mission of Rutgers Universitys Center for Advanced Infrastructure and Transportation (CAIT) Bridge Resource Program (BRP) is to provide bridge engineering support to the New Jersey Department of Transportation (NJDOT)s Bridge Engineering an...

  18. Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Ming Ming

    Full Text Available Natural products represent a rich reservoir of potential small chemical molecules exhibiting anti-proliferative and chemopreventive properties. Here, we show that treatment of pancreatic ductal adenocarcinoma (PDAC cells (PANC-1, MiaPaCa-2 with the isoquinoline alkaloid berberine (0.3-6 µM inhibited DNA synthesis and proliferation of these cells and delay the progression of their cell cycle in G1. Berberine treatment also reduced (by 70% the growth of MiaPaCa-2 cell growth when implanted into the flanks of nu/nu mice. Mechanistic studies revealed that berberine decreased mitochondrial membrane potential and intracellular ATP levels and induced potent AMPK activation, as shown by phosphorylation of AMPK α subunit at Thr-172 and acetyl-CoA carboxylase (ACC at Ser79. Furthermore, berberine dose-dependently inhibited mTORC1 (phosphorylation of S6K at Thr389 and S6 at Ser240/244 and ERK activation in PDAC cells stimulated by insulin and neurotensin or fetal bovine serum. Knockdown of α1 and α2 catalytic subunit expression of AMPK reversed the inhibitory effect produced by treatment with low concentrations of berberine on mTORC1, ERK and DNA synthesis in PDAC cells. However, at higher concentrations, berberine inhibited mitogenic signaling (mTORC1 and ERK and DNA synthesis through an AMPK-independent mechanism. Similar results were obtained with metformin used at doses that induced either modest or pronounced reductions in intracellular ATP levels, which were virtually identical to the decreases in ATP levels obtained in response to berberine. We propose that berberine and metformin inhibit mitogenic signaling in PDAC cells through dose-dependent AMPK-dependent and independent pathways.

  19. Anti-Eimeria activity of berberine and identification of associated gene expression changes in the mouse jejunum infected with Eimeria papillata.

    Science.gov (United States)

    Dkhil, Mohamed A; Metwaly, Mahmoud S; Al-Quraishy, Saleh; Sherif, Nour E; Delic, Denis; Al Omar, Suliman Y; Wunderlich, Frank

    2015-04-01

    Plant-based natural products are promising sources for identifying novel agents with potential anti-Eimeria activity. This study explores possible effects of berberine on Eimeria papillata infections in the jejunum of male Swiss albino mice. Berberine chloride, when daily administered to mice during infection, impairs intracellular development and multiplication of E. papillata, evidenced as 60% reduction of maximal fecal output of oocysts on day 5 p.i. Concomitantly, berberine attenuates the inflammatory response, evidenced as decreased messenger RNA (mRNA) expression of IL-1β, IL-6, TNFα, IFNγ, and iNOS, as well as the oxidative stress response, evidenced as impaired increase in malondialdehyde, nitrate, and H2O2 and as prevented decrease in glutathione and catalase activity. Berberine also alters gene expression in the infected jejunum. On day 5 p.i., mRNA expression of 29 genes with annotated functions is more than 10-fold upregulated and that of 14 genes downregulated. Berberine downregulates the genes Xaf1, Itgb3bp, and Faim3 involved in apoptotic processes and upregulates genes involved in innate immune responses, as e.g., Colec11, Saa2, Klra8, Clec1b, and Crtam, especially the genes Cpa3, Fcer1a, and Mcpt1, Mcpt2, and Mcpt4 involved in mast cell activity. Additionally, 18 noncoding lincRNA species are differentially expressed more than 10-fold under berberine. Our data suggest that berberine induces hosts to exert anti-Eimeria activity by attenuating the inflammatory and oxidative stress response, by impairing apoptotic processes, and by activating local innate immune responses and epigenetic mechanisms in the host jejunum. Berberine has the potential as an anti-Eimeria food additive in animal farming.

  20. Berberine and a Berberis lycium extract inactivate Cdc25A and induce α-tubulin acetylation that correlate with HL-60 cell cycle inhibition and apoptosis

    International Nuclear Information System (INIS)

    Khan, Musa; Giessrigl, Benedikt; Vonach, Caroline; Madlener, Sibylle; Prinz, Sonja; Herbaceck, Irene; Hoelzl, Christine; Bauer, Sabine; Viola, Katharina; Mikulits, Wolfgang; Quereshi, Rizwana Aleem; Knasmueller, Siegfried; Grusch, Michael; Kopp, Brigitte; Krupitza, Georg

    2010-01-01

    Berberis lycium Royle (Berberidacea) from Pakistan and its alkaloids berberine and palmatine have been reported to possess beneficial pharmacological properties. In the present study, the anti-neoplastic activities of different B. lycium root extracts and the major constituting alkaloids, berberine and palmatine were investigated in p53-deficient HL-60 cells. The strongest growth inhibitory and pro-apoptotic effects were found in the n-butanol (BuOH) extract followed by the ethyl acetate (EtOAc)-, and the water (H 2 O) extract. The chemical composition of the BuOH extract was analyzed by TLC and quantified by HPLC. 11.1 μg BuOH extract (that was gained from 1 mg dried root) contained 2.0 μg berberine and 0.3 μg/ml palmatine. 1.2 μg/ml berberine inhibited cell proliferation significantly, while 0.5 μg/ml palmatine had no effect. Berberine and the BuOH extract caused accumulation of HL-60 cells in S-phase. This was preceded by a strong activation of Chk2, phosphorylation and degradation of Cdc25A, and the subsequent inactivation of Cdc2 (CDK1). Furthermore, berberine and the extract inhibited the expression of the proto-oncogene cyclin D1. Berberine and the BuOH extract induced the acetylation of α-tubulin and this correlated with the induction of apoptosis. The data demonstrate that berberine is a potent anti-neoplastic compound that acts via anti-proliferative and pro-apoptotic mechanisms independent of genotoxicity.

  1. Berberine Reduces the Metastasis of Chondrosarcoma by Modulating the αvβ3 Integrin and the PKCδ, c-Src, and AP-1 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Chi-Ming Wu

    2013-01-01

    Full Text Available Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis, especially to the lungs. Patients diagnosed with chondrosarcoma have poor prognosis. Berberine, an active component of the Ranunculaceae and Papaveraceae families of plant, has been proven to induce tumor apoptosis and to prevent the metastasis of cancer cells. However, the effects of berberine in human chondrosarcoma are largely unknown. In this study, we found that berberine did not induce cell apoptosis in human primary chondrocytes and chondrosarcoma cells. However, at noncytotoxic concentrations, berberine reduced the migration and invasion of chondrosarcoma cancer cells. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. We also found that incubation of chondrosarcoma cells with berberine reduced mRNA transcription for, and cell surface expression of, the αvβ3 integrin, with additional inhibitory effects on PKCδ, c-Src, and NF-κB activation. Thus, berberine may be a novel antimetastasis agent for the treatment of metastatic chondrosarcoma.

  2. Potential of berberine to enhance antimicrobial activity of commonly used antibiotics for dairy cow mastitis caused by multiple drug-resistant Staphylococcus epidermidis infection.

    Science.gov (United States)

    Zhou, X; Yang, C; Li, Y; Liu, X; Wang, Y

    2015-08-19

    Berberine is a plant alkaloid with antimicrobial activity against a variety of microorganisms. In this study, the antimicrobial properties of berberine against multi-drug resistant field isolates of Staphylococcus epidermidis were investigated using berberine alone or in combination with a commonly used antibiotics in veterinary clinics, including penicillin, lincomycin, and amoxicillin. The results indicated that the minimum inhibitory concentrations of berberine, penicillin, lincomycin, and amoxicillin against field S. epidermidis isolates were 2-512, 0.8-213, 0.4-1024, and 0.4-256 mg/mL, respectively. Furthermore, the synergistic effects of antimicrobial activity against these multi-drug resistant isolates were observed when the berberine was combined with penicillin, lincomycin, or amoxicillin; no antagonistic effect of the combination was detected in any of the clinical isolates. These observations were further confirmed using a time-killing assay, in which a combination of 2 agents yielded a greater than 2.03-2.44 log10 decrease in colony-forming unit/mL compared with each agent alone. These findings suggest that berberine is a promising compound for preventing and treating multi-drug resistant S. epidermidis infected mastitis in dairy cows either alone or in combination with other commonly used antibiotics, such as penicillin, lincomycin, and amoxicillin.

  3. Biophysical characterization of the strong stabilization of the RNA triplex poly(U•poly(A*poly(U by 9-O-(ω-amino alkyl ether berberine analogs.

    Directory of Open Access Journals (Sweden)

    Debipreeta Bhowmik

    Full Text Available Binding of two 9-O-(ω-amino alkyl ether berberine analogs BC1 and BC2 to the RNA triplex poly(U(•poly(A(*poly(U was studied by various biophysical techniques.Berberine analogs bind to the RNA triplex non-cooperatively. The affinity of binding was remarkably high by about 5 and 15 times, respectively, for BC1 and BC2 compared to berberine. The site size for the binding was around 4.3 for all. Based on ferrocyanide quenching, fluorescence polarization, quantum yield values and viscosity results a strong intercalative binding of BC1 and BC2 to the RNA triplex has been demonstrated. BC1 and BC2 stabilized the Hoogsteen base paired third strand by about 18.1 and 20.5 °C compared to a 17.5 °C stabilization by berberine. The binding was entropy driven compared to the enthalpy driven binding of berbeine, most likely due to additional contacts within the grooves of the triplex and disruption of the water structure by the alkyl side chain.Remarkably higher binding affinity and stabilization effect of the RNA triplex by the amino alkyl berberine analogs was achieved compared to berberine. The length of the alkyl side chain influence in the triplex stabilization phenomena.

  4. Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7.

    Science.gov (United States)

    Tan, Wen; Zhong, Zhangfeng; Wang, Shengpeng; Suo, Zhanwei; Yang, Xian; Hu, Xiaodong; Wang, Yitao

    2015-01-01

    Berberine interfering with cancer reprogramming metabolism was confirmed in our previous study. Lipid metabolism and mitochondrial function were also the core parts in reprogramming metabolism. In the presence of some energy-related inhibitors, including C75, compound C, and TOFA, the discrete roles of berberine in lipid metabolism and mitochondrial function were elucidated. An altered lipid metabolism induced by berberine was observed under the inhibition of FASN, AMPK, and ACC in breast cancer cell MCF-7. And the reversion of berberine-induced lipid suppression indicated that ACC inhibition might be involved in that process instead of FASN inhibition. A robust apoptosis induced by berberine even under the inhibition of AMPK and lipid synthesis was also indicated. Finally, mitochondrial function regulation under the inhibition of AMPK and ACC might be in an ACL-independent manner. Undoubtedly, the detailed mechanisms of berberine interfering with lipid metabolism and mitochondrial function combined with energy-related inhibitors need further investigation, including the potential compensatory mechanisms for ATP production and the upregulation of ACL.

  5. Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7

    Directory of Open Access Journals (Sweden)

    Wen Tan

    2015-01-01

    Full Text Available Berberine interfering with cancer reprogramming metabolism was confirmed in our previous study. Lipid metabolism and mitochondrial function were also the core parts in reprogramming metabolism. In the presence of some energy-related inhibitors, including C75, compound C, and TOFA, the discrete roles of berberine in lipid metabolism and mitochondrial function were elucidated. An altered lipid metabolism induced by berberine was observed under the inhibition of FASN, AMPK, and ACC in breast cancer cell MCF-7. And the reversion of berberine-induced lipid suppression indicated that ACC inhibition might be involved in that process instead of FASN inhibition. A robust apoptosis induced by berberine even under the inhibition of AMPK and lipid synthesis was also indicated. Finally, mitochondrial function regulation under the inhibition of AMPK and ACC might be in an ACL-independent manner. Undoubtedly, the detailed mechanisms of berberine interfering with lipid metabolism and mitochondrial function combined with energy-related inhibitors need further investigation, including the potential compensatory mechanisms for ATP production and the upregulation of ACL.

  6. Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D Symptoms in an Opioid-Receptor Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Chunqiu Chen

    Full Text Available Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI tract and cortical neurons using animal models and in vitro tests.The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D symptoms. Then the opioid antagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons.In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR and delta- (DOR opioid receptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons.Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions.

  7. Enzyme Informatics

    Science.gov (United States)

    Alderson, Rosanna G.; Ferrari, Luna De; Mavridis, Lazaros; McDonagh, James L.; Mitchell, John B. O.; Nath, Neetika

    2012-01-01

    Over the last 50 years, sequencing, structural biology and bioinformatics have completely revolutionised biomolecular science, with millions of sequences and tens of thousands of three dimensional structures becoming available. The bioinformatics of enzymes is well served by, mostly free, online databases. BRENDA describes the chemistry, substrate specificity, kinetics, preparation and biological sources of enzymes, while KEGG is valuable for understanding enzymes and metabolic pathways. EzCatDB, SFLD and MACiE are key repositories for data on the chemical mechanisms by which enzymes operate. At the current rate of genome sequencing and manual annotation, human curation will never finish the functional annotation of the ever-expanding list of known enzymes. Hence there is an increasing need for automated annotation, though it is not yet widespread for enzyme data. In contrast, functional ontologies such as the Gene Ontology already profit from automation. Despite our growing understanding of enzyme structure and dynamics, we are only beginning to be able to design novel enzymes. One can now begin to trace the functional evolution of enzymes using phylogenetics. The ability of enzymes to perform secondary functions, albeit relatively inefficiently, gives clues as to how enzyme function evolves. Substrate promiscuity in enzymes is one example of imperfect specificity in protein-ligand interactions. Similarly, most drugs bind to more than one protein target. This may sometimes result in helpful polypharmacology as a drug modulates plural targets, but also often leads to adverse side-effects. Many cheminformatics approaches can be used to model the interactions between druglike molecules and proteins in silico. We can even use quantum chemical techniques like DFT and QM/MM to compute the structural and energetic course of enzyme catalysed chemical reaction mechanisms, including a full description of bond making and breaking. PMID:23116471

  8. Research progress on berberine with a special focus on its oral bioavailability.

    Science.gov (United States)

    Liu, Chang-Shun; Zheng, Yu-Rong; Zhang, Ying-Feng; Long, Xiao-Ying

    2016-03-01

    The natural product berberine (BBR) has become a potential drug in the treatment of diabetes, hyperlipidemia, and cancer. However, the oral delivery of BBR is challenged by its poor bioavailability. It is necessary to improve the oral bioavailability of BBR before it can be used in many clinical applications. Understanding the pharmacokinetic characteristics of BBR will enable the development of suitable formulas that have improved oral bioavailability. The key considerations for BBR are how to enhance the drug absorption and to avoid the intestinal first-pass effect. This review summarizes the pharmacological activities of BBR and analyzes the factors that lead to its poor oral bioavailability. In particular, the therapeutic potential of BBR in new indications from the aspect of oral bioavailability is discussed. In conclusion, BBR is a promising drug candidate for metabolic disorders and cancer but faces considerable challenges due to its poor oral bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

    Directory of Open Access Journals (Sweden)

    Yan M

    2015-10-01

    Full Text Available Meng Yan,1 Kaiping Zhang,1 Yanhui Shi,1 Lifang Feng,1 Lin Lv,1 Baoxin Li1,2 1Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China Abstract: Berberine (BBR, an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293 cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652 and phenylalanine (Phe656 in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. Keywords: berberine, hERG, cavoline-1, cardiotoxicity, LQTS, pharmacological rescue

  10. Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Xue M

    2013-12-01

    Full Text Available Mei Xue, Ming-xing Yang, Wei Zhang, Xiu-min Li, De-hong Gao, Zhi-min Ou, Zhi-peng Li, Su-huan Liu, Xue-jun Li, Shu-yu Yang Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China Abstract: The high aqueous solubility, poor permeability, and absorption of berberine (BBR result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm, zeta potential (7.87 mV, encapsulation efficiency (58%, and drug loading (4.2%. The power of X-ray diffraction combined with 1H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg oral pharmacokinetic studies in rats showed significant improvement (P<0.05 in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone (P<0.05, suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced. Keywords: berberine, solid lipid nanoparticles, pharmacokinetic, hypoglycemic effect

  11. Aptamer-functionalized Fe3 O4 magnetic nanoparticles as a solid-phase extraction adsorbent for the selective extraction of berberine from Cortex phellodendri.

    Science.gov (United States)

    Jiang, Ling-Feng; Chen, Bo-Cheng; Chen, Ben; Li, Xue-Jian; Liao, Hai-Lin; Zhang, Wen-Yan; Wu, Lin

    2017-07-01

    The extraction adsorbent was fabricated by immobilizing the highly specific recognition and binding of aptamer onto the surface of Fe 3 O 4 magnetic nanoparticles, which not only acted as recognition elements to recognize and capture the target molecule berberine from the extract of Cortex phellodendri, but also could favor the rapid separation and purification of the bound berberine by using an external magnet. The developed solid-phase extraction method in this work was useful for the selective extraction and determination of berberine in Cortex phellodendri extracts. Various conditions such as the amount of aptamer-functionalized Fe 3 O 4 magnetic nanoparticles, extraction time, temperature, pH value, Mg 2+ concentration, elution time and solvent were optimized for the solid-phase extraction of berberine. Under optimal conditions, the purity of berberine extracted from Cortex phellodendri was as high as 98.7% compared with that of 4.85% in the extract, indicating that aptamer-functionalized Fe 3 O 4 magnetic nanoparticles-based solid-phase extraction method was very effective for berberine enrichment and separation from a complex herb extract. The applicability and reliability of the developed solid-phase extraction method were demonstrated by separating berberine from nine different concentrations of one Cortex phellodendri extract. The relative recoveries of the spiked solutions of all the samples were between 95.4 and 111.3%, with relative standard deviations ranging between 0.57 and 1.85%. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats.

    Directory of Open Access Journals (Sweden)

    Xu Zhang

    Full Text Available Berberine, a major pharmacological component of the Chinese herb Coptis chinensis, which was originally used to treat bacterial diarrhea, has recently been demonstrated to be clinically effective in alleviating type 2 diabetes. In this study, we revealed that berberine effectively prevented the development of obesity and insulin resistance in high-fat diet (HFD-fed rats, which showed decreased food intake. Increases in the levels of serum lipopolysaccharide-binding protein, monocyte chemoattractant protein-1, and leptin and decrease in the serum level of adiponectin corrected for body fat in HFD-fed rats were also significantly retarded by the co-administration of berberine at 100 mg/kg body weight. Bar-coded pyrosequencing of the V3 region of 16S rRNA genes revealed a significant reduction in the gut microbiota diversity of berberine-treated rats. UniFrac principal coordinates analysis revealed a marked shift of the gut microbiota structure in berberine-treated rats away from that of the controls. Redundancy analysis identified 268 berberine-responding operational taxonomic units (OTUs, most of which were essentially eliminated, whereas a few putative short-chain fatty acid (SCFA-producing bacteria, including Blautia and Allobaculum, were selectively enriched, along with elevations of fecal SCFA concentrations. Partial least square regression models based on these 268 OTUs were established (Q(2>0.6 for predicting the adiposity index, body weight, leptin and adiponectin corrected for body fat, indicating that these discrete phylotypes might have a close association with the host metabolic phenotypes. Taken together, our findings suggest that the prevention of obesity and insulin resistance by berberine in HFD-fed rats is at least partially mediated by structural modulation of the gut microbiota, which may help to alleviate inflammation by reducing the exogenous antigen load in the host and elevating SCFA levels in the intestine.

  13. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats.

    Science.gov (United States)

    Zhang, Xu; Zhao, Yufeng; Zhang, Menghui; Pang, Xiaoyan; Xu, Jia; Kang, Chaoying; Li, Meng; Zhang, Chenhong; Zhang, Zhiguo; Zhang, Yifei; Li, Xiaoying; Ning, Guang; Zhao, Liping

    2012-01-01

    Berberine, a major pharmacological component of the Chinese herb Coptis chinensis, which was originally used to treat bacterial diarrhea, has recently been demonstrated to be clinically effective in alleviating type 2 diabetes. In this study, we revealed that berberine effectively prevented the development of obesity and insulin resistance in high-fat diet (HFD)-fed rats, which showed decreased food intake. Increases in the levels of serum lipopolysaccharide-binding protein, monocyte chemoattractant protein-1, and leptin and decrease in the serum level of adiponectin corrected for body fat in HFD-fed rats were also significantly retarded by the co-administration of berberine at 100 mg/kg body weight. Bar-coded pyrosequencing of the V3 region of 16S rRNA genes revealed a significant reduction in the gut microbiota diversity of berberine-treated rats. UniFrac principal coordinates analysis revealed a marked shift of the gut microbiota structure in berberine-treated rats away from that of the controls. Redundancy analysis identified 268 berberine-responding operational taxonomic units (OTUs), most of which were essentially eliminated, whereas a few putative short-chain fatty acid (SCFA)-producing bacteria, including Blautia and Allobaculum, were selectively enriched, along with elevations of fecal SCFA concentrations. Partial least square regression models based on these 268 OTUs were established (Q(2)>0.6) for predicting the adiposity index, body weight, leptin and adiponectin corrected for body fat, indicating that these discrete phylotypes might have a close association with the host metabolic phenotypes. Taken together, our findings suggest that the prevention of obesity and insulin resistance by berberine in HFD-fed rats is at least partially mediated by structural modulation of the gut microbiota, which may help to alleviate inflammation by reducing the exogenous antigen load in the host and elevating SCFA levels in the intestine.

  14. A survey of the effects of Raha® and Berberin medicine in toxic and sub toxic doses compare with Clonidine medicine on reducing symptoms of morphine withdrawal

    Directory of Open Access Journals (Sweden)

    Mohammad.J Khoshnood

    2010-09-01

    Full Text Available Background: Opiate withdrawal refers to the wide range of symptoms that occur after stopping or dramatically reducing opiate drugs after heavy and prolonged use. The aim of the present study was to determine the effects of Raha and Berberin medicine in toxic and sub toxic doses compare with Clonidine medicine on reducing symptoms of morphine withdrawal in Syrian mice.Materials and Method: 140 Syrian mice (weight range 70-90 gr were divided randomly into 2 groups; first group; n1=35(receiving drug =21, control=14 & second group; n2=105 (receiving drug=91, control=14. Animals were treated by injected increasing doses of morphine sulfate for physical dependence. Then withdrawal syndrome was induced by administration of Naloxone. In order to evaluate the effect of Raha Berberin and Clonidine on morphine withdrawal syndrome in Syrian mice and also amount of total alkaloids and Berberin value in the Raha® were measured.Result: Total of average of alkaloid and Berberin value was 120, 5.72 mg, respectively in 5 ml of the Raha®. The rate of alcohol in Raha® was shown by using the USP procedure which was 19.34 percent. Toxic doses of Raha® and Berberin were 4, 40 mg/kg, respectively. Results indicated that, Raha increases significantly the percent of occurrence of ptosis and immobility were compared with control group (distilled water receiver (p=0.016. The occurrence rate of sniffing, grooming and rearing behavior in Raha and Berberin treated groups compared with control group, within 15min period, was not found statistically significant (p=0.089.Conclusion: Based on our study both Raha® and Berberin in any dilution had no effect on reducing signs of opioid withdrawal syndrome. According to the lack of its effect in mice, further studies should be undertaken for prescription of this drug in human

  15. A Single Arm Pilot Study of Effects of Berberine on the Menstrual Pattern, Ovulation Rate, Hormonal and Metabolic Profiles in Anovulatory Chinese Women with Polycystic Ovary Syndrome.

    Directory of Open Access Journals (Sweden)

    Lin Li

    Full Text Available To evaluate the effects of berberine on the menstrual pattern, ovulation rate, hormonal and metabolic profiles in anovulatory Chinese women with polycystic ovary syndrome.Berberine 0.4 g three times per day was given for four months to 102 anovulatory Chinese women with polycystic ovary syndrome. The menstrual pattern, ovulation rate, hormonal and metabolic profiles were compared before and after the berberine treatment. Ovulation was confirmed by serum progesterone level ≥10 ng/ml.A total of 98 of 102 subjects (96.1% completed the four month treatment, including 69 (70.4%, 69/98 normal weight and 29 (29.6%, 29/98 overweight/obese. Fourteen women (14.3%, 14/98 had regained regular menses after berberine treatment and there was no significant difference between normal weight and overweight/obese groups. The ovulation rate was 25.0% over four months in the whole group, 22.5% in the normal weight group and 31.0% in the overweight/obese group. Sex hormone binding globulin, insulin resistance, total cholesterol, total triglyceride and low-density lipoprotein cholesterol decreased after berberine treatment in the normal weight group only.Our study found that administration of berberine alone may improve the menstrual pattern and ovulation rate in anovulatory Chinese women with polycystic ovary syndrome. Berberine can also decrease sex hormone binding globulin, insulin resistance, total cholesterol, triglycerides and low-density lipoprotein cholesterol in normal weight polycystic ovary syndrome women.Chictr.org ChiCTR-OO-13003943.

  16. Simultaneous fluorescence light-up and selective multicolor nucleobase recognition based on sequence-dependent strong binding of berberine to DNA abasic site.

    Science.gov (United States)

    Wu, Fei; Shao, Yong; Ma, Kun; Cui, Qinghua; Liu, Guiying; Xu, Shujuan

    2012-04-28

    Label-free DNA nucleobase recognition by fluorescent small molecules has received much attention due to its simplicity in mutation identification and drug screening. However, sequence-dependent fluorescence light-up nucleobase recognition and multicolor emission with individual emission energy for individual nucleobases have been seldom realized. Herein, an abasic site (AP site) in a DNA duplex was employed as a binding field for berberine, one of isoquinoline alkaloids. Unlike weak binding of berberine to the fully matched DNAs without the AP site, strong binding of berberine to the AP site occurs and the berberine's fluorescence light-up behaviors are highly dependent on the target nucleobases opposite the AP site in which the targets thymine and cytosine produce dual emission bands, while the targets guanine and adenine only give a single emission band. Furthermore, more intense emissions are observed for the target pyrimidines than purines. The flanking bases of the AP site also produce some modifications of the berberine's emission behavior. The binding selectivity of berberine at the AP site is also confirmed by measurements of fluorescence resonance energy transfer, excited-state lifetime, DNA melting and fluorescence quenching by ferrocyanide and sodium chloride. It is expected that the target pyrimidines cause berberine to be stacked well within DNA base pairs near the AP site, which results in a strong resonance coupling of the electronic transitions to the particular vibration mode to produce the dual emissions. The fluorescent signal-on and emission energy-modulated sensing for nucleobases based on this fluorophore is substantially advantageous over the previously used fluorophores. We expect that this approach will be developed as a practical device for differentiating pyrimidines from purines by positioning an AP site toward a target that is available for readout by this alkaloid probe. This journal is © The Royal Society of Chemistry 2012

  17. Physicochemical characterization of berberine chloride: a perspective in the development of a solution dosage form for oral delivery.

    Science.gov (United States)

    Battu, Sunil Kumar; Repka, Michael A; Maddineni, Sindhuri; Chittiboyina, Amar G; Avery, Mitchell A; Majumdar, Soumyajit

    2010-09-01

    The objective of the present research was to evaluate the physicochemical characteristics of berberine chloride and to assess the complexation of drug with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a first step towards solution dosage form development. The parameters such as log P value were determined experimentally and compared with predicted values. The pH-dependent aqueous solubility and stability were investigated following standard protocols at 25°C and 37°C. Drug solubility enhancement was attempted utilizing both surfactants and cyclodextrins (CDs), and the drug/CD complexation was studied employing various techniques such as differential scanning calorimetry, Fourier transform infrared, nuclear magnetic resonance, and scanning electron microscopy. The experimental log P value suggested that the compound is fairly hydrophilic. Berberine chloride was found to be very stable up to 6 months at all pH and temperature conditions tested. Aqueous solubility of the drug was temperature dependent and exhibited highest solubility of 4.05 ± 0.09 mM in phosphate buffer (pH 7.0) at 25°C, demonstrating the effect of buffer salts on drug solubility. Decreased drug solubility was observed with increasing concentrations of ionic surfactants such as sodium lauryl sulfate and cetyl trimethyl ammonium bromide. Phase solubility studies demonstrated the formation of berberine chloride-HPβCD inclusion complex with 1:1 stoichiometry, and the aqueous solubility of the drug improved almost 4.5-fold in the presence of 20% HPβCD. The complexation efficiency values indicated that the drug has at least threefold greater affinity for hydroxypropyl-β-CD compared to randomly methylated-β-CD. The characterization techniques confirmed inclusion complex formation between berberine chloride and HPβCD and demonstrated the feasibility of developing an oral solution dosage form of the drug.

  18. Evaluation of Synergetic Anticancer Activity of Berberine and Curcumin on Different Models of A549, Hep-G2, MCF-7, Jurkat, and K562 Cell Lines

    Directory of Open Access Journals (Sweden)

    Acharya Balakrishna

    2015-01-01

    Full Text Available Ayurvedic system of medicine is using Berberis aristata and Curcuma longa herbs to treat different diseases including cancer. The study was performed to evaluate the synergetic anticancer activity of Berberine and Curcumin by estimating the inhibition of the cell proliferation by cytotoxicity assay using MTT method on specified human cell lines (A549, Hep-G2, MCF-7, Jurkat, and K562. All the cells were harvested from the culture and seeded in the 96-well assay plates at seeding density of 2.0 × 104 cells/well and were incubated for 24 hours. Test items Berberine with Curcumin (1 : 1, Curcumin 95% pure, and Berberine 95% pure were exposed at the concentrations of 1.25, 0.001, and 0.5 mg/mL, respectively, and incubated for a period of 48 hours followed by dispensing MTT solution (5 mg/mL. The cells were incubated at 37 ± 1°C for 4 hours followed by addition of DMSO for dissolving the formazan crystals and absorbance was read at 570 nm. Separate wells were prepared for positive control, controls (only medium with cells, and blank (only medium. The results had proven the synergetic anticancer activity of Berberine with Curcumin inducing cell death greater percentage of >77% when compared to pure curcumin with <54% and pure Berberine with <45% on average on all cell line models.

  19. Berberine inhibits the chemotherapy-induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer.

    Science.gov (United States)

    Zhao, Yawei; Cui, Lianzhi; Pan, Yue; Shao, Dan; Zheng, Xiao; Zhang, Fan; Zhang, Hansi; He, Kan; Chen, Li

    2017-12-01

    Cytotoxic chemotherapy is an effective and traditional treatment of ovarian cancer. However, chemotherapy-induced apoptosis may also trigger and ultimately accelerate the repopulation of the small number of adjacent surviving cells. This study mainly focused on the tumour cell repopulation caused by chemotherapy in ovarian cancer and the adjunctive/synergistic effect of Berberine on the prevention of tumour repopulation. The transwell system was used to mimic the co-culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy-treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE 2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot. Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE 2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3-iPLA 2 -AA-COX-2-PGE 2 pathway by inhibiting the expression of iPLA 2 and COX-2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE 2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment. Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation. © 2017 John Wiley & Sons Ltd.

  20. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats.

    Science.gov (United States)

    Zhang, Xu; Zhao, Yufeng; Xu, Jia; Xue, Zhengsheng; Zhang, Menghui; Pang, Xiaoyan; Zhang, Xiaojun; Zhao, Liping

    2015-09-23

    Accumulating evidence suggests that the gut microbiota is an important factor in mediating the development of obesity-related metabolic disorders, including type 2 diabetes. Metformin and berberine, two clinically effective drugs for treating diabetes, have recently been shown to exert their actions through modulating the gut microbiota. In this study, we demonstrated that metformin and berberine similarly shifted the overall structure of the gut microbiota in rats. Both drugs showed reverting effects on the high-fat diet-induced structural changes of gut microbiota. The diversity of gut microbiota was significantly reduced by both berberine- and metformin-treatments. Nearest shrunken centroids analysis identified 134 operational taxonomic units (OTUs) responding to the treatments, which showed close associations with the changes of obese phenotypes. Sixty out of the 134 OTUs were decreased by both drugs, while those belonging to putative short-chain fatty acids (SCFA)-producing bacteria, including Allobaculum, Bacteriodes, Blautia, Butyricoccus, and Phascolarctobacterium, were markedly increased by both berberine and, to a lesser extent, metformin. Taken together, our findings suggest that berberine and metformin showed similarity in modulating the gut microbiota, including the enrichment of SCFA-producing bacteria and reduction of microbial diversity, which may contribute to their beneficial effects to the host.

  1. 1H-NMR-Based Metabonomics of the Protective Effect of Coptis chinensis and Berberine on Cinnabar-Induced Hepatotoxicity and Nephrotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Guangyue Su

    2017-11-01

    Full Text Available Coptis chinensis Franch has been used in Traditional Chinese Medicine (TCM for treating infectious and inflammatory diseases for over two thousand years. Berberine (BN, an isoquinoline alkaloid, is the main component of Coptis chinensis. The pharmacological basis for its therapeutic effects, which include hepatoprotective effects on liver injuries, has been studied intensively, yet the therapy of liver injuries and underlying mechanism remain unclear. We investigated the detoxification mechanism of Coptis chinensis and berberine using metabolomics of urine and serum in the present study. After the treatment with Coptis chinensis and berberine, compared with the cinnabar group, Coptis chinensis and berberine can regulate the concentration of the endogenous metabolites. PLS-DA score plots demonstrated that the urine and serum metabolic profiles in rats of the Coptis chinensis and berberine groups were similar those of the control group, yet remarkably apart from the cinnabar group. The mechanism may be related to the endogenous metabolites including energy metabolism, amino acid metabolism and metabolism of intestinal flora in rats. Meanwhile, liver and kidney histopathology examinations and serum clinical chemistry analysis verified the experimental results of metabonomics.

  2. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    International Nuclear Information System (INIS)

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P.

    2006-01-01

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-κB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment

  3. The Enzyme Function Initiative†

    Science.gov (United States)

    Gerlt, John A.; Allen, Karen N.; Almo, Steven C.; Armstrong, Richard N.; Babbitt, Patricia C.; Cronan, John E.; Dunaway-Mariano, Debra; Imker, Heidi J.; Jacobson, Matthew P.; Minor, Wladek; Poulter, C. Dale; Raushel, Frank M.; Sali, Andrej; Shoichet, Brian K.; Sweedler, Jonathan V.

    2011-01-01

    The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily-specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include: 1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation); 2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia; 3) computational and bioinformatic tools for using the strategy; 4) provision of experimental protocols and/or reagents for enzyme production and characterization; and 5) dissemination of data via the EFI’s website, enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal and pharmaceutical efforts. PMID

  4. The Enzyme Function Initiative.

    Science.gov (United States)

    Gerlt, John A; Allen, Karen N; Almo, Steven C; Armstrong, Richard N; Babbitt, Patricia C; Cronan, John E; Dunaway-Mariano, Debra; Imker, Heidi J; Jacobson, Matthew P; Minor, Wladek; Poulter, C Dale; Raushel, Frank M; Sali, Andrej; Shoichet, Brian K; Sweedler, Jonathan V

    2011-11-22

    The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic, we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include (1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation), (2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia, (3) computational and bioinformatic tools for using the strategy, (4) provision of experimental protocols and/or reagents for enzyme production and characterization, and (5) dissemination of data via the EFI's Website, http://enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal, and pharmaceutical efforts.

  5. Bridge element deterioration rates.

    Science.gov (United States)

    2008-10-01

    This report describes the development of bridge element deterioration rates using the NYSDOT : bridge inspection database using Markov chains and Weibull-based approaches. It is observed : that Weibull-based approach is more reliable for developing b...

  6. Bridge vehicle impact assessment.

    Science.gov (United States)

    2011-12-01

    Bridges in New York State have been experiencing close to 200 bridge hits a year. These : accidents are attributed to numerous factors including: improperly stored equipment on trucks; : violation of vehicle posting signs; illegal commercial vehicles...

  7. Bridge Scour Technology Transfer

    Science.gov (United States)

    2018-01-24

    Scour and flooding are the leading causes of bridge failures in the United States and therefore should be monitored. New applications of tools and technologies are being developed, tested, and implemented to reduce bridge scour risk. The National Coo...

  8. LTBP bridge performance primer.

    Science.gov (United States)

    2013-12-01

    "The performance of bridges is critical to the overall performance of the highway transportation system in the United States. However, many critical aspects of bridge performance are not well understood. The reasons for this include the extreme diver...

  9. Cable Supported Bridges

    DEFF Research Database (Denmark)

    Gimsing, Niels Jørgen

    Cable supported bridges in the form of suspension bridges and cable-stayed bridges are distinguished by their ability to overcome large spans.The book concentrates on the synthesis of cable supported bridges, covering both design and construction aspects. The analytical part covers simple methods...... to quantify the different structural configurations and allows a preliminary optimization of the main structure.Included are the most recent advances in structural design, corrosion protection of cables, aerodynamic safety, and erection procedures....

  10. Effect of berberine on the ratio of high-molecular weight adiponectin to total adiponectin and adiponectin receptors expressions in high-fat diet fed rats.

    Science.gov (United States)

    Wu, Yue-Yue; Zha, Ying; Liu, Jun; Wang, Fang; Xu, Jiong; Chen, Zao-Ping; Ding, He-Yuan; Sheng, Li; Han, Xiao-Jie

    2016-11-17

    To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats. Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg -1 ·day -1 BBR (HF+LBBR group) and 380 mg·kg -1 ·day -1 BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were observed and recorded on daily basis. At the end of 12 weeks, the blood, liver, epididymal fat tissues and quadriceps femoris muscles were collected. Fasting insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin and HMW adiponectin levels were measured by enzyme linked immunosorbent assay method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine the insulinsensitizing. Meanwhile the homeostasis model assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The expressions of adipoR1, adipoR2 and adenosine monophophate activated protein kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were detected by Western blot. Liver and kidney toxicity were evaluated during treatment. The body weight of rats in high- or low-dose BBR group reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels decreased compared with HF+Veh group (Pinsulin resistance by increasing the expression of adiponectin receptors and the ratio of HMW to total adiponectin.

  11. Principles of Bridge Reliability

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle; Nowak, Andrzej S.

    The paper gives a brief introduction to the basic principles of structural reliability theory and its application to bridge engineering. Fundamental concepts like failure probability and reliability index are introduced. Ultimate as well as serviceability limit states for bridges are formulated......, and as an example the reliability profile and a sensitivity analyses for a corroded reinforced concrete bridge is shown....

  12. Automatic Bridge Control System

    OpenAIRE

    M. Niraimathi; S.Sivakumar; R.Vigneshwaran; R.Vinothkumar; P.Babu

    2012-01-01

    Bridge vibration control is an important issue whose purpose is to extend the structural service life of bridges. Normally, the bridge is modeled as an elastic beam or plate subject to a moving vehicle. However, the moving truck on a bridge is a complicated problem that must still be researched. In this paper, wepropose a new method, to overcome the huge load in the bridge a load cell is used at the entry which will monitor the load continuously at both ends. To escape from the heavy water fl...

  13. Berberine diminishes side population and down-regulates stem cell-associated genes in the pancreatic cancer cell lines PANC-1 and MIA PaCa-2.

    Science.gov (United States)

    Park, S H; Sung, J H; Chung, N

    2014-09-01

    Cancer stem cells play an important role in metastasis and the relapse of drug resistant cancers. Side-population (SP) cells are capable of effluxing Hoechst 33342 dye and are referred to as cancer stem cells. We investigated the effect of berberine on pancreatic cancer stem cells of PANC-1 and MIA PaCa-2. For both cell lines, the proportions of SP cells in the presence of berberine were investigated and compared to the proportions in the presence of gemcitabine, a standard pancreatic anti-cancer drug. The proportions of SP cells in the PANC-1 and MIA PaCa-2 cell lines were about 9 and PANC-1 decreased to 5.7 ± 2.0 and 6.8 ± 0.8%, respectively, which compares to the control proportion of (9.7 ± 1.7). After berberine and gemcitabine treatment of PANC-1, of the four stem cell-associated genes (SOX2, POU5F1, NANOG, and NOTCH1), all but NOTCH1 were down-regulated. Unfortunately, the effect of berberine and gemcitabine treatments on MIA PaCa-2 SP cells could not be clearly observed because SP cells represented only a very small proportion of MIA PaCa-2 cells. However, SOX2, POU5F1, and NANOG genes were shown to be effectively down-regulated in the MIA PaCa-2 cell line as a whole. Taken together, these results indicate that berberine is as effective at targeting pancreatic cancer cell lines as gemcitabine. Therefore, we believe that POU5F1, SOX2, and NANOG can serve as potential markers, and berberine may be an effective anti-cancer agent when targeting human pancreatic cancer cells and/or their cancer stem cells.

  14. Effect of Letrozole, Berberine, or Their Combination for Infertility in Women with Polycystic Ovary Syndrome: Statistical Analysis Plan for a Multicenter Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Hong-Li Ma

    2016-11-01

    Full Text Available Introduction: Letrozole showed higher ovulation and live birth rates than clomiphene in infertile women with polycystic ovary syndrome (PCOS. Berberine, a major active component of Chinese herbal medicine rhizomacoptidis, has been used to improve insulin resistance to facilitate ovulation induction in women with PCOS, but there is no study reporting the live birth or its potential as a complementary treatment to letrozole. We aim to determine the efficacy of letrozole with or without berberine in achieving live births among 644 infertile women with PCOS in Mainland China.

  15. The effect of Berberine preparation on diarrheal symptoms due to Linac irradiation

    International Nuclear Information System (INIS)

    Hiasa, Tsuyoshi; Mitao, Satoshi; Tanaka, Motofumi; Matsubayashi, Shigeru; Kato, Koji

    1979-01-01

    Kyoberine, a preparation made from berberine, was administered in 20 cases of malignant tumors (16 cases of cervical carcinoma, 2 cases of corpus uteri carcinoma, and 2 cases of ovarian carcinoma) in which diarrhea was an acute symptom resulting from Linac irradiation. Diarrhea occurred frequently in the patients who received 1600 - 2000 rad. In regard to the characteristics of the feces, this drug was remarkably effective in 25% of the patients and effective in 65% total effectiveness, 90%. In regard to the frequency of diarrhea, it was remarkably effective in 30% of the patients and effective in 60% total effectiveness, 90%. A comprehensive assessment of the effect on the characteristics of the feces and the frequency of diarrhea revealed the drug to be remarkably effective in 7 cases (35%) and effective in 11 (55%). After serial administration of the drug, recurrence of diarrhea was noted only in one case out of 18 in which the drug was effective. Examinations of body weight, peripheral blood, the liver, the kidneys, and electrolytes revealed no side effects. This drug had an excellent effect on diarrhea due to Linac irradiation. Because of its depressant action on peristaltic reflexes and its anti-inflammatory and anti-ulcerative actions, it is hoped that it can be used to prevent radiation injuries. (Ueda, J.)

  16. The natural compound berberine positively affects macrophage functions involved in atherogenesis.

    Science.gov (United States)

    Zimetti, F; Adorni, M P; Ronda, N; Gatti, R; Bernini, F; Favari, E

    2015-02-01

    We investigated the effect of berberine (BBR), an alkaloid showing antiatherogenic properties beyond the cholesterol lowering capacity, on macrophage cholesterol handling upon exposure to human serum and on macrophage responses to excess free cholesterol (FC) loading. Mouse and human macrophages were utilized as cellular models. Cholesterol content was measured by a fluorimetric assay; cholesterol efflux, cytotoxicity and membrane FC distribution were evaluated by radioisotopic assays. Monocyte chemotactic protein-1 (MCP-1) secretion was measured by ELISA; membrane ruffling and macropinocytosis were visualized by confocal microscopy. Exposure of cholesterol-enriched MPM to serum in the presence of 1 μM BBR resulted in a reduction of intracellular cholesterol content twice greater than exposure to serum alone (-52%; p microscope analysis revealed that BBR inhibited macropinocytosis, an independent-receptor process involved in LDL internalization. Macrophage FC-enrichment increased MCP-1 release by 1.5 folds, increased cytotoxicity by 2 fold, and induced membrane ruffling; all these responses were markedly inhibited by BBR. FC-enrichment led to an increase in plasma membrane cholesterol by 4.5 folds, an effect counteracted by BBR. We showed novel potentially atheroprotective activities of BBR in macrophages, consisting in the inhibition of serum-induced cholesterol accumulation, occurring at least in part through an impairment of macropinocytosis, and of FC-induced deleterious effects. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan; Xu, Bo; Wang, Tianchang; Yang, Qi; Yang, Qin [State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing (China); Feng, Xudong, E-mail: xudong.feng@childrens.harvard.edu [Department of Medicine, Children' s Hospital Boston, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115 (United States); Xia, Qing, E-mail: xqing@hsc.pku.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing (China)

    2015-06-10

    As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellular energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress.

  18. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis.

    Directory of Open Access Journals (Sweden)

    Xuan Xia

    2011-02-01

    Full Text Available Berberine (BBR is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French. It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK and Glucose-6-phosphatase (G6Pase, were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1, sterol regulatory element-binding protein 1c (SREBP1 and carbohydrate responsive element-binding protein (ChREBP were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.

  19. Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

    Science.gov (United States)

    Yan, Meng; Zhang, Kaiping; Shi, Yanhui; Feng, Lifang; Lv, Lin; Li, Baoxin

    2015-01-01

    Berberine (BBR), an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG) potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293) cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652) and phenylalanine (Phe656) in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. PMID:26543354

  20. Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

    International Nuclear Information System (INIS)

    Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan; Xu, Bo; Wang, Tianchang; Yang, Qi; Yang, Qin; Feng, Xudong; Xia, Qing

    2015-01-01

    As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellular energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress

  1. Drill pipe bridge plug

    International Nuclear Information System (INIS)

    Winslow, D.W.; Brisco, D.P.

    1991-01-01

    This patent describes a method of stopping flow of fluid up through a pipe bore of a pipe string in a well. It comprises: lowering a bridge plug apparatus on a work string into the pipe string to a position where the pipe bore is to be closed; communicating the pipe bore below a packer of the bridge plug apparatus through the bridge plug apparatus with a low pressure zone above the packer to permit the fluid to flow up through the bridge plug apparatus; engaging the bridge plug apparatus with an internal upset of the pipe string; while the fluid is flowing up through the bridge plug apparatus, pulling upward on the work string and the bridge plug apparatus and thereby sealing the packer against the pipe bore; isolating the pipe bore below the packer from the low pressure zone above the packer and thereby stopping flow of the fluid up through the pipe bore; disconnecting the work string from the bridge plug apparatus; and maintaining the bridge plug apparatus in engagement with the internal upset and sealed against the pipe bore due to an upward pressure differential applied to the bridge plug apparatus by the fluid contained therebelow

  2. Bridge over troubled water?

    DEFF Research Database (Denmark)

    Svendsen, Gunnar Lind Haase; Nannestad, Peter; Svendsen, Gert Tinggaard

    2008-01-01

    The problem of integrating non-Western immigrants into Western welfare states is the focus of this paper. To address this issue, we suggest a social capital approach in which we apply the conceptual pair of bridging social capital (BR), which connects an individual to the broader social structure...... relationship between the levels of bridging and bonding capital, suggesting that bonding social capital in the immigrant group does not seem to impede the establishment of the bridging social capital needed for integration....

  3. Sustainable Bridge Infrastructure Procurement

    DEFF Research Database (Denmark)

    Safi, Mohammed; Du, Guangli; Simonsson, Peter

    2016-01-01

    The lack of a flexible but systematic approach for integrating lifecycle aspects into bridge investment decisions is a major obstacle hindering the procurement of sustainable bridge infrastructures. This paper addresses this obstacle by introducing a holistic approach that agencies could use...... to procure the most “sustainable” (lifecycle-efficient) bridge through a fair design-build (D-B) tendering process, considering all the main aspects: life-cycle cost (LCC), service life-span, aesthetic demands and environmental impacts (LCA)....

  4. The hepatic bridge.

    Science.gov (United States)

    Sugarbaker, Paul H

    2018-07-01

    The hepatic bridge forms a tunnel of liver parenchyma that may obscure peritoneal metastases associated with the round ligament. Visualization and then resection of nodules associated with this structure is necessary. The incidence of a hepatic bridge and the extent that it covered the round ligament was determined in consecutive patients. Extent of coverage of the round ligament by the hepatic bridge was determined: Class 1 indicates up to one-third of the round ligament obscured, Class 2 up to two-thirds and Class 3 more than two-thirds. In 102 patients in whom the round ligament of the liver could be completely visualized, 50 had a hepatic bridge. Class 1 was 22 (44%) of the bridges, Class 2 was 16 (32%) and Class 3 was 12 (24%). A hepatic bridge was more frequently present in 28 of 45 male patients (62%) vs. 22 of 57 female patients (38%). Approximately one-half of our patients having cytoreductive surgery for peritoneal metastases were observed to have a hepatic bridge. Up to 56% of these patients have Class 2 or 3 hepatic bridge and may require division of the hepatic bridge to completely visualize the contents of the tunnel created by this structure. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  5. Bridging the Gap

    DEFF Research Database (Denmark)

    Kramer Overgaard, Majken; Broeng, Jes; Jensen, Monika Luniewska

    Bridging the Gap (BtG) is a 2-year project funded by The Danish Industry Foundation. The goal of Bridging the Gap has been to create a new innovation model which will increase the rate at which Danish universities can spinout new technology ventures.......Bridging the Gap (BtG) is a 2-year project funded by The Danish Industry Foundation. The goal of Bridging the Gap has been to create a new innovation model which will increase the rate at which Danish universities can spinout new technology ventures....

  6. Timber in Bridge Structures

    OpenAIRE

    Detkin, Viktoria

    2016-01-01

    The purpose of this final year project was to study the properties of timber as a structural material and the suitability of wood in load bearing members for bridge structures. For a case study, an existing timber bridge was selected. Due to its condition the bridge should be replaced. The design of a new bridge with steel beams holding a glulam deck was made. During the case study the replacement of steel beams by glulam timber ones was discussed. Some calculations were made in order to ...

  7. Bridge health monitoring metrics : updating the bridge deficiency algorithm.

    Science.gov (United States)

    2009-10-01

    As part of its bridge management system, the Alabama Department of Transportation (ALDOT) must decide how best to spend its bridge replacement funds. In making these decisions, ALDOT managers currently use a deficiency algorithm to rank bridges that ...

  8. Long-term bridge performance high priority bridge performance issues.

    Science.gov (United States)

    2014-10-01

    Bridge performance is a multifaceted issue involving performance of materials and protective systems, : performance of individual components of the bridge, and performance of the structural system as a whole. The : Long-Term Bridge Performance (LTBP)...

  9. Synthesizing a Berberine Derivative and Evaluating Antimicrobial Activity to Reinforce with Students the Potential Significance of Small Chemical Structure Changes for Biological Systems

    Science.gov (United States)

    Rodrigues, Catarina A. B.; Neto, Iris; Rijo, Patricia; Afonso, Carlos A. M.

    2018-01-01

    The convenient synthesis of dihydroberberine by the reduction of berberine is described as an experiment for an upper-division undergraduate organic chemistry laboratory course. Students obtained up to 74% yield of the desired pure product without the use of chromatographic techniques. The antimicrobial activities of both compounds against…

  10. [Primary study on fluro [ 19F] berberine derivative for human hepatocellular carcinoma targetting in vitro].

    Science.gov (United States)

    Zhang, Tong; Wu, Xiaoai; Cai, Huawei; Liang, Meng; Fan, Chengzhong

    2017-04-01

    [ 18 F]HX-01, a Fluorine-18 labeled berberine derivative, is a potential positron emission tomography (PET) tumor imaging agent, while [ 19 F]HX-01 is a nonradioactive reference substance with different energy state and has the same physical and chemical properties. In order to collect data for further study of [ 18 F]HX-01 PET imaging of hepatocellular carcinoma in vivo , this study compared the uptake of [ 19 F]HX-01 by human hepatocellular carcinoma and normal hepatocytes in vitro . The target compound, [ 19 F]HX-01, was synthesized in one step using berberrubine and 3-fluoropropyl 4-methylbenzenesulfonate. Cellular uptake and localization of [ 19 F]HX-01 were performed by a fluorescence microscope in human hepatocellular carcinoma HepG2, SMMC-7721 and human normal hepatocyte HL-7702. Cellular proliferation inhibition and cell cytotoxicity assay of the [ 19 F]HX-01 were conducted using cell counting kit-8 (CCK-8) on HepG2, SMMC-7721 and HL-7702 cells. Fluorescent microscopy showed that the combining ability of [ 19 F]HX-01 to the carcinoma SMMC-7721 and HepG2 was higher than that to the normal HL-7702. Cellular proliferation inhibition assay demonstrated that [ 19 F]HX-01 leaded to a dose-dependent inhibition on SMMC-7721, HepG2, and HL-7702 proliferation. Cell cytotoxicity assay presented that the cytotoxicity of [ 19 F]HX-01 to SMMC-7721 and HepG2 was obviously higher than that to HL-7702. This in vitro study showed that [ 19 F]HX-01 had a higher selectivity on human hepatocellular carcinoma cells (SMMC-7721, HepG2) but has less toxicity to normal hepatocytes (HL-7702). This could set up the idea that the radioactive reference substance [ 18 F]HX-01 may be worthy of further development as a potential molecular probe targeting human hepatocellular carcinoma using PET.

  11. Approaches to improve the oral bioavailability and effects of novel anticancer drugs berberine and betulinic acid.

    Directory of Open Access Journals (Sweden)

    Chandraiah Godugu

    Full Text Available The poor bioavailability of Berberine (BBR and Betulinic acid (BA limits the development of these promising anticancer agents for clinical use. In the current study, BBR and BA in spray dried (SD mucoadhesive microparticle formulations were prepared.A patented dual channel spray gun technology established in our laboratory was used for both formulations. Gastrointestinal (GI permeability studies were carried out using Caco-2 cell monolayer grown in in-vitro system. The oral bioavailability and pharmacokinetic profile of SD formulations were studied in Sprague Dawley rats. A549 orthotopic and H1650 metastatic NSCLC models were utilized for the anticancer evaluations.Pharmacokinetic studies demonstrated that BBR and BA SD formulations resulted in 3.46 and 3.90 fold respectively, significant increase in plasma Cmax concentrations. AUC levels were increased by 6.98 and 7.41 fold in BBR and BA SD formulations, respectively. Compared to untreated controls groups, 49.8 & 53.4% decrease in the tumor volumes was observed in SD formulation groups of BBR and BA, respectively. Molecular studies done on excised tumor (A549 tissue suggested that BBR in SD form resulted in a significant decrease in the survivin, Bcl-2, cyclin D1, MMP-9, HIF-1α, VEGF and CD31 expressions. Cleaved caspase 3, p53 and TUNEL expressions were increased in SD formulations. The RT-PCR analysis on H1650 tumor tissue suggested that p38, Phospho-JNK, Bax, BAD, cleaved caspase 3&8 mRNA expressions were significantly increased in BA SD formulations. Chronic administration of BBR and BA SD formulations did not show any toxicity.Due to significant increase in oral bioavailability and superior anticancer effects, our results suggest that spray drying is a superior alternative formulation approach for oral delivery of BBR and BA.

  12. Molecular mechanisms of action of herbal antifungal alkaloid berberine, in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Sanjiveeni Dhamgaye

    Full Text Available Candida albicans causes superficial to systemic infections in immuno-compromised individuals. The concomitant use of fungistatic drugs and the lack of cidal drugs frequently result in strains that could withstand commonly used antifungals, and display multidrug resistance (MDR. In search of novel fungicidals, in this study, we have explored a plant alkaloid berberine (BER for its antifungal potential. For this, we screened an in-house transcription factor (TF mutant library of C. albicans strains towards their susceptibility to BER. Our screen of TF mutant strains identified a heat shock factor (HSF1, which has a central role in thermal adaptation, to be most responsive to BER treatment. Interestingly, HSF1 mutant was not only highly susceptible to BER but also displayed collateral susceptibility towards drugs targeting cell wall (CW and ergosterol biosynthesis. Notably, BER treatment alone could affect the CW integrity as was evident from the growth retardation of MAP kinase and calcineurin pathway null mutant strains and transmission electron microscopy. However, unlike BER, HSF1 effect on CW appeared to be independent of MAP kinase and Calcineurin pathway genes. Additionally, unlike hsf1 null strain, BER treatment of Candida cells resulted in dysfunctional mitochondria, which was evident from its slow growth in non-fermentative carbon source and poor labeling with mitochondrial membrane potential sensitive probe. This phenotype was reinforced with an enhanced ROS levels coinciding with the up-regulated oxidative stress genes in BER-treated cells. Together, our study not only describes the molecular mechanism of BER fungicidal activity but also unravels a new role of evolutionary conserved HSF1, in MDR of Candida.

  13. Tissue distribution of berberine and its metabolites after oral administration in rats.

    Directory of Open Access Journals (Sweden)

    Xiang-Shan Tan

    Full Text Available Berberine (BBR has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n-IT-TOF as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg. The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1, berberrubine (M2 and jatrorrhizine (M4, which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t (area under the concentration-time curve for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic.

  14. Shining a light on LAMP assays--a comparison of LAMP visualization methods including the novel use of berberine.

    Science.gov (United States)

    Fischbach, Jens; Xander, Nina Carolin; Frohme, Marcus; Glökler, Jörn Felix

    2015-04-01

    The need for simple and effective assays for detecting nucleic acids by isothermal amplification reactions has led to a great variety of end point and real-time monitoring methods. Here we tested direct and indirect methods to visualize the amplification of potato spindle tuber viroid (PSTVd) by loop-mediated isothermal amplification (LAMP) and compared features important for one-pot in-field applications. We compared the performance of magnesium pyrophosphate, hydroxynaphthol blue (HNB), calcein, SYBR Green I, EvaGreen, and berberine. All assays could be used to distinguish between positive and negative samples in visible or UV light. Precipitation of magnesium-pyrophosphate resulted in a turbid reaction solution. The use of HNB resulted in a color change from violet to blue, whereas calcein induced a change from orange to yellow-green. We also investigated berberine as a nucleic acid-specific dye that emits a fluorescence signal under UV light after a positive LAMP reaction. It has a comparable sensitivity to SYBR Green I and EvaGreen. Based on our results, an optimal detection method can be chosen easily for isothermal real-time or end point screening applications.

  15. Bitterness intensity prediction of berberine hydrochloride using an electronic tongue and a GA-BP neural network.

    Science.gov (United States)

    Liu, Ruixin; Zhang, Xiaodong; Zhang, Lu; Gao, Xiaojie; Li, Huiling; Shi, Junhan; Li, Xuelin

    2014-06-01

    The aim of this study was to predict the bitterness intensity of a drug using an electronic tongue (e-tongue). The model drug of berberine hydrochloride was used to establish a bitterness prediction model (BPM), based on the taste evaluation of bitterness intensity by a taste panel, the data provided by the e-tongue and a genetic algorithm-back-propagation neural network (GA-BP) modeling method. The modeling characteristics of the GA-BP were compared with those of multiple linear regression, partial least square regression and BP methods. The determination coefficient of the BPM was 0.99965±0.00004, the root mean square error of cross-validation was 0.1398±0.0488 and the correlation coefficient of the cross-validation between the true and predicted values was 0.9959±0.0027. The model is superior to the other three models based on these indicators. In conclusion, the model established in this study has a high fitting degree and may be used for the bitterness prediction modeling of berberine hydrochloride of different concentrations. The model also provides a reference for the generation of BPMs of other drugs. Additionally, the algorithm of the study is able to conduct a rapid and accurate quantitative analysis of the data provided by the e-tongue.

  16. National Bridge Inventory System (NBI)

    Data.gov (United States)

    Department of Transportation — The NBI System is the collection of bridge inspection information and costs associated with bridge replacements of structurally deficient bridges on and off the NHS....

  17. Virtual Bridge Design Challenge

    Science.gov (United States)

    Mitts, Charles R.

    2013-01-01

    This design/problem-solving activity challenges students to design a replacement bridge for one that has been designated as either structurally deficient or functionally obsolete. The Aycock MS Technology/STEM Magnet Program Virtual Bridge Design Challenge is an authentic introduction to the engineering design process. It is a socially relevant…

  18. Bridge the Gap

    DEFF Research Database (Denmark)

    Marselis, Randi

    2017-01-01

    This article focuses on photo projects organised for teenage refugees by the Society for Humanistic Photography (Berlin, Germany). These projects, named Bridge the Gap I (2015), and Bridge the Gap II (2016), were carried out in Berlin and brought together teenagers with refugee and German...

  19. Covered Bridge Security Manual

    Science.gov (United States)

    Brett Phares; Terry Wipf; Ryan Sievers; Travis Hosteng

    2013-01-01

    The design, construction, and use of covered timber bridges is all but a lost art in these days of pre-stressed concrete, high-performance steel, and the significant growth both in the volume and size of vehicles. Furthermore, many of the existing covered timber bridges are preserved only because of their status on the National Registry of Historic Places or the...

  20. The floating water bridge

    International Nuclear Information System (INIS)

    Fuchs, Elmar C; Woisetschlaeger, Jakob; Gatterer, Karl; Maier, Eugen; Pecnik, Rene; Holler, Gert; Eisenkoelbl, Helmut

    2007-01-01

    When high voltage is applied to distilled water filled in two glass beakers which are in contact, a stable water connection forms spontaneously, giving the impression of a floating water bridge. A detailed experimental analysis reveals static and dynamic structures as well as heat and mass transfer through this bridge

  1. Students design composite bridges

    NARCIS (Netherlands)

    Stark, J.W.B.; Galjaard, J.C.; Brekelmans, J.W.P.M.

    1999-01-01

    The paper gives an overview of recent research on steel-concrete composite bridge design by students of Delft University of Technology doing their master's thesis. Primary objective of this research was to find possibilities for application of steel-concrete composite bridges in the Netherlands,

  2. Effects of berberine on a rat model of chronic stress and depression via gastrointestinal tract pathology and gastrointestinal flora profile assays.

    Science.gov (United States)

    Zhu, Xiaohui; Sun, Yangdong; Zhang, Chenggang; Liu, Haifeng

    2017-05-01

    Chronic stress and depression are challenging conditions to treat, owing to their complexity and lack of clinically available and effective therapeutic agents. The aim of the present study was to investigate the mechanism by which berberine acts, by examining alterations to gastrointestinal tract histopathology and flora profile in a rat model, following the induction of stress. Research associating gastrointestinal flora and depression has increased, thus, the present study hypothesized that stress induces depression and changes in the gastrointestinal system. The chronic mild stress rat model was previously established based on a set of 10 chronic unpredictable stress methods. In the present study, the measurements of body weight, behavior, gastrointestinal tract histopathology and gastrointestinal flora profile were collected in order to elucidate understanding of chronic stress and depression in this region. In the present study, induced stress and the resulting depression was demonstrated to significantly decrease the body weight and sucrose preference of rats, as well as significantly increasing traverse time, vertical movement time, grooming time and motionless time in an open‑field test. Following modeling and subsequent treatment with low or high doses of berberine, the measurements were significantly different when compared with unstressed rats. Berberine appears to reverse the physical damage brought about by stress within the gastric mucosa and intestinal microvilli of the stomach, ileum, cecum and colon. Using enterobacterial repetitive intergenic consensus sequence‑based polymerase chain reaction analysis, several distinctive bands disappeared following modeling; however, novel distinctive bands appeared in response to the graded berberine treatment. In conclusion, the present study identified that high concentrations of berberine markedly protects rats from various symptoms of chronic stress and depression, with the potential of facilitating

  3. Effect of berberine on cell cycle arrest and cell survival during cerebral ischemia and reperfusion and correlations with p53/cyclin D1 and PI3K/Akt.

    Science.gov (United States)

    Chai, Yu-Shuang; Hu, Jun; Lei, Fan; Wang, Yu-Gang; Yuan, Zhi-Yi; Lu, Xi; Wang, Xin-Pei; Du, Feng; Zhang, Dong; Xing, Dong-Ming; Du, Li-Jun

    2013-05-15

    Berberine acted as a natural medicine with multiple pharmacological activities. In the present study, we examined the effect of berberine against cerebral ischemia damage from cell cycle arrest and cell survival. Oxygen-glucose deprivation of PC12 cells and primary neurons, and carotid artery ligation in mice were used as in vitro and in vivo cerebral ischemia models. We found that the effect of berberine on cell cycle arrest during ischemia was mediated by decreased p53 and cyclin D1, increased phosphorylation of Bad (higher expression of p-Bad and higher ratio of p-Bad to Bad) and decreased cleavage of caspase 3. Meanwhile, berberine activated the PI3K/Akt pathway during the reperfusion, especially the phosphor-activation of Akt, to promote the cell survival. The neural protective effect of berberine was remained in the presence of inhibitor of mitogen-activated protein/extracellular signal-regulated kinase (MEK), but was suppressed by the inhibitors of PI3K and Akt. We demonstrated that berberine induced cell cycle arrest and cell survival to resist cerebral ischemia injury. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Bridge technology report

    CERN Document Server

    2013-01-01

    Please note this is a Short Discount publication. As LANs have proliferated, new technologies and system concepts have come to the fore. One of the key issues is how to interconnect networks. One means of interconnection is to use a 'bridge'. Other competing technologies are repeaters, routers, and gateways. Bridges permit traffic isolation, connect network segments together and operate at the MAC layer. Further, because they operate at the MAC layer, they can handle a variety of protocols such as TCP/IP, SNA, and X.25. This report focuses on the specific technology of bridging two netw

  5. Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration.

    Science.gov (United States)

    Feng, Ru; Zhao, Zhen-Xiong; Ma, Shu-Rong; Guo, Fang; Wang, Yan; Jiang, Jian-Dong

    2018-01-01

    Berberine (BBR) is considered a multi-target drug that has significant advantages. In contrast to its significant pharmacological effects in clinic, the plasma level of BBR is very low. Our previous work revealed that dihydroberberine (dhBBR) could be an absorbable form of BBR in the intestine, and butyrate is an active metabolite that is generated by gut bacteria in rats. In this study, for the first time we describe gut microbiota-regulated pharmacokinetics in beagle dogs after oral administration of BBR by single (50 mg/kg) or multiple doses (50 mg/kg/d) for 7 days. GC-MS, GC, LC-MS/MS, and LC/MS n -IT-TOF were used to detect dhBBR, butyrate and BBR as well as its Phase I and II metabolites, respectively. The results showed that dhBBR was not detected in dog plasma but was excreted in small amounts in the feces of dogs examined on days 3 and 7. Butyrate was generated by gut bacteria and increased by 1.3- and 1.2-fold in plasma or feces, respectively, after 7 days of BBR treatment compared to the levels before treatment. Changes of intestinal bacterial composition were analyzed by 16S rRNA genes analysis. The results presented that dogs treated with BBR for 7 days increased both the abundance of the butyrate- and the nitroreductases- producing bacteria. We also identified chemical structures of the Phase I and II metabolites and analyzed their contents in beagle dogs. Eleven metabolites were detected in plasma and feces after BBR oral administration (50 mg/kg) to dogs, including 8 metabolites of Phase I and III metabolites of Phase II. The pharmacokinetic profile indicated that the concentration of BBR in plasma was low, with a C max value of 36.88 ± 23.45 ng/mL. The relative content of glucuronic acid conjugates (M11) was higher than those of other metabolites (M1, M2, M12, and M14) in plasma. BBR was detected in feces, with high excreted amounts on day 3 (2625.04 ± 1726.94 μg/g) and day 7 (2793.43 ± 488.10 μg/g). In summary, this is the first study to

  6. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Ya-Yun [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Tseng, Yu-Ting [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Lo, Yi-Ching, E-mail: yichlo@kmu.edu.tw [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2013-11-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H{sub 2}O{sub 2} neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS

  7. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    International Nuclear Information System (INIS)

    Hsu, Ya-Yun; Tseng, Yu-Ting; Lo, Yi-Ching

    2013-01-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H 2 O 2 neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS production and

  8. Bridge removal plan requirements.

    Science.gov (United States)

    2011-04-15

    This report provides resources that detail specifications and guidelines related to bridge removal plans across the : United States. We have organized the information into three sections: : ! National Guidance : Includes language from AASHTO specific...

  9. Bridged Race Population Estimates

    Data.gov (United States)

    U.S. Department of Health & Human Services — Population estimates from "bridging" the 31 race categories used in Census 2000, as specified in the 1997 Office of Management and Budget (OMB) race and ethnicity...

  10. Bridging Humanism and Behaviorism.

    Science.gov (United States)

    Chu, Lily

    1980-01-01

    Humanistic behaviorism may provide the necessary bridge between behaviorism and humanism. Perhaps the most humanistic approach to teaching is to learn how certain changes will help students and how these changes can be accomplished. (Author/MLF)

  11. Cyclization in concert

    NARCIS (Netherlands)

    Fraaije, Marco W.; Mattevi, Andrea

    2008-01-01

    The berberine bridge enzyme catalyzes the crucial step in the biosynthesis of an important class of alkaloids through a reaction that cannot be carried out using conventional organic chemistry tools. Characterization of the enzyme demonstrates a concerted mechanism that couples two distinct chemical

  12. Cooperativity of complex salt bridges

    OpenAIRE

    Gvritishvili, Anzor G.; Gribenko, Alexey V.; Makhatadze, George I.

    2008-01-01

    The energetic contribution of complex salt bridges, in which one charged residue (anchor residue) forms salt bridges with two or more residues simultaneously, has been suggested to have importance for protein stability. Detailed analysis of the net energetics of complex salt bridge formation using double- and triple-mutant cycle analysis revealed conflicting results. In two cases, it was shown that complex salt bridge formation is cooperative, i.e., the net strength of the complex salt bridge...

  13. Engineering and introduction of de novo disulphide bridges in ...

    Indian Academy of Sciences (India)

    The engineeringof de novo disulphide bridges has been explored as a means to increase the thermal stability of enzymes in the rationalmethod of protein engineering. In this study, Disulphide by Design software, homology modelling and moleculardynamics simulations were used to select appropriate amino acid pairs for ...

  14. Separation of Berberine Hydrochloride and Tetrahydropalmatine and Their Quantitative Analysis with Thin Layer Chromatography Involved with Ionic Liquids

    Directory of Open Access Journals (Sweden)

    Jing Lu

    2015-01-01

    Full Text Available [BMIM]OH was used in mobile and stationary phase of thin layer chromatography (TLC to analyze berberine hydrochloride and tetrahydropalmatine for the first time. Supported imidazole ionic liquid with hydroxide ion on silica gel (SiO2·Im+·OH− was synthesized through simple procedure and characterized by Fourier transform infrared spectroscopy (FT-IR, elemental analysis, and scanning electron microscope (SEM. Moreover, on the plates prepared by SiO2·Im+·OH−, the contents of the above alkaloids in the Chinese patent medicine (CPM of “Stomacheasy” capsule were successfully determined by TLC scanner. The key conditions and chromatographic behaviors were also investigated in detail. According to similar ways, ionic liquids (ILs also can be used in other planar chromatographies in two modes. This study is expected to be helpful in expanding the application of IL and its bonded silica gel in TLC separation field.

  15. Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control

    Directory of Open Access Journals (Sweden)

    Di Pierro F

    2012-07-01

    Full Text Available Francesco Di Pierro,1 Nicola Villanova,2 Federica Agostini,2 Rebecca Marzocchi,2 Valentina Soverini,2 Giulio Marchesini21Scientific Department, Velleja Research, Milano, 2Diseases of Metabolism, S Orsola Malpighi Hospital, Bologna, ItalyBackground: Suboptimal glycemic control is a common situation in diabetes, regardless of the wide range of drugs available to reach glycemic targets. Basic research in diabetes is endeavoring to identify new actives working as insulin savers, use of which could delay the introduction of injectable insulin or reduce the insulin dose needed. Commonly available as a nutraceutical, berberine is a potential candidate.Methods and results: Because its low oral bioavailability can be overcome by P-glycoprotein inhibitors like herbal polyphenols, we have tested the nutraceutical combination of Berberis aristata extract and Silybum marianum extract (Berberol® in type 2 diabetes in terms of its additive effect when combined with a conventional oral regimen for patients with suboptimal glycemic control. After 90 days of treatment, the nutraceutical association had a positive effect on glycemic and lipid parameters, significantly reducing glycosylated hemoglobin, basal insulin, homeostatic model assessment of insulin resistance, total and low-density lipoprotein cholesterol, and triglycerides. A relevant effect was also observed in terms of liver function by measuring aspartate transaminase and alanine transaminase. The product had a good safety profile, with distinctive gastrointestinal side effects likely due to its acarbose-like action.Conclusion: Although further studies should be carried out to confirm our data, Berberol could be considered a good candidate as an adjunctive treatment option in diabetes, especially in patients with suboptimal glycemic control.Keywords: berberine, silymarin, glycosylated hemoglobin, diabetes

  16. Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation.

    Science.gov (United States)

    Tsang, Miranda S M; Jiao, Delong; Chan, Ben C L; Hon, Kam-Lun; Leung, Ping C; Lau, Clara B S; Wong, Eric C W; Cheng, Ling; Chan, Carmen K M; Lam, Christopher W K; Wong, Chun K

    2016-04-20

    Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils.

  17. O-hexadecyl-dextran entrapped berberine nanoparticles abrogate high glucose stress induced apoptosis in primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Radhika Kapoor

    Full Text Available Nanotized phytochemicals are being explored by researchers for promoting their uptake and effectiveness at lower concentrations. In this study, O-hexadecyl-dextran entrapped berberine chloride nanoparticles (BC-HDD NPs were prepared, and evaluated for their cytoprotective efficacy in high glucose stressed primary hepatocytes and the results obtained compared with bulk berberine chloride (BBR treatment. The nanotized formulation treated primary hepatocytes that were exposed to high glucose (40 mM, showed increased viability compared to the bulk BBR treated cells. BC-HDD NPs reduced the ROS generation by ∼ 3.5 fold during co-treatment, prevented GSH depletion by ∼ 1.6 fold, reduced NO formation by ∼ 5 fold and significantly prevented decline in SOD activity in stressed cells. Lipid peroxidation was also prevented by ∼ 1.9 fold in the presence of these NPs confirming the antioxidant capacity of the formulation. High glucose stress increased Bax/Bcl2 ratio followed by mitochondrial depolarization and activation of caspase-9/-3 confirming involvement of mitochondrial pathway of apoptosis in the exposed cells. Co- and post-treatment of BC-HDD NPs prevented depolarization of mitochondrial membrane, reduced Bax/Bcl2 ratio and prevented externalization of phosphatidyl-serine confirming their anti-apoptotic capacity in those cells. Sub-G1 phase apparent in high glucose stressed cells was not seen in BC-HDD NPs treated cells. The present study reveals that BC-HDD NPs at ∼ 20 fold lower concentration are as effective as BBR in preventing high glucose induced oxidative stress, mitochondrial depolarization and downstream events of apoptotic cell death.

  18. Long Span Bridges in Scandinavia

    DEFF Research Database (Denmark)

    Gimsing, Niels Jørgen

    1998-01-01

    The first Scandinavian bridge with a span of more than 500 m was the Lillebælt Suspension Bridge opened to traffic in 1970.Art the end of the 20th century the longest span of any European bridge is found in the Storebælt East Bridge with a main span of 1624 m. Also the third longest span in Europe...... is found in Scandinavia - the 1210 m span of the Höga Kusten Bridge in Sweden.The Kvarnsund Bridge in Norway was at the completion in 1991 the longest cable-stayed bridge in the world, and the span of 530 m is still thge longest for cable-stayed bridges in concrete. The Øresund Bridge with its sapn of 490...

  19. Upregulating reverse cholesterol transport with cholesteryl ester transfer protein inhibition requires combination with the LDL-lowering drug berberine in dyslipidemic hamsters.

    Science.gov (United States)

    Briand, François; Thieblemont, Quentin; Muzotte, Elodie; Sulpice, Thierry

    2013-01-01

    This study aimed to investigate whether cholesteryl ester transfer protein inhibition promotes in vivo reverse cholesterol transport in dyslipidemic hamsters. In vivo reverse cholesterol transport was measured after an intravenous injection of (3)H-cholesteryl-oleate-labeled/oxidized low density lipoprotein particles ((3)H-oxLDL), which are rapidly cleared from plasma by liver-resident macrophages for further (3)H-tracer egress in plasma, high density lipoprotein (HDL), liver, and feces. A first set of hamsters made dyslipidemic with a high-fat and high-fructose diet was treated with vehicle or torcetrapib 30 mg/kg (TOR) over 2 weeks. Compared with vehicle, TOR increased apolipoprotein E-rich HDL levels and significantly increased (3)H-tracer appearance in HDL by 30% over 72 hours after (3)H-oxLDL injection. However, TOR did not change (3)H-tracer recovery in liver and feces, suggesting that uptake and excretion of cholesterol deriving from apolipoprotein E-rich HDL is not stimulated. As apoE is a potent ligand for the LDL receptor, we next evaluated the effects of TOR in combination with the LDL-lowering drug berberine, which upregulates LDL receptor expression in dyslipidemic hamsters. Compared with TOR alone, treatment with TOR+berberine 150 mg/kg resulted in lower apolipoprotein E-rich HDL levels. After (3)H-oxLDL injection, TOR+berberine significantly increased (3)H-tracer appearance in fecal cholesterol by 109%. Our data suggest that cholesteryl ester transfer protein inhibition alone does not stimulate reverse cholesterol transport in dyslipidemic hamsters and that additional effects mediated by the LDL-lowering drug berberine are required to upregulate this process.

  20. Nonlinearity in oscillating bridges

    Directory of Open Access Journals (Sweden)

    Filippo Gazzola

    2013-09-01

    Full Text Available We first recall several historical oscillating bridges that, in some cases, led to collapses. Some of them are quite recent and show that, nowadays, oscillations in suspension bridges are not yet well understood. Next, we survey some attempts to model bridges with differential equations. Although these equations arise from quite different scientific communities, they display some common features. One of them, which we believe to be incorrect, is the acceptance of the linear Hooke law in elasticity. This law should be used only in presence of small deviations from equilibrium, a situation which does not occur in widely oscillating bridges. Then we discuss a couple of recent models whose solutions exhibit self-excited oscillations, the phenomenon visible in real bridges. This suggests a different point of view in modeling equations and gives a strong hint how to modify the existing models in order to obtain a reliable theory. The purpose of this paper is precisely to highlight the necessity of revisiting the classical models, to introduce reliable models, and to indicate the steps we believe necessary to reach this target.

  1. Active Control of Suspension Bridges

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle

    In this paper some recent research on active control of very long suspension bridges, is presented. The presentation is based on research work at Aalborg University, Denmark. The active control system is based on movable flaps attached to the bridge girder. Wind load on bridges with or without...... flaps attached to the girder is briefly presented. A simple active control system is discussed. Results from wind tunnel experiments with a bridge section show that flaps can be used effectively to control bridge girder vibrations. Flutter conditions for suspension bridges with and without flaps...

  2. Characterization of bacterial communities in hybrid upflow anaerobic sludge blanket (UASB)-membrane bioreactor (MBR) process for berberine antibiotic wastewater treatment.

    Science.gov (United States)

    Qiu, Guanglei; Song, Yong-Hui; Zeng, Ping; Duan, Liang; Xiao, Shuhu

    2013-08-01

    Biodegradation of berberine antibiotic was investigated in upflow anaerobic sludge blanket (UASB)-membrane bioreactor (MBR) process. After 118days of operation, 99.0%, 98.0% and 98.0% overall removals of berberine, COD and NH4(+)-N were achieved, respectively. The detailed composition of the established bacterial communities was studied by using 16S rDNA clone library. Totally, 400 clones were retrieved and grouped into 186 operational taxonomic units (OTUs). UASB was dominated by Firmicutes and Bacteroidetes, while Proteobacteria, especially Alpha- and Beta-proteobacteria were prevalent in the MBRs. Clostridium, Eubacterium and Synergistes in the UASB, as well as Hydrogenophaga, Azoarcus, Sphingomonas, Stenotrophomonas, Shinella and Alcaligenes in the MBRs were identified as potential functional species in biodegradation of berberine and/or its metabolites. The bacterial community compositions in two MBRs were significantly discrepant. However, the identical functions of the functional species ensured the comparable pollutant removal performances in two bioreactors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. 47 CFR 80.1007 - Bridge-to-bridge radiotelephone installation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Bridge-to-bridge radiotelephone installation. 80.1007 Section 80.1007 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... Bridge-to-Bridge Act § 80.1007 Bridge-to-bridge radiotelephone installation. Use of the bridge-to-bridge...

  4. Enzyme detection by microfluidics

    DEFF Research Database (Denmark)

    2013-01-01

    Microfluidic-implemented methods of detecting an enzyme, in particular a DNA-modifying enzyme, are provided, as well as methods for detecting a cell, or a microorganism expressing said enzyme. The enzyme is detected by providing a nucleic acid substrate, which is specifically targeted...... by that enzyme...

  5. Istanbul Bridge Conference 2014

    CERN Document Server

    Gülkan, Polat; Mahmoud, Khaled

    2016-01-01

      The book includes peer-reviewed contributions selected from presentations given at the Istanbul Bridge Conference 2014, held from August 11 – 13 in Istanbul, Turkey. It reports on the current challenges in bridge engineering faced by professionals around the globe, giving a special emphasis to recently developed techniques, innovations and opportunities. The book covers key topics in the field, including modeling and analysis methods; construction and erection techniques; design for extreme events and condition assessment and structural health monitoring. There is a balanced presentation of theory, research and practice. This book, which provides the readers with a comprehensive and timely reference guide on current practices in bridge engineering, is intended for professionals, academic researchers and students alike.

  6. Bridge deterioration models to support Indiana's bridge management system.

    Science.gov (United States)

    2016-02-01

    An effective bridge management system that is equipped with reliable deterioration models enables agency engineers to carry out : monitoring and long-term programming of bridge repair actions. At the project level, deterioration models help the agenc...

  7. Development of bridge girder movement criteria for accelerated bridge construction.

    Science.gov (United States)

    2014-06-01

    End diaphragms connect multiple girders to form a bridge superstructure system for effective resistance to earthquake loads. Concrete : girder bridges that include end diaphragms consistently proved to perform well during previous earthquake events. ...

  8. Berberine Attenuates Development of the Hepatic Gluconeogenesis and Lipid Metabolism Disorder in Type 2 Diabetic Mice and in Palmitate-Incubated HepG2 Cells through Suppression of the HNF-4α miR122 Pathway.

    Science.gov (United States)

    Wei, Shengnan; Zhang, Ming; Yu, Yang; Lan, Xiaoxin; Yao, Fan; Yan, Xin; Chen, Li; Hatch, Grant M

    2016-01-01

    Berberine (BBR) has been shown to exhibit protective effects against diabetes and dyslipidemia. Previous studies have indicated that BBR modulates lipid metabolism and inhibits hepatic gluconeogensis by decreasing expression of Hepatocyte Nuclear Factor-4α (HNF-4α). However, the mechanism involved in this process was unknown. In the current study, we examined the mechanism of how BBR attenuates hepatic gluconeogenesis and the lipid metabolism alterations observed in type 2 diabetic (T2D) mice and in palmitate (PA)-incubated HepG2 cells. Treatment with BBR for 4 weeks improve all biochemical parameters compared to T2D mice. Treatment of T2D mice for 4 weeks or treatment of PA-incubated HepG2 cells for 24 h with BBR decreased expression of HNF-4α and the microRNA miR122, the key gluconeogenesis enzymes Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) and the key lipid metabolism proteins Sterol response element binding protein-1 (SREBP-1), Fatty acid synthase-1 (FAS-1) and Acetyl-Coenzyme A carboxylase (ACCα) and increased Carnitine palmitoyltransferase-1(CPT-1) compared to T2D mice or PA-incubated HepG2 cells. Expression of HNF-4α in HepG2 cells increased expression of gluconeogenic and lipid metabolism enzymes and BBR treatment or knock down of miR122 attenuated the effect of HNF-4α expression. In contrast, BBR treatment did not alter expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. In addition, miR122 mimic increased expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. These data indicate that miR122 is a critical regulator in the downstream pathway of HNF-4α in the regulation of hepatic gluconeogenesis and lipid metabolism in HepG2 cells. The effect of BBR on hepatic gluconeogenesis and lipid metabolism is mediated through HNF-4α and is regulated downstream of miR122. Our data provide new evidence to support HNF-4α and miR122

  9. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  10. BUILDING "BRIDGES" WITH QUALITY ASSURANCE

    Science.gov (United States)

    The papr describes how, rather than building "bridges" across centuries, quality assurance (QA) personnel have the opportunity to build bridges across technical disciplines, between public and private organizations, and between different QA groups. As reviewers and auditors of a...

  11. Bridge-Vehicle Impact Assessment

    Science.gov (United States)

    2011-08-01

    Bridges in New York State have been experiencing close to 200 bridge hits a year. These : accidents are attributed to numerous factors including: improperly stored equipment on trucks; : violation of vehicle posting signs; illegal commercial vehicles...

  12. Virginia Bridge Information Systems Laboratory.

    Science.gov (United States)

    2014-06-01

    This report presents the results of applied data mining of legacy bridge databases, focusing on the Pontis and : National Bridge Inventory databases maintained by the Virginia Department of Transportation (VDOT). Data : analysis was performed using a...

  13. Public response to bridge colors.

    Science.gov (United States)

    1973-01-01

    To determine people's reactions to bridges painted in colors as white, yellow, green, blue, red, brown, black, and aluminum, two test bridges were selected in Charlottesville, Virginia. One was painted a different color each month and the other was k...

  14. Existing Steel Railway Bridges Evaluation

    Science.gov (United States)

    Vičan, Josef; Gocál, Jozef; Odrobiňák, Jaroslav; Koteš, Peter

    2016-12-01

    The article describes general principles and basis of evaluation of existing railway bridges based on the concept of load-carrying capacity determination. Compared to the design of a new bridge, the modified reliability level for existing bridges evaluation should be considered due to implementation of the additional data related to bridge condition and behaviour obtained from regular inspections. Based on those data respecting the bridge remaining lifetime, a modification of partial safety factors for actions and materials could be respected in the bridge evaluation process. A great attention is also paid to the specific problems of determination of load-caring capacity of steel railway bridges in service. Recommendation for global analysis and methodology for existing steel bridge superstructure load-carrying capacity determination are described too.

  15. Existing Steel Railway Bridges Evaluation

    Directory of Open Access Journals (Sweden)

    Vičan Josef

    2016-12-01

    Full Text Available The article describes general principles and basis of evaluation of existing railway bridges based on the concept of load-carrying capacity determination. Compared to the design of a new bridge, the modified reliability level for existing bridges evaluation should be considered due to implementation of the additional data related to bridge condition and behaviour obtained from regular inspections. Based on those data respecting the bridge remaining lifetime, a modification of partial safety factors for actions and materials could be respected in the bridge evaluation process. A great attention is also paid to the specific problems of determination of load-caring capacity of steel railway bridges in service. Recommendation for global analysis and methodology for existing steel bridge superstructure load-carrying capacity determination are described too.

  16. Looking Beyond the Bridge

    DEFF Research Database (Denmark)

    Jahn, Elke; Rosholm, Michael

    We perform a comprehensive analysis of the stepping-stone effect of temporary agency employment on unemployed workers. Using the timing-of-events approach, we not only investigate whether agency employment is a bridge into regular employment but also analyze its effect on post-unemployment wages...

  17. Bridging a Cultural Gap

    Science.gov (United States)

    Leviatan, Talma

    2008-01-01

    There has been a broad wave of change in tertiary calculus courses in the past decade. However, the much-needed change in tertiary pre-calculus programmes--aimed at bridging the gap between high-school mathematics and tertiary mathematics--is happening at a far slower pace. Following a discussion on the nature of the gap and the objectives of a…

  18. Building a Straw Bridge

    Science.gov (United States)

    Teaching Science, 2015

    2015-01-01

    This project is for a team of students (groups of two or three are ideal) to design and construct a model of a single-span bridge, using plastic drinking straws as the building material. All steps of the design, construction, testing and critiquing stages should be recorded by students in a journal. Students may like to include labelled diagrams,…

  19. Bridging the Gap?

    Science.gov (United States)

    Salter, Colin

    2009-01-01

    The political context of the conversion of the Historic Tramway Bridge, adjacent to Sandon Point in Bulli (NSW, Australia), and how this was exploited to serve predetermined ends, illustrates that technologies can be designed to have particular social (and political) effects. Through reflection on this relatively small engineering project, this…

  20. Quantum Bidding in Bridge

    Science.gov (United States)

    Muhammad, Sadiq; Tavakoli, Armin; Kurant, Maciej; Pawłowski, Marcin; Żukowski, Marek; Bourennane, Mohamed

    2014-04-01

    Quantum methods allow us to reduce communication complexity of some computational tasks, with several separated partners, beyond classical constraints. Nevertheless, experimental demonstrations of this have thus far been limited to some abstract problems, far away from real-life tasks. We show here, and demonstrate experimentally, that the power of reduction of communication complexity can be harnessed to gain an advantage in a famous, immensely popular, card game—bridge. The essence of a winning strategy in bridge is efficient communication between the partners. The rules of the game allow only a specific form of communication, of very low complexity (effectively, one has strong limitations on the number of exchanged bits). Surprisingly, our quantum technique does not violate the existing rules of the game (as there is no increase in information flow). We show that our quantum bridge auction corresponds to a biased nonlocal Clauser-Horne-Shimony-Holt game, which is equivalent to a 2→1 quantum random access code. Thus, our experiment is also a realization of such protocols. However, this correspondence is not complete, which enables the bridge players to have efficient strategies regardless of the quality of their detectors.

  1. Bridging the Transition Gap

    Science.gov (United States)

    2013-05-23

    period and provide recommendations to guide future research and policy development. 4 DEFINING THE TRANSITIONAL SECURITY GAP There have been...BRIDGING THE TRANSITION GAP A Monograph by MAJ J.D. Hansen United States Army School of Advanced Military Studies United States Army...suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704

  2. Bridging the Gaps.

    Science.gov (United States)

    Netzer, Greg

    1995-01-01

    Discusses a model water quality monitoring project, Project Bridge, established to train minority girls about to enter eighth grade in scientific procedures followed by hands-on experimentation. Students spent a week monitoring water in an urban stream and analyzing results. (LZ)

  3. Bridging the Gap

    DEFF Research Database (Denmark)

    Dahlberg, Rasmus

    2016-01-01

    The fixed link between Denmark and Sweden connects two busy cities and a large international airport with many of its travelers and employees. 18,000 vehicles and 160 passenger trains transport each day more than 70,000 people across the combined road and rail Øresund Bridge and through the Øresu...... in its final report to the Danish and Swedish transport authorities while drawing upon experiences from two recent comparable cases of infrastructure disruptions: The Champlain Bridge (2009) and the Forth Road Bridge (2015).......The fixed link between Denmark and Sweden connects two busy cities and a large international airport with many of its travelers and employees. 18,000 vehicles and 160 passenger trains transport each day more than 70,000 people across the combined road and rail Øresund Bridge and through the Øresund...... Tunnel, approximately 25,000 of them critical to the regional work market. Even though the risk analysis states that the likelihood of a long-term closure (100C days) is very low Danish and Swedish transport authorities have demanded that the infrastructure operator conducts a survey of the preparedness...

  4. Revised Rules for Concrete Bridges

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle; Jensen, F. M.; Middleton, C.

    This paper is based on research performed for the Highway Agency, London, UK under the project DPU/9/44 "Revision of Bridge Assessment Rules Based on Whole Life Performance: Concrete Bridges" It contains details of a methodology which can be used to generate Whole Life (WL) reliability profiles....... These WL reliability profiles may be used to establish revised rules for Concrete Bridges....

  5. Simulation of multivariate diffusion bridges

    DEFF Research Database (Denmark)

    Bladt, Mogens; Finch, Samuel; Sørensen, Michael

    We propose simple methods for multivariate diffusion bridge simulation, which plays a fundamental role in simulation-based likelihood and Bayesian inference for stochastic differential equations. By a novel application of classical coupling methods, the new approach generalizes a previously...... proposed simulation method for one-dimensional bridges to the mulit-variate setting. First a method of simulating approzimate, but often very accurate, diffusion bridges is proposed. These approximate bridges are used as proposal for easily implementable MCMC algorithms that produce exact diffusion bridges...

  6. Integral Abutment and Jointless Bridges

    Directory of Open Access Journals (Sweden)

    Cristian-Claudiu Comisu

    2005-01-01

    Full Text Available Integral bridges, or integral abutment and jointless bridges, as they are more commonly known in the USA, are constructed without any movement joints between spans or between spans and abutments. Typically these bridges have stub-type abutments supported on piles and continuous bridge deck from one embankment to the other. Foundations are usually designed to be small and flexible to facilitate horizontal movement or rocking of the support. Integrally bridges are simple or multiple span ones that have their superstructure cast integrally with their substructure. The jointless bridges cost less to construct and require less maintenance then equivalent bridges with expansion joints. Integral bridges present a challenge for load distribution calculations because the bridge deck, piers, abutments, embankments and soil must all be considered as single compliant system. This paper presents some of the important features of integral abutment and jointless bridge design and some guidelines to achieve improved design. The goal of this paper is to enhance the awareness among the engineering community to use integral abutment and jointless bridges in Romania.

  7. Electrical Actuation Technology Bridging

    Science.gov (United States)

    Hammond, Monica (Compiler); Sharkey, John (Compiler)

    1993-01-01

    This document contains the proceedings of the NASA Electrical Actuation Technology Bridging (ELA-TB) Workshop held in Huntsville, Alabama, September 29-October 1, 1992. The workshop was sponsored by the NASA Office of Space Systems Development and Marshall Space Flight Center (MSFC). The workshop addressed key technologies bridging the entire field of electrical actuation including systems methodology, control electronics, power source systems, reliability, maintainability, and vehicle health management with special emphasis on thrust vector control (TVC) applications on NASA launch vehicles. Speakers were drawn primarily from industry with participation from universities and government. In addition, prototype hardware demonstrations were held at the MSFC Propulsion Laboratory each afternoon. Splinter sessions held on the final day afforded the opportunity to discuss key issues and to provide overall recommendations. Presentations are included in this document.

  8. BALKANS: Building bridges

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    At a time when upheaval and political unrest in some Balkan countries gives cause for concern, it is good to know that physics, once again, is building bridges between nations. The new international mobility in the region was marked by a major activity of the Balkan Physical Union - the first Balkan School of Physics, held on the banks of the Bosphorus during the first two weeks of September

  9. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs.

    Science.gov (United States)

    McCubrey, James A; Lertpiriyapong, Kvin; Steelman, Linda S; Abrams, Steve L; Yang, Li V; Murata, Ramiro M; Rosalen, Pedro L; Scalisi, Aurora; Neri, Luca M; Cocco, Lucio; Ratti, Stefano; Martelli, Alberto M; Laidler, Piotr; Dulińska-Litewka, Joanna; Rakus, Dariusz; Gizak, Agnieszka; Lombardi, Paolo; Nicoletti, Ferdinando; Candido, Saverio; Libra, Massimo; Montalto, Giuseppe; Cervello, Melchiorre

    2017-06-12

    Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric ( Curcuma longa ). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants ( e.g., Coptis chinensis ) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health.

  10. Berberine Protects against NEFA-Induced Impairment of Mitochondrial Respiratory Chain Function and Insulin Signaling in Bovine Hepatocytes

    Directory of Open Access Journals (Sweden)

    Zhen Shi

    2018-06-01

    Full Text Available Fatty liver is a major lipid metabolic disease in perinatal dairy cows and is characterized by high blood levels of non-esterified fatty acid (NEFA and insulin resistance. Berberine (BBR has been reported to improve insulin sensitivity in mice with hepatic steatosis. Mitochondrial dysfunction is considered a causal factor that induces insulin resistance. This study investigates the underlying mechanism and the beneficial effects of BBR on mitochondrial and insulin signaling in bovine hepatocytes. Revised quantitative insulin sensitivity check index (RQUICKI of cows with fatty liver was significantly lower than that of healthy cows. Importantly, the Akt and GSK3β phosphorylation levels, protein levels of PGC-1α and four of the five representative subunits of oxidative phosphorylation (OXPHOS were significantly decreased in cows with fatty liver using Western Blot analysis. In bovine hepatocytes, 1.2 mmol/L NEFA reduced insulin signaling and mitochondrial respiratory chain function, and 10 and 20 umol/L BBR restored these changes. Furthermore, activation of PGC-1α played the same beneficial effects of BBR on hepatocytes treated with NEFA. BBR treatment improves NEFA-impaired mitochondrial respiratory chain function and insulin signaling by increasing PGC-1α expression in hepatocytes, which provides a potential new strategy for the prevention and treatment of fatty liver in dairy cows.

  11. Effect of evodiamine and berberine on miR-429 as an oncogene in human colorectal cancer

    Directory of Open Access Journals (Sweden)

    Liu H

    2016-07-01

    Full Text Available Hong Liu, Chao Huang, Liyun Wu, Bin Wen Institute of Spleen and Stomach, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China Abstract: Loss of epithelial organization and deregulated microRNAs are hallmarks of malignant carcinomas, but the relationship between them has been poorly understood. This study was designed to investigate the changes in the expression of E-cadherin, Par3, and miR-429 during the development of human colorectal cancer (CRC. E-cadherin and Par3 levels were quantitatively detected by immunohistochemistry and Western blotting. An in vitro culture of colorectal tissue was established to analyze the effect of berberine (BER and evodiamine (EVO on the level of miR-429. Our results suggested that E-cadherin and Par3 were remarkably decreased in tumor tissues compared with those in normal tissues, and miR-429 was upregulated in tumor tissues. After treatment of BER and EVO, the level of miR-429 was lower in tumor tissues than in normal tissues. This study investigated the potential relationship between miR-429, E-cadherin, and Par3 in CRC. The data suggested that BER and EVO can be potential therapeutic agents for CRC, as they downregulated the expression level of miR-429. Keywords: microRNAs, tissue culture

  12. Regulation of Th1 and Th17 cell differentiation and amelioration of experimental autoimmune encephalomyelitis by natural product compound berberine.

    Science.gov (United States)

    Qin, Xia; Guo, Bingshi T; Wan, Bing; Fang, Lei; Lu, Limin; Wu, Lili; Zang, Ying Qin; Zhang, Jingwu Z

    2010-08-01

    Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as an anti-inflammatory remedy in traditional Chinese medicine. In this study, we showed that BBR was efficacious in the amelioration of experimental autoimmune encephalomyelitis (EAE) through novel regulatory mechanisms involving pathogenic Th1 and Th17 cells. BBR inhibited differentiation of Th17 cells and, to a lesser degree, Th1 cells through direct actions on the JAK/STAT pathway, whereas it had no effect on the relative number of CD4(+)Foxp3(+) regulatory T cells. In addition, BBR indirectly influenced Th17 and Th1 cell functions through its effect on the expression and function of costimulatory molecules and the production of IL-6, which was attributable to the inhibition of NF-kappaB activity in CD11b(+) APCs. BBR treatment completely abolished the encephalitogenicity of MOG(35-55)-reactive Th17 cells in an adoptive transfer EAE model, and the same treatment significantly inhibited the ability of MOG(35-55)-reactive Th1 cells to induce EAE. This study provides new evidence that natural compounds, such as BBR, are of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.

  13. In vitro and in vivo antitumor efficacy of berberine-nanostructured lipid carriers against H22 tumor

    Science.gov (United States)

    Wang, Zhi-ping; Wu, Jun-biao; Chen, Tong-sheng; Zhou, Qun; Wang, Yi-fei

    2015-03-01

    Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber loaded nanostructured lipid carriers (Ber-NLC) was prepared by hot melting and then high pressure homogenization technique. Both in vitro and in vivo anti-hepatocarcinoma effects of Ber-NLC relative to efficacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-NLC were 189.3 nm and -19.3 mV, respectively. MTT assay showed that Ber-NLC effectively inhibited the proliferation of H22 cells, and the corresponding IC50 values were 6.3 μg/ml (22.1 μg/ml of bulk Ber). In vivo studies also showed higher antitumor efficacy, and inhibition rates was 68.3 % (41.4 % of bulk Ber) at 100 mg/kg intragastric administration in the H22 solid tumor bearing mice. These results suggest that the delivery of Ber-NLC is a promising approach for treating tumors.

  14. Characterization of a Flavoprotein Oxidase from Opium Poppy Catalyzing the Final Steps in Sanguinarine and Papaverine Biosynthesis*

    Science.gov (United States)

    Hagel, Jillian M.; Beaudoin, Guillaume A. W.; Fossati, Elena; Ekins, Andrew; Martin, Vincent J. J.; Facchini, Peter J.

    2012-01-01

    Benzylisoquinoline alkaloids are a diverse class of plant specialized metabolites that includes the analgesic morphine, the antimicrobials sanguinarine and berberine, and the vasodilator papaverine. The two-electron oxidation of dihydrosanguinarine catalyzed by dihydrobenzophenanthridine oxidase (DBOX) is the final step in sanguinarine biosynthesis. The formation of the fully conjugated ring system in sanguinarine is similar to the four-electron oxidations of (S)-canadine to berberine and (S)-tetrahydropapaverine to papaverine. We report the isolation and functional characterization of an opium poppy (Papaver somniferum) cDNA encoding DBOX, a flavoprotein oxidase with homology to (S)-tetrahydroprotoberberine oxidase and the berberine bridge enzyme. A query of translated opium poppy stem transcriptome databases using berberine bridge enzyme yielded several candidate genes, including an (S)-tetrahydroprotoberberine oxidase-like sequence selected for heterologous expression in Pichia pastoris. The recombinant enzyme preferentially catalyzed the oxidation of dihydrosanguinarine to sanguinarine but also converted (RS)-tetrahydropapaverine to papaverine and several protoberberine alkaloids to oxidized forms, including (RS)-canadine to berberine. The Km values of 201 and 146 μm for dihydrosanguinarine and the protoberberine alkaloid (S)-scoulerine, respectively, suggested high concentrations of these substrates in the plant. Virus-induced gene silencing to reduce DBOX transcript levels resulted in a corresponding reduction in sanguinarine, dihydrosanguinarine, and papaverine accumulation in opium poppy roots in support of DBOX as a multifunctional oxidative enzyme in BIA metabolism. PMID:23118227

  15. Characterization of a flavoprotein oxidase from opium poppy catalyzing the final steps in sanguinarine and papaverine biosynthesis.

    Science.gov (United States)

    Hagel, Jillian M; Beaudoin, Guillaume A W; Fossati, Elena; Ekins, Andrew; Martin, Vincent J J; Facchini, Peter J

    2012-12-14

    Benzylisoquinoline alkaloids are a diverse class of plant specialized metabolites that includes the analgesic morphine, the antimicrobials sanguinarine and berberine, and the vasodilator papaverine. The two-electron oxidation of dihydrosanguinarine catalyzed by dihydrobenzophenanthridine oxidase (DBOX) is the final step in sanguinarine biosynthesis. The formation of the fully conjugated ring system in sanguinarine is similar to the four-electron oxidations of (S)-canadine to berberine and (S)-tetrahydropapaverine to papaverine. We report the isolation and functional characterization of an opium poppy (Papaver somniferum) cDNA encoding DBOX, a flavoprotein oxidase with homology to (S)-tetrahydroprotoberberine oxidase and the berberine bridge enzyme. A query of translated opium poppy stem transcriptome databases using berberine bridge enzyme yielded several candidate genes, including an (S)-tetrahydroprotoberberine oxidase-like sequence selected for heterologous expression in Pichia pastoris. The recombinant enzyme preferentially catalyzed the oxidation of dihydrosanguinarine to sanguinarine but also converted (RS)-tetrahydropapaverine to papaverine and several protoberberine alkaloids to oxidized forms, including (RS)-canadine to berberine. The K(m) values of 201 and 146 μm for dihydrosanguinarine and the protoberberine alkaloid (S)-scoulerine, respectively, suggested high concentrations of these substrates in the plant. Virus-induced gene silencing to reduce DBOX transcript levels resulted in a corresponding reduction in sanguinarine, dihydrosanguinarine, and papaverine accumulation in opium poppy roots in support of DBOX as a multifunctional oxidative enzyme in BIA metabolism.

  16. Alkaloid Cluster Gene ccsA of the Ergot Fungus Claviceps purpurea Encodes Chanoclavine I Synthase, a Flavin Adenine Dinucleotide-Containing Oxidoreductase Mediating the Transformation of N-Methyl-Dimethylallyltryptophan to Chanoclavine I

    Czech Academy of Sciences Publication Activity Database

    Lorenz, N.; Olšovská, Jana; Šulc, Miroslav; Tudzynski, P.

    2010-01-01

    Roč. 76, č. 5 (2010), s. 1822-1830 ISSN 0099-2240 Institutional research plan: CEZ:AV0Z50200510 Keywords : BERBERINE BRIDGE ENZYME * BIOSYNTHESIS * IDENTIFICATION Subject RIV: EE - Microbiology, Virology Impact factor: 3.778, year: 2010

  17. Morphological aspects of myocardial bridges.

    Science.gov (United States)

    Lujinović, Almira; Kulenović, Amela; Kapur, Eldan; Gojak, Refet

    2013-11-01

    Although some myocardial bridges can be asymptomatic, their presence often causes coronary disease either through direct compression of the "tunnel" segment or through stimulation and accelerated development of atherosclerosis in the segment proximally to the myocardial bridge. The studied material contained 30 human hearts received from the Department of Anatomy. The hearts were preserved 3 to 5 days in 10% formalin solution. Thereafter, the fatty tissue was removed and arterial blood vessels prepared by careful dissection with special reference to the presence of the myocardial bridges. Length and thickness of the bridges were measured by the precise electronic caliper. The angle between the myocardial bridge fibre axis and other axis of the crossed blood vessel was measured by a goniometer. The presence of the bridges was confirmed in 53.33% of the researched material, most frequently (43.33%) above the anterior interventricular branch. The mean length of the bridges was 14.64 ± 9.03 mm and the mean thickness was 1.23 ± 1.32 mm. Myocardial bridge fibres pass over the descending blood vessel at the angle of 10-90 degrees. The results obtained on a limited sample suggest that the muscular index of myocardial bridge is the highest for bridges located on RIA, but that the difference is not significant in relation to bridges located on other branches. The results obtained suggest that bridges located on other branches, not only those on RIA, could have a great contractive power and, consequently, a great compressive force, which would be exerted on the wall of a crossed blood vessel.

  18. Bridge Aesthetics and Structural Honesty

    DEFF Research Database (Denmark)

    Gimsing, Niels Jørgen

    1999-01-01

    In bridges the overall form must be chosen with due respect to the transmission of forces if efficient structures shall be created, The design must therefore be governed by experienced structural engineers - in some cases assisted by aesthetic advisers on specific issues. Some basic requirements...... decisive for choosing the form of trusses, arches and cable-stayed bridges are outlined, and several examples show bridges designed without giving priority to the structural aspects....

  19. MODERN ASPECTS OF BRIDGES MONITORING

    Directory of Open Access Journals (Sweden)

    M. I. Kazakevych

    2007-12-01

    Full Text Available The major concepts of the elaboration and realization of the bridge construction monitoring systemic approach are presented in this paper. The main peculiarity of the bridge monitoring modern aspect is pointed out here, namely, the transition from the demands of providing the reliability to the demands of providing the whole complex of the structure consumer qualities. The criteria of diagnostics of the bridge exploitation reliability as the fundamental aim of monitoring are formulated here.

  20. Nondestructive testing for bridge diagnosis

    International Nuclear Information System (INIS)

    Oshima, Toshiyuki; Mikami, Shuichi; Yamazaki, Tomoyuki

    1997-01-01

    There are many motivations for bridge diagnosis using Nondestructive testing (NDT) to monitor its integrity. The measured frequency and damping on real bridge are compared in one figure as a function of span length and general aspects are explained. These date were measured in every construction of bridges and applied to design new bridges. Ultrasonic testing is also well used for concrete and steel members mainly to detect internal damages or delaminations. Detail analysis on reflected waves gives us more accurate information about the defect. Experimental results are shown as examples in this paper.

  1. Steel-soil composite bridge

    DEFF Research Database (Denmark)

    Du, Guangli; Pettersson, Lars; Karoumi, Raid

    2017-01-01

    viability, while their environmental performance is overlooked. Today’s designers are urged to seek new design options to reduce the environmental burdens. Sweden owns more than 24574 bridges and most of them are short spans. Among them, the slab frame bridge (CFB) is a common solution. Soil steel composite...... bridge (SSCB), alternatively, is a functionally equivalent solution to CFB and shows advantages in low cost and easy construction. This paper compares the environmental performance between these two bridge types based on life cycle assessment (LCA). The analysis and result shows that, the SSCB...

  2. Comprehensive evaluation of fracture critical bridges.

    Science.gov (United States)

    2014-02-01

    Two-girder steel bridges are classified as fracture critical bridges based on the definition given in the AASHTO LRFD Bridge Design Specifications. In a fracture critical bridge a failure of a tension member leads to collapse of the bridge. However, ...

  3. Bridge Crossing Simulator

    Science.gov (United States)

    2014-10-07

    is counted as. Per the TDTC, a test bridge with longitudinal and/or lateral symmetry under non- eccentric loading can be considered as 1, 2, or 4...Level Run036 3 MLC70T (tracked) BA Run046 6 AB Run055 9 AB Run060 9 BA Run064 12 BA Run071 15 AB Run155 3 MLC96W ( wheeled ) AB...Run331 9 AB Run359 15 AB Run430 12 MLC96W ( wheeled ) BA Run434 12 AB Run447 3 BA Bank Condition: Side Slope, Even Strain Channels High

  4. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  5. The role of salt bridges on the temperature adaptation of aqualysin I, a thermostable subtilisin-like proteinase.

    Science.gov (United States)

    Jónsdóttir, Lilja B; Ellertsson, Brynjar Ö; Invernizzi, Gaetano; Magnúsdóttir, Manuela; Thorbjarnardóttir, Sigríður H; Papaleo, Elena; Kristjánsson, Magnús M

    2014-12-01

    Differences in salt bridges are believed to be a structural hallmark of homologous enzymes from differently temperature-adapted organisms. Nevertheless, the role of salt bridges on structural stability is still controversial. While it is clear that most buried salt bridges can have a functional or structural role, the same cannot be firmly stated for ion pairs that are exposed on the protein surface. Salt bridges, found in X-ray structures, may not be stably formed in solution as a result of high flexibility or high desolvation penalty. More studies are thus needed to clarify the picture on salt bridges and temperature adaptation. We contribute here to this scenario by combining atomistic simulations and experimental mutagenesis of eight mutant variants of aqualysin I, a thermophilic subtilisin-like proteinase, in which the residues involved in salt bridges and not conserved in a psychrophilic homolog were systematically mutated. We evaluated the effects of those mutations on thermal stability and on the kinetic parameters. Overall, we show here that only few key charged residues involved in salt bridges really contribute to the enzyme thermal stability. This is especially true when they are organized in networks, as here attested by the D17N mutation, which has the most remarkable effect on stability. Other mutations had smaller effects on the properties of the enzyme indicating that most of the isolated salt bridges are not a distinctive trait related to the enhanced thermal stability of the thermophilic subtilase. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. 47 CFR 80.331 - Bridge-to-bridge communication procedure.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Bridge-to-bridge communication procedure. 80..., Alarm, Urgency and Safety Procedures § 80.331 Bridge-to-bridge communication procedure. (a) Vessels subject to the Bridge-to-Bridge Act transmitting on the designated navigational frequency must conduct...

  7. 47 CFR 80.163 - Operator requirements of the Bridge-to-Bridge Act.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Operator requirements of the Bridge-to-Bridge... Requirements § 80.163 Operator requirements of the Bridge-to-Bridge Act. Each ship subject to the Bridge-to-Bridge Act must have on board a radio operator who holds a restricted radiotelephone operator permit or...

  8. Field performance of timber bridges. 7, Connell Lake stress-laminated deck bridge

    Science.gov (United States)

    L. E. Hislop; M. A. Ritter

    The Connell Lake bridge was constructed in early 1991 on the Tongass National Forest, Alaska, as a demonstration bridge under the Timber Bridge Initiative. The bridge is a stress-laminated deck structure with an approximate 36-ft length and 18-ft width and is the first known stress-laminated timber bridge constructed in Alaska. Performance of the bridge was monitored...

  9. Monitoring bridge scour using fiber optic sensors.

    Science.gov (United States)

    2015-04-01

    The scouring process excavates and carries away materials from the bed and banks of streams, and from : around the piers and abutments of bridges. Scour undermines bridges and may cause bridge failures due to : structural instability. In the last 30 ...

  10. Faster bridge construction using precast substructures : brief.

    Science.gov (United States)

    2011-07-01

    Bridge replacement often requires road closures and detours that frustrate road users. It remains a key goal of Wisconsin DOT to reduce construction-related road use interruptions. This will be a challenge with bridges: Bridge inspections in 2007 ide...

  11. Lean Construction Applications for Bridge Inspection

    Science.gov (United States)

    2017-10-01

    Lean philosophy was used to analyze the efficiency of bridge inspection. Emphasis was put on identifying activities that add value to the final output, an owner approved bridge inspection report. 26 bridge inspections were shadowed. Time spent on bri...

  12. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine.

    Directory of Open Access Journals (Sweden)

    Saurabh Bundela

    Full Text Available Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine.

  13. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine

    Science.gov (United States)

    Bundela, Saurabh; Sharma, Anjana; Bisen, Prakash S.

    2015-01-01

    Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine. PMID:26536350

  14. Berberine alleviates symptoms of anxiety by enhancing dopamine expression in rats with post-traumatic stress disorder.

    Science.gov (United States)

    Lee, Bombi; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun

    2018-03-01

    Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.

  15. Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages.

    Directory of Open Access Journals (Sweden)

    Weibin Zha

    Full Text Available HIV protease inhibitor (PI-induced inflammatory response in macrophages is a major risk factor for cardiovascular diseases. We have previously reported that berberine (BBR, a traditional herbal medicine, prevents HIV PI-induced inflammatory response through inhibiting endoplasmic reticulum (ER stress in macrophages. We also found that HIV PIs significantly increased the intracellular concentrations of BBR in macrophages. However, the underlying mechanisms of HIV PI-induced BBR accumulation are unknown. This study examined the role of P-glycoprotein (P-gp in HIV PI-mediated accumulation of BBR in macrophages.Cultured mouse RAW264.7 macrophages, human THP-1-derived macrophages, Wild type MDCK (MDCK/WT and human P-gp transfected (MDCK/P-gp cells were used in this study. The intracellular concentration of BBR was determined by HPLC. The activity of P-gp was assessed by measuring digoxin and rhodamine 123 (Rh123 efflux. The interaction between P-gp and BBR or HIV PIs was predicated by Glide docking using Schrodinger program. The results indicate that P-gp contributed to the efflux of BBR in macrophages. HIV PIs significantly increased BBR concentrations in macrophages; however, BBR did not alter cellular HIV PI concentrations. Although HIV PIs did not affect P-gp expression, P-gp transport activities were significantly inhibited in HIV PI-treated macrophages. Furthermore, the molecular docking study suggests that both HIV PIs and BBR fit the binding pocket of P-gp, and HIV PIs may compete with BBR to bind P-gp.HIV PIs increase the concentration of BBR by modulating the transport activity of P-gp in macrophages. Understanding the cellular mechanisms of potential drug-drug interactions is critical prior to applying successful combinational therapy in the clinic.

  16. PEG-lipid-PLGA hybrid nanoparticles loaded with berberine-phospholipid complex to facilitate the oral delivery efficiency.

    Science.gov (United States)

    Yu, Fei; Ao, Mingtao; Zheng, Xiao; Li, Nini; Xia, Junjie; Li, Yang; Li, Donghui; Hou, Zhenqing; Qi, Zhongquan; Chen, Xiao Dong

    2017-11-01

    The natural product berberine (BBR), present in various plants, arouses great interests because of its numerous pharmacological effects. However, the further development and application of BBR had been hampered by its poor oral bioavailability. In this work, we report on polymer-lipid hybrid nanoparticles (PEG-lipid-PLGA NPs) loaded with BBR phospholipid complex using a solvent evaporation method for enhancing the oral BBR efficiency. The advantage of this new drug delivery system is that the BBR-soybean phosphatidylcholine complex (BBR-SPC) could be used to enhance the liposolubility of BBR and improve the affinity with the biodegradable polymer to increase the drug-loading capacity and controlled/sustained release. The entrapment efficiency of the PEG-lipid-PLGA NPs/BBR-SPC was observed to approach approximately 89% which is more than 2.4 times compared with that of the PEG-lipid-PLGA NPs/BBR. To the best of our knowledge, this is the first report on using polymer material for effective encapsulation of BBR to improve its oral bioavailability. The prepared BBR delivery systems demonstrated a uniform spherical shape, a well-dispersed core-shell structure and a small particle size (149.6 ± 5.1 nm). The crystallographic and thermal analysis has indicated that the BBR dispersed in the PEG-lipid-PLGA NPs matrix is in an amorphous form. More importantly, the enhancement in the oral relative bioavailability of the PEG-lipid-PLGA NPs/BBR-SPC was ∼343% compared with that of BBR. These positive results demonstrated that PEG-lipid-PLGA NPs/BBR-SPC may have the potential for facilitating the oral drug delivery of BBR.

  17. MicroRNA-21-Mediated Inhibition of Mast Cell Degranulation Involved in the Protective Effect of Berberine on 2,4-Dinitrofluorobenzene-Induced Allergic Contact Dermatitis in Rats via p38 Pathway.

    Science.gov (United States)

    Li, Weihua; Liu, Fanxiu; Wang, Jun; Long, Man; Wang, Zhigang

    2018-03-01

    The study aimed to investigate the effect of berberine on allergic contact dermatitis (ACD) in rats and explore its underlying mechanisms. Firstly, ACD model was established by sensitizing and challenging with 2,4-dinitrofluorobenzene (DNFB) topically, and the rats were treated with berberine. Ear swelling was assessed, and cytokine, IgE, and histamine productions were measured. The ear biopsies were obtained for histology analysis. Additionally, rat peritoneal mast cells (RPMCs) were isolated for detection of microRNA-21 (miR-21) expression, mitogen-activated protein kinase (MAPK) signaling, and MC degranulation. Lastly, RPMCs were transfected with miR-21 mimic or miR-21 inhibitor to investigate the relationship between miR-21 and p38 pathway in MC. Our results showed that berberine significantly attenuated ear swelling in DNFB-induced ACD (ACD vs high dose of berberine 0.48 ± 0.03 vs. 0.33 ± 0.03 mm, P < 0.01), inhibited inflammatory cell infiltration (86 ± 5.16 vs. 58 ± 4.32 cells/mm 2 , P < 0.01), reduced MC recruitment (61 ± 4.07 vs. 39 ± 3.42 mast cells/mm 2 , P < 0.01), as well as decreased inflammatory cytokine, IgE, and histamine productions (all P < 0.05). Berberine treatment inhibited miR-21 expression, suppressed β-hexosaminidase and histamine release, and prevented p38 phosphorylation (all P < 0.05), which was abrogated by pretreatment with miR-21 overexpression. These findings indicate that miR-21-mediated inhibition of MC degranulation is involved in the anti-ACD effect of berberine via inhibiting p38 pathway, which provide a new insight into the immunopharmacological role of berberine and suggest its potential application for the treatment of allergic inflammation, such as ACD.

  18. The violin bridge as filter.

    Science.gov (United States)

    Bissinger, George

    2006-07-01

    The violin bridge filter role was investigated using modal and acoustic measurements on 12 quality-rated violins combined with systematic bridge rocking frequency f(rock) and wing mass decrements deltam on four bridges for two other violins. No isolated bridge resonances were observed; bridge motions were complex (including a "squat" mode near 0.8 kHz) except for low frequency rigid body pivot motions, all more or less resembling rocking motion at higher frequencies. A conspicuous broad peak near 2.3 kHz in bridge driving point mobility (labeled BH) was seen for good and bad violins. Similar structure was seen in averaged bridge, bridge feet, corpus mobilities and averaged radiativity. No correlation between violin quality and BH driving point, averaged corpus mobility magnitude, or radiativity was found. Increasing averaged-over-f(rock) deltam(g) from 0 to 0.12 generally increased radiativity across the spectrum. Decreasing averaged-over-deltam f(rock) from 3.6 to 2.6 kHz produced consistent decreases in radiativity between 3 and 4.2 kHz, but only few-percent decreases in BH frequency. The lowest f(rock) values were accompanied by significantly reduced radiation from the Helmholtz A0 mode near 280 Hz; this, combined with reduced high frequency output, created overall radiativity profiles quite similar to "bad" violins among the quality-rated violins.

  19. Fatigue test on aluminium bridges

    NARCIS (Netherlands)

    Maljaars, J.; Soetens, F.; Straalen, van IJ.J.

    2005-01-01

    Traffic bridges are subjected to variable loads and should therefore be checked on fatigue. Especially low weight materials, like aluminium, are sensitive to fatigue, because the variable load is a substantial part of the total load. This paper shows the structural design of an aluminium bridge

  20. Vulnerability of bridges to fire

    DEFF Research Database (Denmark)

    Giuliani, Luisa; Crosti, C.; Gentili, F.

    2012-01-01

    Even if recent effort in developing methodology and measures for design structures against fire and explosions has been mostly focused on buildings, bridges can also be very sensitive to those actions, as witnesses by some recent bridge accidents, which caused major economic losses and also endan...

  1. Superconductivity in small metal bridges

    International Nuclear Information System (INIS)

    Hannah, E.C.

    1975-01-01

    Josephson effects in weaklinks are discussed for low and high frequency regimes using simple perturbation techniques. It is proven that no measurement of the supercurrent dependence upon frequency above the Riedel peak frequency can be made using rf sources whose frequencies are below the Riedel peak. Thus the bulk of work done in the field on the high frequency structure of the Josephson current is shown to be invalid. Metal bridges shorter than a newly defined temperature independent length for superconductors, l/sub PHONON/, are proven to be identical in their Josephson current behavior to tunneling junctions. The BCS gap equation is generalized to include voltage gradient effects on pairs within the bridge. The oscillation frequency for long bridges (l/sub BRIDGE/ greater than l/sub PHONON/) is shown to be limited to less than 10'' Hz. An experimental test of the new voltage dependent gap is made as well as tests of the pair reforming time of bridges

  2. Bridging the Evaluation Gap

    Directory of Open Access Journals (Sweden)

    Paul Wouters

    2017-02-01

    Full Text Available Paul Wouters’ essay is concerned with bridging the gap between what we value in our academic work and how we are assessed in formal evaluation exercises. He reflects on the recent evaluation of his own center, and reminds us that it is productive to see evaluations not as the (obviously impossible attempt to produce a true representation of past work, but rather as the exploration and performance of “who one wants to be.” Reflecting on why STS should do more than just play along to survive in the indicator game, he suggests that our field should contribute to changing its very rules. In this endeavor, the attitude and sensibilities developed in our field may be more important than any specific theoretical concepts or methodologies.

  3. Linguistic Barriers and Bridges

    DEFF Research Database (Denmark)

    Thuesen, Frederik

    2016-01-01

    The influence of language on social capital in low-skill and ethnically diverse workplaces has thus far received very limited attention within the sociology of work. As the ethnically diverse workplace is an important social space for the construction of social relations bridging different social...... groups, the sociology of work needs to develop a better understanding of the way in which linguistic diversity influences the formation of social capital, i.e. resources such as the trust and reciprocity inherent in social relations in such workplaces. Drawing on theories about intergroup contact...... and intercultural communication, this article analyses interviews with 31 employees from two highly ethnically diverse Danish workplaces. The article shows how linguistic barriers such as different levels of majority language competence and their consequent misunderstandings breed mistrust and hostility, whilst...

  4. Majorana entanglement bridge

    Science.gov (United States)

    Plugge, Stephan; Zazunov, Alex; Sodano, Pasquale; Egger, Reinhold

    2015-06-01

    We study the concurrence of entanglement between two quantum dots in contact to Majorana bound states on a floating superconducting island. The distance between the Majorana states, the charging energy of the island, and the average island charge are shown to be decisive parameters for the efficiency of entanglement generation. We find that long-range entanglement with basically distance-independent concurrence is possible over wide parameter regions, where the proposed setup realizes a "Majorana entanglement bridge." We also study the time-dependent concurrence obtained after one of the tunnel couplings is suddenly switched on, which reveals the time scales for generating entanglement. Accurate analytical expressions for the concurrence are derived both for the static and the time-dependent cases. Our results indicate that entanglement formation in interacting Majorana devices can be fully understood in terms of an interplay of elastic cotunneling (also referred to as "teleportation") and crossed Andreev reflection processes.

  5. Electrothermally Tunable Bridge Resonator

    KAUST Repository

    Hajjaj, Amal Z.; Alcheikh, Nouha; Ramini, Abdallah; Hafiz, Md Abdullah Al; Younis, Mohammad I.

    2016-01-01

    This paper demonstrates experimentally, theoretically, and numerically a wide-range tunability of an in-plane clamped-clamped microbeam, bridge, and resonator compressed by a force due to electrothermal actuation. We demonstrate that a single resonator can be operated at a wide range of frequencies. The microbeam is actuated electrothermally, by passing a DC current through it. We show that when increasing the electrothermal voltage, the compressive stress inside the microbeam increases, which leads eventually to its buckling. Before buckling, the fundamental frequency decreases until it drops to very low values, almost to zero. After buckling, the fundamental frequency increases, which is shown to be as high as twice the original resonance frequency. Analytical results based on the Galerkin discretization of the Euler Bernoulli beam theory are generated and compared to the experimental data and to simulation results of a multi-physics finite-element model. A good agreement is found among all the results.

  6. Electrothermally Tunable Bridge Resonator

    KAUST Repository

    Hajjaj, Amal Z.

    2016-12-05

    This paper demonstrates experimentally, theoretically, and numerically a wide-range tunability of an in-plane clamped-clamped microbeam, bridge, and resonator compressed by a force due to electrothermal actuation. We demonstrate that a single resonator can be operated at a wide range of frequencies. The microbeam is actuated electrothermally, by passing a DC current through it. We show that when increasing the electrothermal voltage, the compressive stress inside the microbeam increases, which leads eventually to its buckling. Before buckling, the fundamental frequency decreases until it drops to very low values, almost to zero. After buckling, the fundamental frequency increases, which is shown to be as high as twice the original resonance frequency. Analytical results based on the Galerkin discretization of the Euler Bernoulli beam theory are generated and compared to the experimental data and to simulation results of a multi-physics finite-element model. A good agreement is found among all the results.

  7. Half Bridge Inductive Heater

    Directory of Open Access Journals (Sweden)

    Zoltán GERMÁN-SALLÓ

    2015-12-01

    Full Text Available Induction heating performs contactless, efficient and fast heating of conductive materials, therefore became one of the preferred heating procedure in industrial, domestic and medical applications. During induction heating the high-frequency alternating currents that heat the material are induced by means of electromagnetic induction. The material to be heated is placed inside the time-varying magnetic field generated by applying a highfrequency alternating current to an induction coil. The alternating electromagnetic field induces eddy currents in the workpiece, resulting resistive losses, which then heat the material. This paper describes the design of a power electronic converter circuit for induction heating equipment and presents the obtained results. The realized circuit is a low power half bridge resonant inverter which uses power MOS transistors and adequate driver circuits.

  8. Cascaded resonant bridge converters

    Science.gov (United States)

    Stuart, Thomas A. (Inventor)

    1989-01-01

    A converter for converting a low voltage direct current power source to a higher voltage, high frequency alternating current output for use in an electrical system where it is desired to use low weight cables and other circuit elements. The converter has a first stage series resonant (Schwarz) converter which converts the direct current power source to an alternating current by means of switching elements that are operated by a variable frequency voltage regulator, a transformer to step up the voltage of the alternating current, and a rectifier bridge to convert the alternating current to a direct current first stage output. The converter further has a second stage series resonant (Schwarz) converter which is connected in series to the first stage converter to receive its direct current output and convert it to a second stage high frequency alternating current output by means of switching elements that are operated by a fixed frequency oscillator. The voltage of the second stage output is controlled at a relatively constant value by controlling the first stage output voltage, which is accomplished by controlling the frequency of the first stage variable frequency voltage controller in response to second stage voltage. Fault tolerance in the event of a load short circuit is provided by making the operation of the first stage variable frequency voltage controller responsive to first and second stage current limiting devices. The second stage output is connected to a rectifier bridge whose output is connected to the input of the second stage to provide good regulation of output voltage wave form at low system loads.

  9. Enzymes for improved biomass conversion

    Science.gov (United States)

    Brunecky, Roman; Himmel, Michael E.

    2016-02-02

    Disclosed herein are enzymes and combinations of the enzymes useful for the hydrolysis of cellulose and the conversion of biomass. Methods of degrading cellulose and biomass using enzymes and cocktails of enzymes are also disclosed.

  10. Immobilized enzymes and cells

    Energy Technology Data Exchange (ETDEWEB)

    Bucke, C; Wiseman, A

    1981-04-04

    This article reviews the current state of the art of enzyme and cell immobilization and suggests advances which might be made during the 1980's. Current uses of immobilized enzymes include the use of glucoamylase in the production of glucose syrups from starch and glucose isomerase in the production of high fructose corn syrup. Possibilities for future uses of immobilized enzymes and cells include the utilization of whey and the production of ethanol.

  11. Profiling the orphan enzymes

    Science.gov (United States)

    2014-01-01

    The emergence of Next Generation Sequencing generates an incredible amount of sequence and great potential for new enzyme discovery. Despite this huge amount of data and the profusion of bioinformatic methods for function prediction, a large part of known enzyme activities is still lacking an associated protein sequence. These particular activities are called “orphan enzymes”. The present review proposes an update of previous surveys on orphan enzymes by mining the current content of public databases. While the percentage of orphan enzyme activities has decreased from 38% to 22% in ten years, there are still more than 1,000 orphans among the 5,000 entries of the Enzyme Commission (EC) classification. Taking into account all the reactions present in metabolic databases, this proportion dramatically increases to reach nearly 50% of orphans and many of them are not associated to a known pathway. We extended our survey to “local orphan enzymes” that are activities which have no representative sequence in a given clade, but have at least one in organisms belonging to other clades. We observe an important bias in Archaea and find that in general more than 30% of the EC activities have incomplete sequence information in at least one superkingdom. To estimate if candidate proteins for local orphans could be retrieved by homology search, we applied a simple strategy based on the PRIAM software and noticed that candidates may be proposed for an important fraction of local orphan enzymes. Finally, by studying relation between protein domains and catalyzed activities, it appears that newly discovered enzymes are mostly associated with already known enzyme domains. Thus, the exploration of the promiscuity and the multifunctional aspect of known enzyme families may solve part of the orphan enzyme issue. We conclude this review with a presentation of recent initiatives in finding proteins for orphan enzymes and in extending the enzyme world by the discovery of new

  12. Wright-Fisher diffusion bridges.

    Science.gov (United States)

    Griffiths, Robert C; Jenkins, Paul A; Spanò, Dario

    2017-10-06

    The trajectory of the frequency of an allele which begins at x at time 0 and is known to have frequency z at time T can be modelled by the bridge process of the Wright-Fisher diffusion. Bridges when x=z=0 are particularly interesting because they model the trajectory of the frequency of an allele which appears at a time, then is lost by random drift or mutation after a time T. The coalescent genealogy back in time of a population in a neutral Wright-Fisher diffusion process is well understood. In this paper we obtain a new interpretation of the coalescent genealogy of the population in a bridge from a time t∈(0,T). In a bridge with allele frequencies of 0 at times 0 and T the coalescence structure is that the population coalesces in two directions from t to 0 and t to T such that there is just one lineage of the allele under consideration at times 0 and T. The genealogy in Wright-Fisher diffusion bridges with selection is more complex than in the neutral model, but still with the property of the population branching and coalescing in two directions from time t∈(0,T). The density of the frequency of an allele at time t is expressed in a way that shows coalescence in the two directions. A new algorithm for exact simulation of a neutral Wright-Fisher bridge is derived. This follows from knowing the density of the frequency in a bridge and exact simulation from the Wright-Fisher diffusion. The genealogy of the neutral Wright-Fisher bridge is also modelled by branching Pólya urns, extending a representation in a Wright-Fisher diffusion. This is a new very interesting representation that relates Wright-Fisher bridges to classical urn models in a Bayesian setting. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Bridge Creek IMW database - Bridge Creek Restoration and Monitoring Project

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The incised and degraded habitat of Bridge Creek is thought to be limiting a population of ESA-listed steelhead (Oncorhynchus mykiss). A logical restoration approach...

  14. Reliability Assessment of Concrete Bridges

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle; Middleton, C. R.

    This paper is partly based on research performed for the Highways Agency, London, UK under the project DPU/9/44 "Revision of Bridge Assessment Rules Based on Whole Life Performance: concrete bridges". It contains the details of a methodology which can be used to generate Whole Life (WL) reliability...... profiles. These WL reliability profiles may be used to establish revised rules for concrete bridges. This paper is to some extend based on Thoft-Christensen et. al. [1996], Thoft-Christensen [1996] et. al. and Thoft-Christensen [1996]....

  15. Complex Testing of the Bridges

    Directory of Open Access Journals (Sweden)

    Savić Adrijana

    2016-01-01

    Full Text Available This article describes the process of examining bridges. AB road bridge, founded on the columns by the Karpoš system and damaged due to erosive action of the river, is given as an example. The first tests of the bridge are conducted on the impact load of V 300, because of the appearance of longitudinal cracks. The results of the columns testing are presented in this paper, as well as the rehabilitation measures thus increasing the load capacity of the column.

  16. Reliability Modeling of Double Beam Bridge Crane

    Science.gov (United States)

    Han, Zhu; Tong, Yifei; Luan, Jiahui; Xiangdong, Li

    2018-05-01

    This paper briefly described the structure of double beam bridge crane and the basic parameters of double beam bridge crane are defined. According to the structure and system division of double beam bridge crane, the reliability architecture of double beam bridge crane system is proposed, and the reliability mathematical model is constructed.

  17. The stories of two bridges in Ghana

    DEFF Research Database (Denmark)

    Andreasen, Jørgen

    2004-01-01

    Public participation in bridge building was promoted by un habitat in the village of Mankrong. The neighbouring village did not participate in the construction of their bridge. The first flooding washed the second bridge down while the "participative bridge" stood up....

  18. Human Errors and Bridge Management Systems

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle; Nowak, A. S.

    on basis of reliability profiles for bridges without human errors are extended to include bridges with human errors. The first rehabilitation distributions for bridges without and with human errors are combined into a joint first rehabilitation distribution. The methodology presented is illustrated...... for reinforced concrete bridges....

  19. Effects of Electrolyte on Floating Water Bridge

    Directory of Open Access Journals (Sweden)

    Hideo Nishiumi

    2009-01-01

    spontaneously. In this paper, we examined flow direction of water bridge and what effects the addition of electrolytes such as NaCl, NaOH, and NH4Cl to the floating water bridge would give. We found that ionization degree reduced the length of water bridge though insoluble electrolyte Al2O3 had no effect on the length of water bridge.

  20. Longer Lasting Bridge Deck Overlays

    Science.gov (United States)

    2018-04-01

    The objective of this report is to determine the most effective method for bridge deck overlay construction and repair by assessing current practices; examining new products and technologies; and reviewing NCHRP (National Cooperative Highway Research...

  1. Energy harvesting on highway bridges.

    Science.gov (United States)

    2011-01-01

    A concept for harvesting energy from the traffic-induced loadings on a highway bridge using piezoelectric : materials to generate electricity was explored through the prototype stage. A total of sixteen lead-zirconate : titanate (PZT) Type 5A piezoel...

  2. Research notes : listening to bridges.

    Science.gov (United States)

    2008-09-01

    The Federal Highway Administration requires owners of structurally deficient bridges to repair, replace, restrict truck loads, or conduct analysis and testing to maintain a safe highway system. Past experiments on reinforced concrete beams showed aco...

  3. Linear Cracking in Bridge Decks

    Science.gov (United States)

    2018-03-01

    Concrete cracking in bridge decks remains an important issue relative to deck durability. Cracks can allow increased penetration of chlorides, which can result in premature corrosion of the reinforcing steel and subsequent spalling of the concrete de...

  4. Berberine Suppresses Cell Motility Through Downregulation of TGF-β1 in Triple Negative Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sangmin Kim

    2018-01-01

    Full Text Available Background/Aims: Transforming growth factor-beta proteins (TGF-βs are multifunctional growth factors and powerful modulators of the epithelial-mesenchymal transition (EMT in a variety of cancer types including breast and lung cancer cells. Here, we demonstrated the inhibitory effect of berberine (BBR on tumor growth and metastasis of triple negative breast cancer (TNBC cells via suppression of TGF-β1 expression. Methods: The levels of mRNA expression were analyzed by real-time PCR. The levels of MMP-2, MMP-9 and TGF-β1 protein expression were analyzed by zymography and confocal microscopy, respectively. Cell migration was analyzed by wound healing assay. Tumorigenicity of TNBC cells such as tumor growth and metastasis was analyzed using xenograft models. Results: In a clinical data set, aberrant TGF-β1 expression was associated with poor prognosis of breast cancer patients. Our in vitro results using TNBC cells showed that the expression levels of matrix metalloproteinase (MMP-2 and MMP-9 and the capacity for cell migration were increased by TGF-β1 treatment. In contrast, basal levels of MMP-2 and MMP-9 were suppressed by a specific TGF-β receptor I inhibitor, SB431542. In addition, TGF-β1–induced MMP-2 and MMP-9 expression and cell migration were decreased by SB431542. Interestingly, we showed for the first time that BBR decreased the level of TGF-β1, but not TGF-β2, in TNBC cells. Furthermore, BBR significantly decreased the level of MMP-2 expression as well as the capacity for cell migration in TNBC cells. Finally, we examined the effect of BBR on in vivo tumor growth and lung metastasis in MDA-MB231 and 4T1 breast cancer xenograft models and showed that both were significantly decreased following BBR treatment. Conclusion: BBR suppresses tumorigenicity of TNBC cells through inhibition of TGF-β1 expression. Therefore, we demonstrate that BBR could be a promising drug for treatment of TNBC.

  5. Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats

    Directory of Open Access Journals (Sweden)

    Qingjie Chen

    2017-06-01

    Full Text Available Background: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor Aβ42 which was the marker of Alzheimer’s disease. In addition, the impairment of memory in diabetes mellitus was also correlated predominantly with uptake/metabolism of glucose in medial prefrontal cortex (mPFC. Previously, anti-inflammation and hypoglycemic effects of berberine (BBr have been described in peripheral tissues. For better understanding the effects of BBr on cognitive action in diabetics, we investigated the functions of BBr involved in anti-inflammation and ameliorating insulin resistance in prefrontal cortex of diabetic rats.Methods: Intragastric administration of BBr (187.5 mg/Kg/d was used in diabetic rats. Fear-condition assay was applied for cognitive assessment, and relative protein expressions were detected by western-blot. The glucose uptake in prefrontal cortex of diabetic rats was tested by Positron-Emission Tomography imaging. The levels of inflammation mediators were determined by commercial ELISA kits.Results: The inflammation mediator release and insulin resistance in the mPFC of diabetic rats was inhibited by BBr. The activation of PI3K/Akt/mTOR and MAPK signaling pathway, as well as two novel isoforms PKCη and PKC and the translocation of NF-κB in neuron were also down-regulated by BBr; furthermore, the neuron specific glucose transporter GLUT3 was remarkably augmented by 2–3 times when compared with diabetic group; meanwhile, BBr also promoted glucose uptake in the brain. Additionally BBr decreased the expressions of amyloid precursor protein and BACE-1, and the production of oligomeric Aβ42. Finally, it accelerates the reinforcement of the information and ameliorates cognitive impairment.Conclusion: BBr inhibited the activation of inflammation pathway and insulin resistance

  6. Artificial Enzymes, "Chemzymes"

    DEFF Research Database (Denmark)

    Bjerre, Jeannette; Rousseau, Cyril Andre Raphaël; Pedersen, Lavinia Georgeta M

    2008-01-01

    Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models that successf......Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models...... that successfully perform Michaelis-Menten catalysis under enzymatic conditions (i.e., aqueous medium, neutral pH, ambient temperature) and for those that do, very high rate accelerations are seldomly seen. This review will provide a brief summary of the recent developments in artificial enzymes, so called...... "Chemzymes", based on cyclodextrins and other molecules. Only the chemzymes that have shown enzyme-like activity that has been quantified by different methods will be mentioned. This review will summarize the work done in the field of artificial glycosidases, oxidases, epoxidases, and esterases, as well...

  7. Magnetically responsive enzyme powders

    Energy Technology Data Exchange (ETDEWEB)

    Pospiskova, Kristyna, E-mail: kristyna.pospiskova@upol.cz [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Safarik, Ivo, E-mail: ivosaf@yahoo.com [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Department of Nanobiotechnology, Institute of Nanobiology and Structural Biology of GCRC, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic)

    2015-04-15

    Powdered enzymes were transformed into their insoluble magnetic derivatives retaining their catalytic activity. Enzyme powders (e.g., trypsin and lipase) were suspended in various liquid media not allowing their solubilization (e.g., saturated ammonium sulfate and highly concentrated polyethylene glycol solutions, ethanol, methanol, 2-propanol) and subsequently cross-linked with glutaraldehyde. Magnetic modification was successfully performed at low temperature in a freezer (−20 °C) using magnetic iron oxides nano- and microparticles prepared by microwave-assisted synthesis from ferrous sulfate. Magnetized cross-linked enzyme powders were stable at least for two months in water suspension without leakage of fixed magnetic particles. Operational stability of magnetically responsive enzymes during eight repeated reaction cycles was generally without loss of enzyme activity. Separation of magnetically modified cross-linked powdered enzymes from reaction mixtures was significantly simplified due to their magnetic properties. - Highlights: • Cross-linked enzyme powders were prepared in various liquid media. • Insoluble enzymes were magnetized using iron oxides particles. • Magnetic iron oxides particles were prepared by microwave-assisted synthesis. • Magnetic modification was performed under low (freezing) temperature. • Cross-linked powdered trypsin and lipase can be used repeatedly for reaction.

  8. Targeted enzyme prodrug therapies.

    Science.gov (United States)

    Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

    2010-09-01

    The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

  9. Enzymes in Fermented Fish.

    Science.gov (United States)

    Giyatmi; Irianto, H E

    Fermented fish products are very popular particularly in Southeast Asian countries. These products have unique characteristics, especially in terms of aroma, flavor, and texture developing during fermentation process. Proteolytic enzymes have a main role in hydrolyzing protein into simpler compounds. Fermentation process of fish relies both on naturally occurring enzymes (in the muscle or the intestinal tract) as well as bacteria. Fermented fish products processed using the whole fish show a different characteristic compared to those prepared from headed and gutted fish. Endogenous enzymes like trypsin, chymotrypsin, elastase, and aminopeptidase are the most involved in the fermentation process. Muscle tissue enzymes like cathepsins, peptidases, transaminases, amidases, amino acid decarboxylases, glutamic dehydrogenases, and related enzymes may also play a role in fish fermentation. Due to the decreased bacterial number during fermentation, contribution of microbial enzymes to proteolysis may be expected prior to salting of fish. Commercial enzymes are supplemented during processing for specific purposes, such as quality improvement and process acceleration. In the case of fish sauce, efforts to accelerate fermentation process and to improve product quality have been studied by addition of enzymes such as papain, bromelain, trypsin, pepsin, and chymotrypsin. © 2017 Elsevier Inc. All rights reserved.

  10. Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine

    Directory of Open Access Journals (Sweden)

    Arkadiusz Dziedzic

    2016-03-01

    Full Text Available The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628, cultivated with the mixture of Dulbecco's modified Eagle’s medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 μg/mL and to a combination of AgNPs with berberine chloride (BER, 1/2 IC50 concentration during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm ± 4 nm was measured by 3-(4,5-dimethyl-2-thiazyl-2,5-diphenyl-2H-tetrazolium bromide (MTT assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 μg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC50 after 48 h was estimated at 5.19 μg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting

  11. Performance indicators for roadway bridges

    OpenAIRE

    Strauss, A.; Vidovic, A.; Zambon, I.; Dengg, F.; Tanasic, N.; Matos, José C.

    2016-01-01

    Publicado em "Maintenance, monitoring, safety, risk and resilience of bridges and bridge networks". ISBN 978-1-138-02851-7 The performance indicators should, by its definition, allow capturing the life-cycle degradation processes affecting maintenance plans or the remaining lifetime. The qualitative or quantitative performance indicators are obtained through visual inspections, non-destructive tests or monitoring systems. After their quantification and the comparison with the resp...

  12. Bridging the Gap (BRIEFING CHARTS)

    Science.gov (United States)

    2007-03-05

    1 Defense Advanced Research Projects Agency “Bridging the Gap ” Dr. Robert F. Leheny Deputy Director Report Documentation Page Form ApprovedOMB No...comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to...4. TITLE AND SUBTITLE Bridging the Gap 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  13. An Inverse Michaelis–Menten Approach for Interfacial Enzyme Kinetics

    DEFF Research Database (Denmark)

    Kari, Jeppe; Andersen, Morten; Borch, Kim

    2017-01-01

    Interfacial enzyme reactions are ubiquitous both in vivo and in technical applications, but analysis of their kinetics remains controversial. In particular, it is unclear whether conventional Michaelis–Menten theory, which requires a large excess of substrate, can be applied. Here, an extensive...... experimental study of the enzymatic hydrolysis of insoluble cellulose indeed showed that the conventional approach had a limited applicability. Instead we argue that, unlike bulk reactions, interfacial enzyme catalysis may reach a steady-state condition in the opposite experimental limit, where...... for kinetic analyses of interfacial enzyme reactions and that its analogy to established theory provides a bridge to the accumulated understanding of steady-state enzyme kinetics. Finally, we show that the ratio of parameters from conventional and inverted Michaelis–Menten analysis reveals the density...

  14. SURGERY OF SYMPTOMATIC MYOCARDIAL BRIDGING

    Directory of Open Access Journals (Sweden)

    N. Maghamipour N. Safaei

    2007-06-01

    Full Text Available Myocardial bridging with systolic compression of the left anterior descending coronary artery (LAD may be associated with myocardial ischemia. In symptomatic myocardial bridging unresponsive to medical treatment, surgical unroofing of the left LAD can be performed. Little information is available about the long-term prognosis of patients with this coronary anomaly after the surgical unroofing, so we decided to evaluate the result of this operation. A total of 26 patients underwent surgical unroofing of myocardial bridging. Patients had a myocardial bridge of at least 3 cm in length in the middle of LAD and with more than 70% compression during systole. Unroofing was performed with cardiopulmonary bypass in 16 and with off pump technique in 10 patients. In 6 patients repeat angiographies for control of myotomy were done. In one of them a nonsignificant 20% narrowing was seen. Postoperative scintigraphic and angiographic studies demonstrated restoration of coronary flow and myocardial perfusion without residual myocardial bridges under beta-stimulation in 24 patients. Two patients had residual narrowing. With off pump technique, 1 patient had perforation of the right ventricle and 1 patient underwent reoperation because of incomplete unroofing during the first operation. None of the patients with cardiopulmonary bypass technique had residual chest pain or other complications. Surgical unroofing of myocardial bridging with the aid of cardiopulmonary bypass is a safe and easy procedure with low operative risk and with excellent functional results.

  15. Development of Inspection Robots for Bridge Cables

    Directory of Open Access Journals (Sweden)

    Hae-Bum Yun

    2013-01-01

    Full Text Available This paper presents the bridge cable inspection robot developed in Korea. Two types of the cable inspection robots were developed for cable-suspension bridges and cable-stayed bridge. The design of the robot system and performance of the NDT techniques associated with the cable inspection robot are discussed. A review on recent advances in emerging robot-based inspection technologies for bridge cables and current bridge cable inspection methods is also presented.

  16. Development of inspection robots for bridge cables.

    Science.gov (United States)

    Yun, Hae-Bum; Kim, Se-Hoon; Wu, Liuliu; Lee, Jong-Jae

    2013-01-01

    This paper presents the bridge cable inspection robot developed in Korea. Two types of the cable inspection robots were developed for cable-suspension bridges and cable-stayed bridge. The design of the robot system and performance of the NDT techniques associated with the cable inspection robot are discussed. A review on recent advances in emerging robot-based inspection technologies for bridge cables and current bridge cable inspection methods is also presented.

  17. Dynamic assessment of bridge deck performance considering realistic bridge-traffic interaction

    Science.gov (United States)

    2017-09-01

    Concrete bridge decks are directly exposed to daily traffic loads and may experience some surface cracking caused by excessive stress or fatigue accumulation, which requires repair or replacement. Among typical bridges in North America, bridge decks ...

  18. Synthesis, Characterization, and Biological Evaluations of 1,3,5-Triazine Derivatives of Metformin Cyclization with Berberine and Magnolol in the Presence of Sodium Methylate

    Directory of Open Access Journals (Sweden)

    Han Cao

    2017-10-01

    Full Text Available The novel target products were synthesized in the formation of a triazine ring from berberine, magnolol, and metformin catalyzed by sodium methylate. The structures of products 1–3 were firstly confirmed by extensive spectroscopic analyses and single-crystal X-ray diffraction. The crystal structures of the target product 2 and the intermediate product 7b were reported for the first time. All target products were evaluated for their anti-inflammatory and antidiabetic activities against INS-1 and RAW264.1 cells in vitro and all products showed excellent anti-inflammatory effects and anti-insulin resistance effects. Our studies indicated that new compounds 1–3 were found to be active against inflammation and insulin resistance.

  19. 33 CFR 118.100 - Retroreflective panels on bridge piers.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Retroreflective panels on bridge... SECURITY BRIDGES BRIDGE LIGHTING AND OTHER SIGNALS § 118.100 Retroreflective panels on bridge piers. The... 12 inches square. (c) To mark bridge piers or channel sides on bridges not required to have bridge...

  20. Positional isotope exchange studies on enzyme using NMR spectroscopy

    International Nuclear Information System (INIS)

    Matsunaga, T.O.

    1987-01-01

    The isotopically enriched compounds, 18 O-β,γ-ATP and 18 O bridge-labeled pyrophosphate, synthesized previously in this laboratory, were used to investigate and measure the exchange vs. turnover of substrates and products from their central complexes in four selected enzyme systems. Using hi-field 31 P NMR, we were able to differentiate between 18 O labeled in the bridge vs. the non-bridge positions by virtue of the isotope shift upon the phosphorus nuclei. The bridge to non-bridge scrambling of the label was quantitated and the exchange vs. turnover ratios under a variety of conditions was determined. Using the substrate inhibitor carboxycreatinine, PIX experiments with 18 O-β,γ-ATP and creatine kinase were conducted. It was shown that carboxycreatinine and creatine kinase promoted exchange of the 18 O label as determined by NMR. We have concluded that carboxycreatinine is either a substrate that catalyzes very slow turnover or it catalyzes exchange by a dissociative (SN 1 /sub P/) type of mechanism

  1. The Akashi Kaikyo Bridge and the Storebælt Bridge

    DEFF Research Database (Denmark)

    Gimsing, Niels Jørgen

    1999-01-01

    With the completion of the Akashi Kaikyo Bridge and the Storebælt East Bridge the development of the suspension bridge technology in the 20th century has manifested itself in two impressive structures. With the present echnology may bridges of similar (and also more modest) dimensions...... will undoubtedly be built far into the next century. For bridges going beyond the spans of existing bridges it is, however, likely that new concepts will be developed....

  2. 47 CFR 80.309 - Watch required by the Bridge-to-Bridge Act.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Watch required by the Bridge-to-Bridge Act. 80... Safety Watches § 80.309 Watch required by the Bridge-to-Bridge Act. In addition to the watch requirement contained in § 80.148, all vessels subject to the Bridge-to-Bridge Act must keep a watch on the designated...

  3. Guardrails for Use on Historic Bridges: Volume 2—Bridge Deck Overhang Design

    OpenAIRE

    Frosch, Robert J.; Morel, Adam J.

    2016-01-01

    Bridges that are designated historic present a special challenge to bridge engineers whenever rehabilitation work or improvements are made to the bridges. Federal and state laws protect historically significant bridges, and railings on these bridges can be subject to protection because of the role they play in aesthetics. Unfortunately, original railings on historic bridges do not typically meet current crash-test requirements and typically do not meet current standards for railing height and...

  4. Enzymic lactose hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J J; Brand, J C

    1980-01-01

    Acid or enzymic hydrolysis can be used to hydrolyze lactose. Advantages of both are compared and details of enzymic hydrolysis using yeast or fungal enzymes given. The new scheme outlined involves recycling lactase. Because lactose and lactase react to ultrafiltration (UF) membranes differently separation is possible. Milk or milk products are ultrafiltered to separate a concentrate from a lactose-rich permeate which is treated with lactase in a reactor until hydrolysis reaches a required level. The lactase can be removed by UF as it does not permeate the membrane, and it is recycled back to the reactor. Permeate from the second UF stage may or may not be recombined with the concentrate from the first stage to produce a low lactose product (analysis of a typical low-lactose dried whole milk is given). Batch or continuous processes are explained and a batch process without enzyme recovery is discussed. (Refs. 4).

  5. Indicators: Sediment Enzymes

    Science.gov (United States)

    Sediment enzymes are proteins that are produced by microorganisms living in the sediment or soil. They are indicators of key ecosystem processes and can help determine which nutrients are affecting the biological community of a waterbody.

  6. Enzyme Vs. Extremozyme -32 ...

    Indian Academy of Sciences (India)

    Enzymes are biocatalytic protein molecules that enhance the rates of ... to physical forces (hydrogen bonds, hydrophobic 1, electrostatic and Van der ... conformation. In 1995 ... surface against 14.7% in Klenow poll (some of the hydrophobic.

  7. Overproduction of ligninolytic enzymes

    Science.gov (United States)

    Elisashvili, Vladimir; Kachlishvili, Eva; Torok, Tamas

    2014-06-17

    Methods, compositions, and systems for overproducing ligninolytic enzymes from the basidiomycetous fungus are described herein. As described, the method can include incubating a fungal strain of Cerrena unicolor IBB 303 in a fermentation system having growth medium which includes lignocellulosic material and then cultivating the fungal strain in the fermentation system under conditions wherein the fungus expresses the ligninolytic enzymes. In some cases, the lignocellulosic material is mandarin peel, ethanol production residue, walnut pericarp, wheat bran, wheat straw, or banana peel.

  8. Floating liquid bridge charge dynamics

    Science.gov (United States)

    Teschke, Omar; Soares, David Mendez; Gomes, Whyllerson Evaristo; Valente Filho, Juracyr Ferraz

    2016-01-01

    The interaction of liquid with electric fields is investigated in a configuration where up to 13 kV are applied between electrodes resulting in a 106 V/m electric field in the capillaries and where there is the formation of a free-standing fluid bridge in the interelectrode gap. The Mott-Gurney equation was fitted to the measured ionization current vs applied voltage curve which indicates that the ionization rate at the high-voltage anode electrode dimethylsulfoxide (DMSO) interface and space charging in the interelectrode gap determine the floating liquid bridge current for a given cathode-to-anode voltage. Space charge effects were measured in the cathode becker and also at the liquid bridge since the ionized charges at the anode migrate to the bridge outer surface and decrease the interfacial tension from 43 mJ/m2 to 29 mJ/m2. Two distinct structural regions then form the bridge, a charged plastic (bulk modulus ˜100 MPa) conducting outer layer with a surface conductivity of ˜10-9 Ω-1, which shapes and supports the floating fluid structure, and an inner liquid cylinder, where DMSO molecules flow.

  9. Measurement of enzyme activity.

    Science.gov (United States)

    Harris, T K; Keshwani, M M

    2009-01-01

    To study and understand the nature of living cells, scientists have continually employed traditional biochemical techniques aimed to fractionate and characterize a designated network of macromolecular components required to carry out a particular cellular function. At the most rudimentary level, cellular functions ultimately entail rapid chemical transformations that otherwise would not occur in the physiological environment of the cell. The term enzyme is used to singularly designate a macromolecular gene product that specifically and greatly enhances the rate of a chemical transformation. Purification and characterization of individual and collective groups of enzymes has been and will remain essential toward advancement of the molecular biological sciences; and developing and utilizing enzyme reaction assays is central to this mission. First, basic kinetic principles are described for understanding chemical reaction rates and the catalytic effects of enzymes on such rates. Then, a number of methods are described for measuring enzyme-catalyzed reaction rates, which mainly differ with regard to techniques used to detect and quantify concentration changes of given reactants or products. Finally, short commentary is given toward formulation of reaction mixtures used to measure enzyme activity. Whereas a comprehensive treatment of enzymatic reaction assays is not within the scope of this chapter, the very core principles that are presented should enable new researchers to better understand the logic and utility of any given enzymatic assay that becomes of interest.

  10. Noise Considerations in Resistance Bridges

    DEFF Research Database (Denmark)

    Diamond, Joseph M.

    1963-01-01

    A signal-to-noise analysis is made of the Wheatstone bridge, where the unknown and standard resistors may be at different temperatures, a situation which occurs in resistance thermometry. The limiting condition is assumed to be dissipation in the unknown resistor. It is shown that the ratio arms...... thermometry, where the noise in the unknown resistor will predominate strongly. An impedance step-up device (transformer or tuned circuit) is valuable in raising the bridge signal and noise level above the noise of the first amplifier tube. However, as the step-up ratio is increased, two counterfactors appear....... With certain assumptions about the noise and grid current of the first tube it is found that the equivalent temperature of a unity ratio (Mueller) bridge used for liquid helium measurements may be 400°K....

  11. Precast concrete elements for accelerated bridge construction : laboratory testing, field testing, evaluation of a precast concrete bridge, Madison County bridge.

    Science.gov (United States)

    2009-01-01

    The importance of rapid construction technologies has been recognized by the Federal Highway Administration (FHWA) and the Iowa : DOT Office of Bridges and Structures. Recognizing this a two-lane single-span precast box girder bridge was constructed ...

  12. The Wien Bridge Oscillator Family

    DEFF Research Database (Denmark)

    Lindberg, Erik

    2006-01-01

    A tutorial in which the Wien bridge family of oscillators is defined and investigated. Oscillators which do not fit into the Barkhausen criterion topology may be designed. A design procedure based on initial complex pole quality factor is reported. The dynamic transfer characteristic of the ampli......A tutorial in which the Wien bridge family of oscillators is defined and investigated. Oscillators which do not fit into the Barkhausen criterion topology may be designed. A design procedure based on initial complex pole quality factor is reported. The dynamic transfer characteristic...

  13. Bridging the Vector Calculus Gap

    Science.gov (United States)

    Dray, Tevian; Manogue, Corinne

    2003-05-01

    As with Britain and America, mathematicians and physicists are separated from each other by a common language. In a nutshell, mathematics is about functions, but physics is about things. For the last several years, we have led an NSF-supported effort to "bridge the vector calculus gap" between mathematics and physics. The unifying theme we have discovered is to emphasize geometric reasoning, not (just) algebraic computation. In this talk, we will illustrate the language differences between mathematicians and physicists, and how we are trying reconcile them in the classroom. For further information about the project go to: http://www.physics.orst.edu/bridge

  14. 1,2-bridged quadricyclanes

    International Nuclear Information System (INIS)

    Hart, H.; Cheng-Tai Peng

    1982-01-01

    The readily available benzodihydropentalene 6 and dimethyl acetylenedicarboxylate react to give norbornadiene diester 8, with a three-carbon bridge from C 1 to C 2 . Irradiation of 8 gives the corresponding C 1 -C 2 bridged quadricyclane diester 9, a new ring system. Diester 9 is quite stable, reverting to 8 with a tsub(1/2) of 30 min at 170 0 C. The corresponding diacid 11, also prepared, reverts to its norbornadiene precursor at a considerably lower temperature, possibly as a consequence of acid catalysis. (author)

  15. Database of ligand-induced domain movements in enzymes

    Directory of Open Access Journals (Sweden)

    Hayward Steven

    2009-03-01

    Full Text Available Abstract Background Conformational change induced by the binding of a substrate or coenzyme is a poorly understood stage in the process of enzyme catalysed reactions. For enzymes that exhibit a domain movement, the conformational change can be clearly characterized and therefore the opportunity exists to gain an understanding of the mechanisms involved. The development of the non-redundant database of protein domain movements contains examples of ligand-induced domain movements in enzymes, but this valuable data has remained unexploited. Description The domain movements in the non-redundant database of protein domain movements are those found by applying the DynDom program to pairs of crystallographic structures contained in Protein Data Bank files. For each pair of structures cross-checking ligands in their Protein Data Bank files with the KEGG-LIGAND database and using methods that search for ligands that contact the enzyme in one conformation but not the other, the non-redundant database of protein domain movements was refined down to a set of 203 enzymes where a domain movement is apparently triggered by the binding of a functional ligand. For these cases, ligand binding information, including hydrogen bonds and salt-bridges between the ligand and specific residues on the enzyme is presented in the context of dynamical information such as the regions that form the dynamic domains, the hinge bending residues, and the hinge axes. Conclusion The presentation at a single website of data on interactions between a ligand and specific residues on the enzyme alongside data on the movement that these interactions induce, should lead to new insights into the mechanisms of these enzymes in particular, and help in trying to understand the general process of ligand-induced domain closure in enzymes. The website can be found at: http://www.cmp.uea.ac.uk/dyndom/enzymeList.do

  16. Laboratory and field testing of an accelerated bridge construction demonstration bridge : US Highway 6 bridge over Keg Creek.

    Science.gov (United States)

    2013-04-01

    The US Highway 6 Bridge over Keg Creek outside of Council Bluffs, Iowa is a demonstration bridge site chosen to put into practice : newly-developed Accelerated Bridge Construction (ABC) concepts. One of these new concepts is the use of prefabricated ...

  17. Random-walk enzymes

    Science.gov (United States)

    Mak, Chi H.; Pham, Phuong; Afif, Samir A.; Goodman, Myron F.

    2015-09-01

    Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model. Diagrammatic theory and path-integral solutions of these models revealed clearly distinct predictions. Comparison to experimental data from catalyzed deaminations deposited on single-stranded DNA by the enzyme activation-induced deoxycytidine deaminase (AID) demonstrates that catalysis and diffusion are strongly intertwined, where the chemical conversions give rise to new stochastic trajectories that were absent if the substrate DNA was homogeneous. The C →U deamination profiles in both analytical predictions and experiments exhibit a strong contextual dependence, where the conversion rate of each target site is strongly contingent on the identities of other surrounding targets, with the intrusive model showing an excellent fit to the data. These methods can be applied to deduce sequence-dependent catalytic signatures of other DNA modification enzymes, with potential applications to cancer, gene regulation, and epigenetics.

  18. An Expert System for Concrete Bridge Management

    DEFF Research Database (Denmark)

    Brito, J. de; Branco, F. A.; Thoft-Christensen, Palle

    1997-01-01

    The importance of bridge repair versus new bridge construction has risen in recent decades due to high deterioration rates that have been observed in these structures. Budgets both for building new bridges and keeping the existing ones are always limited. To help rational decision-making, bridge...... management systems are presently being implemented by bridge authorities in several countries. The prototype of an expert system for concrete bridge management is presented in this paper, with its functionality relying on two modules. The inspection module relies on a periodic acquisition of field...... information complemented by a knowledge-based interactive system, BRIDGE-1. To optimize management strategies at the headquarters, the BRIDGE-2 module was implemented, including three submodules: inspection strategy, maintenance and repair....

  19. Characterization of bridge foundations workshop report.

    Science.gov (United States)

    2013-11-01

    "In 2013, the Federal Highway Administration proposed a new research program for the characterization of bridge foundations. To narrow the focus and develop a research roadmap for the program, a workshop on Characterization of Bridge Foundations...

  20. IceBridge Mission Flight Reports

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge Mission Flight Reports data set contains flight reports from NASA Operation IceBridge Greenland, Arctic, Antarctic, and Alaska missions. Flight reports...

  1. Risk Mitigation for Highway and Railway Bridges

    Science.gov (United States)

    2009-02-01

    Performance of the transportation network strongly depends on the performance of bridges. Bridges constitute a vital part of the transportation infrastructure system and they are vulnerable to extreme events such as natural disasters (i.e., hurricane...

  2. Fiber reinforced polymer bridge decks : [technical summary].

    Science.gov (United States)

    2011-01-01

    A number of researchers have addressed the use of Fiber Reinforced Polymer (FRP) deck as a replacement solution for deteriorated bridge decks made of traditional materials. The use of new, advanced materials such as FRP is advantageous when the bridg...

  3. Final Environmental Assessment, Horse Creek Bridge Replacement

    Science.gov (United States)

    2010-10-01

    existing bridge pipes that have failed and replace the failed structure with a new, prefabricated pedestrian bridge within the original bridge footprint...vehicles, nor designed for support of standard passenger vehicle loads. The bridge would be a single prefabricated unit consisting of a steel grate...placed on new concrete abutments built on the existing foundations on the creek banks, and put in place by a crane operating from the vehicle parking

  4. Field performance of timber bridges. 5, Little Salmon Creek stress-laminated deck bridge

    Science.gov (United States)

    M. A. Ritter; J. A. Kainz; G. J. Porter

    The Little Salmon Creek bridge was constructed in November 1988 on the Allegheny National Forest in Pennsylvania. The bridge is a simple span, single-lane, stress-laminated deck superstructure that is approximately 26-ft long and 16-ft wide. The bridge is unique in that it is the first known stress-laminated timber bridge to be constructed of hardwood lumber. The...

  5. Bridge Programs in Illinois: Results of the 2010 Illinois Bridge Status Survey

    Science.gov (United States)

    Taylor, J. L.; Harmon, T.

    2010-01-01

    This report provides a summary of major results of the Illinois Bridge Status Survey, administered online between April and June 2010. The purpose of the survey was to understand the extent to which bridge programs are being implemented in Illinois, as well as to build an online directory of bridge programs. Bridge programs are an emerging…

  6. Field performance of timber bridges. 6, Hoffman Run stress-laminated deck bridge

    Science.gov (United States)

    M. A. Ritter; P. D. Hilbrich Lee; G. J. Porter

    The Hoffman Run bridge, located just outside Dahoga, Pennsylvania, was constructed in October 1990. The bridge is a simple-span, single-lane, stress-laminated deck superstructure that is approximately 26 ft long and 16 ft wide. It is the second stress-laminated timber bridge to be constructed of hardwood lumber in Pennsylvania. The performance of the bridge was...

  7. Optimizing Tailored Bus Bridging Paths

    NARCIS (Netherlands)

    Gu, Wei; Yu, Jie; Ji, Yuxiong; van der Gun, J.P.T.; Pel, A.J.; Zhang, H. Michael; van Arem, B.

    2017-01-01

    Metro disruptions due to unexpected events reduce transit system reliability, resulting in significant productivity loss and long passenger delays. Bus bridging strategy is often used to connect stations affected by metro disruptions such that passengers could continue their journey. The literature

  8. Bridge 47--Building Global Citizenship

    Science.gov (United States)

    Lappalainen, Rilli

    2018-01-01

    Preparing young people to solve the world's greatest challenges is necessary to achieve the Sustainable Development Goals, as recognized in Target 4.7 for global citizenship. The Bridge 47 Network brings together different perspectives and approaches in values-based education to provide a forum to examine the skills and competencies needed to be…

  9. Artropathies that produce osseous bridges

    International Nuclear Information System (INIS)

    Restrepo Suarez, Jose Felix; Iglesias Gamarra, Antonio; Calvo Paramo, Enrique

    2001-01-01

    In this paper, it is reviewed the most common artropathies that are presented with osseous bridging, with emphasis in the radiological finding of the spine. Also, it's showed other different radiological finding that can help in the differential diagnosis of this disease, such us the sacroilitis in the ankylosing spondylitis or the osteolysis in the psoriatic arthritis

  10. Exodermic bridge deck performance evaluation.

    Science.gov (United States)

    2010-07-01

    In 1998, the Wisconsin DOT completed a two"leaf bascule bridge in Green Bay with an exodermic deck system. The exodermic deck consisted of 4.5"in thick cast"in"place reinforced concrete supported by a 5.19"in tall unfilled steel grid. The concrete an...

  11. Evaluation of Summer Bridge Programs

    Science.gov (United States)

    Garcia, Lisa D.; Paz, Chiara C.

    2009-01-01

    Many colleges and universities in the United States offer summer programs for their incoming students. While programs are structured and administered in a variety of ways and target various student populations, the most common type of summer bridge program aims to serve historically underrepresented students and students of low socioeconomic…

  12. Intercellular bridges in vertebrate gastrulation.

    Directory of Open Access Journals (Sweden)

    Luca Caneparo

    Full Text Available The developing zebrafish embryo has been the subject of many studies of regional patterning, stereotypical cell movements and changes in cell shape. To better study the morphological features of cells during gastrulation, we generated mosaic embryos expressing membrane attached Dendra2 to highlight cellular boundaries. We find that intercellular bridges join a significant fraction of epiblast cells in the zebrafish embryo, reaching several cell diameters in length and spanning across different regions of the developing embryos. These intercellular bridges are distinct from the cellular protrusions previously reported as extending from hypoblast cells (1-2 cellular diameters in length or epiblast cells (which were shorter. Most of the intercellular bridges were formed at pre-gastrula stages by the daughters of a dividing cell maintaining a membrane tether as they move apart after mitosis. These intercellular bridges persist during gastrulation and can mediate the transfer of proteins between distant cells. These findings reveal a surprising feature of the cellular landscape in zebrafish embryos and open new possibilities for cell-cell communication during gastrulation, with implications for modeling, cellular mechanics, and morphogenetic signaling.

  13. Detection of Ultrafine Anaphase Bridges

    DEFF Research Database (Denmark)

    Bizard, Anna H; Nielsen, Christian F; Hickson, Ian D

    2018-01-01

    Ultrafine anaphase bridges (UFBs) are thin DNA threads linking the separating sister chromatids in the anaphase of mitosis. UFBs are thought to form when topological DNA entanglements between two chromatids are not resolved prior to anaphase onset. In contrast to other markers of defective...

  14. Project LOCAL - Bridging The Gap

    Science.gov (United States)

    Haven, Robert N.

    1975-01-01

    Project LOCAL, a not-for-profit regional consortium, offers a broad spectrum of in-service training courses tailored to meet the needs of educators in various disciplines and levels of experience. The purpose of these offerings is to bridge the communication gap between innovative centers in computer-oriented education and staff members in Boston…

  15. Accelerated bridge paint test program.

    Science.gov (United States)

    2011-07-06

    The accelerated bridge paint (AB-Paint) program evaluated a new Sherwin-Williams two-coat, : fast-curing paint system. The system is comprised of an organic zinc-rich primer (SW Corothane I : Galvapac One-Pack Zinc-Rich Primer B65 G11) and a polyurea...

  16. Nonlinear models of suspension bridges

    Czech Academy of Sciences Publication Activity Database

    Malík, Josef

    2006-01-01

    Roč. 321, č. 2 (2006), s. 828-850 ISSN 0022-247X Institutional research plan: CEZ:AV0Z30860518 Keywords : suspension bridges * principle of minimum energy Subject RIV: BA - General Mathematics Impact factor: 0.758, year: 2006

  17. Matrix Metalloproteinase Enzyme Family

    Directory of Open Access Journals (Sweden)

    Ozlem Goruroglu Ozturk

    2013-04-01

    Full Text Available Matrix metalloproteinases play an important role in many biological processes such as embriogenesis, tissue remodeling, wound healing, and angiogenesis, and in some pathological conditions such as atherosclerosis, arthritis and cancer. Currently, 24 genes have been identified in humans that encode different groups of matrix metalloproteinase enzymes. This review discuss the members of the matrix metalloproteinase family and their substrate specificity, structure, function and the regulation of their enzyme activity by tissue inhibitors. [Archives Medical Review Journal 2013; 22(2.000: 209-220

  18. Lifetime Reliability Assessment of Concrete Slab Bridges

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle

    A procedure for lifetime assesment of the reliability of short concrete slab bridges is presented in the paper. Corrosion of the reinforcement is the deterioration mechanism used for estimating the reliability profiles for such bridges. The importance of using sensitivity measures is stressed....... Finally the produce is illustrated on 6 existing UK bridges....

  19. BRIDGES for Young Adolescents in North Dakota.

    Science.gov (United States)

    Harris, Mary McDonnell

    The BRIDGES Project was initiated to explore ways for North Dakota to provide young people with stronger bridges from childhood to adulthood. This report summarizes recommendations of the 1990-91 Governor's Task Force on Early Adolescence. The recommendations concern practical actions for the building of bridges by the following groups: (1)…

  20. Building Bridges One Line at a Time

    Science.gov (United States)

    Grigsby, Cathy Murray

    2012-01-01

    In this article, first-grade students were taught the different kinds of lines that were part of the construction of various bridges--the curved lines of the arches of stone bridges, straight lines connecting the cables of a suspension bridge, vertical lines, horizontal lines, and so on. They gained practice in drawing structures and in fine brush…

  1. Stabilizer for seismically exposed bridge cranes

    International Nuclear Information System (INIS)

    Engelke, M.; Kuhr, H.

    1982-01-01

    The invention concerns a stabilizer for seismically exposed bridge cranes in reactor buildings. The trolley and the crane bridge are fitted with the stabilizer consisting of a bipartite safety catch which is connected with a joint and able to take up the vertical loads during an earthquake. This stabilizer is suitable for all kinds of bridge cranes operated in seismically active regions

  2. Dynamic behaviour of prestressed concrete bridges

    International Nuclear Information System (INIS)

    Javor, T.

    1982-01-01

    The paper presents the results of experimental research of dynamic effects on prestressed concrete bridges in dynamic load tests using testing vehicles. The bridges were passed over in both directions at various speeds also running over an artificial unevenness to produce impact loads. From investigated bridges are shown the dynamic quantities such as dynamic coefficients, natural frequency, logarithmical decrement of damping, etc. (orig.) [de

  3. Hydrodynamic forces on inundated bridge decks

    Science.gov (United States)

    2009-05-01

    The hydrodynamic forces experienced by an inundated bridge deck have great importance in the design of bridges. Specifically, the drag force, lift force, and the moment acting on the bridge deck under various levels of inundation and a range of flow ...

  4. Remediation: Higher Education's Bridge to Nowhere

    Science.gov (United States)

    Complete College America, 2012

    2012-01-01

    The intentions were noble. It was hoped that remediation programs would be an academic bridge from poor high school preparation to college readiness. Sadly, remediation has become instead higher education's "Bridge to Nowhere." This broken remedial bridge is travelled by some 1.7 million beginning students each year, most of whom will…

  5. Spread prestressed concrete slab beam bridges.

    Science.gov (United States)

    2015-04-01

    TxDOT uses prestressed slab beam bridges for short-span bridges ranging from approximately 3050 ft in : length. These bridges have precast, pretensioned slab beams placed immediately adjacent to one another : with a cast-in-place slab made composi...

  6. 33 CFR 115.70 - Advance approval of bridges.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Advance approval of bridges. 115... BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.70 Advance approval of bridges. (a) The General Bridge Act of 1946 requires the approval of the location and plans of bridges prior...

  7. The surface science of enzymes

    DEFF Research Database (Denmark)

    Rod, Thomas Holm; Nørskov, Jens Kehlet

    2002-01-01

    One of the largest challenges to science in the coming years is to find the relation between enzyme structure and function. Can we predict which reactions an enzyme catalyzes from knowledge of its structure-or from its amino acid sequence? Can we use that knowledge to modify enzyme function......? To solve these problems we must understand in some detail how enzymes interact with reactants from its surroundings. These interactions take place at the surface of the enzyme and the question of enzyme function can be viewed as the surface science of enzymes. In this article we discuss how to describe...... catalysis by enzymes, and in particular the analogies between enzyme catalyzed reactions and surface catalyzed reactions. We do this by discussing two concrete examples of reactions catalyzed both in nature (by enzymes) and in industrial reactors (by inorganic materials), and show that although analogies...

  8. Acute myocardial infarction in a young adult with myocardial bridging and normal coronary arteries

    Directory of Open Access Journals (Sweden)

    Moris Chansky

    2004-09-01

    Full Text Available The authors present a case of a young adult with acute myocardialinfarction, attended at the Emergency Department of HospitalIsraelita Albert Einstein. Acute myocardial infarction caused bymyocardial bridge (intramyocardial tunneled coronary artery is arare clinical entity. The finding of this condition in patients withnormal arteries (non-obstructed vessels is uncommon; it isusually associated with extracardiac triggering factors. The casereported presented an acute myocardial infarction caused by amyocardial bridge as demonstrated in the clinical picture, ECGprogression, enzyme pattern (troponin, CKMB, TGO and LD andventriculography.

  9. Field performance of timber bridges. 4, Graves Crossing stress-laminated deck bridge

    Science.gov (United States)

    J. P. Wacker; M. A. Ritter

    The Graves Crossing bridge was constructed October 1991 in Antrim County, Michigan, as part of the demonstration timber bridge program sponsored by the USDA Forest Service. The bridge is a two-span continuous, stress-laminated deck superstructure and it is 36-ft long and 26-ft wide. The bridge is one of the first stress-laminated deck bridges to be built of sawn lumber...

  10. THE PRIMARY STRUCTURE OF HEVAMINE, AN ENZYME WITH LYSOZYME CHITINASE ACTIVITY FROM HEVEA-BRASILIENSIS LATEX

    NARCIS (Netherlands)

    JEKEL, PA; HARTMANN, JBH; BEINTEMA, JJ

    1991-01-01

    The primary structure of hevamine, an enzyme with lysozyme/chitinase activity from Hevea brasiliensis latex, has been determined predominantly with conventional non-automatic methods. The positions of three disulfide bridges have been determined. The sequence has about 60% identity with that of a

  11. Magnetically responsive enzyme powders

    Czech Academy of Sciences Publication Activity Database

    Pospišková, K.; Šafařík, Ivo

    2015-01-01

    Roč. 380, APR 2015 (2015), s. 197-200 ISSN 0304-8853 R&D Projects: GA MŠk(CZ) LD13021 Institutional support: RVO:67179843 Keywords : enzyme powders * cross-linking * magnetic modification * magnetic separation * magnetic iron oxides particles * microwave-assisted synthesis Subject RIV: CE - Biochemistry Impact factor: 2.357, year: 2015

  12. Enzyme with rhamnogalacturonase activity.

    NARCIS (Netherlands)

    Kofod, L.V.; Andersen, L.N.; Dalboge, H.; Kauppinen, M.S.; Christgau, S.; Heldt-Hansen, H.P.; Christophersen, C.; Nielsen, P.M.; Voragen, A.G.J.; Schols, H.A.

    1998-01-01

    An enzyme exhibiting rhamnogalacturonase activity, capable of cleaving a rhamnogalacturonan backbone in such a manner that galacturonic acids are left as the non-reducing ends, and which exhibits activity on hairy regions from a soy bean material and/or on saponified hairy regions from a sugar beet

  13. Implantable enzyme amperometric biosensors.

    Science.gov (United States)

    Kotanen, Christian N; Moussy, Francis Gabriel; Carrara, Sandro; Guiseppi-Elie, Anthony

    2012-05-15

    The implantable enzyme amperometric biosensor continues as the dominant in vivo format for the detection, monitoring and reporting of biochemical analytes related to a wide range of pathologies. Widely used in animal studies, there is increasing emphasis on their use in diabetes care and management, the management of trauma-associated hemorrhage and in critical care monitoring by intensivists in the ICU. These frontier opportunities demand continuous indwelling performance for up to several years, well in excess of the currently approved seven days. This review outlines the many challenges to successful deployment of chronically implantable amperometric enzyme biosensors and emphasizes the emerging technological approaches in their continued development. The foreign body response plays a prominent role in implantable biotransducer failure. Topics considering the approaches to mitigate the inflammatory response, use of biomimetic chemistries, nanostructured topographies, drug eluting constructs, and tissue-to-device interface modulus matching are reviewed. Similarly, factors that influence biotransducer performance such as enzyme stability, substrate interference, mediator selection and calibration are reviewed. For the biosensor system, the opportunities and challenges of integration, guided by footprint requirements, the limitations of mixed signal electronics, and power requirements, has produced three systems approaches. The potential is great. However, integration along the multiple length scales needed to address fundamental issues and integration across the diverse disciplines needed to achieve success of these highly integrated systems, continues to be a challenge in the development and deployment of implantable amperometric enzyme biosensor systems. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Advances in enzyme bioelectrochemistry

    Directory of Open Access Journals (Sweden)

    ANDRESSA R. PEREIRA

    Full Text Available ABSTRACT Bioelectrochemistry can be defined as a branch of Chemical Science concerned with electron-proton transfer and transport involving biomolecules, as well as electrode reactions of redox enzymes. The bioelectrochemical reactions and system have direct impact in biotechnological development, in medical devices designing, in the behavior of DNA-protein complexes, in green-energy and bioenergy concepts, and make it possible an understanding of metabolism of all living organisms (e.g. humans where biomolecules are integral to health and proper functioning. In the last years, many researchers have dedicated itself to study different redox enzymes by using electrochemistry, aiming to understand their mechanisms and to develop promising bioanodes and biocathodes for biofuel cells as well as to develop biosensors and implantable bioelectronics devices. Inside this scope, this review try to introduce and contemplate some relevant topics for enzyme bioelectrochemistry, such as the immobilization of the enzymes at electrode surfaces, the electron transfer, the bioelectrocatalysis, and new techniques conjugated with electrochemistry vising understand the kinetics and thermodynamics of redox proteins. Furthermore, examples of recent approaches in designing biosensors and biofuel developed are presented.

  15. Cold-Adapted Enzymes

    Science.gov (United States)

    Georlette, D.; Bentahir, M.; Claverie, P.; Collins, T.; D'amico, S.; Delille, D.; Feller, G.; Gratia, E.; Hoyoux, A.; Lonhienne, T.; Meuwis, M.-a.; Zecchinon, L.; Gerday, Ch.

    In the last few years, increased attention has been focused on enzymes produced by cold-adapted micro-organisms. It has emerged that psychrophilic enzymes represent an extremely powerful tool in both protein folding investigations and for biotechnological purposes. Such enzymes are characterised by an increased thermosensitivity and, most of them, by a higher catalytic efficiency at low and moderate temperatures, when compared to their mesophilic counterparts. The high thermosensitivity probably originates from an increased flexibility of either a selected area of the molecular edifice or the overall protein structure, providing enhanced abilities to undergo conformational changes during catalysis at low temperatures. Structure modelling and recent crystallographic data have allowed to elucidate the structural parameters that could be involved in this higher resilience. It was demonstrated that each psychrophilic enzyme adopts its own adaptive strategy. It appears, moreover, that there is a continuum in the strategy of protein adaptation to temperature, as the previously mentioned structural parameters are implicated in the stability of thermophilic proteins. Additional 3D crystal structures, site-directed and random mutagenesis experiments should now be undertaken to further investigate the stability-flexibility-activity relationship.

  16. Embedded enzymes catalyse capture

    Science.gov (United States)

    Kentish, Sandra

    2018-05-01

    Membrane technologies for carbon capture can offer economic and environmental advantages over conventional amine-based absorption, but can suffer from limited gas flux and selectivity to CO2. Now, a membrane based on enzymes embedded in hydrophilic pores is shown to exhibit combined flux and selectivity that challenges the state of the art.

  17. Photoperiodism and Enzyme Activity

    Science.gov (United States)

    Queiroz, Orlando; Morel, Claudine

    1974-01-01

    Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system. PMID:16658749

  18. ISFET based enzyme sensors

    NARCIS (Netherlands)

    van der Schoot, Bart H.; Bergveld, Piet

    1987-01-01

    This paper reviews the results that have been reported on ISFET based enzyme sensors. The most important improvement that results from the application of ISFETs instead of glass membrane electrodes is in the method of fabrication. Problems with regard to the pH dependence of the response and the

  19. One-electron reduction reactions with enzymes in solution

    International Nuclear Information System (INIS)

    Bisby, R.H.; Cundall, R.B.; Redpath, J.L.; Adams, G.E.

    1976-01-01

    At pH 8 and above, hydrated electrons react with ribonuclease lysozyme and α-chymotrypsin to form transient products whose spectra resemble, but are not identical to, those for the RSSR - radical anion already known for simple disulphides. Assuming a value for the extinction coefficient similar to that for RSSR - in simple disulphides, only a fraction of the hydrated electrons are shown to react with the disulphide bridges: the remainder react at other sites in the protein molecule, such as histidine, tyrosine and, in lysozyme, tryptophan residues, giving rise to comparatively weak optical absorptions between 300 and 400 nm. This has been substantiated by studying the reaction of e - sub(aq) with subtilisin Novo (an enzyme which does not contain disulphide bridges), with enzymes in which the sulphur bridges have been oxidised and with some amino acid derivatives. On lowering the pH of the solution the intensity of the RSSR - absorption diminishes as the protonated histidine residues become the favoured reaction sites. In acid solutions (pH 2 to 3) the transient optical absoptions observed are due to reactions of hydrogen atoms with the aromatic amino acids tyrosine, tryptophan and phenylalanine. The CO - 2 radical anion is only observed to transfer an electron to disulphide groups in ribonuclease, although the effect of repeated pulsing shows that some reaction must occur elsewhere in the protein molecule. In acid solutions, protonation of the electron adduct appears to produce the RSSRH. radical, whose spectrum has a maximum at 340 nm. (author)

  20. Effects of Electrolyte on Floating Water Bridge

    OpenAIRE

    Hideo Nishiumi; Fumitaka Honda

    2009-01-01

    Fuchs found phenomena that when high voltage is applied to deionized water filled in two contacted beakers, a floating water bridge forms spontaneously. In this paper, we examined flow direction of water bridge and what effects the addition of electrolytes such as NaCl, NaOH, and N H 4 C l to the floating water bridge would give. We found that ionization degree reduced the length of water bridge though insoluble electrolyte A l 2 O 3 had no effect on the length of water bridge.

  1. Protein thermal stability enhancement by designing salt bridges: a combined computational and experimental study.

    Directory of Open Access Journals (Sweden)

    Chi-Wen Lee

    Full Text Available Protein thermal stability is an important factor considered in medical and industrial applications. Many structural characteristics related to protein thermal stability have been elucidated, and increasing salt bridges is considered as one of the most efficient strategies to increase protein thermal stability. However, the accurate simulation of salt bridges remains difficult. In this study, a novel method for salt-bridge design was proposed based on the statistical analysis of 10,556 surface salt bridges on 6,493 X-ray protein structures. These salt bridges were first categorized based on pairing residues, secondary structure locations, and Cα-Cα distances. Pairing preferences generalized from statistical analysis were used to construct a salt-bridge pair index and utilized in a weighted electrostatic attraction model to find the effective pairings for designing salt bridges. The model was also coupled with B-factor, weighted contact number, relative solvent accessibility, and conservation prescreening to determine the residues appropriate for the thermal adaptive design of salt bridges. According to our method, eight putative salt-bridges were designed on a mesophilic β-glucosidase and 24 variants were constructed to verify the predictions. Six putative salt-bridges leaded to the increase of the enzyme thermal stability. A significant increase in melting temperature of 8.8, 4.8, 3.7, 1.3, 1.2, and 0.7°C of the putative salt-bridges N437K-D49, E96R-D28, E96K-D28, S440K-E70, T231K-D388, and Q277E-D282 was detected, respectively. Reversing the polarity of T231K-D388 to T231D-D388K resulted in a further increase in melting temperatures by 3.6°C, which may be caused by the transformation of an intra-subunit electrostatic interaction into an inter-subunit one depending on the local environment. The combination of the thermostable variants (N437K, E96R, T231D and D388K generated a melting temperature increase of 15.7°C. Thus, this study

  2. Crossing borders via mental bridges

    DEFF Research Database (Denmark)

    Keil, Dirk

    The project studies cross-border regional integration in Europe drawing on the example of the emerging Danish-German Femern Belt Region. It focuses on cross-border networking within public administration as part of regional integra- tion. My central question is how national-cultural differences...... influence coopera- tion, coordination and collaboration in administrative cross-border networks. In this connection the project asks after the perception of regional integration seen from the different national backgrounds. The research concentrates on the group of decision makers within the field of public...... administration, and in specific on the attempt to initiate and promote cross-border regional integration via the building of mental bridges between Danish and German parts of the Femern Belt Region. Here one of the first projects aiming primarily at building mental bridges in the Femern Belt Region...

  3. Evaluation of herb-drug interaction of a polyherbal Ayurvedic formulation through high throughput cytochrome P450 enzyme inhibition assay.

    Science.gov (United States)

    Pandit, Subrata; Kanjilal, Satyajyoti; Awasthi, Anshumali; Chaudhary, Anika; Banerjee, Dipankar; Bhatt, B N; Narwaria, Avinash; Singh, Rahul; Dutta, Kakoli; Jaggi, Manu; Singh, Anu T; Sharma, Neena; Katiyar, Chandra Kant

    2017-02-02

    Arishtas are Ayurvedic formulation made with decoction of herbs. Arjunarishta formulation is being used in Ayurveda for cardio-protective activity. Ashwagandharishta formulation possesses antioxidant, anti-atherosclerotic and anti-stress properties. Ridayarishta, a novel empirical formulation was prepared using combination of selected ingredients from these two formulations to support healthy heart functions and to reduce stress. Aim of the Study was to investigate herb-drug interaction (HDI) of Ridayarishta formulation through human hepatic cytochrome P450 (CYP450) enzyme inhibition assay. Ridayarishta formulation was phyto-chemically standardized against arjunolic acid, arjunetin, berberine, piperine, resveratrol and withaferin-A using high performance thin layer chromatography (HPTLC) analysis. The formulation was standardized with respect to ethanol by gas chromatographic (GC) analysis. HDI was evaluated with Ridayarishta formulation and amlodipine besilate, atenolol, atorvastatin, metformin, glipizide glimepiride cocktail using high throughput CYP450 enzyme inhibition assay; against CYP1A2, 2C19, 2D6 and 3A4 isozymes. Contents of arjunolic acid, arjunetin, berberine, piperine, resveratrol and withaferin-A in Ridayarishta formulation were found to be 1.76±0.12, 1.51±0.09, 1.85±0.05, 3.2±0.12, 1.21±0.08, and 2.16±0.09ppm, respectively. Quantity of ethanol in Ridayarishta was found to be 7.95±0.023% (V/V). Ridayarishta showed significantly higher (Pdrugs showed significantly (P<0.001and P<0.01) less or negligible HDI. Ridayarishta formulation alone and cocktail with amlodipine besilate, atenolol, atorvastatin, metformin, glipizide, glimepiride had negligible or insignificant effect on CYP450 inhibition. It may be concluded that consumption of Ridayarishta along with selective cardio protective, antihypertensive and anti-diabetic conventional medicine is safe with negligible or without any significant CYP450 (CYP1A2, 2C19, 2D6 and 3A4) inhibition mediated

  4. Severe ASR damaged concrete bridges

    DEFF Research Database (Denmark)

    Antonio Barbosa, Ricardo; Gustenhoff Hansen, Søren

    2015-01-01

    Technical University of Denmark (DTU) and University of Southern Denmark (SDU) have conducted several full-scale experiments with severe ASR deteriorated bridges. This paper presents few and preliminary results from both the shear tests and the measuring of the material properties. The shear test...... show that the shear capacity is almost unaffected of ASR despite significant reduction in compressive concrete strength. Furthermore, measurements show a significant tensile reinforcement strain developed due to ASR expansion....

  5. External corners as heat bridges

    Energy Technology Data Exchange (ETDEWEB)

    Berber, J.

    1984-08-01

    The maximum additional heat loss in vertical external corners depending on wall thickness is determined. In order to amire at a low k-value, a much smaller wall thickness is required in externally insulated walls than in monolithic constructions; the greater loss of heat bridge with external insulation stands in contrast to a higher loss in thick, monolithic walls. In relation to total losses, the additional losses through external corners are practically negligible.

  6. Inspection Strategies for Concrete Bridges

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Thoft-Christensen, Palle

    1989-01-01

    In this paper an optimal inspection strategy for concrete bridges based on periodic routine and detailed inspections is presented. The failure mode considered is corrosion of the reinforcement due to chlorides. A simple modelling of the corrosion and of the inspection strategy is presented....... The optimal inspection strategy is determined from an optimization problem, where the design variables are time intervals between detailed inspections and the concrete cover. The strategy is illustrated on a simple structure, namely a reinforced concrete beam....

  7. Cross-Quint-Bridge Resistor

    Science.gov (United States)

    Hannaman, David J.; Lieneweg, Udo; Buehler, Martin G.; Mantalas, Linda

    1991-01-01

    Integrated-circuit conductive test pattern intended to provide data on effects of design widths and design spacings upon actual widths of conductive lines. Provides for electrical measurements both on lines of unknown width and on features having known dimensions. Data from measurements on five bridges used to determine four parameters of mathematical model describing system. In principle, pattern determines effects of width and spacing and interaction between them.

  8. Salt bridges: geometrically specific, designable interactions.

    Science.gov (United States)

    Donald, Jason E; Kulp, Daniel W; DeGrado, William F

    2011-03-01

    Salt bridges occur frequently in proteins, providing conformational specificity and contributing to molecular recognition and catalysis. We present a comprehensive analysis of these interactions in protein structures by surveying a large database of protein structures. Salt bridges between Asp or Glu and His, Arg, or Lys display extremely well-defined geometric preferences. Several previously observed preferences are confirmed, and others that were previously unrecognized are discovered. Salt bridges are explored for their preferences for different separations in sequence and in space, geometric preferences within proteins and at protein-protein interfaces, co-operativity in networked salt bridges, inclusion within metal-binding sites, preference for acidic electrons, apparent conformational side chain entropy reduction on formation, and degree of burial. Salt bridges occur far more frequently between residues at close than distant sequence separations, but, at close distances, there remain strong preferences for salt bridges at specific separations. Specific types of complex salt bridges, involving three or more members, are also discovered. As we observe a strong relationship between the propensity to form a salt bridge and the placement of salt-bridging residues in protein sequences, we discuss the role that salt bridges might play in kinetically influencing protein folding and thermodynamically stabilizing the native conformation. We also develop a quantitative method to select appropriate crystal structure resolution and B-factor cutoffs. Detailed knowledge of these geometric and sequence dependences should aid de novo design and prediction algorithms. Copyright © 2010 Wiley-Liss, Inc.

  9. Remarks on crack-bridging concepts

    International Nuclear Information System (INIS)

    Bao, G.; Suo, Z.

    1992-01-01

    The article draws upon recent work by us and our colleagues on metal and ceramic matrix composites for high temperature engines. The central theme here is to deduce mechanical properties, such as toughness, strength and notch-ductility, from bridging laws that characterize inelastic processes associated with fracture. A particular set of normalization is introduced to present the design charts, segregating the roles played by the shape, and the scale, of a bridging law. A single material length, γ 0 E/σ 0 , emerges, where γ 0 is the limiting-separation, σ 0 the bridging-strength, and E the Young's modulus of the solid. It is the huge variation of this length-from a few manometers for atomic bond, to a meter for cross-over fibers - that underlies the richness in material behaviors. Under small-scale bridging conditions, γ 0 E/σ 0 is the only basic length scale in the mechanics problem and represents, with a pre-factor about 0.4, the bridging zone size. A catalog of small-scale bridging solutions is compiled for idealized bridging laws. Large-scale bridging introduces a dimensionless group, a/(γ 0 E/σ 0 ), where a is a length characterizing the component. The group plays a major role in all phenomena associated with bridging, and provides a focus of discussion in this article. For example, it quantifies the bridging scale when a is the unbridged crack length, and notch-sensitivity when a is hole radius. The difference and the connection between Irwin's fracture mechanics and crack bridging concepts are discussed. It is demonstrated that fracture toughness and resistance curve are meaningful only when small-scale bridging conditions prevail, and therefore of limited use in design with composites. Many other mechanical properties of composites, such as strength and notch-sensitivity, can be simulated by invoking large-scale bridging concepts. 37 refs., 21 figs., 3 tabs

  10. Road Bridges and Culverts, Bridge dataset only includes bridges maintained by Johnson County Public Works in the unincorporated areas, Published in Not Provided, Johnson County Government.

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Road Bridges and Culverts dataset current as of unknown. Bridge dataset only includes bridges maintained by Johnson County Public Works in the unincorporated areas.

  11. Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling.

    Science.gov (United States)

    Zhou, Yan; Liu, Shi-Qing; Yu, Ling; He, Bin; Wu, Shi-Hao; Zhao, Qi; Xia, Shao-Qiang; Mei, Hong-Jun

    2015-09-01

    Chondrocyte apoptosis is an important mechanism involved in osteoarthritis (OA). Berberine (BBR), a plant alkaloid derived from Chinese medicine, is characterized by multiple pharmacological effects, such as anti-inflammatory and anti-apoptotic activities. This study aimed to evaluate the chondroprotective effect and underlying mechanisms of BBR on sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis and surgically-induced rat OA model. The in vitro results revealed that BBR suppressed SNP-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, down-regulated expressions of inducible nitric oxide synthase (iNOS) and caspase-3, and up-regulated Bcl-2/Bax ratio and Type II collagen (Col II) at protein levels, which were accompanied by increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK). Furthermore, the anti-apoptotic effect of BBR was blocked by AMPK inhibitor Compound C (CC) and adenosine-9-β-D-arabino-furanoside (Ara A), and enhanced by p38 MAPK inhibitor SB203580. In vivo experiment suggested that BBR ameliorated cartilage degeneration and exhibited an anti-apoptotic effect on articular cartilage in a rat OA model, as demonstrated by histological analyses, TUNEL assay and immunohistochemical analyses of caspase-3, Bcl-2 and Bax expressions. These findings suggest that BBR suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via activating AMPK signaling and suppressing p38 MAPK activity.

  12. Antibacterial and synergy of berberines with antibacterial agents against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA).

    Science.gov (United States)

    Zuo, Guo-Ying; Li, Yang; Han, Jun; Wang, Gen-Chun; Zhang, Yun-Ling; Bian, Zhong-Qi

    2012-08-29

    Antibacterial activity of berberine (Ber) and 8-acetonyl-dihydroberberine (A-Ber) alone and combined uses with antibacterial agents ampicillin (AMP), azithromycin (AZM), cefazolin (CFZ) and levofloxacin (LEV) was studied on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA). Susceptibility to each agent alone was tested using a broth microdilution method and the chequerboard and time-kill tests for the combined evaluations, respectively. The alone MICs/MBCs (μg/mL) ranges were 32-128/64-256 (Ber) and 32-128/128-512 (A-Ber). Significant synergies were observed for the Ber (A-Ber)/AZM and Ber (A-Ber)/LEV combinations against 90% of the tested MRSA strains, with fractional inhibitory concentration indices (FICIs) values ranged from 0.188 to 0.500. An additivity result was also observed for the Ber/AZM combination by time-kill curves. These results demonstrated for the first time that Ber and A-Ber enhanced the in vitro inhibitory efficacy of AZM and LEV to a same extent, which had potential for further investigation in combinatory therapeutic applications of patients infected with MRSA.

  13. Antibacterial and Synergy of Berberines with Antibacterial Agents against Clinical Multi-Drug Resistant Isolates of Methicillin-Resistant Staphylococcus aureus (MRSA

    Directory of Open Access Journals (Sweden)

    Zhong-Qi Bian

    2012-08-01

    Full Text Available Antibacterial activity of berberine (Ber and 8-acetonyl-dihydroberberine (A-Ber alone and combined uses with antibacterial agents ampicillin (AMP, azithromycin (AZM, cefazolin (CFZ and levofloxacin (LEV was studied on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA. Susceptibility to each agent alone was tested using a broth microdilution method and the chequerboard and time-kill tests for the combined evaluations, respectively. The alone MICs/MBCs (mg/mL ranges were 32–128/64–256 (Ber and 32-128/128-512 (A-Ber. Significant synergies were observed for the Ber (A-Ber/AZM and Ber (A-Ber/LEV combinations against 90% of the tested MRSA strains, with fractional inhibitory concentration indices (FICIs values ranged  from 0.188 to 0.500. An additivity result was also observed for the Ber/AZM combination by time-kill curves. These results demonstrated for the first time that Ber and A-Ber enhanced the in vitro inhibitory efficacy of AZM and LEV to a same extent, which had potential for further investigation in combinatory therapeutic applications of patients infected with MRSA.

  14. HPLC-DAD DETERMINATION OF BERBERINE, CHELERYTHRINE AND SANGUINARINE IN THE MEXICAN PRICKLY POPPY (Argemone mexicana L. PAPAVERACEAE, A MEDICINAL PLANT

    Directory of Open Access Journals (Sweden)

    Jorge F. Xool-Tamayo

    Full Text Available A sensitive, simple, rapid and reliable HPLC-DAD method for the analysis of the benzylisoquinoline alkaloids (BIA's content in Argemone mexicana (Papaveraceae is presented. This method allows the simultaneous separation and quantitation of berberine (Bn, chelerythrine (C and sanguinarine (S in extracts from A. mexicana tissues, reducing time of analysis in comparison to previous reports. Alkaloids were separated on a C18 Hypersil Gold column using an acetonitrile gradient (20 to 70% in 1% acetic acid in water. Alkaloids were identified based on retention times and UV spectra and quantified at 254 nm. Linearity between 0.5-20 µg mL-1 was observed for Bn, C and S, with limits of detection (LOD and quantitation (LOQ of 0.11 and 0.33 for Bn, 0.10 and 0.30 for C and 0.05 and 0.15 for S, respectively. Maximal intra- and inter-day variation values were < 0.49% in all cases, with alkaloids' recoveries higher than 95%. System suitability tests (SST, including resolution (Rs, retention factor (K', selectivity (α, tailing factor and number of theoretical plates were performed according to the United States Pharmacopeia (USP, fulfilling recommended values. The method proved to be efficient and reproducible when analyzing different tissues of field-collected A. mexicana plants.

  15. In vitro antitumor efficacy of berberine: solid lipid nanoparticles against human HepG2, Huh7 and EC9706 cancer cell lines

    Science.gov (United States)

    Meng, Xiang-Ping; Wang, Xiao; Wang, Huai-ling; Chen, Tong-sheng; Wang, Yi-fei; Wang, Zhi-ping

    2016-03-01

    Hepatocarcinoma and esophageal squamous cell carcinomas threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma and esophageal carcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma and antiesophageal carcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber loaded solid lipid nanoparticles (Ber-SLN) was prepared by hot melting and then high pressure homogenization technique. The in vitro anti-hepatocarcinoma and antiesophageal carcinoma effects of Ber-SLN relative to efficacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-SLN were 154.3 ± 4.1 nm and -11.7 ± 1.8 mV, respectively. MTT assay showed that Ber-SLN effectively inhibited the proliferation of human HepG2 and Huh7 and EC9706 cells, and the corresponding IC50 value was 10.6 μg/ml, 5.1 μg/ml, and 7.3 μg/ml (18.3μg/ml, 6.5μg/ml, and 12.4μg/ml μg/ml of bulk Ber solution), respectively. These results suggest that the delivery of Ber-SLN is a promising approach for treating tumors.

  16. Anti-hepatocarcinoma effects of berberine nanosuspension against human HepG2 and Huh7 cells as well as H22 tumor bearing mice

    Science.gov (United States)

    Wang, Zhi-ping; Wu, Jun-biao; Zhou, Qun; Wang, Yi-fei; Chen, Tongsheng

    2014-09-01

    Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Both in vitro and in vivo anti-hepatocarcinoma effects of Ber-NS relative to effcacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-NS were 73.1 +/- 3.7 nm and 6.99 +/- 0.17 mV, respectively. Ber-NS exhibited significant inhibitory effects against human HepG2 and Huh7 cells, and the corresponding IC50 values were 8.1 and 4.7 μg/ml (18.3 and 6.5 μg/ml of Ber solution). In vivo studies also showed higher antitumor efficacy, and inhibition rates was 63.7% (41.4 % of Ber solution) at 100 mg/kg intragastric administration in the H22 solid tumor bearing mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating hepatocarcinoma.

  17. Anti-hepatocarcinoma effects of berberine-nanostructured lipid carriers against human HepG2, Huh7, and EC9706 cancer cell lines

    Science.gov (United States)

    Meng, Xiang-Ping; Fan, Hua; Wang, Yi-fei; Wang, Zhi-ping; Chen, Tong-sheng

    2016-10-01

    Hepatocarcinoma and esophageal squamous cell carcinomas threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma and esophageal carcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma and antiesophageal carcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber loaded nanostructured lipid carriers (Ber-NLC) was prepared by hot melting and then high pressure homogenization technique. The in vitro anti-hepatocarcinoma and antiesophageal carcinoma effects of Ber-NLC relative to efficacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-NLC were 189.3 +/- 3.7 nm and -19.3 +/- 1.4 mV, respectively. MTT assay showed that Ber-NLC effectively inhibited the proliferation of human HepG2 and Huh7 and EC9706 cells, and the corresponding IC50 value was 9.1 μg/ml, 4.4 μg/ml, and 6.3 μg/ml (18.3μg/ml, 6.5μg/ml, and 12.4μg/ml μg/ml of bulk Ber solution), respectively. These results suggest that the delivery of Ber-NLC is a promising approach for treating tumors.

  18. NRSA enzyme decomposition model data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Microbial enzyme activities measured at more than 2000 US streams and rivers. These enzyme data were then used to predict organic matter decomposition and microbial...

  19. Cellulase enzyme and biomass utilization

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-03

    Jun 3, 2009 ... human population grows and economic development. However, the current .... conditions and the production cost of the related enzyme system. Therefore ... Given the importance of this enzyme to these so many industries,.

  20. Gold nanoparticles bridging infra-red spectroscopy and laser desorption/ionization mass spectrometry for direct analysis of over-the-counter drug and botanical medicines.

    Science.gov (United States)

    Chau, Siu-Leung; Tang, Ho-Wai; Ng, Kwan-Ming

    2016-05-05

    With a coating of gold nanoparticles (AuNPs), over-the-counter (OTC) drugs and Chinese herbal medicine granules in KBr pellets could be analyzed by Fourier Transform Infra-red (FT-IR) spectroscopy and Surface-assisted Laser Desorption/Ionization mass spectrometry (SALDI-MS). FT-IR spectroscopy allows fast detection of major active ingredient (e.g., acetaminophen) in OTC drugs in KBr pellets. Upon coating a thin layer of AuNPs on the KBr pellet, minor active ingredients (e.g., noscapine and loratadine) in OTC drugs, which were not revealed by FT-IR, could be detected unambiguously using AuNPs-assisted LDI-MS. Moreover, phytochemical markers of Coptidis Rhizoma (i.e. berberine, palmatine and coptisine) could be quantified in the concentrated Chinese medicine (CCM) granules by the SALDI-MS using standard addition method. The quantitative results matched with those determined by high-performance liquid chromatography with ultraviolet detection. Being strongly absorbing in UV yet transparent to IR, AuNPs successfully bridged FT-IR and SALDI-MS for direct analysis of active ingredients in the same solid sample. FT-IR allowed the fast analysis of major active ingredient in drugs, while SALDI-MS allowed the detection of minor active ingredient in the presence of excipient, and also quantitation of phytochemicals in herbal granules. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Surface reconstitution of glucose oxidase onto a norbornylogous bridge self-assembled monolayer

    International Nuclear Information System (INIS)

    Liu Jingquan; Paddon-Row, Michael N.; Gooding, J. Justin

    2006-01-01

    An electrode construct was fabricated in which a self-assembled monolayer containing a novel norbornylogous bridge was covalently attached to flavin adenine dinucleotide (FAD), the redox active centre of several oxidase enzymes. The electrochemistry of the construct was investigated before and after the reconstitution of glucose oxidase around the surface bound FAD. Rapid rates of electron transfer were observed both before and after the reconstitution of biocatalytically active enzyme. However, no biocatalytic activity was observed under anaerobic conditions suggesting the a lack of enzyme turnover through direct electron transfer. It is proposed that a decrease in the electronic coupling between the redox active FAD and the electrode following reconstitution of the glucose oxidase - a probable consequence of the FAD being immersed in a protein environment - was responsible for the inability of the enzyme to be turned over under anaerobic conditions

  2. Role of the Water–Metal Ion Bridge in Mediating Interactions between Quinolones and Escherichia coli Topoisomerase IV

    Science.gov (United States)

    2015-01-01

    Although quinolones have been in clinical use for decades, the mechanism underlying drug activity and resistance has remained elusive. However, recent studies indicate that clinically relevant quinolones interact with Bacillus anthracis (Gram-positive) topoisomerase IV through a critical water–metal ion bridge and that the most common quinolone resistance mutations decrease drug activity by disrupting this bridge. As a first step toward determining whether the water–metal ion bridge is a general mechanism of quinolone–topoisomerase interaction, we characterized drug interactions with wild-type Escherichia coli (Gram-negative) topoisomerase IV and a series of ParC enzymes with mutations (S80L, S80I, S80F, and E84K) in the predicted bridge-anchoring residues. Results strongly suggest that the water–metal ion bridge is essential for quinolone activity against E. coli topoisomerase IV. Although the bridge represents a common and critical mechanism that underlies broad-spectrum quinolone function, it appears to play different roles in B. anthracis and E. coli topoisomerase IV. The water–metal ion bridge is the most important binding contact of clinically relevant quinolones with the Gram-positive enzyme. However, it primarily acts to properly align clinically relevant quinolones with E. coli topoisomerase IV. Finally, even though ciprofloxacin is unable to increase levels of DNA cleavage mediated by several of the Ser80 and Glu84 mutant E. coli enzymes, the drug still retains the ability to inhibit the overall catalytic activity of these topoisomerase IV proteins. Inhibition parallels drug binding, suggesting that the presence of the drug in the active site is sufficient to diminish DNA relaxation rates. PMID:25115926

  3. Horizontal bridges in polar dielectric liquids

    Science.gov (United States)

    Woisetschläger, Jakob; Wexler, Adam D.; Holler, Gert; Eisenhut, Mathias; Gatterer, Karl; Fuchs, Elmar C.

    2012-01-01

    When a high-voltage direct-current is applied to two beakers filled with polar liquid dielectrica like water or methanol, a horizontal bridge forms between the two beakers. By repeating a version of Pellat's experiment, it is shown that a horizontal bridge is stable by the action of electrohydrodynamic pressure. Thus, the static and dynamic properties of the phenomenon called a `floating water bridge' can be explained by the gradient of Maxwell pressure, replenishing the liquid within the bridge against any drainage mechanism. It is also shown that a number of liquids can form stable and long horizontal bridges. The stability of such a connection, and the asymmetry in mass flow through such bridges caused by the formation of ion clouds in the vicinity of the electrodes, is also discussed by two further experiments.

  4. Horizontal bridges in polar dielectric liquids

    Energy Technology Data Exchange (ETDEWEB)

    Woisetschlaeger, Jakob [Graz University of Technology, Experimental Turbomachinery Research and Optical Measurement Group, Institute for Thermal Turbomachinery and Machine Dynamics, Graz (Austria); Wexler, Adam D.; Fuchs, Elmar C. [Wetsus, Center of Excellence for Sustainable Water Technology, Leeuwarden (Netherlands); Holler, Gert [Graz University of Technology, Institute of Electrical Measurement and Measurement Signal Processing, Graz (Austria); Eisenhut, Mathias [Graz University of Technology, Institute of Analytical Chemistry and Food Chemistry, Graz (Austria); Gatterer, Karl [Graz University of Technology, Institute of Physical and Theoretical Chemistry, Graz (Austria)

    2012-01-15

    When a high-voltage direct-current is applied to two beakers filled with polar liquid dielectrica like water or methanol, a horizontal bridge forms between the two beakers. By repeating a version of Pellat's experiment, it is shown that a horizontal bridge is stable by the action of electrohydrodynamic pressure. Thus, the static and dynamic properties of the phenomenon called a 'floating water bridge' can be explained by the gradient of Maxwell pressure, replenishing the liquid within the bridge against any drainage mechanism. It is also shown that a number of liquids can form stable and long horizontal bridges. The stability of such a connection, and the asymmetry in mass flow through such bridges caused by the formation of ion clouds in the vicinity of the electrodes, is also discussed by two further experiments. (orig.)

  5. Dynamic assessment of bridge deck performance considering realistic bridge-traffic interaction : research brief

    Science.gov (United States)

    2017-09-01

    This study is to develop simulation methodology to conduct the dynamic assessment of bridge deck performance subjected to traffic. Concrete bridge decks are exposed to daily traffic loads and may experience some surface cracking caused by excessive s...

  6. Development of a precast bridge deck overhang system for the rock creek bridge.

    Science.gov (United States)

    2008-12-01

    Precast, prestressed panels are commonly used at interior beams for bridges in Texas. The use of these : panels provides ease of construction, sufficient capacity, and good economy for the construction of : bridges in Texas. Current practice for the ...

  7. 硫糖铝联合黄连素治疗慢性顽固性胃炎的临床疗效分析%Comprehensive Analysis Sucralfate Joint Berberine for the Treatment of Chronic Intractable Chronic Gastritis

    Institute of Scientific and Technical Information of China (English)

    董智常; 苏家新; 陈佩容

    2014-01-01

    Objective To analyze sucralfate joint berberine effect on the treatment of chronic stubborn gastritis. Methods Select 180 cases of patients who have confirmed with chronic stubborn gastritis, then all patients start taking sucralfate and berberine, and own symptoms before treatment and after treatment in patients with symptoms were compared, so we obtain the effective rate. Results Two drug combination treatment of chronic stubborn gastritis is very effective. Conclusions Sucralfate joint berberine treat chronic stubborn gastritis, making the patients symptoms improved after treatment, the total effective rate is higher, and severe side effects rarely only a handful of constipation, dry mouth, find out a way for clinical treatment of chronic stubborn gastritis.%目的:分析硫糖铝联合黄连素对慢性顽固性胃炎的治疗效果。方法选取已确诊的慢性顽固性胃炎患者180例,所有患者均开始服用硫糖铝和黄连素,将患者自身治疗前症状与治疗后症状进行对照,从而得出有效率。结果两药物联用治疗慢性顽固性胃炎极为有效。结论硫糖铝联合黄连素治疗慢性顽固性胃炎,使得患者治疗后症状大为改善,总有效率较高,且严重副作用极少仅少数出现便秘、口干,为临床上治疗慢性顽固性胃炎寻得出路。

  8. A data management infrastructure for bridge monitoring

    Science.gov (United States)

    Jeong, Seongwoon; Byun, Jaewook; Kim, Daeyoung; Sohn, Hoon; Bae, In Hwan; Law, Kincho H.

    2015-04-01

    This paper discusses a data management infrastructure framework for bridge monitoring applications. As sensor technologies mature and become economically affordable, their deployment for bridge monitoring will continue to grow. Data management becomes a critical issue not only for storing the sensor data but also for integrating with the bridge model to support other functions, such as management, maintenance and inspection. The focus of this study is on the effective data management of bridge information and sensor data, which is crucial to structural health monitoring and life cycle management of bridge structures. We review the state-of-the-art of bridge information modeling and sensor data management, and propose a data management framework for bridge monitoring based on NoSQL database technologies that have been shown useful in handling high volume, time-series data and to flexibly deal with unstructured data schema. Specifically, Apache Cassandra and Mongo DB are deployed for the prototype implementation of the framework. This paper describes the database design for an XML-based Bridge Information Modeling (BrIM) schema, and the representation of sensor data using Sensor Model Language (SensorML). The proposed prototype data management framework is validated using data collected from the Yeongjong Bridge in Incheon, Korea.

  9. Railway bridge monitoring during construction and sliding

    Science.gov (United States)

    Inaudi, Daniele; Casanova, Nicoletta; Kronenberg, Pascal; Vurpillot, Samuel

    1997-05-01

    The Moesa railway bridge is a composite steel concrete bridge on three spans of 30 m each. The 50 cm thick concrete deck is supported on the lower flanges of two continuous, 2.7 m high I-beams. The bridge has been constructed alongside an old metallic bridge. After demolishing this one, the new bridge has been slid for 5 m by 4 hydraulic jacks and positioned on the refurbished piles of the old bridge. About 30 fiber optic, low-coherence sensors were imbedded in the concrete deck to monitor its deformations during concrete setting and shrinkage, as well as during the bridge sliding phase. In the days following concrete pour it was possible to follow its thermal expansion due to the exothermic setting reaction and the following thermal and during shrinkage. The deformations induced by the additional load produced by the successive concreting phases were also observed. During the bridge push, which extended over six hours, the embedded and surface mounted sensors allowed the monitoring of the curvature variations in the horizontal plane due to the slightly uneven progression of the jacks. Excessive curvature and the resulting cracking of concrete could be ruled out by these measurements. It was also possible to observe the bridge elongation under the heating action of the sun.

  10. Review of Energy Harvesters Utilizing Bridge Vibrations

    Directory of Open Access Journals (Sweden)

    Farid Ullah Khan

    2016-01-01

    Full Text Available For health monitoring of bridges, wireless acceleration sensor nodes (WASNs are normally used. In bridge environment, several forms of energy are available for operating WASNs that include wind, solar, acoustic, and vibration energy. However, only bridge vibration has the tendency to be utilized for embedded WASNs application in bridge structures. This paper reports on the recent advancements in the area of vibration energy harvesters (VEHs utilizing bridge oscillations. The bridge vibration is narrowband (1 to 40 Hz with low acceleration levels (0.01 to 3.8 g. For utilization of bridge vibration, electromagnetic based vibration energy harvesters (EM-VEHs and piezoelectric based vibration energy harvesters (PE-VEHs have been developed. The power generation of the reported EM-VEHs is in the range from 0.7 to 1450000 μW. However, the power production by the developed PE-VEHs ranges from 0.6 to 7700 μW. The overall size of most of the bridge VEHs is quite comparable and is in mesoscale. The resonant frequencies of EM-VEHs are on the lower side (0.13 to 27 Hz in comparison to PE-VEHs (1 to 120 Hz. The power densities reported for these bridge VEHs range from 0.01 to 9539.5 μW/cm3 and are quite enough to operate most of the commercial WASNs.

  11. A Polish approach to FRP bridges

    Science.gov (United States)

    Siwowski, Tomasz; Rajchel, Mateusz

    2017-12-01

    The paper presents initial results of a new approach to FRP composite bridge construction that is presently being developed and tested in Poland. The concept combines lightweight concrete with FRP composites to create a durable highly optimised structure. The paper describes the bridge system itself and presents the research results on its development. The basic design is presented together with research results on its development: FEM analysis and a range of static test results of full-scale bridge beam experiments. The paper finishes with some test results of a full scale bridge that was constructed near Rzeszow in December 2015.

  12. SURVEY RESULTS AND TESTING OF RAILWAY BRIDGES

    Directory of Open Access Journals (Sweden)

    I. H. Haniiev

    2010-03-01

    Full Text Available The article is devoted to the survey and testing of railway bridges by the State Joint-Stock Railway Company «Uzbekiston Temir Yollari» («Uzbekistan Railways». It is stated that in the existing rules on determination of the capacity of bridges the recommendations on taking into account the cumulative deflection to the moment of technical diagnostics of spans on the bridge capacity are absent. The author states on the need to develop a method for determining the wear of spans on restriction of the residual deflection in the bridge floor slabs.

  13. 23 CFR 650.409 - Evaluation of bridge inventory.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Evaluation of bridge inventory. 650.409 Section 650.409... Evaluation of bridge inventory. (a) Sufficiency rating of bridges. Upon receipt and evaluation of the bridge inventory, a sufficiency rating will be assigned to each bridge by the Secretary in accordance with the...

  14. 23 CFR 650.809 - Movable span bridges.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Movable span bridges. 650.809 Section 650.809 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Navigational Clearances for Bridges § 650.809 Movable span bridges. A fixed bridge...

  15. 33 CFR 118.90 - Bridges crossing channel obliquely.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Bridges crossing channel obliquely. 118.90 Section 118.90 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LIGHTING AND OTHER SIGNALS § 118.90 Bridges crossing channel obliquely. Bridges...

  16. 33 CFR 118.70 - Lights on swing bridges.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Lights on swing bridges. 118.70 Section 118.70 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LIGHTING AND OTHER SIGNALS § 118.70 Lights on swing bridges. (a) Swing span lights on through bridges. Each...

  17. 33 CFR 118.85 - Lights on vertical lift bridges.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Lights on vertical lift bridges... BRIDGES BRIDGE LIGHTING AND OTHER SIGNALS § 118.85 Lights on vertical lift bridges. (a) Lift span lights. The vertical lift span of every vertical lift bridge shall be lighted so that the center of the...

  18. 33 CFR 118.65 - Lights on fixed bridges.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Lights on fixed bridges. 118.65 Section 118.65 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LIGHTING AND OTHER SIGNALS § 118.65 Lights on fixed bridges. (a) Each fixed bridge span over a navigable...

  19. Field performance of timber bridges. 9, Big Erick`s stress-laminated deck bridge

    Science.gov (United States)

    J. A. Kainz; J. P. Wacker; M. Nelson

    The Big Erickas bridge was constructed during September 1992 in Baraga County, Michigan. The bridge is 72 ft long, 16 ft wide, and consists of three simple spans: two stress-laminated deck approach spans and a stress-laminated box center span. The bridge is unique in that it is one of the first known stress-laminated timber bridge applications to use Eastern Hemlock...

  20. Laboratory Testing of Precast Bridge Beck Panel Transverse Connections for Use in Accelerated Bridge Construction

    OpenAIRE

    Porter, Scott D.

    2009-01-01

    Precast concrete bridge deck panels have been used for decades to accelerate bridge construction. Cracking of the transverse connection between panels is a common problem that can damage deck overlays and cause connection leaking leading to corrosion of lower bridge elements. To better understand the behavior of bridge deck transverse female-to-female connections, shear and moment lab testing were performed at Utah State University for the Utah Department of Transportation. Two existing UDOT ...

  1. Thermal bridges of modern windows

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan de Place; Møller, Eva B.; Nielsen, Anker

    2013-01-01

    if the window has an U-factor of 1 W/(m2·K) or lower. This paper describes the development of modern, energy efficient Danish windows with reduced thermal bridges. It focuses on materials, geometry, and sealing of window panes based on a literature review. Examples of modern windows are presented. Experience...... been an important driver for the development of new window solutions in Denmark, increasing the inner-surface temperature at the sealing of window panes. However, it will not stop complaints fromconsumers, as this temperature is calculated under standardized conditions. Increasing requirements...

  2. A bridge to advanced mathematics

    CERN Document Server

    Sentilles, Dennis

    2011-01-01

    This helpful workbook-style ""bridge"" book introduces students to the foundations of advanced mathematics, spanning the gap between a practically oriented calculus sequence and subsequent courses in algebra and analysis with a more theoretical slant. Part 1 focuses on logic and number systems, providing the most basic tools, examples, and motivation for the manner, method, and concerns of higher mathematics. Part 2 covers sets, relations, functions, infinite sets, and mathematical proofs and reasoning. Author Dennis Sentilles also discusses the history and development of mathematics as well a

  3. Nanoclusters a bridge across disciplines

    CERN Document Server

    Jena, Purusottam

    2010-01-01

    This comprehensive book on Nanoclusters comprises sixteen authoritative chapters written by leading researchers in the field. It provides insight into topics that are currently at the cutting edge of cluster science, with the main focus on metal and metal compound systems that are of particular interest in materials science, and also on aspects related to biology and medicine. While there are numerous books on clusters, the focus on clusters as a bridge across disciplines sets this book apart from others. Delivers cutting edge coverage of cluster science Covers a broad range of topics in

  4. Quantum Bridge Fabrication Using Photolithography

    International Nuclear Information System (INIS)

    Quinones, R.

    2001-01-01

    The need for high-speed performance electronics in computers integrated circuits and sensors, require the fabrication of low energy consumption diodes. Nano fabrication methods require new techniques and equipment. We are currently developing a procedure to fabricate a diode based on quantum-effects. The device will act like a traditional diode, but the nanometer scale will allow it to reach high speeds without over heating. This new diode will be on a nano-bridge so it can be attenuated by an electromagnetic wave. The goal is to obtain similar current vs voltage response as in a silicon diode

  5. Enzyme recycling in lignocellulosic biorefineries

    DEFF Research Database (Denmark)

    Jørgensen, Henning; Pinelo, Manuel

    2017-01-01

    platform. Cellulases are the most important enzymes required in this process, but the complex nature of lignocellulose requires several other enzymes (hemicellulases and auxiliary enzymes) for efficient hydrolysis. Enzyme recycling increases the catalytic productivity of the enzymes by reusing them...... for several batches of hydrolysis, and thereby reduces the overall cost associated with the hydrolysis. Research on this subject has been ongoing for many years and several promising technologies and methods have been developed and demonstrated. But only in a very few cases have these technologies been...... upscaled and tested in industrial settings, mainly because of many difficulties with recycling of enzymes from the complex lignocellulose hydrolyzate at industrially relevant conditions, i.e., high solids loadings. The challenges are associated with the large number of different enzymes required...

  6. Characterising Complex Enzyme Reaction Data.

    Directory of Open Access Journals (Sweden)

    Handan Melike Dönertaş

    Full Text Available The relationship between enzyme-catalysed reactions and the Enzyme Commission (EC number, the widely accepted classification scheme used to characterise enzyme activity, is complex and with the rapid increase in our knowledge of the reactions catalysed by enzymes needs revisiting. We present a manual and computational analysis to investigate this complexity and found that almost one-third of all known EC numbers are linked to more than one reaction in the secondary reaction databases (e.g., KEGG. Although this complexity is often resolved by defining generic, alternative and partial reactions, we have also found individual EC numbers with more than one reaction catalysing different types of bond changes. This analysis adds a new dimension to our understanding of enzyme function and might be useful for the accurate annotation of the function of enzymes and to study the changes in enzyme function during evolution.

  7. Field performance of timber bridges. 15, Pueblo County, Colorado, stress-laminated deck bridge

    Science.gov (United States)

    L. E. Hislop

    The Pueblo County 204B bridge was constructed in March 1990 in Pueblo, Colorado, as a demonstration bridge under the USDA Forest Service Timber Bridge Initiative. The stress-laminated deck superstructure is approximately 10 m long, 9 m wide, and 406 mm deep, with a skew of 10 degrees. Performance monitoring was conducted for 3 years, beginning at...

  8. 49 CFR 236.312 - Movable bridge, interlocking of signal appliances with bridge devices.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Movable bridge, interlocking of signal appliances with bridge devices. 236.312 Section 236.312 Transportation Other Regulations Relating to... SYSTEMS, DEVICES, AND APPLIANCES Interlocking Standards § 236.312 Movable bridge, interlocking of signal...

  9. Light-weight aluminium bridges and bridge decks. An overview of recent applications

    NARCIS (Netherlands)

    Maljaars, J.; Soetens, F.; Kluyver, D. de

    2008-01-01

    The last decades have shown a large increase in the application of aluminium alloys for light-weight bridges. For bridge construction, aluminium alloys have some specific advantages, but also some points of attention. This paper deals with some recent projects of aluminium bridges, and for these

  10. A bridge with a view, a view with a bridge : Identifying design considerations for bridges to strengthen regional identity

    NARCIS (Netherlands)

    Smits, J.E.P.; van der Hoeven, F.D.

    2015-01-01

    This paper discusses design considerations for creating high quality infrastructural artefacts with an emphasis on bridges. The authors pursue a design study and analysis approach to highlight the specifics of infrastructure design for regional identity, based on their own work on a bridge

  11. Salt-bridge energetics in halophilic proteins.

    Science.gov (United States)

    Nayek, Arnab; Sen Gupta, Parth Sarthi; Banerjee, Shyamashree; Mondal, Buddhadev; Bandyopadhyay, Amal K

    2014-01-01

    Halophilic proteins have greater abundance of acidic over basic and very low bulky hydrophobic residues. Classical electrostatic stabilization was suggested as the key determinant for halophilic adaptation of protein. However, contribution of specific electrostatic interactions (i.e. salt-bridges) to overall stability of halophilic proteins is yet to be understood. To understand this, we use Adaptive-Poison-Boltzmann-Solver Methods along with our home-built automation to workout net as well as associated component energy terms such as desolvation energy, bridge energy and background energy for 275 salt-bridges from 20 extremely halophilic proteins. We then perform extensive statistical analysis on general and energetic attributes on these salt-bridges. On average, 8 salt-bridges per 150 residues protein were observed which is almost twice than earlier report. Overall contributions of salt-bridges are -3.0 kcal mol-1. Majority (78%) of salt-bridges in our dataset are stable and conserved in nature. Although, average contributions of component energy terms are equal, their individual details vary greatly from one another indicating their sensitivity to local micro-environment. Notably, 35% of salt-bridges in our database are buried and stable. Greater desolvation penalty of these buried salt-bridges are counteracted by stable network salt-bridges apart from favorable equal contributions of bridge and background terms. Recruitment of extensive network salt-bridges (46%) with a net contribution of -5.0 kcal mol-1 per salt-bridge, seems to be a halophilic design wherein favorable average contribution of background term (-10 kcal mol-1) exceeds than that of bridge term (-7 kcal mol-1). Interiors of proteins from halophiles are seen to possess relatively higher abundance of charge and polar side chains than that of mesophiles which seems to be satisfied by cooperative network salt-bridges. Overall, our theoretical analyses provide insight into halophilic signature in its

  12. Bridging history and social psychology

    DEFF Research Database (Denmark)

    Glaveanu, Vlad Petre; Yamamoto, Koji

    2012-01-01

    This special issue aims to bridge history and social psychology by bringing together historians and social psychologists in an exercise of reading and learning from each other’s work. This interdisciplinary exercise is not only timely but of great importance for both disciplines. Social psycholog......This special issue aims to bridge history and social psychology by bringing together historians and social psychologists in an exercise of reading and learning from each other’s work. This interdisciplinary exercise is not only timely but of great importance for both disciplines. Social...... psychologists can benefit from engaging with historical sources by being able to contextualise their findings and enrich their theoretical models. It is not only that all social and psychological phenomena have a history but this history is very much part of present-day and future developments. On the other...... hand historians can enhance their analysis of historical sources by drawing upon the conceptual tools developed in social psychology. They can “test” these tools and contribute to their validation and enrichment from completely different perspectives. Most important, as contributions to this special...

  13. The Bridge of Mandolin County

    Science.gov (United States)

    Lantz, Juliette M.; Feindt, Jenny E.; Lewellyn, Eric P. B.; Walczak, Mary M.

    1999-12-01

    The Bridge of Mandolin County is a case designed to teach the general chemistry principles of molar mass, ions and aqueous reactions, solubility rules, and inorganic nomenclature. Through the instructor-facilitated class discussion, students consider the options before the Mandolin Town Council regarding deicing the newly constructed bridge connecting Mandolin with a large nearby city. The students must decipher contradictory claims made on behalf of sodium chloride, the traditional deicer, and calcium magnesium acetate, a new environmentally friendly deicer, to arrive at the most cost-effective and environmentally appropriate deicing product. As they work through the analysis they raise questions that can be addressed in a laboratory setting. Four optional role-playing experiments are included, which can be used by the students to gather information helpful to resolution of the case. The case is intended to be used over two class periods, with a laboratory period in between, though suggestions for other models are provided. Laboratory procedures include an EDTA titration for Ca2+ and Mg2+, a gravimetric analysis, a qualitative examination of ions and solubility, an introduction to freezing point depression and measurement, and an experimental design activity. This case can also successfully be used without alteration in non-majors chemistry or environmental chemistry courses, or upper-level analytical or environmental chemistry courses.

  14. Design aids of NU I-girders bridges.

    Science.gov (United States)

    2010-05-01

    Precast prestressed concrete I-Girder bridges have become the most dominant bridge system in the United States. In the early design : stages, preliminary design becomes a vital first step in designing an economical bridge. Within the state of Nebrask...

  15. An expert system for the esthetic rating of bridges.

    Science.gov (United States)

    1990-01-01

    The expert system presented should facilitate the in-depth analysis of bridge esthetics and encourage high standards for the appearance of bridges. The procedure described systematically evaluates features of a target bridge in relation to a similar ...

  16. Long-term behavior of integral abutment bridges : [technical summary].

    Science.gov (United States)

    2011-01-01

    Integral abutment bridges, a type of jointless bridge, are the construction option of choice when designing highway bridges in many parts of the country. Rather than providing an expansion joint to separate the substructure from the superstructure to...

  17. Implementation of sustainability in bridge design, construction and maintenance.

    Science.gov (United States)

    2012-12-01

    The focus of this research is to develop a framework for more sustainable design and construction : processes for new bridges, and sustainable maintenance practices for existing bridges. The framework : includes a green rating system for bridges. The...

  18. Seismic retrofit of spliced sleeve connections for precast bridge piers.

    Science.gov (United States)

    2017-03-01

    Grouted Splice Sleeve (GSS) connectors are being considered for connecting bridge columns, footings, and pier caps in Accelerated Bridge Construction (ABC). A repair technique for precast reinforced concrete bridge column-to-footing and column-to-pie...

  19. 0-6722 : spread prestressed concrete slab beam bridges.

    Science.gov (United States)

    2014-08-01

    The Texas Department of Transportation uses : precast prestressed concrete slab beam bridges for : shorter-span bridges of approximately 3050 ft in : length. Conventional slab beam bridges have slab : beams placed immediately adjacent to one anoth...

  20. Measuring the Enzyme Activity of Arabidopsis Deubiquitylating Enzymes.

    Science.gov (United States)

    Kalinowska, Kamila; Nagel, Marie-Kristin; Isono, Erika

    2016-01-01

    Deubiquitylating enzymes, or DUBs, are important regulators of ubiquitin homeostasis and substrate stability, though the molecular mechanisms of most of the DUBs in plants are not yet understood. As different ubiquitin chain types are implicated in different biological pathways, it is important to analyze the enzyme characteristic for studying a DUB. Quantitative analysis of DUB activity is also important to determine enzyme kinetics and the influence of DUB binding proteins on the enzyme activity. Here, we show methods to analyze DUB activity using immunodetection, Coomassie Brilliant Blue staining, and fluorescence measurement that can be useful for understanding the basic characteristic of DUBs.

  1. Re-Assessment of Concrete Bridges

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle

    In this paper two aspects of re-assessment of the reliability of concrete bridges are discussed namely modelling of the corrosion of reinforcement and updating of uncertain variables. The main reason for deterioration of concrete bridges is corrosion of the reinforcement. Therefore, modelling...

  2. STUDY OF BRIDGE DECK A REVIEW

    OpenAIRE

    MISS. KSHITIJA S. BALWAN , MR. V. G. KHURD , MR. S. S. CHOUGULE

    2018-01-01

    The objective of this study was to understand the meaning of bridge deck. To know the different forms of decks used in bridge design. To understand different methods used for analysis of deck and study of box girder and its evolution

  3. Rapid replacement/construction of bridges.

    Science.gov (United States)

    2012-11-01

    Bridges are a key element of the transportation system because they control system capacity and are normally built at : the highest cost to the system. Once a bridge reaches its useful design service life, it needs to be replaced or : reconstructed i...

  4. History of cable-stayed bridges

    DEFF Research Database (Denmark)

    Gimsing, Niels Jørgen

    1999-01-01

    The principle of supporting a bridge deck by inclined tension members leading to towers on either side of the span has been known for centuries. However, the real development of cable-stayed bridges did not begin before the 1950s. Since then the free span has been increased from 183 m in the Strö...

  5. Neighborhood Bridges: 2010-2011 Evaluation Report

    Science.gov (United States)

    Ingram, Debra

    2011-01-01

    In 2010-2011, students in twenty-five classrooms from eleven schools in the Minneapolis-Saint Paul metropolitan area participated in The Children's Theatre Company's Neighborhood Bridges (Bridges) program. The Children's Theatre Company contracted with the University of Minnesota's Center for Applied Research and Educational Improvement (CAREI) to…

  6. Planar Hall effect bridge magnetic field sensors

    DEFF Research Database (Denmark)

    Henriksen, A.D.; Dalslet, Bjarke Thomas; Skieller, D.H.

    2010-01-01

    Until now, the planar Hall effect has been studied in samples with cross-shaped Hall geometry. We demonstrate theoretically and experimentally that the planar Hall effect can be observed for an exchange-biased ferromagnetic material in a Wheatstone bridge topology and that the sensor signal can...... Hall effect bridge sensors....

  7. Analysis of Biaxially Stressed Bridge Deck Plates

    DEFF Research Database (Denmark)

    Jönsson, Jeppe; Bondum, Tommi Højer

    2012-01-01

    The ultimate state analysis of bridge deck plates at the intersection zone between main girders and transverse beams is complicated by biaxial membrane stresses, which may be in compression or tension in either direction depending on the bridge configuration and the specific location. This paper...

  8. Chapter 10:Hardwoods for timber bridges

    Science.gov (United States)

    James P. Wacker; Ed T. Cesa

    2005-01-01

    This chapter describes the joint efforts of the Forest Service and the FHWA to administer national programs including research, demonstration bridges, and technology transfer components. Summary information on a number of Forest Service-WIT demonstration bridges constructed with hardwoods is also provided.

  9. Bridges Over Troubled Waters: Theoretical Linguistics And ...

    African Journals Online (AJOL)

    This paper tries to construct a bridge between the concerns of theoretical linguistics and those of multilingualism and code-switching (CS) research. It argues that the primary special point of interaction between these fields lies in the question of potential equivalence between elements or categories, bridging across ...

  10. Strategies For The Replacement Of Historic Bridge Guardrails

    OpenAIRE

    Clauss, Adam J.

    2014-01-01

    Bridges that are designated historic present a special challenge to bridge engineers whenever rehabilitation work or improvements are made to the bridges. Federal and state laws protect historically significant bridges, and railings on these bridges can be subject to protection because of the role they play in aesthetics. Unfortunately, original railings on historic bridges do not typically meet current crash-test requirements and typically do not meet current standards for railing height and...

  11. The I-35W bridge Project Website

    DEFF Research Database (Denmark)

    Kampf, Constance

    How can websites be used to rebuild trust?  In August 2007, the Interstate Highway 35-W bridge in Minneapolis, MN collapsed during rush hour.  Although many people were rescued and casualties were as limited as could be expected due to quick and effective intervention, the image of a major bridge...... collapsing during rush hour damaged the Minnesota Department of Transportation's reputation and resulted in the loss of public trust for the organization.  The ensuing bridge reconstruction project included a project website intended to rebuild this trust through transparency, community involvement......, and the use of multimodal features.  This paper looks at the I35-W bridge reconstruction project in Minneapolis through web-based communication by the Minnesota Department of Transportation (MnDOT) about the project. The MnDOT bridge reconstruction website will be examined using a combination of 1). Weick...

  12. Optimum Maintenance Strategies for Highway Bridges

    DEFF Research Database (Denmark)

    Frangopol, Dan M.; Thoft-Christensen, Palle; Das, Parag C.

    As bridges become older and maintenance costs become higher, transportation agencies are facing challenges related to implementation of optimal bridge management programs based on life cycle cost considerations. A reliability-based approach is necessary to find optimal solutions based on minimum...... expected life-cycle costs or maximum life-cycle benefits. This is because many maintenance activities can be associated with significant costs, but their effects on bridge safety can be minor. In this paper, the program of an investigation on optimum maintenance strategies for different bridge types...... is described. The end result of this investigation will be a general reliability-based framework to be used by the UK Highways Agency in order to plan optimal strategies for the maintenance of its bridge network so as to optimize whole-life costs....

  13. Enzyme Molecules in Solitary Confinement

    Directory of Open Access Journals (Sweden)

    Raphaela B. Liebherr

    2014-09-01

    Full Text Available Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities.

  14. DGAT enzymes and triacylglycerol biosynthesis

    Science.gov (United States)

    Yen, Chi-Liang Eric; Stone, Scot J.; Koliwad, Suneil; Harris, Charles; Farese, Robert V.

    2008-01-01

    Triacylglycerols (triglycerides) (TGs) are the major storage molecules of metabolic energy and FAs in most living organisms. Excessive accumulation of TGs, however, is associated with human diseases, such as obesity, diabetes mellitus, and steatohepatitis. The final and the only committed step in the biosynthesis of TGs is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. The genes encoding two DGAT enzymes, DGAT1 and DGAT2, were identified in the past decade, and the use of molecular tools, including mice deficient in either enzyme, has shed light on their functions. Although DGAT enzymes are involved in TG synthesis, they have distinct protein sequences and differ in their biochemical, cellular, and physiological functions. Both enzymes may be useful as therapeutic targets for diseases. Here we review the current knowledge of DGAT enzymes, focusing on new advances since the cloning of their genes, including possible roles in human health and diseases. PMID:18757836

  15. Enzyme stabilization for pesticide degradation

    Energy Technology Data Exchange (ETDEWEB)

    Rivers, D.B.; Frazer, F.R. III; Mason, D.W.; Tice, T.R.

    1988-01-01

    Enzymes offer inherent advantages and limitations as active components of formulations used to decontaminate soil and equipment contaminated with toxic materials such as pesticides. Because of the catalytic nature of enzymes, each molecule of enzyme has the potential to destroy countless molecules of a contaminating toxic compound. This degradation takes place under mild environmental conditions of pH, temperature, pressure, and solvent. The basic limitation of enzymes is their degree of stability during storage and application conditions. Stabilizing methods such as the use of additives, covalent crosslinking, covalent attachment, gel entrapment, and microencapsulation have been directed developing an enzyme preparation that is stable under extremes of pH, temperature, and exposure to organic solvents. Initial studies were conducted using the model enzymes subtilisin and horseradish peroxidase.

  16. Berberine ameliorates chronic kidney injury caused by atherosclerotic renovascular disease through the suppression of NFκB signaling pathway in rats.

    Directory of Open Access Journals (Sweden)

    Xin Wan

    Full Text Available BACKGROUND AND OBJECTIVES: Impaired renal function in atherosclerotic renovascular disease (ARD may be the result of crosstalk between atherosclerotic renovascular stenosis and amplified oxidative stress, inflammation and fibrosis. Berberine (BBR regulates cholesterol metabolism and exerts antioxidant effects. Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and also suppression of the pathways involved in oxidative stress, inflammation and NFκB activation. METHODS: Male rats were subjected to unilateral renal artery stenosis with silver-irritant coil, and then fed with 12-week hypercholesterolemic diet. Rats with renal artery stenosis were randomly assigned to two groups (n = 6 each - ARD, or ARD+BBR - according to diet alone or in combination with BBR. Similarly, age-matched rats underwent sham operation and were also fed with hypercholesterolemic diet alone or in combination with BBR as two corresponding controls. Single-kidney hemodynamic metrics were measured in vivo with Doppler ultrasound to determine renal artery flow. The metrics reflecting hyperlipidemia, oxidative stress, renal structure and function, inflammation and NFκB activation were measured, respectively. RESULTS: Compared with control rats, ARD rats had a significant increase in urinary albumin, plasma cholesterol, LDL and thiobarbituric acid reactive substances (TBARS and a significant decrease in SOD activity. When exposed to 12-week BBR, ARD rats had significantly lower levels in blood pressure, LDL, urinary albumin, and TBARS. In addition, there were significantly lower expression levels of iNOS and TGF-β in the ARD+BBR group than in the ARD group, with attenuated NFκB-DNA binding activity and down-regulated protein levels of subunits p65 and p50 as well as IKKβ. CONCLUSIONS: We conclude that BBR can improve hypercholesterolemia and redox status in the kidney, eventually ameliorating

  17. Berberine activates Nrf2 nuclear translocation and inhibits apoptosis induced by high glucose in renal tubular epithelial cells through a phosphatidylinositol 3-kinase/Akt-dependent mechanism.

    Science.gov (United States)

    Zhang, Xiuli; Liang, Dan; Lian, Xu; Jiang, Yan; He, Hui; Liang, Wei; Zhao, Yue; Chi, Zhi-Hong

    2016-06-01

    Apoptosis of tubular epithelial cells is a major feature of diabetic kidney disease, and hyperglycemia triggers the generation of free radicals and oxidant stress in tubular cells. Berberine (BBR) is identified as a potential anti-diabetic herbal medicine due to its beneficial effects on insulin sensitivity, glucose metabolism and glycolysis. In this study, the underlying mechanisms involved in the protective effects of BBR on high glucose-induced apoptosis were explored using cultured renal tubular epithelial cells (NRK-52E cells) and human kidney proximal tubular cell line (HK-2 cells). We identified the pivotal role of phosphatidylinositol 3-kinase (PI3K)/Akt in BBR cellular defense mechanisms and revealed the novel effect of BBR on nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2) and heme oxygenase (HO)-1 in NRK-52E and HK-2 cells. BBR attenuated reactive oxygen species production, antioxidant defense (GSH and SOD) and oxidant-sensitive proteins (Nrf2 and HO-1), which also were blocked by LY294002 (an inhibitor of PI3K) in HG-treated NRK-52E and HK-2 cells. Furthermore, BBR improved mitochondrial function by increasing mitochondrial membrane potential. BBR-induced anti-apoptotic function was demonstrated by decreasing apoptotic proteins (cytochrome c, Bax, caspase3 and caspase9). All these findings suggest that BBR exerts the anti-apoptosis effects through activation of PI3K/Akt signal pathways and leads to activation of Nrf2 and induction of Nrf2 target genes, and consequently protecting the renal tubular epithelial cells from HG-induced apoptosis.

  18. Berberine Induces Apoptotic Cell Death via Activation of Caspase-3 and -8 in HL-60 Human Leukemia Cells: Nuclear Localization and Structure-Activity Relationships.

    Science.gov (United States)

    Okubo, Shinya; Uto, Takuhiro; Goto, Aya; Tanaka, Hiroyuki; Nishioku, Tsuyoshi; Yamada, Katsushi; Shoyama, Yukihiro

    2017-01-01

    Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5[Formula: see text]min to 15[Formula: see text]min after BBR treatment in HL-60 human promyelocytic leukemia cells. Next, we examined the antiproliferative activity of BBR (1) and its biosynthetically related compounds (2-7) in HL-60 cells. BBR exerted strongest antiproliferative activity among 1-7 and the results of structures and activity relation suggested that a methylenedioxyl group in ring A, an [Formula: see text]-alkyl group at C-9 position, and the frame of isoquinoline may be necessary for antiproliferative activity. Moreover, BBR showed the most potent antiproliferative activity in HL-60 cells among human cancer and normal cell lines tested. Next, we examined the effect of BBR on molecular events known as apoptosis induction. In HL-60 cells, BBR induced chromatin condensation and DNA fragmentation, and triggered the activation of PARP, caspase-3 and caspase-8 without the activation of caspase-9. BBR-induced DNA fragmentation was abolished by pretreatment with inhibitors against caspase-3 and caspase-8, but not against caspase-9. ERK and p38 were promptly phosphorylated after 15 min of BBR treatment, and this was correlated with time of localization to the nucleus of BBR. These results demonstrated that BBR translocated into nucleus immediately after treatments and induced apoptotic cell death by activation of caspase-3 and caspase-8.

  19. Berberine reduces fibronectin expression by suppressing the S1P-S1P2 receptor pathway in experimental diabetic nephropathy models.

    Directory of Open Access Journals (Sweden)

    Kaipeng Huang

    Full Text Available The accumulation of glomerular extracellular matrix (ECM is one of the critical pathological characteristics of diabetic renal fibrosis. Fibronectin (FN is an important constituent of ECM. Our previous studies indicate that the activation of the sphingosine kinase 1 (SphK1-sphingosine 1- phosphate (S1P signaling pathway plays a key regulatory role in FN production in glomerular mesangial cells (GMCs under diabetic condition. Among the five S1P receptors, the activation of S1P2 receptor is the most abundant. Berberine (BBR treatment also effectively inhibits SphK1 activity and S1P production in the kidneys of diabetic models, thus improving renal injury. Based on these data, we further explored whether BBR could prevent FN production in GMCs under diabetic condition via the S1P2 receptor. Here, we showed that BBR significantly down-regulated the expression of S1P2 receptor in diabetic rat kidneys and GMCs exposed to high glucose (HG and simultaneously inhibited S1P2 receptor-mediated FN overproduction. Further, BBR also obviously suppressed the activation of NF-κB induced by HG, which was accompanied by reduced S1P2 receptor and FN expression. Taken together, our findings suggest that BBR reduces FN expression by acting on the S1P2 receptor in the mesangium under diabetic condition. The role of BBR in S1P2 receptor expression regulation could closely associate with its inhibitory effect on NF-κB activation.

  20. New conceptual design of portable bamboo bridge for emergency purposes

    Science.gov (United States)

    Musthaffa, A. A.; Nor, N. M.; Yusof, M. A.; Yuhazri, M. Y.

    2018-02-01

    Portable bridges serve as routes for troops during the military operations and the disaster relief operation. Nowadays, bamboo has been regarded as one of the alternative construction materials for building and bridge structures. This paper presents the conceptual design of the portable bridge. Several types of portable bridges and bamboo bridges are reviewed in the current work. The characteristics, capability and method of construction of each bridge are discussed. Finally, the conceptual of the portable bamboo bridge for emergency purposes is presented. The idea of producing portable bridge is proposed in the current work as it is crucial for providing route for communities affected by natural disasters.

  1. Design and introduction of a disulfide bridge in firefly luciferase: increase of thermostability and decrease of pH sensitivity.

    Science.gov (United States)

    Imani, Mehdi; Hosseinkhani, Saman; Ahmadian, Shahin; Nazari, Mahboobeh

    2010-08-01

    The thermal sensitivity and pH-sensitive spectral properties of firefly luciferase have hampered its application in a variety of fields. It is proposed that the stability of a protein can be increased by introduction of disulfide bridge that decreases the configurational entropy of unfolding. A disulfide bridge is introduced into Photinus pyralis firefly luciferase to make two separate mutant enzymes with a single bridge. Even though the A103C/S121C mutant showed remarkable thermal stability, its specific activity decreased, whereas the A296C/A326C mutant showed tremendous thermal stability, relative pH insensitivity and 7.3-fold increase of specific activity. Moreover, the bioluminescence emission spectrum of A296C/A326C was resistant against higher temperatures (37 degrees C). Far-UV CD analysis showed slight secondary structure changes for both mutants. Thermal denaturation analysis showed that conformational stabilities of A103C/S121C and A296C/A326C are more than native firefly luciferase. It is proposed that since A296 and A326 are situated in the vicinity of the enzyme active site microenvironment in comparison with A103 and S121, the formation of a disulfide bridge in this region has more impact on enzyme kinetic characteristics.

  2. Direct comparison of enzyme histochemical and immunohistochemical methods to localize an enzyme

    NARCIS (Netherlands)

    van Noorden, Cornelis J. F.

    2002-01-01

    Immunohistochemical localization of enzymes is compared directly with localization of enzyme activity with (catalytic) enzyme histochemical methods. The two approaches demonstrate principally different aspects of an enzyme. The immunohistochemical method localizes the enzyme protein whether it is

  3. Enzyme Mimics: Advances and Applications.

    Science.gov (United States)

    Kuah, Evelyn; Toh, Seraphina; Yee, Jessica; Ma, Qian; Gao, Zhiqiang

    2016-06-13

    Enzyme mimics or artificial enzymes are a class of catalysts that have been actively pursued for decades and have heralded much interest as potentially viable alternatives to natural enzymes. Aside from having catalytic activities similar to their natural counterparts, enzyme mimics have the desired advantages of tunable structures and catalytic efficiencies, excellent tolerance to experimental conditions, lower cost, and purely synthetic routes to their preparation. Although still in the midst of development, impressive advances have already been made. Enzyme mimics have shown immense potential in the catalysis of a wide range of chemical and biological reactions, the development of chemical and biological sensing and anti-biofouling systems, and the production of pharmaceuticals and clean fuels. This Review concerns the development of various types of enzyme mimics, namely polymeric and dendrimeric, supramolecular, nanoparticulate and proteinic enzyme mimics, with an emphasis on their synthesis, catalytic properties and technical applications. It provides an introduction to enzyme mimics and a comprehensive summary of the advances and current standings of their applications, and seeks to inspire researchers to perfect the design and synthesis of enzyme mimics and to tailor their functionality for a much wider range of applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Phage lytic enzymes: a history.

    Science.gov (United States)

    Trudil, David

    2015-02-01

    There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of 'bacteria-eaters' or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal flora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well (Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specific disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay (Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes-from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.

  5. [The rise of enzyme engineering in China].

    Science.gov (United States)

    Li, Gaoxiang

    2015-06-01

    Enzyme engineering is an important part of the modern biotechnology. Industrial biocatalysis is considered the third wave of biotechnology following pharmaceutical and agricultural waves. In 25 years, China has made a mighty advances in enzyme engineering research. This review focuses on enzyme genomics, enzyme proteomics, biosynthesis, microbial conversion and biosensors in the Chinese enzyme engineering symposiums and advances in enzyme preparation industry in China.

  6. Root coverage with bridge flap

    Directory of Open Access Journals (Sweden)

    Pushpendra Kumar Verma

    2013-01-01

    Full Text Available Gingival recession in anterior teeth is a common concern due to esthetic reasons or root sensitivity. Gingival recession, especially in multiple anterior teeth, is of huge concern due to esthetic reasons. Various mucogingival surgeries are available for root coverage. This case report presents a new bridge flap technique, which allows the dentist not only to cover the previously denuded root surfaces but also to increase the zone of attached gingiva at a single step. In this case, a coronally advanced flap along with vestibular deepening technique was used as root coverage procedure for the treatment of multiple recession-type defect. Here, vestibular deepening technique is used to increase the width of the attached gingiva. The predictability of this procedure results in an esthetically healthy periodontium, along with gain in keratinized tissue and good patient′s acceptance.

  7. Building bridges … and accelerators

    CERN Multimedia

    2009-01-01

    Lyn Evans, the LHC project leader, was awarded an honorary doctorate from the University of Geneva (UNIGE) to celebrate his role not just in building accelerators, but also in building bridges between nations. He was one of four notables honoured at the event on Friday 5 June, coinciding with the University’s 450th Anniversary. Lyn Evans arriving at the ceremony with Archbishop Desmond Tutu. "It was a big surprise when I found out I’d been nominated," recounts Evans, "but it was an even bigger surprise to find out with whom I’d been nominated". At the ceremony Evans was awarded the honorary doctorate along with three others: Archbishop Desmond Tutu, who was acclaimed for his fight against apartheid in South Africa, Mary Robinson, first woman president of Ireland and former United Nations’ high commissioner of human rights, and Pascal Lamy, Director-General of the World Trade Organization. The award ceremony, known as the �...

  8. Enzyme structure, enzyme function and allozyme diversity in ...

    African Journals Online (AJOL)

    In estimates of population genetic diversity based on allozyme heterozygosity, some enzymes are regularly more variable than others. Evolutionary theory suggests that functionally less important molecules, or parts of molecules, evolve more rapidly than more important ones; the latter enzymes should then theoretically be ...

  9. Computational enzyme design: transitioning from catalytic proteins to enzymes.

    Science.gov (United States)

    Mak, Wai Shun; Siegel, Justin B

    2014-08-01

    The widespread interest in enzymes stem from their ability to catalyze chemical reactions under mild and ecologically friendly conditions with unparalleled catalytic proficiencies. While thousands of naturally occurring enzymes have been identified and characterized, there are still numerous important applications for which there are no biological catalysts capable of performing the desired chemical transformation. In order to engineer enzymes for which there is no natural starting point, efforts using a combination of quantum chemistry and force-field based protein molecular modeling have led to the design of novel proteins capable of catalyzing chemical reactions not catalyzed by naturally occurring enzymes. Here we discuss the current status and potential avenues to pursue as the field of computational enzyme design moves forward. Published by Elsevier Ltd.

  10. Immobilized enzymes: understanding enzyme - surface interactions at the molecular level.

    Science.gov (United States)

    Hoarau, Marie; Badieyan, Somayesadat; Marsh, E Neil G

    2017-11-22

    Enzymes immobilized on solid supports have important and industrial and medical applications. However, their uses are limited by the significant reductions in activity and stability that often accompany the immobilization process. Here we review recent advances in our understanding of the molecular level interactions between proteins and supporting surfaces that contribute to changes in stability and activity. This understanding has been facilitated by the application of various surface-sensitive spectroscopic techniques that allow the structure and orientation of enzymes at the solid/liquid interface to be probed, often with monolayer sensitivity. An appreciation of the molecular interactions between enzyme and surface support has allowed the surface chemistry and method of enzyme attachement to be fine-tuned such that activity and stability can be greatly enhanced. These advances suggest that a much wider variety of enzymes may eventually be amenable to immobilization as green catalysts.

  11. Stability of Enzymes in Granular Enzyme Products for Laundry Detergents

    DEFF Research Database (Denmark)

    Biran, Suzan; Bach, Poul; Simonsen, Ole

    Enzymes have long been of interest to the detergent industry due to their ability to improve the cleaning efficiency of synthetic detergents, contribute to shortening washing times, and reduce energy and water consumption, provision of environmentally friendlier wash water effluents and fabric care....... However, incorporating enzymes in detergent formulations gives rise to numerous practical problems due to their incompatibility with and stability against various detergent components. In powdered detergent formulations, these issues can be partly overcome by physically isolating the enzymes in separate...... particles. However, enzymes may loose a significant part of their activity over a time period of several weeks. Possible causes of inactivation of enzymes in a granule may be related to the release of hydrogen peroxide from the bleaching chemicals in a moisture-containing atmosphere, humidity, autolysis...

  12. The Anti-trichomonas Activity of Berberine by Applying the Bromocresol Purple Colorimetric Spectroscopic Assay in vitro%溴甲酚紫法测定黄连素的体外抗阴道毛滴虫作用

    Institute of Scientific and Technical Information of China (English)

    陈熙; 周本江

    2013-01-01

    目的 溴甲酚紫法体外测试黄连素的抗阴道毛滴虫活性.方法 设计实验组、已知疗效对照组和阴性对照组,溴甲酚紫比色法体外测定药物作用于阴道毛滴虫后不同时间、不同药物浓度的培养基OD值,经线性回归分析,绘制IC50曲线图,进行药效学比较分析.结果 药物作用早期(2 h),黄连素IC50值高于甲硝唑;4~6h2种药物的IC50值较接近,12 h时,甲硝唑的IC50值为11.64 μg/mL,黄连素的IC50值为10.58 μg/mL,24 h,黄连素、甲硝唑的IC50值继续下降,在9.53~9.61 μg/mL之间.48 h,两药的IC50值在5.38~6.03 μg/mL之间,黄连素IC50值稍高.结论 黄连素体外抗阴道毛滴虫的活性与甲硝唑相当,作为治疗阴道毛滴虫感染或治疗耐甲硝唑虫株的替代药物,具有很好的开发利用前景.%Objective To test in vitro the anti-trichomonas vaginalis activity of berberine by bromocresol purple assay.Methods The Trichmonas vaginals in experimental group,known-efficacy group and negative group,were tested by applying the bromocresol purple colorimetric spectroscopic assay.Before and after the treatment,the OD values of culture medium were measured at different times to make the linear regression analysis and draw IC50 curves.Results Compared at the earlier incubation period (2 h),the IC50 value of berberine was higher than that of metronidazole.During the 4 h and 6 h,the IC50 values of two medicaments were similar.At 12 h,the IC50 value of metronidazole was 11.64 μg/mL and that of berberine was 10.58 μg/mL.At 24 h,the the IC50 values of two medicaments kept decreasing,were between 9.53 and 9.61 μg/mL.At 48 h,the IC50 values of two medicaments were between 5.38 and 6.03 μg/mL while the IC50 value of berberine was higher.Conclusion The berberine has similar anti-trichomonas vaginalis activity with metronidazole,and can substitute metronidazole in treating the trichomonas vaginalis infection and the metronidazole-resistant strains infection

  13. Enzymes in Human Milk.

    Science.gov (United States)

    Dallas, David C; German, J Bruce

    2017-01-01

    Milk proteins are a complex and diverse source of biological activities. Beyond their function, intact milk proteins also act as carriers of encrypted functional sequences that, when released as peptides, exert biological functions, including antimicrobial and immunomodulatory activity, which could contribute to the infant's competitive success. Research has now revealed that the release of these functional peptides begins within the mammary gland itself. A complex array of proteases produced in mother's milk has been shown to be active in the milk, releasing these peptides. Moreover, our recent research demonstrates that these milk proteases continue to digest milk proteins within the infant's stomach, possibly even to a larger extent than the infant's own proteases. As the neonate has relatively low digestive capacity, the activity of milk proteases in the infant may provide important assistance to digesting milk proteins. The coordinated release of these encrypted sequences is accomplished by selective proteolytic action provided by an array of native milk proteases and infant-produced enzymes. The task for scientists is now to discover the selective advantages of this protein-protease-based peptide release system. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

  14. Implementation of Bridge Management System on Interurban Bridge in Maluku Province

    Directory of Open Access Journals (Sweden)

    Erwin Marasabessy

    2015-05-01

    Full Text Available Bridges as transport infrastructures play a vital role in smoothing traffic flows. The success of a bridge in playing its role and serving its function depends on its management. The Directorate General of Highways of the Ministry of Public Work has used a system to manage bridges known as the Bridge Management System (BMS. The system allows a systematic plan and provides a uniform procedure for all bridge operation activities on the national and provincial level. Data from Implementation Agency of National Inter-Urban Roads of Area IX, Northern Maluku in 2011 indicates that the total length of national roads in Maluku Province is 15,238.01 M, with a total of 562 bridges. In Ambon Island, especially, there are 52 bridges totaling 1,176.25 m in length. The study was conducted at several inter-urban bridges in Maluku Province of Ambon Island: Wai Batu Merah, Wai Ruhu, Wai Lawa, Wai Yari and Wai Tua bridges. Assessment of bridge structure conditions was conducted visually to determine the conditions of the existing bridges comprehensively by referring to the Bridge Management System (BMS complemented with a computer-based Bridge Management Information System (BMIS. Condition scores for the five bridges—Wai Batu Merah, Wai Ruhu, Wai Lawa, Wai Yari, and Wai Tua, according to Bridge Management System, are 2, 1, 2, 1, and 2 respectively. The scores of the five bridges indicate that their physical condition can be categorized as good or with minor defects. Based on technical screening, the proposed treatment for Wai Batu Merah, Wai Ruhu, Wai Lawa, dan Wai Tua bridges is the rehabilitation of their sub-elements. As for the Wai Yari Bridge, the treatment will be maintained regularly. The defect repair costs are IDR 149,138,238.00, IDR 81,048,000.00, IDR 174,579,106.10, IDR 79,233,324.01 and IDR 238,323,258.60 for Wai Batu, Wai Ruhu, Wai Lawa, Wai Yari, and Wai Tua Bridges, respectively.

  15. Hydraulic modeling of flow impact on bridge structures: a case study on Citarum bridge

    Science.gov (United States)

    Siregar, R. I.

    2018-02-01

    Flood waves because of the rapid catchment response to high intense rainfall, breaches of flood defenses may induce huge impact forces on structures, causing structural damage or even failures. Overflowing stream that passes over the bridge, it means to discharge flood water level is smaller than the capacity of the river flow. In this study, the researches present the methodological approach of flood modeling on bridge structures. The amount of force that obtained because of the hydrostatic pressure received by the bridge at the time of the flood caused the bridge structure disrupted. This paper presents simulation of flow impact on bridge structures with some event flood conditions. Estimating the hydrostatic pressure developed new model components, to quantify the flow impact on structures. Flow parameters applied the model for analyzing, such as discharge, velocity, and water level or head that effect of bridge structures. The simulation will illustrate the capability of bridge structures with some event flood river and observe the behavior of the flow that occurred during the flood. Hydraulic flood modeling use HEC-RAS for simulation. This modeling will describe the impact on bridge structures. Based on the above modelling resulted, in 2008 has flood effect more than other years on the Citarum Bridge, because its flow overflow on the bridge.

  16. Track-Bridge Longitudinal Interaction of Continuous Welded Rails on Arch Bridge

    Directory of Open Access Journals (Sweden)

    Rong Chen

    2013-01-01

    Full Text Available Taking arch bridges, including deck, half-through, and through arch bridges (short for DAB, HTAB, and TAB as examples, mechanics analysis models of longitudinal interaction between continuously welded rails (short for CWRs and arch bridges are established. Based on the finite element method (FEM, the longitudinal interaction calculation software of CWR on arch bridges has been developed. Focusing on an HTAB, the tension, compression, and deflection conditions are calculated and analyzed. The results show that the mechanics analysis models of three types of arch bridges can truly reflect the real state of the structure; the calculation software can be used for systematic research of the CWR on arch bridge; as for HTAB, temperature difference of arch rib has a small effect on rail tension/compression, and arch bridge can be simplified as a continuous beam for rail tension/compression additional force calculation; in calculation of deflection conditions of HTAB, it is suggested that train loads are arranged on half span and full span and take the direction of load entering bridge into account. Additionally, the deflection additional force variation of CFST basket handle arch bridge is different from that of ordinary bridge.

  17. Digestive enzymes of some earthworms.

    Science.gov (United States)

    Mishra, P C; Dash, M C

    1980-10-15

    4 species of tropical earthworms differed with regard to enzyme activity. The maximum activity of protease and of cellulase occurred in the posterior region of the gut of the earthworms. On the average Octochaetona surensis shows maximum activity and Drawida calebi shows minimum activity for all the enzymes studied.

  18. “On a bridge in Berlin”

    DEFF Research Database (Denmark)

    Pihl, Ole Verner

    2013-01-01

    This is a self-reflective case study based on the development of the Graphic Novel: “On a bridge in Berlin.” The GN will be used as an introduction to the history of architecture as a part of the curriculum in Architecture and Design at Aalborg University, and as a more broadly introduction...... that jumps in time and place: it begins with Martin Heidegger´s quotation “The Bridge gathers to itself in its own way earth and sky, divinities and mortals”, and the bridge is a state of mind, a chronotope, a portal in time between past, present, and future. The methodological approach is based...

  19. Gust loading on streamlined bridge decks

    DEFF Research Database (Denmark)

    Larose, Guy; Mann, Jakob

    1998-01-01

    The current analytical description of the buffeting action of wind on long-span bridges is based on the strip assumption. However, recent experiments on closed-box girder bridge decks have shown that this assumption is not valid and is the source of an important part of the error margin...... of the analytical prediction methods. In this paper, an analytical model that departs from the strip assumption is used to describe the gust loading on a thin airfoil. A parallel is drawn between the analytical model and direct measurements of gust loading on motionless closed-box girder bridge decks. Empirical...

  20. Heavy Vehicles on Minor Highway Bridges

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Nielsen, Søren R. K.; Enevoldsen, I.

    of heavier trucks moving at larger speeds, and partly because the authorities want to permit transportation of special heavy goods at a larger part of the road net. These needs will in many cases cause the strengthening of the bridges becomes necessary. In order to keep the expenses of such strengthening...... the results obtained using the numerical models given in details in "Heavy Vehicles on Minor Highway Bridges : dynamic modelling of vehicles and bridges". The models are established using a ordinary vehicle which consists of a 48 t Scania with a 3 axle tractor and a 3 axle trailer, joined in a flexible hinge...

  1. Noise measurements on proximity effect bridges

    International Nuclear Information System (INIS)

    Decker, S.K.; Mercereau, J.E.

    1975-01-01

    Audio frequency noise density measurements were performed on weakly superconducting proximity effect bridges on using a cooled transformer and room temperature low noise preamplifier. The noise temperature of the measuring system is approximately 4 0 K for a 0.9 Ω resistor. Noise density was measured as a function of bias current and temperature for the bridges. Excess noise above that expected from Johnson noise for a resistor equal to the dynamic resistance of the bridges was observed in the region near the critical current of the device. At high currents compared to the critical current, the noise density closely approaches that given by Johnson noise

  2. Building the Clinical Bridge: An Australian Success

    Directory of Open Access Journals (Sweden)

    Marianne Wallis

    2012-01-01

    Full Text Available Nursing effectiveness science includes primary, secondary, and translational, clinically focused research activities which aim to improve patient or client outcomes. It is imperative, for the successful conduct of a program of nursing effectiveness science, that a clinical bridge is established between academic and healthcare service facilities. An Australian example of the development of a robust clinical bridge through the use of jointly funded positions at the professorial level is outlined. In addition, an analysis of the practical application of Lewin’s model of change management and the contribution of both servant and transformational leadership styles to the bridge building process is provided.

  3. Photoreactivating enzyme from Escherichia coli

    International Nuclear Information System (INIS)

    Snapka, R.M.; Fuselier, C.O.

    1977-01-01

    Escherichia coli photoreactivating enzyme (PRE) has been purified in large amounts from an E.coli strain lysogenic for a defective lambda bacteriophage carrying the phr gene. The resulting enzyme had a pH optimum of 7.2 and an ionic strength optimum of 0.18. It consisted of an apoprotein and cofactor, both of which were necessary for catalytic activity. The apoprotein had a monomer molecular weight of 35,200 and showed stable aggregates under denaturing conditions. The amino acid analysis of the E.coli enzyme was very similar to that of the photoreactivating enzyme from orchid seedlings (Cattelya aurantiaca). Both had arginine at the amino terminus. The cofactor, like the holoenzyme, showed absorption, magnetic circular dichroism, and emission properties indicative of an adenine moiety. Although the isolated enzyme had an action spectrum which peaked at about 360 nm, neither the cofactor, apoenzyme nor holoenzyme showed any detectable absorption between 300 and 400 nm. (author)

  4. Positron emitter labeled enzyme inhibitors

    International Nuclear Information System (INIS)

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.; Langstrom, B.

    1990-01-01

    This invention involves a new strategy for imagining and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography

  5. Photoreactivating enzyme from Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Snapka, R M; Fuselier, C O [California Univ., Irvine (USA)

    1977-05-01

    Escherichia coli photoreactivating enzyme (PRE) has been purified in large amounts from an E.coli strain lysogenic for a defective lambda bacteriophage carrying the phr gene. The resulting enzyme had a pH optimum of 7.2 and an ionic strength optimum of 0.18. It consisted of an apoprotein and cofactor, both of which were necessary for catalytic activity. The apoprotein had a monomer molecular weight of 35,200 and showed stable aggregates under denaturing conditions. The amino acid analysis of the E.coli enzyme was very similar to that of the photoreactivating enzyme from orchid seedlings (Cattelya aurantiaca). Both had arginine at the amino terminus. The cofactor, like the holoenzyme, showed absorption, magnetic circular dichroism, and emission properties indicative of an adenine moiety. Although the isolated enzyme had an action spectrum which peaked at about 360 nm, neither the cofactor, apoenzyme nor holoenzyme showed any detectable absorption between 300 and 400 nm.

  6. Field performance of timber bridges. 16, North Siwell Road stress-laminated bridge

    Science.gov (United States)

    J. A. Kainz

    The North Siwell Road bridge was constructed during December 1994 in Hinds County, Mississippi. The bridge is a single-span, stress-laminated T-beam structure that measures 9.1 m (30 ft) long and 8.7 m (28.5 ft) wide. Performance of the bridge was monitored for 24 months, beginning at the time of installation. Monitoring involved gathering and evaluating data relative...

  7. Field performance of timber bridges. 17, Ciphers stress-laminated deck bridge

    Science.gov (United States)

    James P. Wacker; James A. Kainz; Michael A. Ritter

    In September 1989, the Ciphers bridge was constructed within the Beltrami Island State Forest in Roseau County, Minnesota. The bridge superstructure is a two-span continuous stress-laminated deck that is approximately 12.19 m long, 5.49 m wide, and 305 mm deep (40 ft long, 18 ft wide, and 12 in. deep). The bridge is one of the first to utilize red pine sawn lumber for...

  8. Field performance of timber bridges. 10, Sanborn Brook stress-laminated deck bridge

    Science.gov (United States)

    P. D. Hilbrich Lee; J. P. Wacker; M. A. Ritter

    The Sanborn Brook bridge was constructed in August 1991, 10 miles northeast of Concord, New Hampshire, as part of the demonstration timber bridge program of the USDA Forest Service. The bridge is a simple-span, double-lane, stress-laminated deck superstructure constructed from Southern Pine lumber and is approximately 25 ft long and 28 ft wide with a skew of 14 degrees...

  9. Field performance of timber bridges. 12, Christian Hollow stress-laminated box-beam bridge

    Science.gov (United States)

    J. P. Wacker; S. C. Catherman; R. G. Winnett

    In January 1992, the Christian Hollow bridge was constructed in Steuben County, New York. The bridge is a single-span, stress-laminated box-beam superstructure that is 9.1 m long, 9.8 m wide, and 502 mm deep (30 ft long, 32 ft wide, and 19-3/4 in. deep). The performance of the bridge was continuously monitored for 28 months, beginning shortly after installation....

  10. Field performance of timber bridges. 8, Lynches Woods Park stress-laminated deck bridge

    Science.gov (United States)

    J. P. Wacker; M. A. Ritter; D. Conger

    The Lynches Woods Park bridge was constructed during the summer of 1990 in Newberry, South Carolina. It is a single-span, single-lane, stress-laminated deck superstructure that measures approximately 30 ft long, 16 ft wide, and 14 in. deep. The bridge is unique in that is one of the first known stress-laminated deck bridges to be constructed of Southern Pine lumber...

  11. Model predictive control for a dual active bridge inverter with a floating bridge

    OpenAIRE

    Chowdhury, Shajjad; Wheeler, Patrick W.; Gerada, C.; Patel, Chintan

    2016-01-01

    This paper presents a Model Predictive Control technique applied to a dual active bridge inverter where one of the bridges is floating. The proposed floating bridge topology eliminates the need for isolation transformer in a dual inverter system and therefore reduces the size, weight and losses in the system. To achieve multilevel output voltage waveforms the floating inverter DC link capacitor is charged to the half of the main DC link voltage. A finite-set Model Predictive Control technique...

  12. TMACS test procedure TP012: Panalarm software bridge

    International Nuclear Information System (INIS)

    Washburn, S.J.

    1994-01-01

    This Test Procedure addresses the testing of the functionality of the Tank Monitor and Control System (TMACS) Panalarm bridge software. The features to be tested are: Bridge Initialization Options; Bridge Communication; Bridge Performance; Testing Checksum Errors; and Testing Command Reject Errors. Only the first three could be tested; the last two have been deferred to a later date

  13. 33 CFR 118.80 - Lights on bascule bridges.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Lights on bascule bridges. 118.80 Section 118.80 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LIGHTING AND OTHER SIGNALS § 118.80 Lights on bascule bridges. (a) Lift span lights. Each lift span of...

  14. 49 CFR 236.766 - Locking, movable bridge.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Locking, movable bridge. 236.766 Section 236.766... Locking, movable bridge. The rail locks, bridge locks, bolt locks, circuit controllers, and electric locks used in providing interlocking protection at a movable bridge. ...

  15. 33 CFR 118.140 - Painting bridge piers.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Painting bridge piers. 118.140 Section 118.140 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LIGHTING AND OTHER SIGNALS § 118.140 Painting bridge piers. The District Commander may require...

  16. 23 CFR 650.705 - Application for discretionary bridge funds.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Application for discretionary bridge funds. 650.705... TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Discretionary Bridge Candidate Rating Factor § 650.705 Application for discretionary bridge funds. Each year through its field offices, the FHWA will...

  17. Inspection Based Evaluation of a Danish Road Bridge

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle

    In this paper it is shown how an inspection-based evaluation of a Danish road bridge may be performed using the BRIDGE1 and BRIDGE2 bridge management systems produced within the EC-supported research programme "Assessment of Performance and Optimal Strategies for Inspection and Maintenance...

  18. An efficient CMOS bridging fault simulator with SPICE accuracy

    NARCIS (Netherlands)

    Di, C.; Jess, J.A.G.

    1996-01-01

    This paper presents an alternative modeling and simulation method for CMOS bridging faults. The significance of the method is the introduction of a set of generic-bridge tables which characterize the bridged outputs for each bridge and a set of generic-cell tables which characterize how each cell

  19. Detection of salt bridges to lysines in solution in barnase

    DEFF Research Database (Denmark)

    Hansen, Poul Erik; Williamson, Michael P.; Hounslow, Andrea M.

    2013-01-01

    We show that salt bridges involving lysines can be detected by deuterium isotope effects on NMR chemical shifts of the sidechain amine. Lys27 in the ribonuclease barnase is salt bridged, and mutation of Arg69 to Lys retains a partially buried salt bridge. The salt bridges are functionally important....

  20. Two high-frequency mutual inductance bridges with high resolution

    NARCIS (Netherlands)

    Flokstra, Jakob; Gerritsma, G.J.; Kreuwel, H.J.M.; van der Marel, L.C.

    1980-01-01

    Two mutual inductance bridges are described for operation up to about 100 kHz. Special attention is paid to the sensitivity and resolution of the bridges. Both bridges can be used to measure variations of about 10 pH in the mutual inductance. The first bridge consists of passive elements only

  1. The future of rapid bridge deck replacement.

    Science.gov (United States)

    2015-06-01

    Replacing aging, deteriorated infrastructure often requires road closures and traffic detours which impose : inconvenience and delay on commerce and members of the motoring public. Accelerated bridge construction : techniques often use precast member...

  2. Behavior of micropiles in bridge bent applications.

    Science.gov (United States)

    2010-12-01

    This project concerned the behavior of micropiles under lateral loads. The North Carolina Department of Transportation was specifically interested in the use of micropiles to support bridge bents. In this configuration micropiles would be subjected t...

  3. Active Control of Long Bridges Using Flaps

    DEFF Research Database (Denmark)

    Hansen, H. I.; Thoft-Christensen, Palle

    The main problem in designing ultra-long span suspension bridges is flutter. A solution to this problem might be to introduce an active flap control system to increase the flutter wind velocity. The investigated flap control system consists of flaps integrated in the bridge girder so each flap...... is the streamlined part of the edge of the girder. Additional aerodynamic derivatives are shown for the flaps and it is shown how methods already developed can be used to estimate the flutter wind velocity for a bridge section with flaps. As an example, the flutter wind velocity is calculated for different flap...... configurations for a bridge section model by using aerodynamic derivatives for a flat plate. The example shows that different flap configurations can either increase or decrease the flutter wind velocity. for optimal flap configurations flutter will not occur....

  4. Active aerodynamic stabilisation of long suspension bridges

    DEFF Research Database (Denmark)

    Nissen, Henrik Ditlev; Sørensen, Paul Haase; Jannerup, Ole Erik

    2004-01-01

    The paper describes the addition of actively controlled appendages (flaps) attached along the length of the bridge deck to dampen wind-induced oscillations in long suppension bridges. A novel approach using control systems methods for the analysis of dynamic stability is presented. In order to make...... use of control analysis and design techniques, a linear model of the structural and aerodynamic motion around equilibriun is developed. The model is validated through comparison with finite element calculations and wind tunnel experimental data on the Great Belt East Bridge in Denmark. The developed...... active control scheme is local in that the flap control signal at a given longitudinal position along the bridge only depends on local motion measurements. The analysis makes use of the Nyquist stability criteria and an anlysis of the sensitivity function for stability analysis. The analysis shows...

  5. Assuring bridge safety and serviceability in Europe

    Science.gov (United States)

    2010-08-01

    U.S. engineers need advanced tools and protocols to better assess and assure safety and serviceability of bridges. The Federal Highway Administration, American Association of State Highway and Transportation Officials, and National Cooperative Highwa...

  6. Influence of Icing on Bridge Cable Aerodynamics

    DEFF Research Database (Denmark)

    Koss, Holger; Frej Henningsen, Jesper; Olsen, Idar

    2013-01-01

    In recent years the relevance of ice accretion for wind-induced vibration of structural bridge cables has been recognised and became a subject of research in bridge engineering. Full-scale monitoring and observation indicate that light precipitation at moderate low temperatures between zero and -5......°C may lead to large amplitude vibrations of bridge cables under wind action. For the prediction of aerodynamic instability quasi-steady models have been developed estimating the cable response magnitude based on structural properties and aerodynamic force coefficients for drag, lift and torsion...... forces of different bridge cables types. The experiments were conducted in a wind tunnel facility capable amongst others to simulate incloud icing conditions....

  7. Pilot testing of a hydraulic bridge exciter

    Directory of Open Access Journals (Sweden)

    Andersson Andreas

    2015-01-01

    Full Text Available This paper describes the development of a hydraulic bridge exciter and its first pilot testing on a full scale railway bridge in service. The exciter is based on a hydraulic load cylinder with a capacity of 50 kN and is intended for controlled dynamic loading up to at least 50 Hz. The load is applied from underneath the bridge, enabling testing while the railway line is in service. The system is shown to produce constant load amplitude even at resonance. The exciter is used to experimentally determine frequency response functions at all sensor locations, which serve as valuable input for model updating and verification. An FE-model of the case study bridge has been developed that is in good agreement with the experimental results.

  8. Deterioration and cost information for bridge management.

    Science.gov (United States)

    2012-05-01

    This study applies contract bid tabulations and elementlevel condition records to develop elementlevel actions, : costs for actions, transition probabilities for models of deterioration of bridge elements, and transition probabilities : for imp...

  9. Key Royale bridge five year evaluation.

    Science.gov (United States)

    2013-06-01

    This report describes the design, construction, instrumentation, and five-year evaluation of the Key Royale Bridge substructure. The primary focus was the evaluation of the implementation of highly reactive supplementary cementitious materials (SCM) ...

  10. Recessed floating pier caps for highway bridges.

    Science.gov (United States)

    1973-01-01

    Presented are alternate designs for two existing bridges in Virginia - one with steel beams and the other with prestressed concrete beams - whereby the pier caps are recessed within the depth of the longitudinal beams. The purpose of this recession i...

  11. Aesthetic coatings for concrete bridge components

    Science.gov (United States)

    Kriha, Brent R.

    This thesis evaluated the durability and aesthetic performance of coating systems for utilization in concrete bridge applications. The principle objectives of this thesis were: 1) Identify aesthetic coating systems appropriate for concrete bridge applications; 2) Evaluate the performance of the selected systems through a laboratory testing regimen; 3) Develop guidelines for coating selection, surface preparation, and application. A series of site visits to various bridges throughout the State of Wisconsin provided insight into the performance of common coating systems and allowed problematic structural details to be identified. To aid in the selection of appropriate coating systems, questionnaires were distributed to coating manufacturers, bridge contractors, and various DOT offices to identify high performing coating systems and best practices for surface preparation and application. These efforts supplemented a literature review investigating recent publications related to formulation, selection, surface preparation, application, and performance evaluation of coating materials.

  12. Improved bridge joint materials and design details.

    Science.gov (United States)

    2017-06-01

    Expansion joints accommodate bridge movements that result from factors such as thermal expansion and contraction, concrete shrinkage, creep effects, live loading, settlement of the foundation and substructure, and environmental stressors. Expansion j...

  13. Life-cycle assessment of Nebraska bridges.

    Science.gov (United States)

    2013-05-01

    Life-cycle cost analysis (LCCA) is a necessary component in bridge management systems (BMSs) for : assessing investment decisions and identifying the most cost-effective improvement alternatives. The : LCCA helps to identify the lowest cost alternati...

  14. Life cycle costs for Alaska bridges.

    Science.gov (United States)

    2014-08-01

    A study was implemented to assist the Alaska Department of Transportation and Public Facilities (ADOT&PF) with life cycle costs for : the Alaska Highway Bridge Inventory. The study consisted of two parts. Part 1 involved working with regional offices...

  15. Multimedia package for LRFD concrete bridge design.

    Science.gov (United States)

    2009-02-01

    This Project developed a Load and Resistance Factor Design (LRFD) multimedia package to provide a practical introduction and an in-depth understanding of the technological advances in the design of concrete bridges. This package can be used to train ...

  16. Eddy current testing device using unbalance bridge

    International Nuclear Information System (INIS)

    Hoshikawa, H.; Koido, J.; Ishibashi, Y.

    1976-01-01

    An easily readjustable unbalance bridge has been invented and in utilizing the same, an eddy current testing equipment excellent in suppression of the lift-off effect and high in the detection sensitivity has been developed

  17. ERA OF NEW TECHNOLOGIES FOR BRIDGES CONSTRUCTIONS

    Directory of Open Access Journals (Sweden)

    S. V. Klyuchnyk

    2010-03-01

    Full Text Available In this paper the possibilities of protection of bridge structures from corrosion by thermal spraying of aluminum or zinc, which provides the long-term protection (approximately 50 years, are presented.

  18. Allegheny County-Owned Bridges Points

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This dataset shows the location of bridges owned by Allegheny County as centroids. If viewing this description on the Western Pennsylvania Regional Data Center’s...

  19. BAKERY ENZYMES IN CEREAL TECHNOLOGIES

    Directory of Open Access Journals (Sweden)

    Václav Koman

    2012-10-01

    Full Text Available Normal 0 21 false false false SK X-NONE X-NONE Bread is the most common and traditional food in the world. For years, enzymes such as malt and fungal alpha-amylase have been used in bread making. Due to the changes in the baking industry and the ever-increasing demand for more natural products, enzymes have gained real importance in bread-making. If an enzyme is added, it is often destroyed by the heat during the baking process. For generations, enzymes have been used for the improvement of texture and appearance, enhancement of nutritional values and generation of appealing flavours and aromas. Enzymes used in bakery industry constitute nearly one third of the market. The bakery products have undergone radical improvements in quality over the past years in terms of flavour, texture and shelf-life. The the biggest contributor for these improvementsis the usage of enzymes. Present work seeks to systematically describe bakery enzymes, their classification, benefits, usage and chemical reactions in the bread making process.doi:10.5219/193

  20. Identifying hidden sexual bridging communities in Chicago.

    Science.gov (United States)

    Youm, Yoosik; Mackesy-Amiti, Mary Ellen; Williams, Chyvette T; Ouellet, Lawrence J

    2009-07-01

    Bridge populations can play a central role in the spread of human immunodeficiency virus (HIV) by providing transmission links between higher and lower prevalence populations. While social network methods are well suited to the study of bridge populations, analyses tend to focus on dyads (i.e., risk between drug and/or sex partners) and ignore bridges between distinct subpopulations. This study takes initial steps toward moving the analysis of sexual network linkages beyond individual and risk group levels to a community level in which Chicago's 77 community areas are examined as subpopulations for the purpose of identifying potential bridging communities. Of particular interest are "hidden" bridging communities; that is, areas with above-average levels of sexual ties with other areas but whose below-average AIDS prevalence may hide their potential importance for HIV prevention. Data for this analysis came from the first wave of recruiting at the Chicago Sexual Acquisition and Transmission of HIV Cooperative Agreement Program site. Between August 2005 through October 2006, respondent-driven sampling was used to recruit users of heroin, cocaine, or methamphetamine, men who have sex with men regardless of drug use, the sex partners of these two groups, and sex partners of the sex partners. In this cross-sectional study of the sexual transmission of HIV, participants completed a network-focused computer-assisted self-administered interview, which included questions about the geographic locations of sexual contacts with up to six recent partners. Bridging scores for each area were determined using a matrix representing Chicago's 77 community areas and were assessed using two measures: non-redundant ties and flow betweenness. Bridging measures and acquired immunodeficiency syndrome (AIDS) case prevalence rates were plotted for each community area on charts representing four conditions: below-average bridging and AIDS prevalence, below-average bridging and above