Input: There are many types of vinegar in China.


Input: How to control the quality of vinegar is problem.


Input: Near infrared spectroscopy (NIR) transmission technique was applied to achieve this purpose.


Input: Ninety-five vinegar samples from 14 origins covering 11 provinces in China were collected.


Input: They were classified into mature vinegar, aromatic vinegar, rice vinegar, fruit vinegar, and white vinegar.


Input: Fruit vinegar and white vinegar were separated from the other traditional categories in the two-dimension principal component space of NIR after principle component analysis (PCA).


Input: Least-squares support vector machine (LS-SVM) as the pattern recognition was firstly applied to identify mature vinegar, aromatic vinegar, rice vinegar in this study.


Input: The top two principal components (PCs) were extracted as the input of LS-SVM classifiers by principal component analysis (PCA).


Input: The best experimental results were obtained using the radial basis function (RBF) LS-SVM classifier with sigma = 0. 8.


Input: The accuracies of identification were more than 85% for three traditional vinegar categories.


Input: Compared with the back propagation artificial neural network (BP-ANN) approach, LS-SVM algorithm showed its excellent generalisation for identification results.


Input: As total acid content (TAC) is highly connecting with the quality of vinegar, NIR was used to prediction the TAC of samples.


Input: LS-SVM was applied to building the TAC prediction model based on spectral transmission rate.


Input: Compared with partial least-square (PLS) model, LS-SVM model gave better precision and accuracy in predicting TAC.


Input: The determination coefficient for prediction (R (p)) of the LS-SVM model was 0. 919 and root mean square error for prediction (RMSEP) was 0. 3226.


Input: This work demonstrated that near infrared spectroscopy technique coupled with LS-SVM could be used as a quality control method for vinegar.


Input: Microwave distillation followed by headspace single drop microextraction coupled to gas chromatography-mass spectrometry (GC-MS) for fast analysis of volatile components of Echinophora platyloba DC.


Input: To avoid the traditional and time consuming hydrodistillation, the analyses of volatile components in aerial parts of Echinophora platyloba DC was carried out by a simple microwave distillation followed by headspace single drop microextraction (MD-HS-SDME) coupled to gas chromatography-mass spectrometry (GC-MS).


Input: The headspace volatile compounds were collected after irradiation using a single drop of n-heptadecan.

n-heptadecan


Input: The extraction conditions were optimised using the relative peak areas as index.


Input: The chemical composition of the MD-HS-SDME extracts was confirmed according to their retention indexes and mass spectra.


Input: Fifty-three components were extracted and identified by using the MD-HS-SDME method.


Input: E-beta-ocimene (53. 81%), R-D-decalactone (12. 75%), alpha-pinene (6. 43%), n-heptanol (6. 27%), beta-phellanderne (2. 70%) and linalool (1. 89%) were the major constituents.

E-beta-ocimene

alpha-pinene

n-heptanol

beta-phellanderne

linalool


Input: Compositional analysis of leaf cuticular membranes isolated from tea plants (Camellia sinensis L.).


Input: Chemical constituents of cuticular membranes (CMs) isolated from three tea cultivars (Camellia sinensis (L.) O. Kuntze cvs. Yabukita, Samidori and Gokou) were compared.


Input: All CMs from the adaxial side of the leaves showed higher accumulation of wax, cutin and polysaccharide, while those from the abaxial side were abundant in cutan, showing the adaptation of the adaxial side to abiotic stresses, such as wind and rain, in contrast to the abaxial side, which provides defence against pathogens.


Input: Yabukita, a major tea cultivar in Japan, developed thick CMs while Samidori and Gokou, shade-cultivated tea cultivars, had lighter CMs, reflecting their thin and soft leaves.


Input: CMs rapidly accumulated 9, 10-epoxy-18-hydroxyoctadecanoic acid at a very early stage of leaf development.

9, 10-epoxy-18-hydroxyoctadecanoic acid


Input: Additionally, shade treatment did not influence cutin biosynthesis in CMs, reflecting high adaptation of tea leaves under low light levels.


Input: UPLC and HPLC of caffeoyl esters in wild and cultivated Arctium lappa L.

caffeoyl esters


Input: Analytical methods including ultra-performance liquid chromatography (UPLC) and high-performance liquid chromatography (HPLC) with photodiode array (PDA) detector were developed for the analysis of caffeoylquinic acid derivatives in seeds, leaves and roots of Arctium lappa L.

caffeoylquinic acid


Input: Separation was performed on C (18) column utilising 5% (v/v) acetic acid in water and acetonitrile at 330 nm.

acetic acid

acetonitrile


Input: Both methodologies were validated in terms of linearity, precision, and recovery.


Input: The results showed that the major advantages of UPLC, over HPLC were the fast analysis, narrow peaks, high sensitivity, and reduction of solvent consumption.


Input: Subsequently the methods were applied for the identification and quantification of chlorogenic acid (5-CQA) and 1, 5-dicaffeoylquinic acid (1, 5-DCQA) as main compounds in samples.

chlorogenic acid

1, 5-dicaffeoylquinic acid

1, 5-DCQA


Input: The total phenolic content of samples ranged from 3. 93 to 14. 13 g of 5-CQA equivalent/100g dry weight (DW).


Input: There was a significant variability from 89 to 571 mg/100g for 5-CQA and 48 to 486 mg/100g for 1, 5-DCQA in dry material.

1, 5-DCQA


Input: Structural property of soybean lunasin and development of a method to quantify lunasin in plasma using an optimized immunoassay protocol.


Input: Lunasin is a 43-amino acid naturally occurring chemopreventive peptide with demonstrated anti-cancer and anti-inflammatory properties.


Input: The objectives of this study were to determine the effect of temperature on the secondary structure of lunasin, to develop a method of isolating lunasin from human plasma using an ion-exchange microspin column and to quantify the amount of lunasin using an optimized enzyme-linked immunosorbent assay.


Input: Lunasin was purified using a combination of ion-exchange chromatography, ultrafiltration and gel filtration chromatography.


Input: Circular dichroism showed that increased in temperature from 25 to 100 degrees C resulted in changes on the secondary structure of lunasin and its capability to interact with rabbit polyclonal antibody.


Input: Enzyme linked immunosorbent assay showed that lunasin rabbit polyclonal antibody has a titer of 250 and a specific activity of 0. 05 mL/mu g.


Input: A linear response was detected between 16 to 48 ng lunasin per mL (y = 0. 03x-0. 38, R (2) = 0. 96).


Input: The use of diethylaminoethyl microspin column to isolate spiked lunasin in human plasma showed that most lunasin (37. 8-46. 5%) bound to the column eluted with Tris-HCl buffer, pH 7. 5 with a yield up to 76. 6%.

diethylaminoethyl

Tris-HCl


Input: In conclusion, lunasin can be isolated from human plasma by a simple DEAE microspin column technique and can be quantified using a validated and optimized immunoassay procedure.


Input: This method can be used directly to quantify lunasin from plasma in different human and animal studies aiming to determine its bioavailability.


Input: Influence of extraction procedures on phenolic content and antioxidant activity of Cretan barberry herb.


Input: The main goal of present study was the development, optimization and application of different extraction protocols, especially those employing green technologies, in order to obtain from Berberis cretica extracts with high antioxidant capacity.


Input: For this purpose, the applied methods: maceration, ASE and SFE coupled with ASE were incorporated.


Input: The antioxidant assessment was carried out using DPPH and total phenolic content (Folin-Ciocalteu) assays.

DPPH


Input: Major constituents were elucidated using HPLC-DAD and UHPLC-HRMS/MS (hybrid IT-Orbital trap spectrometer) equipped with an ESI probe.


Input: The chromatographic and spectral data revealed the presence of several simple phenolic acids, derivatives of both caffeic and benzoic acids, and flavonoids in the produced extracts.

phenolic acids

caffeic and benzoic acids

flavonoids


Input: It was clearly evidenced that the extraction method and solvents used affected both the activity and the chemical content of the results, significantly.


Input: The most beneficial conditions were calculated for methanol and water: ethanol (50: 50) extracts derived from the combination of SFE and ASE methodologies.

methanol

ethanol


Input: Obtained results classify Cretan barberry as a strong antioxidant agent.


Input: Purification, antioxidant activity and protein-precipitating capacity of punicalin from pomegranate husk.

punicalin


Input: Punicalin is a kind of ellagitannin, existing in pomegranate husk, and has shown remarkable biological activities.

Punicalin


Input: A rapid and large-scale separation method of punicalin from pomegranate husk was established, using medium pressure liquid chromatography (MPLC).

punicalin


Input: The optimal mobile phase consisted of 5% methanol and 0. 1% (v/v) TFA in water, and the optimal loading amount and flow rate were 1. 0 g and 80 ml/min, respectively.

methanol

TFA


Input: Under this condition, 339 mg of 95. 9% punicalin could be obtained in 40 min.

punicalin


Input: 59. 7 mg of 78. 0% gallic acid could be separated simultaneously.

gallic acid


Input: This method was practical for industrial utilisation of pomegranate husk.


Input: Afterwards, the antioxidant and protein-precipitating capacities of the purified punicalin, together with punicalagin, were evaluated.

punicalin

punicalagin


Input: Results showed that punicalin had strong antioxidant activity, and it exhibited a low affinity for protein.

punicalin


Input: This suggested that the antioxidant of punicalin would not be greatly masked by tannin-protein precipitation in application, and hence confirmed punicalin to be a promising antioxidant.

punicalin

tannin

punicalin


Input: Binding of vitamin A with milk alpha-and beta-caseins.

vitamin A


Input: The binding sites of retinol and retinoic acid with milk alpha-and beta-caseins were determined, using constant protein concentration and various retinoid contents.

retinol

retinoic acid


Input: FTIR, UV-visible and fluorescence spectroscopic methods as well as molecular modelling were used to analyse retinol and retinoic acid binding sites, the binding constant and the effect of retinoid complexation on the stability and conformation of caseins.

retinol

retinoic acid

retinoid


Input: Structural analysis showed that retinoids bind caseins via both hydrophilic and hydrophobic contacts with overall binding constants of K (retinol-) (alpha) (-caseins) = 1. 21 (+/- 0. 4) x 10 (5) M (-1) and K (retinol-) (beta) (-caseins) = 1. 11 (+/- 0. 5) x 10 (5) M (-1) and K (retinoic acid-) (alpha) (-caseins) = 6. 2 (+/- 0. 6) x 10 (4) M (-1) and K (retinoic acid-) (beta) (-caseins) = 6. 3 (+/- 0. 6) x 10 (4) M (-1).

retinoids

retinol

retinol

retinoic acid

retinoic acid


Input: The number of bound retinol molecules per protein (n) was 1. 5 (+/- 0. 1) for alpha-casein and 1. 0 (+/- 0. 1) for beta-casein, while 1 molecule of retinoic acid was bound in the alpha-and beta-casein complexes.

retinol

retinoic acid


Input: Molecular modelling showed different binding sites for retinol and retinoic acid on alpha-and beta-caseins with more stable complexes formed with alpha-casein.

retinol

retinoic acid


Input: Retinoid-casein complexation induced minor alterations of protein conformation.

Retinoid


Input: Caseins might act as carriers for transportation of retinoids to target molecules.

retinoids


Input: Effect of genotype, environment, and their interaction on phytochemical compositions and antioxidant properties of soft winter wheat flour.


Input: The effect of genotype (G), growing environment (E), and their interaction (G x E) on the antioxidant properties and chemical compositions were investigated using the flour samples of 10 wheat varieties grown in four different locations in Maryland.


Input: Lutein content of wheat flour ranged from 0. 10 to 0. 69 mu g/g, and alpha-tocopherol ranged from 0. 12 to 0. 83 mu g/g.

Lutein

alpha-tocopherol


Input: Total carotenoids were primarily affected by E (45. 7%), while G x E interaction had a larger effect on the level of total tocopherols (71. 6%).

tocopherols


Input: E had the largest effect on antioxidant activity against oxygen, hydroxyl, and ABTS (. +) radicals.

oxygen

hydroxyl

ABTS (. +)


Input: G had the least influence on the measured phytochemicals and antioxidant activity assays.


Input: Total carotenoids had a significant correlation with average low air temperature (r = 0. 359, p < 0. 01) as well as precipitation level (r = 0. 214, p < 0. 01).


Input: ABTS (. +) radical scavenging capacity had a positive correlation with average air temperature (r = 0. 705, p < 0. 01), while hydroxyl radical scavenging capacity had a negative correlation with temperature (r =-0. 269. p < 0. 01).

ABTS (. +)

hydroxyl


Input: These results show that environment, genotype, and their interaction could influence the levels of lipophilic antioxidants and antioxidant activities of wheat flour.


Input: Arsenic speciation analysis in mono-varietal wines by on-line ionic liquid-based dispersive liquid-liquid microextraction.

Arsenic


Input: A highly efficient separation and pre-concentration method for arsenic species determination, based on ionic liquid (IL) dispersive microextraction technique implemented in a flow analysis system, is proposed.

arsenic


Input: Highly selective separation of arsenite species [As (III)] was achieved by chelation with sodium diethyldithiocarbamate (DDTC) followed by dispersion with 40 mg of 1-octyl-3-methylimidazolium hexafluorophosphate ([C (8) mim] [PF (6)]) IL.

arsenite

As (III)

sodium diethyldithiocarbamate

DDTC

1-octyl-3-methylimidazolium hexafluorophosphate

[C (8) mim] [PF (6)]


Input: Analyte extraction, retention and separation of IL phase were achieved with a packed microcolumn and As (III) was determined in eluent solution by electrothermal atomic absorption spectrometry (ETAAS).

As (III)


Input: Concentration of As (V) was deduced by the difference between total inorganic arsenic and As (III).

As (V)

arsenic

As (III)


Input: Thus, determination of total arsenic was performed by previous degradation of organo-arsenic species, followed by a reduction.

arsenic

organo-arsenic


Input: Under optimal conditions, As (III) extraction efficiency was 100% and a sensitivity enhancement factor of 46 was obtained with only 4. 0 ml of sample The method was successfully applied for arsenic speciation studies in mono-varietal wines.

As (III)

arsenic


Input: Stabilization of anthocyanin and skullcap flavone complexes--investigations with computer simulation and experimental methods.

anthocyanin

flavone


Input: We examined the stabilization of anthocyanins with flavones from the practical and theoretical perspective.

anthocyanins

flavones


Input: The influence of addition of skullcap flavones, heating to 50 degrees C, and 12 day storage time (in the presence and absence of light) on the stability of anthocyanins in honeysuckle concentrates was investigated experimentally.

flavones

anthocyanins


Input: Theoretical study was conducted with molecular dynamics methods in a model system, preceded by simulated annealing and thermalization.


Input: By the methods of the computer simulation of the copigmentation process we determined the sites responsible for the stabilization of a cyanidin quinoidal base-baicalin complex.

cyanidin quinoidal base

baicalin


Input: We revealed both direct and water-mediated hydrogen bondings that keep the lamellar stacking structure of these molecules in the bounded form in water medium.

hydrogen


Input: The stacking occurs also due to hydrophobic interactions of the rings of both molecules.


Input: The experimental part of the study confirmed the effectiveness of anthocyanins stabilization in a concentrate of honeysuckle with the use of skullcap flavones.

anthocyanins

flavones


Input: Burdock fructooligosaccharide induces fungal resistance in postharvest Kyoho grapes by activating the salicylic acid-dependent pathway and inhibiting browning.

salicylic acid


Input: Burdock fructooligosaccharide (BFO) is a natural elicitor from Arcitum lappa.


Input: The effects of BFO in controlling postharvest disease in grape, apple, banana, kiwi, citrus, strawberry, and pear were investigated.


Input: The disease index, decay percentage, and area under the disease progress curve indicated that BFO has general control effects on postharvest disease of fruits.


Input: Kyoho grapes were studied to elucidate the mechanism of BFO in boosting the resistance of grapes to Botrytis cinerea infection.


Input: BFO treatment induced upregulation of the npr1, pr1, pal, and sts genes, and inhibited the total phenol content decrease, which activated chitinase and beta-1, 3-glucanase.

phenol


Input: These results indicated that the salicylic acid-dependent signalling pathway was induced.

salicylic acid


Input: The delayed colour change and peroxidase and polyphenoloxidase activity suggested that BFO delayed grape browning.


Input: The reduced respiration rate, weight loss, and titratable acidity prolonged the shelf life of postharvest grapes.


Input: BFO is a promising elicitor in postharvest disease control.


Input: Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.).


Input: Legumes are the bas e s diet in several countries.


Input: They hold a high nutritional value, but other properties related to human health are nowadays being studied.


Input: The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c. v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability.

phenolic


Input: Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS.

Phenolic


Input: The antioxidant activity was evaluated by ORAC.


Input: Astrocytes cultures (U-373) have been used to test their neuroprotective effect.


Input: Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method.

sulphorhodamine B


Input: Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity.

phenolic


Input: Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins.

oxygen

phenolic

anthocyanins


Input: This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level.

phenolic


Input: Glucose, fructose and sucrose increase the solubility of protein-tannin complexes and at high concentration, glucose and sucrose interfere with bisulphite bleaching of wine pigments.

Glucose

fructose

sucrose

tannin

glucose

sucrose

bisulphite


Input: Wines were modified with increasing sugar concentrations and decreasing tannin concentrations and analysed by a combination of protein precipitation and bisulphite bleaching.

sugar

tannin

bisulphite


Input: Increasing sugar concentration decreased the precipitation of tannin and protein-precipitable polymeric pigments (PPP).

sugar

tannin


Input: The use of a hydrogen bond disruptor (urea) to reduce protein-tannin and protein-pigment complex formation showed that the effect of sugar concentration occurred by increasing the solubility of the tannin-protein complex, not by interfering with protein-tannin complex formation.

hydrogen

urea

tannin

sugar

tannin

tannin


Input: By increasing the solubility of pigment-protein complexes, non-protein-precipitable polymeric pigments (nPPP) appeared to increase.


Input: There was also an increase in total polymeric pigments at each tannin concentration with increasing glucose and sucrose concentration, indicating that sugar concentration might also affect bisulphite bleaching of wine pigments.

tannin

glucose

sucrose

sugar

bisulphite


Input: While a significant effect of sugar concentration on tannin-protein complex solubility was observed, these effects were greatest at sugar concentrations far in excess of normal wine making conditions.

sugar

tannin

sugar


Input: Under normal wine making conditions, sugar concentration will have a negligible effect on protein-precipitable tannin, PPP and nPPP concentrations.

sugar

tannin


Input: Structure and antioxidant activity of beta-lactoglobulin-glycoconjugates obtained by high-intensity-ultrasound-induced Maillard reaction in aqueous model systems under neutral conditions.


Input: Sonication is a new processing technology in the dairy industry.


Input: The aim of this study was to test glycation of beta-lactoglobulin (BLG) in Maillard reaction (MR) induced by high-intensity ultrasound in aqueous solution under neutral conditions at 10-15 degrees C, which is not favourable for the MR.


Input: BLG was sonicated in the presence of glucose, galactose, lactose, fructose, ribose and arabinose.

glucose

galactose

lactose

fructose

ribose

arabinose


Input: Formation of Maillard reaction products (MRPs) was monitored by mass spectrometry, spectrophotometry and fluorimetry.


Input: Ultrasound treatment resulted in formation of MRPs with all tested carbohydrates.

carbohydrates


Input: Ribose induced the highest degree of modification resulting in 76% of BLG modified and an average of three anhydroribose units attached.

Ribose

anhydroribose


Input: Circular dichroism spectra analyses indicated only minor alterations in secondary and tertiary structures.


Input: MRP obtained by ultrasound exhibited 1, 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity and possessed increased iron-chelating activity and reducing power.

1, 1-diphenyl-2-picrylhydrazyl

DPPH

iron


Input: High-intensity ultrasound efficiently promotes BLG-glycoconjugates formation by MR in aqueous solutions under non-denaturing conditions.


Input: Influence of processing on the volatile profile of strawberry spreads made with isomaltulose.

isomaltulose


Input: A new strawberry spread formulated with fructose and isomaltulose (replacing sucrose partially or totally) and a high percentage of fruit was developed in line with the new trend of healthier products.

fructose

isomaltulose

sucrose


Input: This work studies the influence of some process variables (percentage of sugar, pectin and citric acid, and time of thermal treatment) on the volatile profile of these spreads with different formulations.

sugar

citric acid


Input: The ripeness of the raw strawberries influences the concentrations of some of the compounds in the spreads, such as isobutyl acetate, butyl butyrate, 3-hexen-1-yl acetate or propan-2-ol.

isobutyl acetate

butyl butyrate

3-hexen-1-yl acetate


Input: The process conditions have an important effect on the volatile profiles.


Input: Most of the esters and alcohols decreased whereas 13 new compounds appear, mostly furans (furfural, 2-acetylfurane, 5-methyl furfural, mesifurane) and aldehydes (octanal, nonanal, decanal and benzaldeyhde).

esters

alcohols

furans

furfural

5-methyl furfural

mesifurane

aldehydes

octanal

nonanal

decanal

benzaldeyhde


Input: In general, the spreads formulated with sucrose-isomaltulose that contained higher levels of pectin and citric acid gave better results in the preservation of the original aromatic compounds in raw strawberries.

sucrose

isomaltulose

citric acid


Input: Optimization of ABTS radical cation assay specifically for determination of antioxidant capacity of intracellular extracts of microalgae and cyanobacteria.

ABTS radical cation


Input: A renewed interest in antioxidants has arisen in recent years; microalgae and cyanobacteria are potential sources thereof for use as food/feed ingredients.


Input: However, improved methods for comprehensive screening of antioxidant capacity specifically in intracellular extracts of marine microorganisms are required-encompassing lipophilic and hydrophilic compounds simultaneously.


Input: The original ABTS method was thus improved, and in particular the procedures of cell disruption and storage were optimized.

ABTS


Input: The best solvent found was ethanol/water (1: 1, v/v).

ethanol


Input: The reaction to form ABTS (+) in said solvent was essentially complete by eight hours, and this radical cation was stable for at least 6 days; at room temperature, the ABTS (+) solution remained within an allowable analytical range for up to 13 h.

ABTS (+)

ABTS (+)


Input: Ultra Turrax was the best cell disruption method, and refrigeration was the best preservation method.


Input: This improved methodology was validated with four representative strains that respond poorly to cell disruption.


Input: Biogenic amines formation in Streptococcus thermophilus isolated from home-made natural yogurt.

amines


Input: Twelve different biogenic amines formation in 58 isolates of Streptococcus thermophilus from home-made natural yogurt were investigated in histidine (HDB) and lysine decarboxylase broth (LDB).

amines

histidine

lysine


Input: All S. thermophilus isolates had an ability to produce twelve different biogenic amines in HDB and LDB.

amines


Input: Most of the S. thermophilus isolates formed low amounts of histamine (1-50 mg/L) from histidine.

histamine

histidine


Input: Apart from one isolate, S. thermophilus produced tyramine at low (47 isolates) and medium (10 isolates) levels.

tyramine


Input: The amount of each specific biogenic amine produced by S. thermophilus was generally lower than 100 mg L (-1).

amine


Input: Also, the presence of hdcA gene was investigated using PCR technique and relation between gene and histamine production was conducted in S. thermophilus isolates.

histamine


Input: This study showed that most of the S. thermophilus isolates have the ability to form biogenic amines, especially histamine, and tyramine, which is an important consideration when selecting strains as starter cultures.

amines

histamine

tyramine


Input: Shelf-life of infrared dry-roasted almonds.


Input: Infrared heating was recently used to develop a more efficient roasting technology than traditional hot air roasting.


Input: Therefore, in this study, we evaluated the shelf-life of almonds roasted with three different approaches, namely infrared (IR), sequential infrared and hot air (SIRHA) and regular hot air (HA).


Input: Nine medium roasted almond samples produced by the aforementioned heating methods were processed at three different temperatures (130, 140 and 150 degrees C), packed in paper bags and then stored at 37 degrees C for three, six or eight months.


Input: Shelf-life of the roasted almonds was determined by measuring the changes in colour, peroxide value, moisture content, water activity, volatile components and sensory quality.

peroxide


Input: No significant difference was observed in moisture content and water activity among the almond samples processed with different roasting methods and stored under the same conditions.


Input: GC/MS analysis showed that aldehydes, alcohols, and pyrazines were the main volatile components of almonds.

aldehydes

alcohols

pyrazines


Input: Aliphatic aldehydes such as hexanal, (E)-2-octenal, and nonanal were produced as off-odours during storage.

Aliphatic aldehydes

hexanal

nonanal


Input: Although the overall quality of roasted almonds produced with SIRHA and HA heating was similar during the first three months of storage, their peroxide value and concentration of aliphatic aldehydes differed significantly for different roasting methods and increased significantly in all roasted samples during storage.

peroxide

aliphatic aldehydes


Input: We postulate that hexanal and nonanal might be better indicators of the shelf life of roasted almonds than the current standard, peroxide value.

hexanal

nonanal

peroxide


Input: Synthesis of new triazole acetamides with inotropic effects.

triazole acetamides


Input: A series of new triazole acetamides 5a-w were synthesized and evaluated for their positive inotropic activity of left atrium stroke volume on isolated rabbit-heart preparations.

triazole acetamides


Input: The majority of the derivatives presented favorable in vitro activity compared with the reference drug, milrinone.

milrinone


Input: Among them triazole acetamide 5a was identified as the most potent with 20. 29 +/- 0. 18% increased stroke volume (milrinone: 2. 46 +/- 0. 07%) at a concentration of 3 x 10 (-5) M.

triazole acetamide

milrinone


Input: The chronotropic effects of the compounds having inotropic effects were also evaluated.


Input: Novel limonene and citral based 2, 5-disubstituted-1, 3, 4-oxadiazoles: a natural product coupled approach to semicarbazones for antiepileptic activity.

limonene

citral

2, 5-disubstituted-1, 3, 4-oxadiazoles

semicarbazones


Input: Two novel series of N (4)-(5-(2/3/4-substituted-phenyl)-1, 3, 4-oxadiazol-2-yl)-N (1)-(2-methyl-5-(prop-1-en-2-yl) cyclohex-2-enylidene) semicarbazide and N (4)-(5-(2/3/4-substituted-phenyl)-1, 3, 4-oxadiazol-2-yl)-N (1)-(3, 7-dimethylocta-3, 6-dienylidene)-semicarbazide were synthesized to meet structural prerequisite indispensable for anticonvulsant activity.

N (4)-(5-(2/3/4-substituted-phenyl)-1, 3, 4-oxadiazol-2-yl)-N (1)-(2-methyl-5-(prop-1-en-2-yl) cyclohex-2-enylidene) semicarbazide

N (4)-(5-(2/3/4-substituted-phenyl)-1, 3, 4-oxadiazol-2-yl)-N (1)-(3, 7-dimethylocta-3, 6-dienylidene)-semicarbazide


Input: The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES), subcutaneous pentylenetrtrazole (scPTZ) and subcutaneous strychnine (scSTY) models.

pentylenetrtrazole

strychnine


Input: The rotorod test was conducted to evaluate neurotoxicity.


Input: Some of the selected active compounds were subjected to GABA assay to confirm their mode of action.

GABA


Input: The outcome of the present investigations proved that the four binding sites pharmacophore model is vital for anticonvulsant activity.


Input: The efforts were also made to establish structure-activity relationships among test compounds.


Input: Lead optimization of isocytosine-derived xanthine oxidase inhibitors.

isocytosine

xanthine


Input: We report our attempts at improving the oral efficacy of low-nanomolar inhibitors of xanthine oxidase from isocytosine series through chemical modifications.

xanthine

isocytosine


Input: Our lead compound had earlier shown good in vivo efficacy when administered intraperitoneally but not orally.


Input: Several modifications are reported here which achieved more than twofold improvement in exposure.


Input: A compound with significant improvement in oral efficacy was also obtained.


Input: Discovery and preliminary structure-activity relationship analysis of 1, 14-sperminediphenylacetamides as potent and selective antimalarial lead compounds.

1, 14-sperminediphenylacetamides


Input: Screening of synthesized and isolated marine natural products for in vitro activity against four parasitic protozoa has identified the ascidian metabolite 1, 14-sperminedihomovanillamide (orthidine F, 1) as being a non-toxic, moderate growth inhibitor of Plasmodium falciparum (IC (50) 0. 89 mu M).

1, 14-sperminedihomovanillamide

orthidine F


Input: Preliminary structure-activity relationship investigation identified essentiality of the spermine polyamine core and the requirement for 1, 14-disubstitution for potent activity.

spermine polyamine


Input: One analogue, 1, 14-spermine-di-(2-hydroxyphenylacetamide) (3), exhibited two orders of magnitude increased anti-P.

1, 14-spermine-di-(2-hydroxyphenylacetamide)


Input: f activity (IC (50) 8. 6 nM) with no detectable in vitro toxicity.


Input: The ease of synthesis of phenylacetamido-polyamines, coupled with potent nM levels of activity towards dual drug resistant strains of P. falciparum makes this compound class of interest in the development of new antimalarial therapeutics.

phenylacetamido-polyamines


Input: Lead optimization of a dihydropyrrolopyrimidine inhibitor against phosphoinositide 3-kinase (PI3K) to improve the phenol glucuronic acid conjugation.

dihydropyrrolopyrimidine

phenol glucuronic acid


Input: Our lead compound for a phosphoinositide 3-kinase (PI3K) inhibitor (1) was metabolically unstable because of rapid glucuronidation of the phenol moiety.

phenol


Input: Based on structure-activity relationship (SAR) information and a FlexSIS docking simulation score, aminopyrimidine was identified as a bioisostere of phenol.

aminopyrimidine

phenol


Input: An X-ray structure study revealed a hydrogen bonding pattern of aminopyrimidine derivatives.

hydrogen

aminopyrimidine


Input: Finally, aminopyrimidine derivatives 33 showed strong tumor growth inhibition against a KPL-4 breast cancer xenograft model in vivo.

aminopyrimidine


Input: Heterobivalent dual-target probe for targeting GRP and Y1 receptors on tumor cells.


Input: Receptor targeting ligands for imaging and/or therapy of cancer are limited by heterogeneity of receptor expression by tumor cells, both inter-patient and intra-patient.


Input: It is often more important for imaging agents to identify local and distant spread of disease than it is to identify a specific receptor presence.


Input: Two natural hormone peptide receptors, GRPR and Y1, are specifically interesting because expression of GRPR, Y1 or both is up-regulated in most breast cancers.


Input: We describe here the design and development of a new heterobivalent peptide ligand, truncated bombesin (t-BBN)/BVD15-DO3A, for dual-targeting of GRPR and Y1, and validation of its dual binding capability.

bombesin


Input: Such a probe should be useful in imaging cells, tissues and tumors that are GRPR and/or Y1 positive and should target radioisotopes, for example, (68) Ga and/or (177) Lu, to more tumors cells than single GRPR or Y1 targeted probes.


Input: A GRP targeting ligand, J-G-Abz4-QWAVGHLM-NH (2) (J-G-Abz4-t-BBN), and an Y1 targeting ligand, INP-K [epsilon-J-(alpha-DO3A-epsilon-DGa)-K]-YRLRY-NH (2) ([epsilon-J-(alpha-DO3A-epsilon-DGa)-K]-BVD-15), were synthesized and coupled to produce the heterobivalent ligand, t-BBN/BVD15-DO3A.


Input: Competitive displacement binding assays using t-BBN/BVD15-DO3A against (125) I-Tyr (4)-BBN yielded an IC (50) value of 18 +/- 0. 7 nM for GRPR in T-47D cells, a human breast cancer cell line.

(125) I

Tyr


Input: A similar assay using t-BBN/BVD15-DO3A against porcine (125) I-NPY showed IC (50) values of 80 +/- 11 nM for Y1 receptor in MCF7 cells, another human breast cancer cell line.

(125) I


Input: In conclusion, it is possible to construct a single DO3A chelate containing probe that can target both GRPR and Y1 on human tumor cells.


Input: Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole.

benzimidazole


Input: A chemically diverse library of about 400, 000 small molecules was screened for antiviral activity against lentiviral pseudotypes with the Lassa virus envelope glycoprotein (LASV GP) gene incorporated.


Input: High-throughput screening resulted in discovery of a hit compound (ST-37) possessing a benzimidazole core which led to a potent compound series.

benzimidazole


Input: Herein, we report SAR studies which involved structural modifications to the phenyl rings and methylamino linker portion attached to the benzimidazole core.

phenyl

methylamino

benzimidazole


Input: Many analogs in this study possessed single digit nanomolar potency against LASV pseudotypes.


Input: Compounds in this benzimidazole series also exhibited nanomolar antiviral activity against pseudotypes generated from other arenavirus envelopes indicating the potential for development of a broad-spectrum inhibitor.

benzimidazole


Input: Ultimately, lead compound ST-193 was identified and later found to be efficacious in a lethal LASV guinea pig model showing superior protection compared to ribavirin treatment.


Input: Calpains participate in nerve terminal degeneration induced by spider and snake presynaptic neurotoxins.


Input: alpha-latrotoxin and snake presynaptic phospholipases A2 neurotoxins target the presynaptic membrane of axon terminals of the neuromuscular junction causing paralysis.


Input: These neurotoxins display different biochemical activities, but similarly alter the presynaptic membrane permeability causing Ca (2 +) overload within the nerve terminals, which in turn induces nerve degeneration.

Ca (2 +)


Input: Using different methods, here we show that the calcium-activated proteases calpains are involved in the cytoskeletal rearrangements that we have previously documented in neurons exposed to alpha-latrotoxin or to snake presynaptic phospholipases A2 neurotoxins.

calcium


Input: These results indicate that calpains, activated by the massive calcium influx from the extracellular medium, target fundamental components of neuronal cytoskeleton such as spectrin and neurofilaments, whose cleavage is functional to the ensuing nerve terminal fragmentation.

calcium


Input: Spontaneous and experimental poisoning by Marsdenia megalantha Goyder & Morillo in ruminants and a pig.


Input: Marsdenia megalantha is a rupicolous shrub with succulent roots from the semiarid region of Brazil that is known to cause fatal poisoning in livestock.


Input: We reported spontaneous cases of poisoning by M. megalantha roots in bovine, caprine, ovine, and equine species.


Input: The clinical and pathological findings of experimental administration of M. megalantha to sheep, goats, a calf and a pig are reported.


Input: Three goats, two sheep and a calf were dosed once orally with freshly chopped roots at dose of 25 g wet plant/kg bw; another sheep and a pig were dosed with 10 g wet plant/kg bw.


Input: Poisoning occurred in all of the animals except the three goats.


Input: Clinical signs of poisoning included tachycardia, opisthotonus, ruminal bloat, dyspnea, nystagmus, mydriasis, ataxia, and recumbence with paddling movements.


Input: Pathological evaluation showed segmental laminar neuronal necrosis and spongiosis in the telencephalic cortex and degeneration of Purkinje cells.


Input: The picrate paper procedure detected no cyanide in the plant roots, but the reaction used for nitrate detection gave a strongly positive response.

cyanide

nitrate


Input: In conclusion, M. megalantha is a poisonous plant that produces acute poisoning characterized mainly by nervous disturbances.


Input: Livestock producers should offer alternative food during the dry and early rainy seasons to avoid the poisoning by this plant.


Input: Small and colorful stones make beautiful mosaics: fragment-based chemogenomics.


Input: Smaller stones with a wide variety of colors make a higher resolution mosaic.


Input: In much the same way, smaller chemical entities that are structurally diverse are better able to interrogate protein binding sites.


Input: This feature article describes the construction of a diverse fragment library and an analysis of the screening of six representative protein targets belonging to three diverse target classes (G protein-coupled receptors ADRB2, H1R, H3R, and H4R, the ligand-gated ion channel 5-HT3R, and the kinase PKA) using chemogenomics approaches.


Input: The integration of experimentally determined bioaffinity profiles across related and unrelated protein targets and chemogenomics analysis of fragment binding and protein structure allow the identification of: (i) unexpected similarities and differences in ligand binding properties, and (ii) subtle ligand affinity and selectivity cliffs.


Input: With a wealth of fragment screening data being generated in industry and academia, such approaches will contribute to a more detailed structural understanding of ligand-protein interactions.


Input: Retinol deprivation partially rescues the skeletal mineralization defects of Phex-deficient Hyp mice.

Retinol


Input: X-linked hypophosphatemic rickets (XLH) is a genetic disorder caused by mutational inactivation of the PHEX gene, encoding a transmembrane endopeptidase expressed in osteoblasts.


Input: Since several experiments involving Phex-deficient Hyp mice have demonstrated that an increased expression of Fgf23 in osteoblasts is causative for the renal phosphate loss characteristic of XLH, we performed genome-wide expression analysis to compare differentiated osteoblasts from wildtype and Hyp mice.

phosphate


Input: Here we did not only observe the expected increase of Fgf23 expression in the latter ones, but also a differential expression of genes that are either induced by or involved in retinoic acid signaling, which led us to analyze whether dietary retinol deprivation would influence the phenotype of Hyp mice.

retinoic acid

retinol


Input: Unexpectedly, feeding a retinol-free diet resulted in a partial rescue of the growth plate and bone mineralization defects in 6 weeks old Hyp mice.


Input: When we fed the same diet for 24 weeks the amount of non-mineralized bone matrix (osteoid) was reduced by more than 70%, although phosphate homeostasis was unaffected.

phosphate


Input: In contrast, a dietary normalization of serum phosphate levels in Hyp mice reduced the osteoid amount by less than 30%, thereby demonstrating a previously unknown impact of retinol on the cell-autonomous mineralization defect of Phex-deficient osteoblasts.

phosphate


Input: Effects of baicalein on apoptosis, cell cycle arrest, migration and invasion of osteosarcoma cells.

baicalein


Input: Baicalein is a bioactive flavonoid that is widely used in ancient China.

Baicalein

flavonoid


Input: However, its effects on the most common primary malignant bone tumor, osteosarcoma, remain unknown.


Input: In the present study, we investigated the effects of baicalein in osteosarcoma cells.

baicalein


Input: Our results indicate baicalein might be an efficacious anti-osteosarcoma drug.

baicalein


Input: We found that baicalein could inhibit cell proliferation in a time-and dose-dependent manner.

baicalein


Input: Additionally, we demonstrated that baicalein promotes osteosarcoma cell apoptosis, and our mechanistic studies suggest that this is mediated by caspase activation, especially caspase-3.

baicalein


Input: We also showed that the down-regulation of Bcl-2 and concurrent increase in Bax and Bim levels contribute to the apoptosis induced by baicalein.

baicalein


Input: In addition, we observed that baicalein induces G1 cell cycle arrest by decreasing cyclin D1 and cyclin-dependent kinase 4 (CDK4).

baicalein


Input: Furthermore, our data verifies that baicalein can reduce osteosarcoma cell adhesion, migration and invasion in vitro, which indicates its potential to inhibit osteosarcoma metastasis.

baicalein


Input: The decrease in expression of matrix metalloproteinases (MMP)-2 and MMP-9 may contribute to the effects of baicalein.

baicalein


Input: Taken together, our results provide evidence that baicalein plays important roles in anti-osteosarcoma therapy, and thus may serve as a novel and efficient candidate agent for osteosarcoma treatment.

baicalein


Input: Tri-and diorganotin (IV) complexes of biologically important orotic acid: synthesis, spectroscopic studies, in vitro anti-cancer, DNA fragmentation, enzyme assays and in vivo anti-inflammatory activities.

Tri-and diorganotin (IV)

orotic acid


Input: Tri-and diorganotin (IV) orotates of general formula, R (n) Sn (H (2) Or) (m) [n = 3/2, m = 1/2, R = Me, n-Bu, n-Oct and Ph; H (2) Or (-) = monoanion of orotic acid (H (3) Or)] (n-Bu (2) Sn (HOr) as an exception) have been synthesized.

Tri-and diorganotin (IV) orotates

R (n) Sn (H (2) Or) (m)

Me

n-Bu

n-Oct

Ph

H (2) Or (-)

orotic acid

H (3) Or

n-Bu (2) Sn (HOr)


Input: On the basis of various spectroscopic studies it is revealed that R (3) Sn (H (2) Or) and R (2) Sn (H (2) Or) (2) exhibit distorted trigonal-bipyramidal and distorted octahedral geometry, respectively, and n-Bu (2) Sn (HOr) shows both five and six coordination geometry around tin.

R (3) Sn (H (2) Or)

R (2) Sn (H (2) Or) (2)

n-Bu (2) Sn (HOr)


Input: In vitro anti-cancer screening against MCF-7 (mammary), HEK-293 (kidney), PC-3 (prostate), HCT-15 (colon) and HepG-2 (liver) cancer cell lines suggest that the n-Oct (2) Sn (H (2) Or) (2) is the most active complex among all of the studied complexes.

n-Oct (2) Sn (H (2) Or) (2)


Input: DNA fragmentation and antioxidant enzyme assays suggest that cytotoxic effect of the complexes is selectively mediated through the induction of apoptosis.


Input: They also exhibit low toxicity and good anti-inflammatory activity (in vivo).


Input: Determination of bioactive, free isothiocyanates from a glucosinolate-containing phytotherapeutic agent: a pilot study with in vitro models and human intervention.

isothiocyanates

glucosinolate


Input: Isothiocyanates (ITCs) derived from plants of the order Brassicales are known for their antibacterial, anti-inflammatory or anticarcinogenic potential.

Isothiocyanates

ITCs


Input: Although only the free ITCs exert bioactivity, quantification in vivo is almost exclusively performed on total ITC/metabolite content.

ITCs

ITC


Input: We therefore investigated in a pilot study the amount of free ITC at different steps critical for therapeutic efficacy.

ITC


Input: A sensitive and specific GC-MS/MS method for the simultaneous quantification of individual free ITC after solid-phase extraction (SPE) was developed.

ITC


Input: We show here that release of biologically active ITC from plants occurs at not only alkaline but also acidic pH.

ITC


Input: Furthermore, in human urine conversion of the ultimate, inactive mercapturic acid conjugate back into its corresponding bioactive form is increased at alkaline as compared to neutral pH.

mercapturic acid


Input: This was also observed in the urine of human volunteers, where-in correlation with the pH value-a mean of 0. 16 to 1. 03 mu mol ITC was detected after oral application of a phytotherapeutic agent containing 30. 4 mu mol of the initial pro-drugs.

ITC


Input: The amounts of free ITC being necessary for bioactivity in vitro were found to be indeed achieved in vivo.

ITC


Input: These data might be helpful to better understand the beneficial effects of ITC observed in vivo.

ITC


Input: Fucoidan prevents multiple myeloma cell escape from chemotherapy-induced drug cytotoxicity.


Input: Minimal residual disease (MRD) occurrence with some chemotherapy drugs that promote tumor cell escape is also a key factor in blood malignancy relapse.


Input: We observed that cytarabine promotes multiple myeloma (MM) cell escape and that the number of cells in the lower chamber increased with increasing clinical disease stage in in vitro model which was constructed by a Boyden chamber, matrigel glue and serum from MM patients in different disease stages.

cytarabine


Input: The mechanism of cytarabine that promotes MM cell escape is closely associated with the up-regulation of CXCR4.

cytarabine


Input: SDF-1 alpha can up-regulate the expression of MMP9 and RHoC proteins in MM cells with up-regulated CXCR4, and further promote the cell escape.


Input: Fucoidan, a sulfated polysaccharide in the cell wall matrix of brown algae, has attracted much attention for its multiple biological activities, and we further explored the effects and possible underlying mechanisms of fucoidan on MM cell escape from cytarabine cytotoxicity.

cytarabine


Input: The results show that fucoidan may decrease MM cell escape from cytarabine cytotoxicity, and that fucoidan can down-regulate CXCR4, MMP9 and RHoC expression.

cytarabine


Input: This research provides new direction for investigating MRD occurrence and prevention.


Input: Cytotoxicity and structure activity relationships of phytosterol from Phyllanthus emblica.

phytosterol


Input: Fourteen sterols (1-14), including two new sterols, trihydroxysitosterol (2) and 5 alpha, 6 beta, 7 alpha-7 alpha-acetoxysitosterol (3), were isolated from the branches and leaves of Phyllanthus emblica L.

sterols

sterols

trihydroxysitosterol

5 alpha, 6 beta, 7 alpha-7 alpha-acetoxysitosterol


Input: The isolated compounds and a structurally related sterol 15 from Aphanamixis grandifolia were screened for cytotoxicity in two tumor cell lines (HL-60 and SMMC-7721) and a non-tumor cell line (HL-7702) using RSB assay.

sterol


Input: Within the series of phytosterol derivatives tested, compound 15 was the most active, displaying potent cytotoxicity against HL-60 with IC (50) of 5. 10 mu mol/L, and most of the active compounds showed selective cytotoxicity against tumor and non-tumor cell lines, especially compound 10 with a safety index of 4. 42.

phytosterol


Input: Talin1 has unique expression versus talin 2 in the heart and modifies the hypertrophic response to pressure overload.


Input: Integrins are adhesive, signaling, and mechanotransduction proteins.


Input: Talin (Tln) activates integrins and links it to the actin cytoskeleton.


Input: Vertebrates contain two talin genes, tln1 and tln2.


Input: How Tln1 and Tln2 function in cardiac myocytes (CMs) is unknown.


Input: Tln1 and Tln2 expression were evaluated in the normal embryonic and adult mouse heart as well as in control and failing human adult myocardium.


Input: Tln1 function was then tested in the basal and mechanically stressed myocardium after cardiomyocyte-specific excision of the Tln1 gene.


Input: During embryogenesis, both Tln forms are highly expressed in CMs, but in the mature heart Tln2 becomes the main Tln isoform, localizing to the costameres.


Input: Tln1 expression is minimal in the adult CM.


Input: With pharmacological and mechanical stress causing hypertrophy, Tln1 is up-regulated in CMs and is specifically detected at costameres, suggesting its importance in the compensatory response to CM stress.


Input: In human failing heart, CM Tln1 also increases compared with control samples from normal functioning myocardium.


Input: To directly test Tln1 function in CMs, we generated CM-specific Tln1 knock-out mice (Tln1cKO).


Input: Tln1cKO mice showed normal basal cardiac structure and function but when subjected to pressure overload showed blunted hypertrophy, less fibrosis, and improved cardiac function versus controls.


Input: Acute responses of ERK1/2, p38, Akt, and glycogen synthase kinase 3 after mechanical stress were strongly blunted in Tln1cKO mice.


Input: Given these results, we conclude that Tln1 and Tln2 have distinct functions in the myocardium.


Input: Our data show that reduction of CM Tln1 expression can lead to improved cardiac remodeling following pressure overload.


Input: A novel non-radioactive primase-pyrophosphatase activity assay and its application to the discovery of inhibitors of Mycobacterium tuberculosis primase DnaG.


Input: Bacterial DNA primase DnaG synthesizes RNA primers required for chromosomal DNA replication.


Input: Biochemical assays measuring primase activity have been limited to monitoring formation of radioactively labelled primers because of the intrinsically low catalytic efficiency of DnaG.


Input: Furthermore, DnaG is prone to aggregation and proteolytic degradation.


Input: These factors have impeded discovery of DnaG inhibitors by high-throughput screening (HTS).


Input: In this study, we expressed and purified the previously uncharacterized primase DnaG from Mycobacterium tuberculosis (Mtb DnaG).


Input: By coupling the activity of Mtb DnaG to that of another essential enzyme, inorganic pyrophosphatase from M. tuberculosis (Mtb PPiase), we developed the first non-radioactive primase-pyrophosphatase assay.


Input: An extensive optimization of the assay enabled its efficient use in HTS (Z' = 0. 7 in the 384-well format).


Input: HTS of 2560 small molecules to search for inhibitory compounds yielded several hits, including suramin, doxorubicin and ellagic acid.

suramin

doxorubicin

ellagic acid


Input: We demonstrate that these three compounds inhibit Mtb DnaG.


Input: Both suramin and doxorubicin are potent (low-micro M) DNA-and nucleotide triphosphate-competitive priming inhibitors that interact with more than one site on Mtb DnaG.

suramin

doxorubicin

nucleotide triphosphate


Input: This novel assay should be applicable to other primases and inefficient DNA/RNA polymerases, facilitating their characterization and inhibitor discovery.


Input: Electrical method to quantify nanoparticle interaction with lipid bilayers.


Input: Understanding as well as rapidly screening the interaction of nanoparticles with cell membranes is of central importance for biological applications such as drug and gene delivery.


Input: Recently, we have shown that " striped " mixed-monolayer-coated gold nanoparticles spontaneously penetrate a variety of cell membranes through a passive pathway.


Input: Here, we report an electrical approach to screen and readily quantify the interaction between nanoparticles and bilayer lipid membranes.


Input: Membrane adsorption is monitored through the capacitive increase of suspended planar lipid membranes upon fusion with nanoparticles.


Input: We adopt a Langmuir isotherm model to characterize the adsorption of nanoparticles by bilayer lipid membranes and extract the partition coefficient, K, and the standard free energy gain by this spontaneous process, for a variety of sizes of cell-membrane-penetrating nanoparticles.


Input: We believe that the method presented here will be a useful qualitative and quantitative tool to determine nanoparticle interaction with lipid bilayers and consequently with cell membranes.


Input: Development of hypoxia-inducible factor (HIF)-1 alpha inhibitors: effect of ortho-carborane substituents on HIF transcriptional activity under hypoxia.

ortho-carborane


Input: A series of substituted ortho-carboranylphenoxyacetanilides were synthesized and evaluated for their ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell-based reporter assay in HeLa cells expressing the HRE-dependent firefly luciferase reporter construct (HRE-Luc) and constitutively expressing CMV-driven Renilla luciferase reporter, and their ability to inhibit cell growth (GI (50)) using the MTT assay.

ortho-carboranylphenoxyacetanilides

MTT


Input: Among the compounds synthesized, 1g and 1l showed significant inhibition of hypoxia-induced HIF-1 transcriptional activity (IC (50): 1. 9 +/- 0. 4 and 1. 4 +/- 0. 2 mu M, respectively).


Input: Both compounds suppressed HIF-1 alpha accumulation in a concentration-dependent manner.


Input: The porcine heart malate dehydrogenase (MDH) refolding assay revealed that compound 1l inhibited human Hsp60 chaperone activity (IC (50): 6. 80 +/- 0. 25 mu M) and this inhibition activity was higher than that of ETB (IC (50): 10. 9 +/- 0. 63 mu M).

malate

ETB


Input: NMDA and AMPA receptor mediated excitotoxicity in cerebral cortex of streptozotocin induced diabetic rat: ameliorating effects of curcumin.

NMDA

AMPA

streptozotocin

curcumin


Input: Functional activity of neurotransmitter receptor and their sensitivity to regulation are altered in DM.


Input: We evaluated the neuroprotective effect of curcumin in glutamate mediated excitotoxicity in cerebral cortex of streptozotocin induced diabetic rats.

curcumin

glutamate

streptozotocin


Input: Gene expression studies in diabetic rats showed a down regulation of glutamate decarboxylase mRNA leading to accumulation of glutamate.

glutamate

glutamate


Input: Radioreceptor binding assays showed a significant increase in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and N-methyl-D-aspartate receptors density which was confirmed by immunohistochemical studies.

alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate

N-methyl-D-aspartate


Input: Decreased glutathione peroxidases gene expression indicates enhanced oxidative stress in diabetic rats.

glutathione


Input: This leads to decreased expression of glutamate aspartate transporter, which in turn reduces glutamate transport.

glutamate aspartate

glutamate


Input: All these events lead to excitotoxic neuronal death in the cerebral cortex, which was confirmed by the increased expression of caspase 3, caspase 8 and BCL2-associated X protein.


Input: Curcumin and insulin treatment reversed these altered parameters to near control.

Curcumin


Input: We establish, a novel therapeutic role of curcumin by reducing the glutamate mediated excitotoxicity in cerebral cortex of diabetes through modulating the altered neurochemical parameters.

curcumin

glutamate


Input: First-time-in-human study with GSK249320, a myelin-associated glycoprotein inhibitor, in healthy volunteers.


Input: GSK249320, a monoclonal antibody directed against myelin-associated glycoprotein (MAG), is being developed for the enhancement of recovery of function poststroke.


Input: Potential safety concerns of adverse effects on myelin led to the inclusion of pharmacodynamic measures of peripheral and central neuronal function in this first-time-in-human (FTIH) study.


Input: The study also evaluated general safety, pharmacokinetics, and immunogenicity of GSK249320.


Input: Single intravenous infusions of GSK249320 (0. 04, 0. 4, 1. 2, 3. 5, 10, and 25 mg/kg) or placebo were administered to 47 healthy subjects aged 18-60 years.


Input: GSK249320 was well tolerated at all doses.


Input: No clinically significant abnormalities were observed in neurological examinations, nerve conduction tests (NCTs), quantitative sensory tests (QSTs), clinical laboratory tests, or electrocardiograms.


Input: There were no severe or serious adverse events.


Input: GSK249320 had a half-life (HL) of 21 days and a volume of distribution at steady state of 45. 8 ml/kg, with AUC showing dose linearity.


Input: GSK249320 did not induce antidrug antibodies.


Input: Antioxidant properties of Neu2000 on mitochondrial free radicals and oxidative damage.


Input: Neu2000 [2-hydroxy-5-(2, 3, 5, 6-tetrafluoro-4 trifluoromethylbenzylamino) benzoic acid] is a dual-acting neuroprotective agent that functions both as a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist and a free radical scavenger.

2-hydroxy-5-(2, 3, 5, 6-tetrafluoro-4 trifluoromethylbenzylamino) benzoic acid

N-methyl-d-aspartate


Input: In the present study, we investigated the scavenging activity of Neu2000 on various classes of reactive oxygen species and reactive nitrogen species (ROS/RNS) as well as its efficacy for reducing free radicals and oxidative stress/damage induced in spinal cord mitochondrial preparations.

oxygen

nitrogen


Input: Neu2000 exerted scavenging activity against superoxide, nitric oxide, and hydroxyl radicals, and efficiently scavenged peroxynitrite.

superoxide

nitric oxide

hydroxyl

peroxynitrite


Input: In the mitochondrial studies, Neu2000 markedly inhibited ROS/RNS and hydrogen peroxide levels following antimycin treatment.

hydrogen peroxide

antimycin


Input: In addition, Neu2000 effectively scavenged hydroxyl radicals generated by iron (III)-ascorbate, reduced protein carbonyl formation mediated by hydroxyl radicals and peroxynitrite, and prevented glutathione oxidation caused by tert-butyl hydroperoxide in isolated mitochondria.

hydroxyl

iron (III)-ascorbate

carbonyl

hydroxyl

peroxynitrite

glutathione

tert-butyl hydroperoxide


Input: Interestingly, incubation of isolated mitochondria with Neu2000 followed by centrifugation and removal of the supernatant also resulted in a concentration-dependent decrease in lipid peroxidation.


Input: This observation suggests that Neu2000 enters mitochondria to target free radicals or indirectly affects mitochondrial function in a manner that promotes antioxidant activity.


Input: The results of the present study demonstrate that Neu2000 possesses potent in vitro antioxidant activity due, most likely, to its active phenoxy group.

phenoxy


Input: GBSA: a comprehensive software for analysing whole genome bisulfite sequencing data.

bisulfite


Input: High-throughput sequencing is increasingly being used in combination with bisulfite (BS) assays to study DNA methylation at nucleotide resolution.

bisulfite

nucleotide


Input: Although several programmes provide genome-wide alignment of BS-treated reads, the resulting information is not readily interpretable and often requires further bioinformatic steps for meaningful analysis.


Input: Current post-alignment BS-sequencing programmes are generally focused on the gene-specific level, a restrictive feature when analysis in the non-coding regions, such as enhancers and intergenic microRNAs, is required.


Input: Here, we present Genome Bisulfite Sequencing Analyser (GBSA-http://ctrad-csi. nus. edu. sg/gbsa), a free open-source software capable of analysing whole-genome bisulfite sequencing data with either a gene-centric or gene-independent focus.

Bisulfite

bisulfite


Input: Through analysis of the largest published data sets to date, we demonstrate GBSA' s features in providing sequencing quality assessment, methylation scoring, functional data management and visualization of genomic methylation at nucleotide resolution.


Input: Additionally, we show that GBSA' s output can be easily integrated with other high-throughput sequencing data, such as RNA-Seq or ChIP-seq, to elucidate the role of methylated intergenic regions in gene regulation.


Input: In essence, GBSA allows an investigator to explore not only known loci but also all the genomic regions, for which methylation studies could lead to the discovery of new regulatory mechanisms.


Input: Mitochondrial Permeability Transition Pore Inhibitors Prevent Ethanol-Induced Neuronal Death in Mice.

Ethanol


Input: Ethanol induces brain injury by a mechanism that remains partly unknown.

Ethanol


Input: Mitochondria play a key role in cell death processes, notably through the opening of the permeability transition pore (PTP).


Input: Here, we tested the effect of ethanol and PTP inhibitors on mitochondrial physiology and cell viability both in vitro and in vivo.

ethanol


Input: Direct addition of ethanol up to 100 mM on isolated mouse brain mitochondria slightly decreased oxygen consumption but did not affect PTP regulation.

ethanol

oxygen


Input: In comparison, when isolated from ethanol-treated (two doses of 2 g/kg, 2 h apart) 7-day-old mouse pups, brain mitochondria displayed a transient decrease in oxygen consumption but no change in PTP regulation or H (2) O (2) production.

ethanol

oxygen

H (2) O (2)


Input: Conversely, exposure of primary cultured astrocytes and neurons to 20 mM ethanol for 3 days led to a transient PTP opening in astrocytes without affecting cell viability and to a permanent PTP opening in 10 to 20% neurons with the same percentage of cell death.

ethanol


Input: Ethanol-treated mouse pups displayed a widespread caspase-3 activation in neurons but not in astrocytes and dramatic behavioral alterations.

Ethanol


Input: Interestingly, two different PTP inhibitors (namely, cyclosporin A and nortriptyline) prevented both ethanol-induced neuronal death in vivo and ethanol-induced behavioral modifications.

cyclosporin A

nortriptyline

ethanol

ethanol


Input: We conclude that PTP opening is involved in ethanol-induced neurotoxicity in the mouse.

ethanol


Input: A simplified confinement method for calculating absolute free energies and free energy and entropy differences.


Input: A simple and robust formulation of the path-independent confinement method for the calculation of free energies is presented.


Input: The simplified confinement method (SCM) does not require matrix diagonalization or switching off the molecular force field, and has a simple convergence criterion.


Input: The method can be readily implemented in molecular dynamics programs with minimal or no code modifications.


Input: Because the confinement method is a special case of thermodynamic integration, it is trivially parallel over the integration variable.


Input: The accuracy of the method is demonstrated using a model diatomic molecule, for which exact results can be computed analytically.


Input: The method is then applied to the alanine dipeptide in vacuum, and to the alpha-helix <--> beta-sheet transition in a 16-residue peptide modeled in implicit solvent.


Input: The SCM requires less effort for the calculation of free energy differences than previous formulations because it does not require computing normal modes.


Input: The SCM has a diminished advantage for determining absolute free energy values, because it requires decreasing the MD integration step to obtain accurate results.


Input: An approximate confinement procedure is introduced, which can be used to estimate directly the configurational entropy difference between two macrostates, without the need for additional computation of the difference in the free energy or enthalpy.


Input: The approximation has convergence properties similar to those of the standard confinement method for the calculation of free energies.


Input: The use of the approximation requires about 5 times less wall-clock simulation time than that needed to compute enthalpy differences to similar precision from an MD trajectory.


Input: For the biomolecular systems considered in this study, the errors in the entropy approximation are under 10%.


Input: Practical applications of the methods to proteins are currently limited to implicit solvent simulations.


Input: The selective metabotropic glutamate 2/3 receptor agonist MGS0028 reverses psychomotor abnormalities and recognition memory deficits in mice lacking the pituitary adenylate cyclase-activating polypeptide.

glutamate


Input: Previous studies suggest that metabotropic glutamate 2/3 receptors are involved in psychiatric disorders.

glutamate


Input: In this study, we examined the effects of the selective metabotropic glutamate 2/3 (mGlu2/3) receptor agonist MGS0028 on behavioral abnormalities in mice lacking the pituitary adenylate cyclase-activating polypeptide (PACAP), an experimental model of psychiatric disorders such as schizophrenia and attention-deficit/hyperactivity disorder.

glutamate


Input: We found that PACAP-deficient mice showed impairments in the novel object recognition test and these impairments were improved by MGS0028 (0. 1 mg/kg).


Input: Similarly, MGS0028 improved hyperactivity and jumping behaviors, but did not reverse increased immobility times in the forced swim test in PACAP-deficient mice.


Input: These results suggest that MGS0028 may be a potential, novel treatment for psychiatric disorders.


Input: Challenges of bringing next generation sequencing technologies to clinical molecular diagnostic laboratories.


Input: Molecular diagnosis of complex dual genome mitochondrial disorders is a challenge.


Input: It requires the identification of deleterious mutations in one of the ~ 1, 500 nuclear genes and the mitochondrial genome.


Input: If the molecular defect is in the mitochondrial genome, quantification of degree of mutation load (heteroplasmy) in affected tissues is important.


Input: Due to the extreme clinical and genetic heterogeneity, conventional sequence analysis of the candidate genes one-by-one is impractical, if not impossible.


Input: The newly developed massively parallel next generation sequencing (NGS) technique, that allows simultaneous sequence analysis of multiple target genes, when appropriately validated with deep coverage and proper quality controls, can be used as an effective comprehensive diagnostic approach in CLIA certified clinical laboratories.


Input: Differential Effects of Crambescins and Crambescidin 816 in Voltage-Gated Sodium, Potassium and Calcium Channels in Neurons.

Crambescidin 816

Sodium

Potassium

Calcium


Input: Crambescins and crambescidins are two families of guanidine alkaloids from the marine sponge Crambe crambe.

Crambescins

crambescidins

guanidine alkaloids


Input: Although very little information about their biological effect has been reported, it is known that crambescidin 816 (Cramb816) blocks calcium channels in a neuroblastoma X glioma cell line.

crambescidin 816

calcium


Input: Taking this into account, and the fact that ion channels are frequent targets for natural toxins, we examined the effect of Cramb816 and three compounds from the crambescin family, norcrambescin A2 (NcrambA2), crambescin A2 (CrambA2), and crambescin C1 (CrambC1), in the main voltage-dependent ion channels in neurons: sodium, potassium, and calcium channels.

crambescin

norcrambescin A2

crambescin A2

crambescin C1

sodium

potassium

calcium


Input: Electrophysiological recordings of voltage gated sodium, potassium, and calcium currents, in the presence of these guanidine alkaloids, were performed in cortical neurons from embryonic mice.

sodium

potassium

calcium

guanidine alkaloids


Input: Different effects were discovered: crambescins inhibited K (+) currents with the following potency: NcrambA2 > CrambC1 > CrambA2, while Cramb816 lacked an effect.

crambescins

K (+)


Input: Only CrambC1 and Cramb816 partially blocked Na (+) total current.

Na (+)


Input: However, Cramb816 partially blocked Ca (2 +), while NcrambA2 did not.

Ca (2 +)


Input: Since the blocking effect of Cramb816 on calcium currents has not been previously reported in detail, we further pharmacologically isolated the two main fractions of HVA Ca (2 +) channels in neurons and investigated the Cramb816 effect on them.

calcium

Ca (2 +)


Input: Here, we revealed that Cav1 or L-type calcium channels are the main target for Cramb816.

calcium


Input: These two families of guanidine alkaloids clearly showed a structure-activity relationship with the crambescins acting on voltage-gated potassium channels, while Cramb816 blocks the voltage-gated calcium channel Cav1 with higher potency than nifedipine.

guanidine alkaloids

crambescins

potassium

calcium

nifedipine


Input: The novel evidence that Cramb816 partially blocked Ca (V) and Na (V) channels in neurons suggests that this compound might be involved in decreasing the neurotransmitter release and synaptic transmission in the central nervous system.

Ca


Input: The findings presented here provide the first detailed approach on the different effects of crambescin and crambescidin compounds in voltage-gated sodium, potassium, and calcium channels in neurons and thus provide a basis for future studies.

crambescin

crambescidin

sodium

potassium

calcium


Input: Protein synthesis inhibition and oxidative stress induced by cylindrospermopsin elicit apoptosis in primary rat hepatocytes.

cylindrospermopsin


Input: The increasing presence of cyanotoxin producers in several regions of the world is hazardous for humans and animals.


Input: Cylindrospermopsin (CYN) is nowadays recognized as a widely distributed freshwater cyanobacterial toxin.

Cylindrospermopsin

CYN


Input: This toxin has been shown to induce protein synthesis inhibition as well as inhibition of glutathione synthesis.

glutathione


Input: Given that the liver seems to be the main target of cylindrospermopsin, in this work we used cultures of primary rat hepatocytes to study the type of cell death induced by CYN nanomolar concentrations.

cylindrospermopsin

CYN


Input: The involvement of reactive oxygen species in toxin induced cell death, the relationship between protein synthesis inhibition and toxicity, and the cell endogenous antioxidant response regulation were studied.

oxygen


Input: We show that cylindrospermopsin induces apoptosis in primary rat hepatocytes.

cylindrospermopsin


Input: At the concentrations used in this work, protein synthesis inhibition and oxidative stress were involved in the cytotoxic effect elicited by the toxin.


Input: Finally, activation of the cell antioxidant response was observed at the transcriptional and translational levels.


Input: Noncovalent tailoring of the binding pocket of self-assembled cages by remote bulky ancillary groups.


Input: The binding properties of a self-assembled coordination cage were subtly tuned by ancillary groups on the metal corners of the cage.


Input: Since the bulky mesityl groups of the ligand hang over the cage cavity, the effective cavity volume is reduced.

mesityl


Input: Due to the tighter guest packing inside the shrunken cavity, smaller guests were efficiently bound and guest motion was restricted even at high temperatures.


Input: Synthesis and insight into the structure-activity relationships of chalcones as antimalarial agents.

chalcones


Input: Licochalcone A (I), isolated from the roots of Chinese licorice, is the most promising antimalarial compound reported so far.

Licochalcone A


Input: In continuation of our drug discovery program, we isolated two similar chalcones, medicagenin (II) and munchiwarin (III), from Crotalaria medicagenia, which exhibited antimalarial activity against Plasmodium falciparum.

chalcones

medicagenin

munchiwarin


Input: A library of 88 chalcones were synthesized and evaluated for their in vitro antimalarial activity.

chalcones


Input: Among these, 67, 68, 74, 77, and 78 exhibited good in vitro antimalarial activity against P. falciparum strains 3D7 and K1 with low cytotoxicity.


Input: These chalcones also showed reduction in parasitemia and increased survival time of Swiss mice infected with Plasmodium yoelii (strain N-67).

chalcones


Input: Pharmacokinetic studies indicated that low oral bioavailability due to poor ADME properties.


Input: Molecular docking studies revealed the binding orientation of these inhibitors in active sites of falcipain-2 (FP-2) enzyme.


Input: Compounds 67, 68, and 78 showed modest inhibitory activity against the major hemoglobin degrading cysteine protease FP-2.


Input: Exploring key orientations at protein-protein interfaces with small molecule probes.


Input: Small molecule probes that selectively perturb protein-protein interactions (PPIs) are pivotal to biomedical science, but their discovery is challenging.


Input: We hypothesized that conformational resemblance of semirigid scaffolds expressing amino acid side-chains to PPI-interface regions could guide this process.

amino acid


Input: Consequently, a data mining algorithm was developed to sample huge numbers of PPIs to find ones that match preferred conformers of a selected semirigid scaffold.


Input: Conformations of one such chemotype (1aaa; all methyl side-chains) matched several biomedically significant PPIs, including the dimerization interface of HIV-1 protease.

methyl


Input: On the basis of these observations, four molecules 1 with side-chains corresponding to the matching HIV-1 dimerization interface regions were prepared; all four inhibited HIV-1 protease via perturbation of dimerization.


Input: These data indicate this approach may inspire design of small molecule interface probes to perturb PPIs.


Input: Coming full circle: contributions of central and peripheral oxytocin actions to energy balance.

oxytocin


Input: The neuropeptide oxytocin has emerged as an important anorexigen in the regulation of energy balance.

oxytocin

anorexigen


Input: Its effects on food intake have largely been attributed to limiting meal size through interactions in key regulatory brain regions such as the hypothalamus and hindbrain.


Input: Pharmacologic and pair-feeding studies indicate that its ability to reduce body mass extends beyond that of food intake, affecting multiple factors that determine energy balance such as energy expenditure, lipolysis, and glucose regulation.

glucose


Input: Systemic administration of oxytocin recapitulates many of its effects when administered centrally, raising the questions of whether and to what extent circulating oxytocin contributes to energy regulation.

oxytocin

oxytocin


Input: Its therapeutic potential to treat metabolic conditions remains to be determined, but data from diet-induced and genetically obese rodent models as well as application of oxytocin in humans in other areas of research have revealed promising results thus far.

oxytocin


Input: Safrole-2', 3'-oxide induces atherosclerotic plaque vulnerability in apolipoprotein E-knockout mice.

Safrole-2', 3'-oxide


Input: Safrole-2', 3'-oxide (SFO) is the major electrophilic metabolite of safrole (4-allyl-1, 2-methylenedioxybenzene), a natural plant constituent found in essential oils of numerous edible herbs and spices and in food containing these herbs, such as pesto sauce, cola beverages and bologna sausages.

Safrole-2', 3'-oxide

SFO

safrole

4-allyl-1, 2-methylenedioxybenzene


Input: The effects of SFO in mammalian systems, especially the cardiovascular system, are little known.

SFO


Input: Disruption of vulnerable atherosclerotic plaques in atherosclerosis, a chronic inflammatory disease, is the main cause of cardiovascular events.


Input: In this study, we investigated SFO-induced atherosclerotic plaque vulnerability (possibility of rupture) in apolipoprotein E-knockout (apoE (-/-)) mice.

SFO


Input: Lipid area in vessel wall reached 59. 8% in high dose SFO (SFO-HD) treated group, which is only 31. 2% in control group.

SFO

SFO


Input: SFO treatment changed the lesion composition to an unstable phenotype, increased the number of apoptotic cells in plaque and the endothelium in plaques was damaged after SFO treatment.

SFO

SFO


Input: Furthermore, compared with control groups, the plaque endothelium level of p75 (NTR) was 3-fold increased and the liver level of p75 (NTR) was 17. 4-fold increased by SFO-HD.

SFO


Input: Meanwhile, the serum level of KC (a functional homolog of IL-8 and the main proinflammatory alpha chemokine in mice) in apoE (-/-) mice was up to 357pg/ml in SFO-HD treated group.

SFO


Input: Thus, SFO contributes to the instability of atherosclerotic plaque in apoE (-/-) mice through activating p75 (NTR) and IL-8 and cell apoptosis in plaque.

SFO


Input: The interactions of apamin and tetraethylammonium are differentially affected by single mutations in the pore mouth of small conductance calcium-activated potassium (SK) channels.

tetraethylammonium

calcium

potassium


Input: Valine residues in the pore region of SK2 (V366) and SK3 (V520) were replaced by either an alanine or a phenylalanine to evaluate the impact on the interactions with the allosteric blocker apamin.

Valine

alanine

phenylalanine


Input: Unlike TEA which showed high sensitivity to phenylalanine mutated channels, the binding affinity of apamin to the phenylalanine mutants was strongly reduced.

TEA

phenylalanine

phenylalanine


Input: In addition, currents from phenylalanine mutants were largely resistant to block by apamin.

phenylalanine


Input: On the other hand, when the valine residue was replaced by an alanine residue, an increase of the binding affinity and the amount of block by apamin was observed for alanine mutated SK2 channels, but not for mutated SK3 channels.

valine

alanine

alanine


Input: Interestingly, the VA mutation reduced the sensitivity to TEA.

TEA


Input: In silico data confirmed these experimental results.


Input: Therefore, such mutations in the pore region of SK channels show that the three-dimensional structure of the SK tetramers can be disorganized in the outer pore region leading to reduced interaction of apamin with its target.


Input: Curcumin reverses glomerular hemodynamic alterations and oxidant stress in 5/6 nephrectomized rats.

Curcumin


Input: The administration of curcumin before and throughout the study attenuates oxidant stress and glomerular hemodynamic alterations induced by 5/6 nephrectomy (5/6NX).

curcumin


Input: The purpose of this work was to study if curcumin is able to reverse established glomerular hemodynamic alterations (e. g. hyperfiltration and glomerular hypertension) and oxidant stress in rats with 5/6NX.

curcumin


Input: Curcumin (120 mg/kg) was given to rats with established renal injury (30 days after surgery) and continued for 30 days (days 31-60 of the study).

Curcumin


Input: All rats were studied on day 60 after surgery.


Input: Curcumin was able (a) to reverse 5/6NX-induced glomerular hypertension and hyperfiltration, (b) to induce cell proliferation and nuclear translocation of Nrf2 and (c) to reverse 5/6NX-induced oxidant stress and decrease in antioxidant enzymes.

Curcumin


Input: These beneficial effects of curcumin were associated with the ability of this antioxidant to reverse renal structural alterations, proteinuria, hypertension, interstitial fibrosis, fibrotic glomeruli, tubular atrophy and mesangial expansion.

curcumin


Input: It has been shown for the first time that curcumin is able to reverse established oxidants stress glomerular hypertension and hyperfiltration in rats with 5/6NX.

curcumin


Input: These novel findings may play a key role in the attenuation of proteinuria and progression of renal damage in rats with 5/6NX.


Input: These data suggest that curcumin may be useful to reverse established hemodynamic alterations and renal injury in patients with chronic renal failure.

curcumin


Input: In vitro and in vivo anti-inflammatory effects of 4-methoxy-5-hydroxycanthin-6-one, a natural alkaloid from Picrasma quassioides.


Input: In the present study, we evaluated the anti-inflammatory effect of 4-methoxy-5-hydroxycanthin-6-one (CAN), a natural alkaloid isolated from Picrasma quassioides.

CAN


Input: CAN significantly inhibited the production of NO and the release of TNF-alpha induced by LPS in macrophage RAW 264. 7.

CAN

NO


Input: Western blot showed that CAN can downregulate the expression of iNOS protein.

CAN


Input: After oral administration, CAN (3, 9, and 27 mg/kg) reduced the development of carrageenan-induced paw edema and complete Freund' s adjuvant (CFA)-induced chronic arthritis in rats.

CAN


Input: The observed results indicated that pre-treatment with CAN might be an effective therapeutic intervention against inflammatory diseases including chronic arthritis.

CAN


Input: Ovarian function is restored after grafting of cryopreserved immature ovary in ewes.


Input: As a result of advances in medical treatment, almost 80% of children who are diagnosed with cancer survive long-term.


Input: The adverse consequences of cancer treatments include impaired puberty and fertility.


Input: In prepubertal girls, the only therapeutic option is the cryopreservation of an ovary.


Input: To date, a dozen births have been reported after reimplantation of cryopreserved mature ovaries.


Input: To analyze ovarian function after immature grafts, we performed ovarian grafting in a ewe model.


Input: Fresh or cryopreserved ovaries from immature ewes were autografted in prepubertal or adult ewes.


Input: Cyclic hormonal activity was recovered 3 mo after grafting.


Input: Histological analysis demonstrated the presence of all follicle populations and corpora lutea not affected by cryopreservation.


Input: After 3 reproductive seasons, births had been observed in all groups, and the follicle-stimulating hormone status was under the limit, which indicated an exhausted ovary.


Input: As an indicator of potential imprinting default, the methylation status of the Igf2r gene was analyzed and did not show significant alteration compared with that of nonmanipulated animals.


Input: Taken together, these results demonstrate that immature ovarian grafting is able to restore spontaneous puberty and fertility and could guide the reimplantation of immature cortex in women.-Sauvat, F., Bouilly, J., Capito, C., Lef e vre, A., Blach e re, T., Borenstein, N., Sarnacki, S., Dandolo, L., Binart, N.


Input: Ovarian function is restored after grafting of cryopreserved immature ovary in ewes.


Input: Bioavailability of stabilised ferrous gluconate with glycine in fresh cheese matrix: a novel iron compound for food fortification.

ferrous gluconate

glycine

iron


Input: Iron fortification of foods continues to be one of the preferred ways of improving the iron status of the population.

Iron

iron


Input: Dairy product is a common product in the diet; therefore, it is a plausible vehicle for iron fortification.

iron


Input: This study aims to investigate the bioavailability of ferrous gluconate stabilised with glycine (FGSG) in a fresh cheese fortified with zinc.

ferrous gluconate

glycine

zinc


Input: The iron bioavailability of fresh cheese fortified with either FGSG and with or without zinc and FGSG in aqueous solution and a water solution of ferrous ascorbate (reference dose) was studied using double radio iron ((55) Fe and (59) Fe) erythrocyte incorporation in 15 male subjects.

iron

zinc

ferrous ascorbate

radio iron

(55) Fe

(59) Fe


Input: All subjects presented with normal values for iron status parameters.

iron


Input: The geometric mean of iron bioavailability for the water solution of FGSG was 38. 2%, adjusted to 40% from reference doses (N. S.).

iron


Input: Iron bioavailability in fresh cheese fortified with Ca and Zn was 15. 4% and was 23. 1% without Zn, adjusted to 40% from reference doses (N. S.).

Iron

Ca

Zn

Zn


Input: The results of the present study show that the novel iron compound ferrous gluconate stabilised with glycine in a fresh cheese matrix is a good source of iron and can be used in iron fortification programmes.

iron

ferrous gluconate

glycine

iron

iron


Input: Source apportionment of trace element pollution in surface sediments using positive matrix factorization combined support vector machines: application to the Jinjiang River, China.


Input: In this study, a method of positive matrix factorization (PMF) combined support vector machines (SVMs) was adopted to identify possible sources and apportion contributions for trace element pollution in surface sediments from the Jinjiang River, Southeastern China.


Input: Utilizing diagnostics tools, four significant factors were extracted from sediment samplers, which were collected in December 2010 at 15 different sites.


Input: By treating source identification as a pattern recognition problem, the factor loadings derived from PMF were classified by SVM classifiers which have been trained and validated with fingerprints of eight potential source categories.


Input: Using SVM, industrial wastewater from lead ore mining and metal handcraft manufacture, atmospheric deposition, and natural background were identified as main sources of trace element pollution in surface sediments from the Jinjiang River, which were affirmed by visually comparing compound patterns and the differences between the predicted and actual fractional compositions.


Input: Apportionment results showed that source of lead ore mining made the largest contribution (33. 62%), followed by atmospheric deposition (30. 99%), metal handcraft manufacture (30. 09%), and natural background (5. 29%).


Input: Interaction of cisplatin with adenine and guanine: a combined IRMPD, MS/MS, and theoretical study.

cisplatin

adenine

guanine


Input: Infrared multiple photon dissociation (IRMPD) spectroscopy of cis-[Pt (NH (3)) (2) (G) Cl] (+) and cis-[Pt (NH (3)) (2) (A) Cl] (+) ions (where A is adenine and G is guanine) has been performed in two spectral regions, 950-1900 and 2900-3700 cm (-1).

cis-[Pt (NH (3)) (2) (G) Cl] (+)

cis-[Pt (NH (3)) (2) (A) Cl] (+)

adenine

guanine


Input: Quantum chemical calculations at the B3LYP/LACV3P/6-311G * * level yield the optimized geometries and IR spectra for the conceivable isomers of cis-[Pt (NH (3)) (2) (G) Cl] (+) and cis-[Pt (NH (3)) (2) (A) Cl] (+), whereby the cisplatin residue is attached to the N7, N3, or carbonyl oxygen atom, (O6), of guanine and to the N7, N3, or N1 position of adenine, respectively.

cis-[Pt (NH (3)) (2) (G) Cl] (+)

cis-[Pt (NH (3)) (2) (A) Cl] (+)

cisplatin

carbonyl oxygen

guanine

adenine


Input: In addition to the conventional binding sites of native adenine, complexes with N7-H tautomers have also been considered.

adenine


Input: In agreement with computational results, the IR characterization of cis-[Pt (NH (3)) (2) (G) Cl] (+) points to a covalent structure where Pt is bound to the N7 atom of guanine.

cis-[Pt (NH (3)) (2) (G) Cl] (+)

Pt

guanine


Input: The characterized conformer has a hydrogen-bonding interaction between a hydrogen atom of one NH (3) ligand and the carbonyl group of guanine.

hydrogen

hydrogen

NH (3)

carbonyl

guanine


Input: The experimental C = O stretching feature of cis-[Pt (NH (3)) (2) (G) Cl] (+) at 1718 cm (-1), remarkably red-shifted with respect to an unperturbed C = O stretching mode, is indicative of a lengthened CO bond in guanine, a signature that this group is involved in hydrogen bonding.

C = O

cis-[Pt (NH (3)) (2) (G) Cl] (+)

C = O

CO

guanine

hydrogen


Input: The IRMPD spectra of cis-[Pt (NH (3)) (2) (A) Cl] (+) are consistent with the presence of two major isomers, PtAN3 and PtAN1, where Pt is bound to the N3 and N1 positions of native adenine, respectively.

cis-[Pt (NH (3)) (2) (A) Cl] (+)

Pt

adenine


Input: Non-productive DNA damage binding by DNA glycosylase-like protein Mag2 from Schizosaccharomyces pombe.


Input: Schizosaccharomyces pombe contains two paralogous proteins, Mag1 and Mag2, related to the helix-hairpin-helix (HhH) superfamily of alkylpurine DNA glycosylases from yeast and bacteria.

alkylpurine


Input: Phylogenetic analysis of related proteins from four Schizosaccharomyces and other fungal species shows that the Mag1/Mag2 duplication is unique to the genus Schizosaccharomyces and most likely occurred in its ancestor.


Input: Mag1 excises N3-and N7-alkylguanines and 1, N (6)-ethenoadenine from DNA, whereas Mag2 has been reported to have no detectible alkylpurine base excision activity despite high sequence and active site similarity to Mag1.

N3-and N7-alkylguanines

1, N (6)-ethenoadenine

alkylpurine


Input: To understand this discrepancy we determined the crystal structure of Mag2 bound to abasic DNA and compared it to our previously determined Mag1-DNA structure.


Input: In contrast to Mag1, Mag2 does not flip the abasic moiety into the active site or stabilize the DNA strand 5' to the lesion, suggesting that it is incapable of forming a catalytically competent protein-DNA complex.


Input: Subtle differences in Mag1 and Mag2 interactions with the DNA duplex illustrate how Mag2 can stall at damage sites without fully engaging the lesion.


Input: We tested our structural predictions by mutational analysis of base excision and found a single amino acid responsible at least in part for Mag2' s lack of activity.

amino acid


Input: Substitution of Mag2 Asp56, which caps the helix at the base of the DNA intercalation loop, with the corresponding serine residue in Mag1 endows Mag2 with epsilon A excision activity comparable to Mag1.

serine


Input: This work provides novel insight into the chemical and physical determinants by which the HhH glycosylases engage DNA in a catalytically productive manner.


Input: Nanodomain coupling at an excitatory cortical synapse.


Input: The coupling distance between presynaptic Ca (2 +) influx and the sensor for vesicular transmitter release determines speed and reliability of synaptic transmission.

Ca (2 +)


Input: Nanodomain coupling (< 100 nm) favors fidelity and is employed by synapses specialized for escape reflexes and by inhibitory synapses involved in synchronizing fast network oscillations.


Input: Cortical glutamatergic synapses seem to forgo the benefits of tight coupling, yet quantitative detail is lacking.


Input: The reduced transmission fidelity of loose coupling, however, raises the question whether it is indeed a general characteristic of cortical synapses.


Input: Here we analyzed excitatory parallel fiber to Purkinje cell synapses, major processing sites for sensory information and well suited for analysis because they typically harbor only a single active zone.


Input: We quantified the coupling distance by combining multiprobability fluctuation analyses, presynaptic Ca (2 +) imaging, and reaction-diffusion simulations in wild-type and calretinin-deficient mice.

Ca (2 +)


Input: We found a coupling distance of < 30 nm at these synapses, much shorter than at any other glutamatergic cortical synapse investigated to date.


Input: Our results suggest that nanodomain coupling is a general characteristic of conventional cortical synapses involved in high-frequency transmission, allowing for dense gray matter packing and cost-effective neurotransmission.


Input: eRNAs are required for p53-dependent enhancer activity and gene transcription.


Input: Binding within or nearby target genes involved in cell proliferation and survival enables the p53 tumor suppressor gene to regulate their transcription and cell-cycle progression.


Input: Using genome-wide chromatin-binding profiles, we describe binding of p53 also to regions located distantly from any known p53 target gene.


Input: Interestingly, many of these regions possess conserved p53-binding sites and all known hallmarks of enhancer regions.


Input: We demonstrate that these p53-bound enhancer regions (p53BERs) indeed contain enhancer activity and interact intrachromosomally with multiple neighboring genes to convey long-distance p53-dependent transcription regulation.


Input: Furthermore, p53BERs produce, in a p53-dependent manner, enhancer RNAs (eRNAs) that are required for efficient transcriptional enhancement of interacting target genes and induction of a p53-dependent cell-cycle arrest.


Input: Thus, our results ascribe transcription enhancement activity to p53 with the capacity to regulate multiple genes from a single genomic binding site.


Input: Moreover, eRNA production from p53BERs is required for efficient p53 transcription enhancement.


Input: Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein.


Input: The pharmacokinetics of various important drugs are known to be significantly influenced by the human ABC transporter P-glycoprotein (P-gp), which may lead to clinically relevant drug-drug interactions.


Input: In contrast to therapeutic drugs, emerging drugs of abuse (DOA) are sold and consumed without any safety pharmacology testing.


Input: Only some studies on their metabolism were published, but none about their affinity to the transporter systems.


Input: Therefore, 47 DOAs from various classes were tested for their P-gp affinity using human P-gp (hP-gp) to predict possible drug-drug interactions.


Input: DOAs were initially screened for general hP-gp affinity and further characterized by modeling classic Michaelis-Menten kinetics and assessing their K (m) and V (max) values.


Input: Among the tested drugs, 12 showed a stimulation of ATPase activity.


Input: The most intensive stimulating DOAs were further investigated and compared with the known P-gp model substrates sertraline and verapamil.

sertraline

verapamil


Input: ATPase stimulation kinetics could be modeled for the entactogen 3, 4-methylenedioxy-alpha-ethylphenethylamine (3, 4-BDB), the hallucinogen 2, 5-dimethoxy-4-iodoamphetamine (DOI), the abused alkaloid glaucine, the opioid-like drugs N-iso-propyl-1, 2-diphenylethylamine (NPDPA), and N-(1-phenylcyclohexyl)-3-ethoxypropanamine (PCEPA), with K (m) and V (max) values within the same range as for verapamil or sertraline.

3, 4-methylenedioxy-alpha-ethylphenethylamine

3, 4-BDB

2, 5-dimethoxy-4-iodoamphetamine

DOI

glaucine

N-iso-propyl-1, 2-diphenylethylamine

NPDPA

N-(1-phenylcyclohexyl)-3-ethoxypropanamine

PCEPA

verapamil

sertraline


Input: As a consequence interactions with other drugs being P-gp substrates might be considered to be very likely and further studies should be encouraged.


Input: 6-OHDA-induced apoptosis and mitochondrial dysfunction are mediated by early modulation of intracellular signals and interaction of Nrf2 and NF-kappa B factors.


Input: 6-Hydroxydopamine (6-OHDA) is a neurotoxin that generates an experimental model of Parkinson' s disease in rodents and is commonly employed to induce a lesion in dopaminergic pathways.


Input: The characterization of those molecular mechanisms linked to 6-OHDA-induced early toxicity is needed to better understand the cellular events further leading to neurodegeneration.


Input: The present work explored how 6-OHDA triggers early downstream signaling pathways that activate neurotoxicity in the rat striatum.


Input: Mitochondrial function, caspases-dependent apoptosis, kinases signaling (Akt, ERK 1/2, SAP/JNK and p38) and crosstalk between nuclear factor kappa B (NF-kappa B) and nuclear factor-erythroid-2-related factor 2 (Nrf2) were evaluated at early times post-lesion.


Input: We found that 6-OHDA initiates cell damage via mitochondrial complex I inhibition, cytochrome c and apoptosis-inducing factor (AIF) release, as well as activation of caspases 9 and 3 to induce apoptosis, kinase signaling modulation and NF-kappa B-mediated inflammatory responses, accompanied by inhibition of antioxidant systems regulated by the Nrf2 pathway.


Input: Our results suggest that kinases SAP/JNK and p38 up-regulation may play a role in the early stages of 6-OHDA toxicity to trigger intrinsic pathways for apoptosis and enhanced NF-kappa B activation.


Input: In turn, these cellular events inhibit the activation of cytoprotective mechanisms, thereby leading to a condition of general damage.


Input: The transcription bubble of the RNA polymerase-promoter open complex exhibits conformational heterogeneity and millisecond-scale dynamics: implications for transcription start-site selection.


Input: Bacterial transcription is initiated after RNA polymerase (RNAP) binds to promoter DNA, melts ~ 14 bp around the transcription start site and forms a single-stranded " transcription bubble " within a catalytically active RNAP-DNA open complex (RP (o)).


Input: There is significant flexibility in the transcription start site, which causes variable spacing between the promoter elements and the start site; this in turn causes differences in the length and sequence at the 5' end of RNA transcripts and can be important for gene regulation.


Input: The start-site variability also implies the presence of some flexibility in the positioning of the DNA relative to the RNAP active site in RP (o).