Input: This review discusses the biological rationale for the most promising new agents and the results of recent studies conducted in pediatric patients with relapsed leukemia.


Input: Profiling glycosyltransferase activities by tritium imaging of glycan microarrays.

tritium


Input: High-throughput microarray technology has been combined with ultrasensitive and high-resolution tritium autoradiography to create a new platform for the quantitative detection of glycosyltransferase activity on glycan arrays.

tritium


Input: In addition, we show full compatibility with the use of fluorescently labeled lectins to help with the stereochemical assignment of newly formed glycoside linkages.


Input: Potent Inhibitors of Phosphatidylinositol 3 (PI3) Kinase that have Antiproliferative Activity Only When Delivered as Prodrug Forms.

Phosphatidylinositol


Input: Prodrugs for PI3K: A series of substituted analogues of the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 were prepared and found to potently inhibit the isolated enzyme but not MCF7 cell proliferation.

phosphatidylinositol


Input: Two tetrazolyl-substituted analogues were further derivatized as prodrugs resulting in restoration of cell-based activity.

tetrazolyl


Input: These data provide a conceptual model for development of tumor-targeting prodrug forms of cell-impermeable PI3K inhibitors.


Input: Rhenium Complexes with Visible-Light-Induced Anticancer Activity.

Rhenium


Input: Shedding light on the matter: Rhenium (I) indolato complexes with highly potent visible-light-triggered antiproliferative activity (complex 1: EC50 light = 0. 1 mu M vs EC50 dark = 100 mu M) in 2D-and 3D-organized cancer cells are reported and can be traced back to an efficient generation of singlet oxygen, causing rapid morphological changes and an induction of apoptosis.

Rhenium (I) indolato complexes

oxygen


Input: Toxicokinetics of acrylamide in primary rat hepatocytes: coupling to glutathione is faster than conversion to glycidamide.

acrylamide

glutathione

glycidamide


Input: Acrylamide (AA), classified as class 2A carcinogen (probably carcinogenic to humans) by the International Agency for Research on Cancer (IARC), is formed during heating of food from reducing carbohydrates and asparagine by Maillard reaction chemistry.

Acrylamide

carbohydrates

asparagine


Input: After dietary uptake, AA is in part metabolically converted into the proximate genotoxic phase I metabolite glycidamide (GA).

glycidamide


Input: GA reacts with nucleophilic base positions in DNA, primarily forming N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GA-Gua) adducts.

N7-(2-carbamoyl-2-hydroxyethyl) guanine


Input: In a competing phase II biotransformation pathway AA, as well as its phase I metabolite GA, is coupled to glutathione (GSH).

glutathione

GSH


Input: The GSH coupling products are further biotransformed and excreted via urine as mercapturic acids (MA), N-acetyl-S-(2-carbamoylethyl) cysteine (AAMA), and N-acetyl-S-(2-hydroxy-2-carbamoylethyl) cysteine (GAMA).

GSH

mercapturic acids

N-acetyl-S-(2-carbamoylethyl) cysteine

AAMA

N-acetyl-S-(2-hydroxy-2-carbamoylethyl) cysteine

GAMA


Input: In the present study, hepatic biotransformation pathways and DNA adduct formation were studied in primary rat hepatocytes, incubated with AA (0. 2-2, 000 mu M) for up to 24 h.


Input: Contents of AA-GSH, GA, AAMA, and GAMA were measured in the cell culture medium after solid phase extraction (SPE).

AA-GSH

AAMA

GAMA


Input: N7-GA-Gua adducts in DNA of hepatocytes were determined by HPLC-ESI-MS/MS after lysis of the cells and neutral thermal hydrolysis.


Input: Formation of AA-GSH was linear with AA concentration and incubation time and became detectable already at 0. 2 mu M (4 h).

AA-GSH


Input: In contrast to AA, GA was not detected before 16 h incubation at 10-fold higher AA concentration (2 mu M).


Input: In summary, the rate of AA-GSH formation was found to be about 1. 5-3 times higher than that of GA formation.

AA-GSH


Input: N7-GA-Gua adducts were found only at the highest AA concentration tested (2, 000 mu M).


Input: Differential levels of brain amino acids in rat models presenting learned helplessness or non-learned helplessness.

amino acids


Input: RATIONALE: Glutamatergic and gamma-aminobutyric acid (GABA) ergic abnormalities have recently been proposed to contribute to depression.

gamma-aminobutyric acid

GABA


Input: The learned helplessness (LH) paradigm produces a reliable animal model of depression that expresses a deficit in escape behavior (LH model); an alternative phenotype that does not exhibit LH is a model of resilience to depression (non-LH model).


Input: OBJECTIVES: We measured the contents of amino acids in the brain to investigate the mechanisms involved in the pathology of depression.

amino acids


Input: METHODS: LH and non-LH models were subjected to inescapable electric footshocks at random intervals following a conditioned avoidance test to determine acquirement of predicted escape deficits.


Input: Tissue amino acid contents in eight brain regions were measured via high-performance liquid chromatography.

amino acid


Input: RESULTS: The non-LH model showed increased GABA levels in the dentate gyrus and nucleus accumbens and increased glutamine levels in the dentate gyrus and the orbitofrontal cortex.

GABA

glutamine


Input: The LH model had reduced glutamine levels in the medial prefrontal cortex.

glutamine


Input: Changes in the ratios of GABA, glutamine, and glutamate were detected in the non-LH model, but not in the LH model.

GABA

glutamine

glutamate


Input: Reductions in threonine levels occurred in the medial prefrontal cortex in both models, whereas elevated alanine levels were detected in the medial prefrontal cortex in non-LH animals.

threonine

alanine


Input: CONCLUSIONS: The present study demonstrates region-specific compensatory elevations in GABA levels in the dentate gyrus and nucleus accumbens of non-LH animals, supporting the implication of the GABAergic system in the recovery of depression.

GABA


Input: On the persistence of cocaine-induced place preferences and aversions in rats.

cocaine


Input: RATIONALE: Rats develop preferences for places associated with the immediate rewarding effects of cocaine and aversions for places paired with the drug' s delayed negative effects.

cocaine


Input: The motivation to seek cocaine should therefore depend upon the relative magnitude of these two opposing effects of the drug.

cocaine


Input: OBJECTIVE: The current study tested this notion by assessing the relative persistence of the positive and negative associations formed between environmental cues and the immediate or delayed effects of cocaine.

cocaine


Input: METHODS: Rats were administered 1. 0 mg/kg intravenous cocaine and placed into a distinctive environment either immediately or 15-min after injection, alternating daily with pairings of a second environment with saline.

cocaine


Input: After four drug-place and four saline-place pairings, rats were returned to their home cages for 1, 7, or 21 days after which a 15-min place preference test was conducted.


Input: In a second experiment, the effectiveness of a single reconditioning session (one drug-place and one saline-place pairing) to reactivate learned cocaine-place associations was assessed after 1 or 3 weeks of drug abstinence.

cocaine


Input: RESULTS: Places associated with the immediate effects of cocaine were preferred (CPP), while places associated with the delayed effects of cocaine were avoided (CPA).

cocaine

cocaine


Input: The persistence of these effects differed with CPP remaining viable at 3 weeks of withdrawal, while CPA was no longer present after 1 week.


Input: Reconditioning with an additional cocaine-place pairing failed to reinstate the CPA.

cocaine


Input: CONCLUSIONS: Cue-induced " relapse " of cocaine-seeking behavior may be fueled in part by an increased persistence of positive relative to negative associations with drug-paired stimuli.

cocaine


Input: Direct measurement of contact angles of silica particles in relation to double inversion of pickering emulsions.

silica


Input: In an alkane-water system containing submicrometer silica particles at high pH, double emulsion inversion from oil-in-water (o/w) to water-in-oil (w/o) to oil-in-water can be effected by increasing the concentration of a dichain cationic surfactant in water.

silica


Input: The contact angle theta of the particles at the planar oil-water interface has been measured directly using freeze-fracture shadow-casting cryo-scanning electron microscopy, enabling single-particle measurements of high accuracy.


Input: theta passes through a maximum with respect to surfactant concentration.


Input: It is shown that particles undergo a hydrophilic-hydrophobic-hydrophilic transition corresponding closely to the o/w-w/o-o/w transformation observed in emulsions.


Input: These results unequivocally link the single-particle contact angles to the type of particle-stabilized emulsion, confirming macroscopic emulsion inversion on the microscopic level.


Input: Modular stitching to image single-molecule DNA transport.


Input: For study of time-dependent conformation, all previous single-molecule imaging studies of polymer transport involve fluorescence labeling uniformly along the chain, which suffers from limited resolution due to the diffraction limit.


Input: Here we demonstrate the concept of submolecular single-molecule imaging with DNA chains assembled from DNA fragments such that a chain is labeled at designated spots with covalently attached fluorescent dyes and the chain backbone with dyes of different color.


Input: High density of dyes ensures good signal-to-noise ratio to localize the designated spots in real time with nanometer precision and prevents significant photobleaching for long-time tracking purposes.


Input: To demonstrate usefulness of this approach, we image electrophoretic transport of lambda-DNA through agarose gels.


Input: The unexpected pattern is observed that one end of each molecule tends to stretch out in the electric field while the other end remains quiescent for some time before it snaps forward and the stretch-recoil cycle repeats.


Input: These features are neither predicted by prevailing theories of electrophoresis mechanism nor detectable by conventional whole-chain labeling methods, which demonstrate pragmatically the usefulness of modular stitching to reveal internal chain dynamics of single molecules.


Input: Chemoselective metal-free aerobic alcohol oxidation in lignin.


Input: An efficient organocatalytic method for chemoselective aerobic oxidation of secondary benzylic alcohols within lignin model compounds has been identified.

benzylic alcohols


Input: Extension to selective oxidation in natural lignins has also been demonstrated.


Input: The optimal catalyst system consists of 4-acetamido-TEMPO (5 mol%; TEMPO = 2, 2, 6, 6-tetramethylpiperidine-N-oxyl) in combination with HNO3 and HCl (10 mol% each).

TEMPO

2, 2, 6, 6-tetramethylpiperidine-N-oxyl

HCl


Input: Preliminary studies highlight the prospect of combining this method with a subsequent oxidation step to achieve C-C bond cleavage.

C-C


Input: Ultrafast Charge Transfer at Monolayer Graphene Surfaces with Varied Substrate Coupling.

Graphene


Input: The charge transfer rates of a localized excited electron to graphene monolayers with variable substrate coupling have been investigated by the core hole clock method with adsorbed argon.

graphene


Input: Expressed as charge transfer times, we find strong variations between ~ 3 fs (on graphene " valleys " on Ru (0001)) to ~ 16 fs (quasi-free graphene on SiC, O/Ru (0001), or SiO2/Ru).

graphene

Ru

graphene

SiC

O

Ru

Ru


Input: The values for the " hills " on Gr/Ru and on Gr/Pt (111) are in between, with the ratio 1. 7 between the charge transfer times measured on " hills " and " valleys " of Gr/Ru.

Ru

Pt (111)

Ru


Input: We discuss the results for Gr on metals in terms of hybridized Ru-C orbitals, which change with the relative Gr-Ru alignment and distance.

Ru

C

Ru


Input: The charge transfer on the decoupled graphene layers must represent the intrinsic coupling to the graphene empty pi * states.

graphene

graphene


Input: Its low rate may be influenced by processes retarding the spreading of charge after transfer.


Input: Coalescence of Repelling Colloidal Droplets: A Route to Monodisperse Populations.


Input: Populations of droplets or particles dispersed in a liquid may evolve through Brownian collisions, aggregation, and coalescence.


Input: We have found a set of conditions under which these populations evolve spontaneously toward a narrow size distribution.


Input: The experimental system consists of poly (methyl methacrylate) (PMMA) nanodroplets dispersed in a solvent (acetone) + nonsolvent (water) mixture.

poly (methyl methacrylate)

PMMA

acetone


Input: These droplets carry electrical charges, located on the ionic end groups of the macromolecules.


Input: We used time-resolved small angle X-ray scattering to determine their size distribution.


Input: We find that the droplets grow through coalescence events: the average radius < R > increases logarithmically with elapsed time while the relative width sigma R/< R > of the distribution decreases as the inverse square root of < R >.


Input: We interpret this evolution as resulting from coalescence events that are hindered by ionic repulsions between droplets.


Input: We generalize this evolution through a simulation of the Smoluchowski kinetic equation, with a kernel that takes into account the interactions between droplets.


Input: In the case of vanishing or attractive interactions, all droplet encounters lead to coalescence.


Input: The corresponding kernel leads to the well-known " self-preserving " particle distribution of the coalescence process, where sigma R/< R > increases to a plateau value.


Input: However, for droplets that interact through long-range ionic repulsions, " large + small " droplet encounters are more successful at coalescence than " large + large " encounters.


Input: We show that the corresponding kernel leads to a particular scaling of the droplet-size distribution-known as the " second-scaling law " in the theory of critical phenomena, where sigma R/< R > decreases as 1/sqrt < R > and becomes independent of the initial distribution.


Input: We argue that this scaling explains the narrow size distributions of colloidal dispersions that have been synthesized through aggregation processes.


Input: Disclosure of individual pharmacogenomic results in research projects: when and what kind of information to return to research participants.


Input: In the growing field of genomics, the utility of returning certain research results to participants has become a highly debated issue.


Input: Existing guidelines are not explicit as to the kind of genomic information that should be returned to research participants.


Input: Moreover, very few current recommendations and articles in the literature address the return of pharmacogenomic results.


Input: Although genetics and pharmacogenomics have many similarities, the circumstances in which disclosure could have a benefit for the participants are different.


Input: This review aims to describe the conditions in which disclosure of pharmacogenomic results is appropriate.


Input: Polymersomes from Dual Responsive Block Copolymers: Drug Encapsulation by Heating and Acid-Triggered Release.


Input: A series of well-defined thermoresponsive diblock copolymers (PEO45-b-PtNEAn, n = 22, 44, 63, 91, 172) were prepared by the atom transfer radical polymerization of trans-N-(2-ethoxy-1, 3-dioxan-5-yl) acrylamide (tNEA) using a poly (ethylene oxide) (PEO45) macroinitiator.

trans-N-(2-ethoxy-1, 3-dioxan-5-yl) acrylamide

tNEA

poly (ethylene oxide)


Input: All copolymers are water-soluble at low temperature, but upon quickly heating to 37 degrees C, laser light scattering (LLS) and transmission electron microscopy (TEM) characterizations indicate that these copolymers self-assemble into aggregates with different morphologies depending on the chain length of PtNEA and the polymer concentration; the morphologies gradually evolved from spherical solid nanoparticles to a polymersome as the degree of polymerization (" n ") of PtNEA block increased from 22 to 172, with the formation of clusters with rod-like structure at the intermediate PtNEA length.

PtNEA

PtNEA

PtNEA


Input: Both the spherical nanoparticle and the polymersome are stable at physiological pH but susceptible to the mildly acidic medium.


Input: Acid-triggered hydrolysis behaviors of the aggregates were investigated by LLS, Nile red fluorescence, TEM, and (1) H NMR spectroscopy.

(1) H


Input: The results revealed that the spherical nanoparticles formed from PEO45-b-PtNEA44 dissociated faster than the polymersomes of PEO45-b-PtNEA172, and both aggregates showed an enhanced hydrolysis under acidic conditions.


Input: Both the spherical nanoparticle and polymersome are able to efficiently load the hydrophobic doxorubicin (DOX), and water-soluble fluorescein isothiocyanate-lysozyme (FITC-Lys) can be conveniently encapsulated into the polymersome without using any organic solvent.

doxorubicin

DOX

fluorescein isothiocyanate

FITC


Input: Moreover, FITC-Lys and DOX could be coloaded in the polymersome.

FITC

DOX


Input: The drugs loaded either in the polymersome or in the spherical nanoparticle could be released by acid triggering.


Input: Finally, the DOX-loaded assemblies display concentration-dependent cytotoxicity to HepG2 cells, while the copolymers themselves are nontoxic.

DOX


Input: Discovery of Thieno [3, 2-d] pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3.

Thieno [3, 2-d] pyrimidine-6-carboxamides


Input: The sirtuins SIRT1, SIRT2, and SIRT3 are NAD (+) dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders.

NAD (+)


Input: Encoded library technology (ELT) was used to affinity screen a 1. 2 million heterocycle enriched library of DNA encoded small molecules, which identified pan-inhibitors of SIRT1/2/3 with nanomolar potency (e. g., 11c: IC50 = 3. 6, 2. 7, and 4. 0 nM for SIRT1, SIRT2, and SIRT3, respectively).


Input: Subsequent SAR studies to improve physiochemical properties identified the potent drug like analogues 28 and 31.


Input: Crystallographic studies of 11c, 28, and 31 bound in the SIRT3 active site revealed that the common carboxamide binds in the nicotinamide C-pocket and the aliphatic portions of the inhibitors extend through the substrate channel, explaining the observable SAR.

carboxamide

nicotinamide


Input: These pan SIRT1/2/3 inhibitors, representing a novel chemotype, are significantly more potent than currently available inhibitors, which makes them valuable tools for sirtuin research.


Input: Laccase-mediated coupling of nonpolar chains for the hydrophobization of lignocellulose.


Input: We investigate the use of laccase enzymes for coupling short nonpolar chains containing aromatic rings onto flax fibers and nanofibrillated cellulose (NFC) with different lignin contents.

lignin


Input: Trametes villosa, Pycnoporus cinnabarinus and Myceliophthora thermophila were used to facilitate surface coupling and to produce materials with different levels of hydrophobicity.


Input: Heat treatment of fiber webs after lacccase-mediated coupling markedly increased the resistance to water absorption.


Input: The highest hydrophobization levels of flax fibers was achieved by coupling dodecyl 3, 4, 5-trihydroxybenzoate (HB-C12), which yielded water contact angles (WCA) of 80-96 degrees and water absorption times (drop tests) of ca.

dodecyl 3, 4, 5-trihydroxybenzoate


Input: 73 min.


Input: The results from apparent aromatic content and FTIR analyses confirmed the laccase-mediated coupling of HB-C12 onto the cellulose fibers.


Input: Substrates consisting of ultrathin films of NFC were also used as substrates for enzyme-mediated hydrophobization with HB-C12.


Input: In these cases water contact angles in the range of 87-104 degrees were achieved, depending on the conditions.


Input: Quartz crystal microgravimetry (QCM) was used to study the dynamics and the extent of the coupling process onto cellulose.

Quartz


Input: The results help to better understand the mechanisms involved in laccase-mediated hydrophobization and provide a proof of a biotechnological platform for the development of added-value fiber products.


Input: Retention and Release of Cinnamaldehyde from Wheat Protein Matrices.

Cinnamaldehyde


Input: Cinnamaldehyde treatment of gliadin films provided a means of decreasing their solubility, increasing their molecular weight profile, and reducing their overall migration into food simulants as a consequence of the high degree of polymerization achieved.

Cinnamaldehyde


Input: Despite losses incurred in the film manufacturing process, and the amount that remained covalently bonded with protein because of cross-linking, the addition of 1. 5, 3, and 5% of cinnamaldehyde (g/100 g protein) to gliadins at pH 2 rendered 1. 8, 4. 8, and 11. 0 mg cinnamaldehyde/g film, respectively, available to be released, and therefore to exert antimicrobial activity.

cinnamaldehyde

cinnamaldehyde


Input: Cinnamaldehyde diffusivity was largely dependent on environmental conditions, increasing from 0. 49 x 10 (-15) m (2)/s at 30% relative humidity (RH) to 13. 1 x 10 (-15) m (2)/s at 90% RH and 23 degrees C.

Cinnamaldehyde


Input: This water sensitivity of films provides a mechanism with a noteworthy potential to retain the compound before its use, to trigger its release when needed, and to modulate the release rate according to the product humidity.


Input: Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors.

Urea


Input: RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC).


Input: Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease.


Input: In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents.

urea


Input: These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (~ 7 mmHg).


Input: (22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied.

urea


Input: The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed.


Input: Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.


Input: Self-Repair of a Biological Fiber Guided by an Ordered Elastic Framework.


Input: Incorporating sacrificial cross-links into polymers represents an exciting new avenue for the development of self-healing materials, but it is unclear to what extent their spatial arrangement is important for this functionality.


Input: In this respect, self-healing biological materials, such as mussel byssal threads, can provide important chemical and structural insights.


Input: In this study, we employ in situ small-angle X-ray scattering (SAXS) measurements during mechanical deformation to show that byssal threads consist of a partially crystalline protein framework capable of large reversible deformations via unfolding of tightly folded protein domains.


Input: The long-range structural order is destroyed by stretching the fiber but reappears rapidly after removal of load.


Input: Full mechanical recovery, however, proceeds more slowly, suggesting the presence of strong and slowly reversible sacrificial cross-links.


Input: One likely role of the highly ordered elastic framework is to bring sacrificial binding sites back into register upon stress release, facilitating bond reformation and self-repair.


Input: Design and evaluation of polyamidoamine dendrimer conjugate with PEG, alpha-cyclodextrin and lactose as a novel hepatocyte-selective gene carrier in vitro and in vivo.

polyamidoamine

PEG

alpha-cyclodextrin

lactose


Input: Abstract To develop a novel hepatocyte-selective gene carrier, we prepared polyamidoamine starburst dendrimer (generation 3, G3) conjugates with three functional molecules, i. e. alpha-cyclodextrin, polyethylene glycol (PEG, molecular weight = 2170) and lactose (PEG-L alpha Cs), and evaluated gene delivery efficiency of these conjugates in vitro and in vivo.

polyamidoamine

alpha-cyclodextrin

polyethylene glycol

PEG

lactose

PEG-L alpha Cs


Input: PEG-L alpha C (G3, degrees of substitution of the PEG moiety (DSP) 2. 1) showed higher gene transfer activity than other PEG-L alpha Cs (G3, DSP4. 0, 6. 2) in HepG2 cells, expressing asialoglycoprotein receptor, and the activity decreased in HeLa cells, non-expressing the receptor and in the presence of asialofetuin.

PEG-L alpha C

PEG

PEG-L alpha Cs


Input: High gene transfer activity of PEG-L alpha C (G3, DSP2. 1) was retained even in the presence of 50% serum, although the activity of alpha-cyclodextrin/lactosylated dendrimer (G3) conjugate (Lac-alpha-CDE (G3)), which is lacking a PEG moiety, was severely decreased in the presence of 20% serum.

PEG-L alpha C

alpha-cyclodextrin

Lac-alpha-CDE

PEG


Input: PEG-L alpha C (G3, DSP2. 1) provided negligible cytotoxicity up to a charge ratio of 50 (carrier/pDNA) in HepG2 cells and less acute organ toxicity.

PEG-L alpha C


Input: PEG-L alpha C (G3, DSP2. 1) showed selective gene transfer activity to hepatic parenchymal cells rather than hepatic non-parenchymal cells.

PEG-L alpha C


Input: These results suggest that PEG-L alpha C (G3, DSP2. 1) is useful as a hepatocyte-selective gene carrier in vitro and in vivo.

PEG-L alpha C


Input: New dimeric and trimeric coumarin glucosides from Daphne retusa Hemsl.

coumarin


Input: New dimeric and a trimeric coumarin glucosides namely Daphneretusin A (1) Daphneretusin B (2) along with three known oligomers (3-5) were obtained as a result of bioassay guided fractionation of Daphne retusa Hemsl.

coumarin

Daphneretusin A

Daphneretusin B


Input: Fractions (n-hexane, CHCl3, AcOEt, CH3OH and water) exhibited potent radical scavenging activity in relevant non-physiological bioassays.

n-hexane

AcOEt


Input: The structures of isolated compounds were elucidated by UV, IR, EIMS, FAB-MS, 1D, and 2D NMR spectroscopic analysis.


Input: Goniolandrene A and B from Goniothalamus macrophyllus.

Goniolandrene A and B


Input: Goniothalamus macrophyllus (Blume) Hook.


Input: f.


Input: & Thoms.


Input: is a plant widely distributed in Malaysia.


Input: The aim of this study is to identify compounds from the roots of G. macrophyllus.


Input: The ground roots were extracted with aqueous methanol and partitioned sequentially with n-hexane, chloroform and butanol.

methanol

n-hexane

chloroform

butanol


Input: Purification from this extracts afforded six compounds with two new compounds, namely goniolandrene-A (1),-B (2).

goniolandrene-A (1),-B (2)


Input: The absolute configuration of goniolandrene B (2) was established by circular dichrosim.

goniolandrene B


Input: The compounds were cytotoxic against the P388 cells with IC50 values ranging from 0. 42 to 160 mu M.


Input: Goniothalamin (3) exhibited the highest inhibition of 0. 42 mu M.

Goniothalamin


Input: Electromagnetic-pulse-induced activation of p38 MAPK pathway and disruption of blood-retinal barrier.


Input: The blood-retinal barrier (BRB) is critical for maintaining retina homeostasis and low permeability.


Input: In this study, we evaluated the effects of electromagnetic pulse (EMP) exposure on the permeability of BRB, alterations of tight junction (TJ) proteins of BRB and if any, involvement of mitogen-activated protein kinase (MAPK) pathway.


Input: Male Sprague-Dawley (SD) rats and RF/6A cells which were pretreated with or without MAPKs inhibitors were sham exposed or exposed to EMP at 200kV/m for 200 pulses.


Input: The alteration of BRB permeability was examined through fluorescence microscope and quantitatively assessed using Evans blue (EB) and endogenous albumin as tracers.


Input: The expressions of TJ proteins and some signaling molecules of MAPK pathway were measured by Western blots.


Input: The observations were that EMP exposure resulted in increased BRB permeability concurrent with the decreased expressions of occludin and claudin-5, which were correlated with the increased expressions of phospho-p38, phospho-JNK and phospho-ERK and could be blocked when pretreated with p38 MAPK inhibitor.


Input: Thus, the results suggested that the alterations of occludin and claudin-5 may play an important role in the disruption of TJs, which may lead to the transient breakdown of BRB after EMP exposure with the involvement of p38 MAPK pathway through phosphorylation of signaling molecules.


Input: Suppression of nuclear factor erythroid 2-related factor 2 via extracellular signal-regulated kinase contributes to bleomycin-induced oxidative stress and fibrogenesis.

bleomycin


Input: Pulmonary fibrosis is a serious and irreversible lung injury with obscure etiologic mechanisms and no effective treatment to date.


Input: This study explored a crucial link between oxidative stress and pulmonary fibrogenesis, focusing on nuclear factor erythroid 2-related factor 2 (Nrf2), a core transcription factor in antioxidative regulation systems.


Input: Treatment of C57 BL/6 mice with bleomycin increased fibroblast viability and collagen production and significantly downregulated Nrf2.

bleomycin


Input: In addition, prominent oxidative stress was indicated by changes in superoxide dismutase, catalase activity, and glutathione and thiobarbituric acid-reactive substance levels.

superoxide

glutathione

thiobarbituric acid


Input: In a cell-based model, bleomycin suppressed Nrf2 activation via extracellular signal-related kinase phosphorylation, enhancing intracellular reactive oxygen species in lung fibroblasts and stimulating abnormal cell proliferation and collagen secretion.

bleomycin

oxygen


Input: To confirm this novel mechanism of bleomycin-induced fibrogenesis, we attempted to upregulate Nrf2 and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance.

bleomycin

caffeic acid phenethyl ester

bleomycin


Input: Collectively, these results disclose a potential regulatory mechanism in pulmonary fibrosis that will aid the development of new therapies.


Input: Proteomic Analysis of Arsenic-Exposed Zebrafish (Danio rerio) Identifies Altered Expression in Proteins Involved in Fibrosis and Lipid Uptake in a Gender-Specific Manner.

Arsenic


Input: The zebrafish (Danio rerio) was used to investigate protein expression in the liver following arsenic exposure.

arsenic


Input: Several disorders have been linked to arsenic exposure, including cancer, diabetes, and cardiovascular disease.

arsenic


Input: The mechanisms of arsenic toxicity are poorly understood.

arsenic


Input: Prior studies have described altered gene expression, inflammation, and mitogenic signaling in acute or chronic exposure models.


Input: A proteomic approach was employed to investigate arsenic-induced alteration in the zebrafish liver proteome following a 7-day exposure to 50 ppb sodium arsenite.

arsenic

sodium arsenite


Input: Over 740 unique proteins were identified, with fewer than 2% showing differential expression.


Input: Molecular pathway analysis software identified lipid metabolism and transport as potential molecular targets.


Input: Immunoblots were used to confirm protein expression changes, whereas qPCR was employed to investigate gene expression changes.


Input: Overall, 25 proteins were differentially expressed in a gender-specific manner, 11 in males and 14 in females.


Input: Of these 25, a single protein, hydroxysteroid dehydrogenase like 2, showed decreased expression in both males and females following arsenic exposure.

hydroxysteroid

arsenic


Input: These findings indicate that protein expression is altered following arsenic exposure.

arsenic


Input: The changes presented here seem to be most prevalent in lipid transport and metabolic pathways, suggesting a potential increase in fibrosis in males and decreased lipid accumulation and uptake in females.


Input: Additional Histopathologic Examination of the Lungs from a 3-Month Inhalation Toxicity Study with Multiwall Carbon Nanotubes in Rats.

Carbon


Input: For hazard assessment of multiwalled carbon nanotubes (MWCNTs), a 90-day inhalation toxicity study has been performed with Nanocyl NC 7000 in accordance with OECD 413 test guideline.

carbon


Input: MWCNTs produced no systemic toxicity.


Input: However, increased lung weights, multifocal granulomatous inflammation, diffuse histiocytic and neutrophilic infiltrates, and intra-alveolar lipoproteinosis were observed in lung and lung-associated lymph nodes at 0. 5 and 2. 5mg/m (3).


Input: Additional investigations of the lungs were performed, including special stains for examination of connective tissue, and electron microscopy was performed to determine the location of the MWCNTs.


Input: The alveolar walls revealed no increase of collagen fibers, whereas within the microgranulomas a slight increase of collagen fibers was observed.


Input: The pleura did not reveal any increase in collagen fibers.


Input: Only a slight increase in reticulin fibers in the alveolar walls in animals of the 0. 5 and 2. 5mg/m (3) concentration group was noted.


Input: In the 0. 1mg/m (3) group, the only animal revealing minimal granulomas exhibited a minimal increase in collagen within the granuloma.


Input: No increase in reticulin was observed.


Input: Electron microscopy demonstrated entangled MWCNTs within alveolar macrophages.


Input: Occasionally electron dense particles/detritus were observed within membrane-bound vesicles (interpreted as phagosomes), which could represent degraded MWCNTs.


Input: If so, MWCNTs were degradable by alveolar macrophages and not persistent within the lung.


Input: Inhalation of MWCNTs caused granulomatous inflammation within the lung parenchyma but not the pleura in any of the concentration groups.


Input: Thus, there are some similarities to effects caused by inhaled asbestos, but the hallmark effects, namely pleural inflammation and/or fibrosis leading to mesotheliomas, are absent.


Input: Assessment of the role of flavonoids for inducing osteoblast differentiation in isolated mouse bone marrow derived mesenchymal stem cells.

flavonoids


Input: Quercetin and rutin are common flavonoids in fruit and vegetables, and have been reported to affect bone development.

Quercetin

rutin

flavonoids


Input: However, the effect of flavonoids on osteoblast differentiation remains a matter of controversy.

flavonoids


Input: In the present study, mouse bone marrow mesenchymal stem cells (BMMSCs) were isolated and characterized for their use in osteoblast differentiation using two flavonoids, quercetin and rutin.

flavonoids

quercetin

rutin


Input: BMMSCs were cultured in various concentrations of quercetin and rutin during the osteoblast differentiation period of 10 days.

quercetin

rutin


Input: Both quercetin and rutin were found to up regulate the osteoblast differentiation in dose dependent manner, albeit to lesser extent in case of former than that of latter.

quercetin

rutin


Input: Quercetin and rutin also increased alkaline phosphatase activity by about 150 and 240% and demonstrated mineralization up to 110 and 200% respectively as compared to control (which was considered as 100%).

Quercetin

rutin


Input: Further, both the flavonoids were also found to increase the expression of some of the prominent markers for differentiation of osteoblast like osteopontin, osterix, RunX2, osteoprotegerin and osteocalcin.

flavonoids


Input: The current data suggests that certain classes of flavonoids like rutin and quercetin can be used in the cure and management of osteodegenerative disorders due to their osteoblast specific differentiation activities.

flavonoids

rutin

quercetin


Input: Quantification of the Young' s modulus of the primary plant cell wall using Bending-Lab-On-Chip (BLOC).


Input: Biomechanical and mathematical modeling of plant developmental processes requires quantitative information about the structural and mechanical properties of living cells, tissues and cellular components.


Input: A crucial mechanical property of plant cells is the mechanical stiffness or Young' s modulus of its cell wall.


Input: Measuring this property in situ at single cell wall level is technically challenging.


Input: Here, a bending test is implemented in a chip, called Bending-Lab-On-a-Chip (BLOC), to quantify this biomechanical property for a widely investigated cellular model system, the pollen tube.


Input: Pollen along with culture medium is introduced into a microfluidic chip and the growing pollen tube is exposed to a bending force created through fluid loading.


Input: The flexural rigidity of the pollen tube and the Young' s modulus of the cell wall are estimated through finite element modeling of the observed fluid-structure interaction.


Input: An average value of 350 MPa was experimentally estimated for the Young' s modulus in longitudinal direction of the cell wall of Camellia pollen tubes.


Input: This value is in agreement with the result of an independent method based on cellular shrinkage after plasmolysis and with the mechanical properties of in vitro reconstituted cellulose-callose material.


Input: Therapeutic Cleavage of Anti-Aquaporin-4 Autoantibody in Neuromyelitis Optica by an Igg-Selective Proteinase.


Input: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system caused by binding of pathogenic IgG autoantibodies (NMO-IgG) to astrocyte water channel aquaporin-4 (AQP4).


Input: Astrocyte damage and downstream inflammation require NMO-IgG effector function to initiate complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC).


Input: Here, we evaluated the potential therapeutic utility of the bacterial enzyme IdeS (IgG-degrading enzyme of Streptococcus pyogenes), which selectively cleaves IgG antibodies to yield Fc and F (ab') 2 fragments.


Input: In AQP4-expressing cell cultures, IdeS treatment of monoclonal NMO-IgGs and NMO patient sera abolished CDC and ADCC, even when IdeS was added after NMO-IgG was bound to AQP4.


Input: Binding of NMO-IgG to AQP4 was similar to that of the NMO-F (ab') 2 generated by IdeS cleavage.


Input: NMO-F (ab') 2 competitively displaced pathogenic NMO-IgG, preventing cytotoxicity, and the Fc fragments generated by IdeS cleavage reduced CDC and ADCC.


Input: IdeS efficiently cleaved NMO-IgG in mice in vivo, and greatly reduced NMO lesions in mice administered NMO-IgG and human complement.


Input: IgG-selective cleavage by IdeS thus neutralizes NMO-IgG pathogenicity, and yields therapeutic F (ab') 2 and Fc fragments.


Input: IdeS treatment, by therapeutic apheresis or direct administration, may be beneficial in NMO.


Input: Structure-based Identification of OATP1B1/3 Inhibitors.


Input: Several recent studies show that inhibition of the hepatic transport proteins organic-anion transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI).


Input: To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process.


Input: In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily.


Input: A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1 or 1B3-transfected CHO cells.

sodium fluorescein


Input: At an equimolar substrate-inhibitor concentration of 10 mu M, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (min 50% inhibition).


Input: For 69 compounds, previously not identified as OATP1B inhibitors, concentration dependent inhibition was also determined, yielding Ki values ranging from 0. 06 to 6. 5 mu M.


Input: Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%).


Input: Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified.


Input: Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset.


Input: This validation indicated that 80% and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.


Input: Pomalidomide: first global approval.

Pomalidomide


Input: Pomalidomide (Pomalyst ((R))) is a small molecule analogue of thalidomide under development with Celgene Corporation for the oral treatment of haematological and connective tissue diseases.

Pomalidomide

Pomalyst

thalidomide


Input: Pomalidomide has been approved in the USA and is awaiting approval in the EU for use with low-dose dexamethasone for the treatment of relapsed and refractory multiple myeloma that has progressed following at least two prior therapies, including lenalidomide and bortezomib.

Pomalidomide

dexamethasone

lenalidomide

bortezomib


Input: The efficacy and safety of pomalidomide as monotherapy in patients with relapsed and refractory multiple myeloma has also been evaluated in a phase III trial.

pomalidomide


Input: The agent is in phase III clinical development for the treatment of myelofibrosis and in phase II development for systemic sclerosis.


Input: Pomalidomide is also being investigated in patients with amyloidosis, prostate cancer, small cell lung cancer, pancreatic cancer, graft-versus-host disease, and Waldenstrom' s macroglobulinaemia.

Pomalidomide


Input: This article summarizes the milestones in the development of pomalidomide leading to this first global approval for relapsed and refractory multiple myeloma.

pomalidomide


Input: S-nitrosation of glutathione transferase P1-1 is controlled by the conformation of a dynamic active-site helix.

S

glutathione


Input: S-nitrosation is a post-translational modification of protein cysteine residues which occurs in response to cellular oxidative stress.

S

cysteine


Input: Although it is increasingly being linked to physiologically important processes, the molecular basis for protein regulation by this modification remains poorly understood.


Input: We used transient kinetic methods to determine a minimal mechanism for spontaneous GSNO-mediated transnitrosation of human glutathione transferase (GST) P1-1, a major detoxification enzyme and key regulator of cell proliferation.

glutathione


Input: C47 of GSTP1-1 is S-nitrosated in two steps, with the chemical step limited by a pre-equilibrium between the open and closed conformations of helix alpha 2 at the active site.


Input: C101, in contrast, is S-nitrosated in a single step but is subject to negative cooperativity due to steric hindrance at the dimer interface.

S


Input: Despite the presence of a GSNO binding site at the active site of GSTP1-1, isothermal titration calorimetry as well as nitrosation experiments using CysNO demonstrate that GSNO binding does not precede S-nitrosation of GSTP1-1.

CysNO


Input: Kinetics experiments using the cellular reductant GSH show that C101-NO is substantially more resistant to denitrosation than C47-NO, suggesting a potential role for C101-NO in long term nitric oxide storage or transfer.

GSH

NO

NO

NO

nitric oxide


Input: These results constitute the first report of the molecular mechanism of spontaneous protein transnitrosation, providing insight into the post-translational control of GSTP1-1 as well as the process of protein transnitrosation in general.


Input: HCV NS5A Replication Complex Inhibitors.


Input: Part 4.


Input: (1) Optimization for Genotype 1a Replicon Inhibitory Activity.


Input: A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and genotype 1b (G-1b) replicon inhibition and selectivity against BVDV and cytotoxicity.

E-stilbene prolinamides


Input: SAR emerging from an examination of the prolinamide cap region revealed 11 to be a selective HCV NS5A inhibitor exhibiting submicromolar potency against both G-1a and G-1b replicons.

prolinamide


Input: Additional structural refinements resulted in the identification of 30 as a potent, dual G-1a/1b HCV NS5A inhibitor.


Input: Tailoring of morphology and surface properties of syndiotactic polystyrene aerogels.

syndiotactic polystyrene


Input: This study evaluates a method for rendering syndiotactic polystyrene (sPS) aerogels hydrophilic using polyethylene oxide (PEO) of different molecular weights.

syndiotactic polystyrene

sPS

polyethylene oxide

PEO


Input: The highly porous sPS aerogels are inherently hydrophobic although applications involving absorption of moisture and removal of particulate solids may benefit from the high surface area of sPS aerogels provided some degree of hydrophilicity is induced in these materials.

sPS

sPS


Input: In this work, sPS gels are prepared by thermo-reversible gelation in tetrahydrofuran in the presence of PEO.

sPS

tetrahydrofuran

PEO


Input: The gels are dried under supercritical conditions to obtain aerogels.


Input: The aerogels are characterized by scanning electron microscopy, nitrogen-adsorption porosimetry, helium pycnometry, and contact angle measurements.

nitrogen

helium


Input: The data reveal that the pore structures and surface energy can be controlled by varying the concentration and molecular weight of PEO and using different cooling rates during thermo-reversible gelation.

PEO


Input: In the first case, sPS aerogels, aerogels containing PEO of a low molecular weight or low concentration show superhydrophobic surface presenting the " lotus effect ".

sPS

PEO


Input: In the second case, PEO at a higher concentration or with higher molecular weight forms phase-separated domains yielding new hydrophilic macropores (> 10 mu m) in the aerogel structures.

PEO


Input: These macropores contribute to the superhydrophobic surface with the " petal effect ".


Input: The cooling rate during gelation shows a strong influence on these two cases.


Input: Photorheological Response of Aqueous Wormlike Micelles with Photocleavable Surfactant.


Input: Recently, we have reported a new cinnamic acid-type photocleavable surfactant, C4-C-N-PEG9 that experiences a photocleavage through UV-induced cyclization in aqueous solution, yielding a coumarin derivative (7-butoxy-2H-chromen-2-one) and an aminated polyoxyethylene compound.

cinnamic acid

coumarin

polyoxyethylene


Input: Here, we have studied the effects of C4-C-N-PEG9 on the photorheological behavior of viscoelastic wormlike micelles formed by aqueous mixture of nonionic surfactants, polyoxyethylene phytosterol ether (PhyEO20) and tetraoxyethylene dodecyl ether (C12EO4).

polyoxyethylene phytosterol ether

tetraoxyethylene dodecyl ether


Input: The 4. 9 wt% PhyEO20/H2O + 2. 4 wt% C12EO4 solution forms wormlike micelles, and its viscosity is ~ 10 Pa. s.


Input: We have found that the addition of C4-C-N-PEG9 into this viscous, non-Newtonian fluid system decreases the viscosity.


Input: Viscosity decreased in parallel to the C4-C-N-PEG9 concentration reaching ~ 0. 003 Pa. s at 2. 5 wt% of C4-C-N-PEG9.


Input: However, viscosity of the C4-C-N-PEG9 incorporated system increased significantly (~ 200 times at 1. 5 wt% of C4-C-N-PEG9 system) upon UV irradiation.


Input: Small-Angle X-ray scattering studies have shown that addition of C4-C-N-PEG9 favors wormlike-to-sphere type transition in the micellar structure.


Input: However, UV irradiation in the C4-C-N-PEG9 incorporated system causes one-dimensional micellar growth.


Input: Since C4-C-N-PEG9 has relatively bigger headgroup size compared to the C12EO4, addition of C4-C-N-PEG9 into wormlike micelles reduces the critical packing parameter resulting in the formation of spherical aggregates.


Input: UV irradiation induced one-dimensional micellar growth is caused due to photocleavage of the C4-C-N-PEG9 into a less surface-active coumarin derivative and an aminated polyoxyethylene compound, as confirmed by UV-vis spectrometry and HPLC measurements.

coumarin

polyoxyethylene


Input: The hydrophobic coumarin derivative formed after cleavage of C4-C-N-PEG9 goes to the micellar core and is responsible for decreasing the viscosity.

coumarin


Input: However, the hydrophilic aminated polyoxyethylene prefers to reside at the vicinity of headgroup of PhyEO20 reducing the interhead repulsion, increasing the critical packing parameter and the viscosity as well.

polyoxyethylene


Input: Dual-Purpose Polymer Labels for Fluorescent and Mass Cytometric Affinity Bioassays.


Input: We describe the synthesis and characterization of a family of poly (N-alkylacrylamide) polymers carrying 2-6 fluorescent dye molecules, ~ 70 pendant DTPA (diethylenetriaminepentaacetic acid) groups, and an orthogonal maleimide end-group for covalent attachment to an antibody (Ab).

poly (N-alkylacrylamide)

DTPA

diethylenetriaminepentaacetic acid

maleimide


Input: These dual-purpose labels were designed for use in multiplexed immunoassays based on both mass cytometry and fluorescent flow cytometry.


Input: A challenge in the polymer synthesis was finding conditions for attaching a sufficient number of dye molecules to each polymer chain.


Input: Although attachment of a terminal maleimide to the polymers was not as efficient as anticipated, the end-functional polymers were still effective in labeling Abs.

maleimide


Input: Secondary goat antimouse IgG was labeled with the four dual-label polymers as well as a control polymer, and while the resultant antibody-polymer conjugates showed positive performance in mass cytometric and fluorescent assays, some trials showed problems such as low signal and nonspecific adsorption.


Input: Four primary antibody conjugates were prepared and used to stain cells in 4-plex assays.


Input: The results of both primary assays are bittersweet in that the CD3-FITC and CD45-DyLight 649 conjugates performed well, while the CD13-DyLight 405 and the CD38-DyLight 549 conjugates did not.


Input: A Facile Integration of Zero-(I-III-VI Quantum Dots) and One-(Single SnO2 Nanowire) Dimensional Nanomaterials: Fabrication of a Nanocomposite Photodetector with Ultrahigh Gain and Wide Spectral Response.


Input: Via the integration of nanocomposites comprising I-III-VI semiconductor quantum dots (QDs) decorated onto a single SnO2 nanowire (NW), we successfully fabricate an ultrahigh-sensitivity and wide spectral-response photodetector.


Input: Under the illumination of He-Cd laser (325 nm) with the photon energy larger than the band gap of SnO2 nanowire, remarkably, an ultrahigh photocurrent gain up to 2. 5 x 10 (5) has been achieved, and an enhancement factor can reach up to 700% (cf. bare SnO2 NW) as light illumination onto the wire with an excitation intensity of 15 W/m (2).

He

Cd


Input: Also, a high gain value up to 1. 3 x 10 (5) is attained with the excited photon energy (488 nm) smaller than the band gap of SnO2 nanowire.


Input: Several key factors contribute to ultrahigh photocurrent gain and wide spectral response.


Input: First, the decorated quantum dot processes an inherent nature of a large absorption coefficient above its band gap.


Input: Furthermore, the single SnO2 nanowire provides an excellent conduction path for the photogenerated carriers as well as bears a large surface-to-volume ratio so that the coupling strength with quantum dots can be greatly enhanced.


Input: Most importantly, the spatial separation of photogenerated electrons and holes can be easily achieved due to the charge transfer arising from a type II band alignment between QDs and SnO2 NW.


Input: This work thus demonstrates a new approach in which by selectively decorating suitable QDs the photocurrent gain of SnO2 NWs can be greatly enhanced and extended to a wide spectral range of photoresponse previously inaccessible, providing a very useful guideline to create cheap, nontoxic, and highly efficient photodetectors.


Input: Antinociceptive Activity of Stephanolepis hispidus Skin Aqueous Extract Depends Partly on Opioid System Activation.


Input: Stephanolepis hispidus is one of the most common filefish species in Brazil.


Input: Its skin is traditionally used as a complementary treatment for inflammatory disorders.


Input: However, there are very few studies on chemical and pharmacological properties using the skin of this fish.


Input: This study was undertaken in order to investigate the effect of aqueous crude extract of S. hispidus skin (SAE) in different nociception models.


Input: Here, we report that intraperitoneal administration of SAE inhibited the abdominal constrictions induced by acetic acid in mice.

acetic acid


Input: In addition to the effect seen in the abdominal constriction model, SAE was also able to inhibit the hyperalgesia induced by carrageenan and prostaglandin E2 (PGE2) in mice.

prostaglandin E2


Input: This potent antinociceptive effect was observed in the hot plate model too, but not in tail-flick test.


Input: Naloxone, an opioid receptor antagonist, was able to block the antinociceptive effect of SAE in the abdominal constriction and hot plate models.

Naloxone


Input: In addition, SAE did not present cytotoxic or genotoxic effect in human peripheral blood cells.


Input: Our results suggest that aqueous crude extract from S. hispidus skin has antinociceptive activity in close relationship with the partial activation of opioid receptors in the nervous system.


Input: Moreover, aqueous crude extract from S. hispidus skin does not present toxicity and is therefore endowed with the potential for pharmacological control of pain.


Input: Solution processed zinc oxide nanopyramid/silver nanowire transparent network films with highly tunable light scattering properties.

zinc oxide

silver


Input: Metal nanowire transparent networks are promising replacements to indium tin oxide (ITO) transparent electrodes for optoelectronic devices.

indium tin oxide

ITO


Input: While the transparency and sheet resistance are key metrics for transparent electrode performance, independent control of the film light scattering properties is important to developing multifunctional electrodes for improved photovoltaic absorption.


Input: Here we show that controlled incorporation of ZnO nanopyramids into a metal nanowire network film affords independent, highly tunable control of the scattering properties (haze) with minimal effects on the transparency and sheet resistance.

ZnO


Input: Varying the zinc oxide/silver nanostructure ratios prior to spray deposition results in sheet resistances, transmission (600 nm), and haze (600 nm) of 6-30 Omega * (-1), 68-86%, and 34-66%, respectively.

zinc oxide

silver


Input: Incorporation of zinc oxide nanopyramid scattering agents into the conducting nanowire mesh has a negligible effect on mesh connectivity, providing a straightforward method of controlling electrode scattering properties.

zinc oxide


Input: The decoupling of the film scattering power and electrical characteristics makes these films promising candidates for highly scattering transparent electrodes in optoelectronic devices and can be generalized to other metal nanowire films as well as carbon nanotube transparent electrodes.

carbon


Input: Sarmentosumols A to F, New Mono-and Dimeric Alkenylphenols from Piper sarmentosum.

Sarmentosumols A to F

Mono-and Dimeric Alkenylphenols


Input: Two new mono-and four new dimeric alkenylphenols, namely sarmentosumols A to F (1-6), were isolated from the aerial parts of Piper sarmentosum.

dimeric alkenylphenols

sarmentosumols A to F


Input: The structures of these compounds were determined through a detailed analysis of NMR and MS data.


Input: Their antimicrobial activity against Escherichia coli, Staphyloccocus aureus, and Candida albicans, and their cytotoxic activity against human myeloid leukemia (K562) and human lung adenocarcinoma (A549) cell lines were also evaluated.


Input: Except for sarmentosumol A (1), whose MIC on S. aureus was reported to be 7. 0 micro g/mL, none of the other newly discovered compounds exhibited antimicrobial property.

sarmentosumol A


Input: The studied compounds did not possess any cytotoxic property.


Input: In Vitro and In Vivo Enzyme-Mediated Biomineralization of Oligo (poly (ethylene glycol) Fumarate Hydrogels.

Oligo (poly (ethylene glycol) Fumarate


Input: The enzyme alkaline phosphatase (ALP) is added at different concentrations (i. e., 0, 2. 5, and 10 mg. ml (-1)) to oligo (poly (ethylene glycol) fumarate) (OPF) hydrogels.

oligo (poly (ethylene glycol) fumarate)

OPF


Input: The scaffolds are either incubated in 10 mM calcium glycerophosphate (Ca-GP) solution for 2 weeks or implanted in a rat subcutaneous model for 4 weeks.

calcium glycerophosphate

Ca-GP


Input: Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and alizarin red staining show a strong ability to form minerals exclusively in ALP-containing hydrogels in vitro.

alizarin red


Input: Additionally, the calcium content increases with increasing ALP concentration.

calcium


Input: Similarly, only ALP-containing hydrogels induce mineralization in vivo.


Input: Specifically, small (=~ 5-20 micro m) mineral deposits are observed at the periphery of the hydrogels near the dermis/scaffold interface using Von Kossa and alizarin red staining.

alizarin red


Input: " Raisin Bun "-Like Nanocomposites of Palladium Clusters and Porphyrin for Superior Formic Acid Oxidation.

Palladium

Porphyrin

Formic Acid


Input: A novel " raisin bun "-like nanocomposite, where Pd clusters are embedded in porphyrin matrix, is developed as a promising electrocatalyst.

Pd

porphyrin


Input: Thanks to the synergy between the Pd clusters and the porphyrin matrix, this composite exhibits a low oxidation potential, high mass activity and excellent stability toward electrochemical oxidation of formic acid, which opens new routes for the design of high-performance catalysts in fuel cells.

Pd

porphyrin

formic acid


Input: Carboxylate-Assisted Formation of Alkylcarbonate Species from CO2 and Tetramethylammonium Salts with a beta-Amino Acid Anion.

Carboxylate

Alkylcarbonate

Tetramethylammonium

beta-Amino Acid


Input: Tetramethylammonium-based molten salts bearing a beta-amino acid anion (TMAAs) are synthesized through Michael addition reactions of amines with methyl acrylate followed by hydrolysis and subsequent neutralization by using aqueous tetramethylammonium hydroxide.

Tetramethylammonium

beta-amino acid

amines

methyl acrylate

tetramethylammonium hydroxide


Input: The CO2 capture performances of the TMAAs are evaluated and are shown to interact with CO2 in a 1: 1 mode in both water and alcohol.

alcohol


Input: FTIR and (13) C NMR spectroscopic studies on the interactions of TMAAs with CO2 indicate that the type of CO2 adduct varies with the solvent used.

(13) C


Input: When water is used as the solvent, a bicarbonate species is produced, whereas hydroxyethylcarbonate and methylcarbonate species are generated in ethylene glycol and methanol, respectively.

bicarbonate

hydroxyethylcarbonate

methylcarbonate

ethylene glycol

methanol


Input: Computational calculations show that the carboxylate groups of TMAAs contribute towards the formation and stabilization of 1: 1 CO2 adducts through hydrogen bonding interactions with the hydrogen atoms of the amino groups.

carboxylate

hydrogen

hydrogen

amino


Input: Synthesis and evaluation of biphenyl compounds as Kinesin spindle protein inhibitors.

biphenyl


Input: Kinesin spindle protein (KSP), an ATP-dependent motor protein, plays an essential role in bipolar spindle formation during the mitotic phase (M phase) of the normal cell cycle.

ATP


Input: KSP has emerged as a novel target for antimitotic anticancer drug development.


Input: In this work, we synthesized a range of new biphenyl compounds and investigated their properties in vitro as potential antimitotic agents targeting KSP expression.

biphenyl


Input: Antiproliferation (MTT (= 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide)) assays, combined with fluorescence-assisted cell sorting (FACS) and Western blot studies analyzing cell-cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines.

MTT

3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide

biphenyl


Input: Structural variants revealed that functionalization of biphenyl compounds with bulky aliphatic or aromatic groups led to a loss of activity.

biphenyl


Input: However, replacement of the urea group with a thiourea led to an increase in antiproliferative activity in selected cell lines.

urea


Input: Further studies using confocal fluorescence microscopy confirmed that the most potent biphenyl derivative identified thus far, compound 7, exerts its pharmacologic effect specifically in the M phase and induces monoaster formation.

biphenyl


Input: These studies confirm that chemical scope remains for improving the potency and treatment efficacy of antimitotic KSP inhibition in this class of biphenyl compounds.

biphenyl


Input: Tirucallane Triterpenoids from the Stems of Brucea mollis.

Tirucallane Triterpenoids


Input: Three new tirucallane triterpenoids, brumollisols A-C (1-3, resp.), together with five known analogues, (23R, 24S)-23, 24, 25-trihydroxytirucall-7-ene-3, 6-dione (4), piscidinol A (5), 24-epipiscidinol A (6), 21 alpha-methylmelianodiol (7), and 21 beta-methylmelianodiol (8), were isolated from an EtOH extract of the stems of Brucea mollis.

tirucallane triterpenoids

brumollisols A-C

(23R, 24S)-23, 24, 25-trihydroxytirucall-7-ene-3, 6-dione

piscidinol A

24-epipiscidinol A

21 alpha-methylmelianodiol

21 beta-methylmelianodiol

EtOH


Input: Their structures were elucidated by means of spectroscopic methods including 1D-and 2D-NMR techniques and mass spectrometry.


Input: In the in vitro assays, compound 6 exhibited significant cytotoxic activity against A549 and BGC-823 cancer cells with IC50 values of 1. 16 and 3. 01 mu M, respectively.


Input: At a concentration of 10 mu M, compounds 1-5, 7, and 8 were found to inhibit NO production in mouse peritoneal macrophages with inhibitory ratios ranging from 39. 8 +/- 7. 7 to 68. 2 +/- 4. 5%.

NO


Input: Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug-Resistant Bacteria.

Demethylvancomycin


Input: Five novel N-substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure-based approach.

demethylvancomycin


Input: The in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), gentamicin-resistant Enterococcus faecalis (GRE), methicillin-resistant Streptococcus pneumoniae (MRS), and vancomycin-resistant Enterococcus faecalis (VRE) were evaluated.

methicillin

gentamicin

methicillin

vancomycin


Input: One of the compounds, N-(6-phenylheptyl) demethylvancomycin (12 a), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin.

N-(6-phenylheptyl) demethylvancomycin

vancomycin

demethylvancomycin


Input: Compound 12 a was also found to be ~ 18-fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS.

vancomycin


Input: Furthermore, compound 12 a exhibited a favorable pharmacokinetic profile with a half-life of 5. 11 +/- 0. 52 h, which is longer than that of vancomycin (4. 3 +/- 1. 9 h).

vancomycin


Input: These results suggest that 12 a is a promising antibacterial drug candidate for further preclinical evaluation.


Input: Microrheology of highly crosslinked microtubule networks is dominated by force-induced crosslinker unbinding.


Input: We determine the time-and force-dependent viscoelastic responses of reconstituted networks of microtubules that have been strongly crosslinked by biotin-streptavidin bonds.

biotin


Input: To measure the microscale viscoelasticity of such networks, we use a magnetic tweezers device to apply localized forces.


Input: At short time scales, the networks respond nonlinearly to applied force, with stiffening at small forces, followed by a reduction in the stiffening response at high forces, which we attribute to the force-induced unbinding of crosslinks.


Input: At long time scales, force-induced bond unbinding leads to local network rearrangement and significant bead creep.


Input: Interestingly, the network retains its elastic modulus even under conditions of significant plastic flow, suggesting that crosslinker breakage is balanced by the formation of new bonds.


Input: To better understand this effect, we developed a finite element model of such a stiff filament network with labile crosslinkers obeying force-dependent Bell model unbinding dynamics.


Input: The coexistence of dissipation, due to bond breakage, and the elastic recovery of the network is possible because each filament has many crosslinkers.


Input: Recovery can occur as long as a sufficient number of the original crosslinkers are preserved under the loading period.


Input: When these remaining original crosslinkers are broken, plastic flow results.


Input: Flexibly timed once-daily dosing with degludec: a new ultra-long-acting basal insulin.


Input: Insulin treatment in type 1 and type 2 diabetes (T1D and T2D) is highly efficacious, but in practice, non-adherence and ineffective dose titration limit its effectiveness.


Input: Barriers to more effective insulin treatment are numerous, including hypoglycaemia, fear of hypoglycaemia and concern about weight gain.


Input: The regular treatment timing needed with conventional basal insulins [neutral protamine Hagedorn (NPH) insulin and the first-generation analogues glargine and detemir] may also make adherence to these treatments problematic for many patients.


Input: Indeed, surveys indicate that the rigidity of this schedule induces some patients with T1D and T2D to omit insulin doses.


Input: Degludec is a novel, ultra-long-acting basal insulin analogue that is as effective as insulin glargine, but significantly reduces patients' risk of nocturnal hypoglycaemia.


Input: Because of its peakless, extended and highly predictable glucose-lowering effect, once-daily dosing on a flexible schedule may be feasible with degludec.

glucose


Input: Studies testing this possibility suggest that degludec tolerates day-to-day variation in dose timing while maintaining full efficacy and low risk of nocturnal hypoglycaemia.


Input: Degludec would appear to be an appropriate choice for patients being considered for a basal analogue, and it may be particularly well suited to patients with unpredictable social or work schedules, those who travel frequently and those who find rigid scheduling of their insulin injections a burden or barrier to regular treatment.


Input: New dipyranocoumarin from the leaves of Calophyllum apetalum Willd.

dipyranocoumarin


Input: A new dipyranocoumarin, alpha-hydroxytomentolide A (1) was isolated from the leaves of Calophyllum apetalum together with the known compounds friedelin (2), apetalactone (3), inophyllum C (4) and canophyllol (5).

dipyranocoumarin

alpha-hydroxytomentolide A

friedelin

apetalactone

inophyllum C

canophyllol


Input: The structure of the new compound was established by spectroscopic studies which include (1) H NMR, (13) C NMR, NOESY, HetCOSY, COLOC experiments and single crystal X-ray diffraction analysis.

(1) H

(13) C


Input: In vitro antimicrobial activity of 20 selected climber species from the Bignoniaceae family.


Input: Hydroalcoholic and aqueous extracts of some climber species from the Bignoniaceae family that grow in the north of Argentina were evaluated for in vitro antibacterial activity against Gram-positive and Gram-negative strains.


Input: By means of bioautography and disc diffusion methods, it could be determined that all infusions were not active, whereas the hydroalcoholic extracts of seven species were able to inhibit bacterial growth.


Input: The minimum inhibitory concentration and minimum bactericidal concentration observed were between 62. 5 and 1000 mu g gallic acid equivalent (GAE)/mL and between 125 and 1000 mu g GAE/mL, respectively.

gallic acid


Input: The tested extracts were more active against Gram-positive microorganisms.


Input: Time-kill experiments indicated that all extracts have bacteriostatic activity.


Input: Phytochemical screening showed the presence of terpenoids, phenols and flavonoids.

terpenoids

phenols

flavonoids


Input: The amount of phenolic compounds and flavonoids was higher in tinctures when compared with infusions.

phenolic

flavonoids


Input: These results suggest the presence of antibacterial substances in the hydroalcoholic extracts, which could be used for the treatment of infections.


Input: The potential role of T cell migration and chemotaxis as targets of glucocorticoids in multiple sclerosis and experimental autoimmune encephalomyelitis.


Input: Glucocorticoids (GCs) are the most commonly prescribed drugs for the treatment of acute disease bouts in multiple sclerosis (MS) patients.


Input: While T lymphocytes were shown to be essential targets of GC therapy, at least in animal models of MS, the mechanisms by which GCs modulate T cell function are less clear.


Input: Until now, apoptosis induction and repression of pro-inflammatory cytokines in T cells have been considered the most critical mechanisms in ameliorating disease symptoms.


Input: However, this notion is being challenged by increasing evidence that the control of T cell migration and chemotaxis by GCs might be even more important for the treatment of neuroinflammatory diseases.


Input: In this review we aim to provide an overview of how GCs impact the morphological alterations that T cells undergo during activation and migration as well as the influences that GCs have on the directed movement of T cells under the influence of chemokines.


Input: A deeper understanding of these processes should not only help to advance our understanding of how GCs exert their beneficial effects in MS therapy but may reveal future strategies to intervene in the pathogenesis of neuroinflammatory diseases.


Input: Significance of the transient receptor potential canonical 2 (TRPC2) channel in the regulation of rat thyroid FRTL-5 cell proliferation, migration, adhesion and invasion.


Input: Mammalian transient receptor potential (TRP) channels are involved in many physiologically important processes.


Input: Here, we have studied the significance of the TRPC2 channel in the regulation of rat thyroid FRTL-5 cell proliferation, migration, adhesion and invasion, using stable TRPC2 (shTRPC2) knock-down cells.


Input: In the shTRPC2 cells, proliferation was decreased due to a prolonged G1/S cell cycle phase.


Input: The tumor suppressor p53 and the cyclin-dependant kinase inhibitors p27 and p21 were upregulated.


Input: Cell invasion, adhesion and migration were also attenuated in shTRPC2 cells, probably due to decreased activity of both Rac and calpain, and a decreased secretion and activity of matrix metalloproteinase 2.


Input: The attenuated proliferation, migration, invasion and ATP-evoked calcium entry was mimicked by overexpressing a non-conducting, truncated TRPC2 (TRPC2-DN) in wild type cells, and was reversed by overexpression of TRPC2-GFP in shTRPC2 cells.

ATP

calcium


Input: In conclusion, TRPC2 is an important regulator of rat thyroid cell function.


Input: Inhibitory effect of skullcap (Scutellaria baicalensis) extract on ovalbumin permeation in vitro and in vivo.


Input: Scutellaria baicalensis Georgi (skullcap) has been widely used as a dietary ingredient.


Input: The purpose of this study was to reveal novel function of skullcap and its mechanism on allergen permeation in intestinal epithelial cells.


Input: Intestinal epithelial Caco-2 cell monolayers were used to evaluate the inhibitory effect of skullcap on ovalbumin (OVA) permeation by measuring transepithelial electrical resistance (TEER) and the quantity of permeated OVA.


Input: TEER increased and the OVA flux decreased in a dose-dependent manner through up-regulating tight junction-related proteins in cells incubated with increasing concentrations of skullcap extract.


Input: In the in vivo study, the amounts of OVA from orally ingested albumen reduced on administration of the skullcap extract.


Input: We also revealed for the first time that the active component of skullcap extract for inhibition of OVA permeation was baicalein.

baicalein


Input: These findings demonstrated that skullcap extract might attenuate a food allergic response by inhibiting allergen permeation in vitro and in vivo.


Input: Volatile release and structural stability of beta-lactoglobulin primary and multilayer emulsions under simulated oral conditions.


Input: The relationship between emulsion structure and the release of volatile organic compounds (VOCs) was investigated using a model mouth system under oral conditions (tongue mastication, artificial saliva, pH and salt).


Input: The VOCs were monitored on-line by proton transfer reaction mass spectrometry (PTR-MS).


Input: Two types of emulsion system were compared: primary and multilayer oil-in-water (P-O/W, M-O/W) emulsions consisting of soy oil coated by beta-lactoglobulin and pectin layers.


Input: The P-O/W emulsions showed intensive flocculation at pH 5 and above 200mM NaCl where the electrostatic repulsive charge was at a minimum.

NaCl


Input: Bridging and depletion flocculation were mostly observed for P-O/W emulsions containing artificial saliva with 1wt% mucin.


Input: The VOC release was found to increase when the emulsion droplets flocculated, thus changing the oil volume phase distribution.


Input: The adsorbed pectin layer stabilised the emulsion structure under conditions of short-time oral processing, and hindered the release of hydrophobic VOCs.


Input: LC/MS analysis of proteolytic peptides in wheat extracts for determining the content of the allergen amylase/trypsin inhibitor CM3: Influence of growing area and variety.


Input: Food allergy from wheat is triggered by several protein classes, such as LTPs, omega 5-gliadins and alpha-amylase/trypsin inhibitors.


Input: The latter proteins, belonging to the prolamin superfamily, are mostly involved in baker' s asthma, a form of occupational allergy in which the sensitization occurs through the respiratory tract.


Input: alpha-Amylase/trypsin inhibitors were also found to be involved in wheat-related atopic dermatitis.


Input: In this work, the allergen Tri a 30 (the CM3 alpha-amylase/trypsin inhibitor) was quantified in durum wheat salt soluble extracts using a peptidomic approach.


Input: CM3 protein identification was confirmed by using LTQ-OrbiTrap analysis on peptides obtained from the enzymatically digested protein separated by gel electrophoresis.


Input: Then, marker peptides derived from the protein after enzymatic cleavage of the full wheat extracts were identified by LC-MS/MS.


Input: One of them was used as marker for quantitative determination on an UPLC/ESI-MS system by using its isotopically labelled analogue as internal standard, allowing to assess the protein content in the different samples.


Input: The CM3 allergenic proteins were found to greatly vary among different cultivation areas.


Input: A study of the precursors of the natural antioxidant phenol 3, 4-dihydroxyphenylglycol in olive oil waste.

phenol 3, 4-dihydroxyphenylglycol


Input: 3, 4-Dihydroxyphenylglycol (DHPG) is a potent antioxidant recently found in the free form in olive oil and table olives.

3, 4-Dihydroxyphenylglycol

DHPG


Input: DHPG can be recovered from olive oil solid waste by a hydrothermal treatment.

DHPG


Input: It was observed that an increase in the concentration of DHPG occurred when alperujo aqueous extracts were subjected to mild thermal conditions (post-treatment).

DHPG


Input: This fact indicates that certain solubilized compounds or precursors containing DHPG which is released with the post-treatment.

DHPG


Input: In the present study, the precursors of DHPG were identified and characterized after extraction from alperujo using thermal treatment and purification by fractionation on Amberlite (R) XAD16 polyamide and semi-preparative reverse-phase HPLC columns.

DHPG


Input: Their structures were elucidated using HPLC coupled to diode array detector (DAD) and electrospray ionization mass spectrometry (ESI-MS).


Input: The results identified three compounds as precursors, and their structures can be attributed to the diastereoisomeric forms of the two beta-hydroxy derivatives of verbascoside and isoverbascoside (beta-hydroxyacteoside and beta-hydroxyisoacteoside), and 2''-hydroxyoleuropein, all of which contain a DHPG moiety, potentially explaining the increases in the concentration of this phenolic compound in olive oil waste.

beta-hydroxy

verbascoside

isoverbascoside

beta-hydroxyacteoside

beta-hydroxyisoacteoside

DHPG

phenolic


Input: Antioxidant ability of fractionated apple peel phenolics to inhibit fish oil oxidation.


Input: Polyphenols isolated from frozen and dried apple peels were studied as potential natural antioxidants to stabilize omega-3 polyunsaturated fatty acid (omega 3 PUFA) enriched fish oil.

Polyphenols

omega-3 polyunsaturated fatty acid

omega 3 PUFA


Input: The ethanolic extracts of apple peels were fractionated by reversed phase chromatography using gradient elution of 20-100% aqueous ethanol.

ethanolic


Input: The collected fractions were analyzed by ultra pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS).


Input: The total phenolic content and antioxidant capacity of each fraction were evaluated by Folin-Ciocalteu (FC), ferric reducing antioxidant power (FRAP) and 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging assays.

ferric

1, 1-diphenyl-2-picrylhydrazyl

DPPH


Input: Inhibition of fish oil oxidation was studied using the thiobarbituric acid reactive substances (TBARS) assay.

thiobarbituric acid


Input: Polyphenols fractionated using frozen apple peel extract had significantly higher FC, FRAP and DPPH (.) scavenging values than those of dried apple peel (p < 0. 05).

Polyphenols

DPPH (.)


Input: The flavonol-rich fractions inhibited fish oil oxidation by 40-62% at a total phenolic concentration of 200 mu g/ml.


Input: The fractionated polyphenols from both dried and frozen apple peel showed higher inhibition of lipid oxidation compared to alpha-tocopherol, butylated hydroxytoluene and crude apple peel extracts.

polyphenols

alpha-tocopherol

butylated hydroxytoluene


Input: Pilot study on levels of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in selected foodstuffs and human milk from Italy.

perfluorooctane sulfonic acid

PFOS

perfluorooctanoic acid

PFOA


Input: Despite the health risks associated with perfluorinated compounds (PFC) exposure and the detection of these compounds in many countries around the world, little is known on their occurrence in Italy.


Input: The results of a study on levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), analysed by HPLC-ESI-MS, in human milk and food samples from the city of Siena and its province (central Italy) are here reported.

perfluorooctane sulfonate

PFOS

perfluorooctanoic acid

PFOA


Input: PFOS was found in 13 out of 49 breast milk samples (0. 76 +/- 1. 27ng/g), while PFOA was detected in one sample (8. 04ng/g).

PFOS

PFOA


Input: Only PFOS was found in food samples.

PFOS


Input: Fish were the most contaminated samples (7. 65 +/- 34. 2ng/g); mean concentrations in meat and milk and dairy products were similar (1. 43 +/- 7. 21ng/g and 1. 35 +/- 3. 45ng/g, respectively).


Input: In all cereal-based food, eggs, vegetables, honey and beverages PFOS concentration was < LOD.

PFOS


Input: These data show that consumption of most breast milk analysed would not result in children exceeding their total daily intakes for perfluorinated compounds.


Input: Effect of salt solutions applied during wheat conditioning on lipase activity and lipid stability of whole wheat flour.


Input: Lipolytic activity in whole wheat flour (WWF) is largely responsible for the loss in baking quality during storage.


Input: Metal ions affect the activity of seed lipases; however, no previous studies have applied this information to WWF in a way that reduces lipase activity, is practical for commercial manufacture, and uses common food ingredients.


Input: NaCl, KCl, Ca-propionate, or FeNa-ethylenediaminetetraacetic acid (FeNa-EDTA) were applied to hard red winter (HRW) and hard white spring (HWS) wheats during conditioning as aqueous solutions at concentrations that would be acceptable in baked goods.

NaCl

KCl

Ca-propionate

FeNa-ethylenediaminetetraacetic acid

FeNa-EDTA


Input: Salts affected lipase activity to different degrees depending on the type of wheat used.


Input: Inhibition was greater in HRW compared with HWS WWF, probably due to higher lipase activity in HRW wheat.


Input: In HRW WWF, 1% NaCl (flour weight) reduced hydrolytic and oxidative rancidity and resulted in higher loaf volume and lower firmness than untreated WWF after 24weeks of storage.

NaCl


Input: Garnacha Tintorera-based sweet wines: Chromatic properties and global phenolic composition by means of UV-Vis spectrophotometry.


Input: Valdeorras (the N. W. corner of Spain) wants to promote the production and marketing of new sweet wines.


Input: The present work represents the first study on sweet wines manufactured with red grapes Vitis vinifera L.


Input: Garnacha Tintorera, a teinturier cultivar.


Input: Two different red sweet wines were elaborated: the first one was made with dried grapes; Vitis vinifera L.


Input: Garnacha Tintorera has excellent potential to produce wines from raisined grapes; the second one, a fortified sweet wine aged in oak barrels.


Input: Different red Garnacha Tintorera-based wines (a dry base wine, GBW; a naturally sweet wine, GNSW; and a fortified sweet wine, GFSW) were characterized.


Input: Chromatic characteristics and phenolic compounds were established by spectrophotometric methods in order to assess the technology of Garnacha Tintorera-based sweet wines.

phenolic


Input: High molecular weight brown polymers, produced during the grape drying process and isolated from sweet wines by the dialysis process, were responsible for the brown colour of sweet wines.


Input: As a consequence, yellowness of sweet wines was also higher which was confirmed by colorimetric indexes.


Input: With respect to phenolic content, GFSW presented the lowest content because the maceration-alcoholic fermentation was stopped through the addition of alcohol before the diffusion of red pigments from skins to must was complete.

alcoholic

alcohol


Input: GNSW presented the highest phenolic content due to the concentration effect resulting from evaporation of water from the grapes.


Input: Anthocyanins of sweet wines were polymerised in great extent.

Anthocyanins


Input: The percentage of polymerised tannins was sufficient to guarantee the aging process of sweet wines.

tannins


Input: C-Phycocyanin from Oscillatoria tenuis exhibited an antioxidant and in vitro antiproliferative activity through induction of apoptosis and G0/G1 cell cycle arrest.


Input: This study was undertaken to develop an efficient single step chromatographic method for purification of C-phycocyanin (CPC) from species of Oscillatoria tenuis.


Input: Purification of CPC involves a multistep treatment of the crude extract by precipitation with ammonium sulphate, followed by gel filtration chromatography.

ammonium sulphate


Input: Pure CPC was finally obtained from O. tenuis with purity ratio (A620/A280) 4. 88.


Input: SDS-PAGE of pure CPC yielded two bands corresponding to alpha and beta subunits; the molecular weight of alpha subunit is 17. 0kDa, whereas the molecular weight of beta subunit is 19. 5kDa.


Input: Fluorescence and phase contrast microscopy revealed characteristic apoptotic features like cell shrinkage, membrane blebbing, nuclear condensation and DNA fragmentation.


Input: CPC exhibited antioxidant and antiproliferative activity against human cancer cells through apoptosis; nuclear apoptosis induction was accompanied by G0/G1 phase arrest and DNA fragmentation.


Input: CPC is a natural pigment with potential as an anticancer agent.


Input: Effect of 5-hydroxymethylfurfural derived from processed Cornus officinalis on the prevention of high glucose-induced oxidative stress in human umbilical vein endothelial cells and its mechanism.

glucose


Input: The aim of this study was to investigate the protective effect of 5-HMF on human umbilical vein endothelial cells (HUVECs) injured by high glucose in vitro, and the mechanism underlying this process.

glucose


Input: Our results demonstrated that high glucose-induced oxidative stress in HUVECs was mainly mediated through activation of reactive oxygen species (ROS), Jun N-kinase 2/3 (JNK2/3) and plasma interleukin-8 (IL-8), and inactivation of phosphorylated protein kinase B (P-Akt).

glucose

oxygen


Input: Treatment of HUVECs with media containing high glucose (4. 5%) in the presence of 5-HMF (100, 200 and 400 mu M) resulted in significant inhibition of high glucose-induced oxidative stress and expression of JNK1 and JNK2/3.

glucose

glucose


Input: Furthermore, 5-HMF rapidly inhibited high glucose-induced activation of IL-8, a downstream activator of P-Akt.

glucose


Input: Diabetes mellitus can cause a wide variety of vascular complications and high glucose can induce vascular endothelial cell apoptosis.

glucose


Input: Free radicals are formed disproportionately in diabetes by glucose oxidation.

glucose


Input: The finding of this study highlights the pharmacological application of 5-HMF for preventing cardiovascular and diabetes mellitus diseases, and provides the theoretical basis for further development of a Cornus officinalis agent for diabetes-associated vascular diseases.


Input: Development and validation of ethylenethiourea determination in foods using methanol-based extraction, solid-phase extraction cleanup and LC-MS/MS.

ethylenethiourea

methanol


Input: To response to the need for a rapid, cost-effective, eco-friendly and efficient extraction process, a sensitive method for the determination of ethylenethiourea (ETU) in food matrices by high-performance liquid chromatography-mass spectrometry (HPLC-LC/MS) was developed and validated.

ethylenethiourea

ETU


Input: ETU was extracted from food commodities with methanol, cleaned up by alumina-SPE column, and then determined by HPLC-MS/MS.

ETU

methanol

alumina


Input: The MS detection was operated in positive ionization mode.


Input: For confirmation of target compound, two precursor ion > product ion transitions were selected by multi-reaction monitoring mode (MRM).


Input: The method showed good linearity with correlation coefficient higher than 0. 9950.


Input: Recoveries at three spiked levels (10, 50, 100ng/g) in random selected food matrices were in range of 71-121% with RSDs not larger than 25%.


Input: The limit of quantitation for the analyte was estimated at 5ng/g.


Input: Comparison of antioxidant activity of hydroethanolic fresh and aged garlic extracts and their effects on cerebral ischemia.

hydroethanolic


Input: Antioxidant properties and protective effect of aged garlic extract (AGE) and of 20% hydroethanolic fresh extracts from garlic clove (GCE) and skin (GSE) on cerebral ischemia were evaluated by administering extracts at the beginning of reperfusion in a rat model of stroke.

hydroethanolic


Input: All three extracts scavenged superoxide anion, peroxynitrite anion, and peroxyl radicals, but with different efficiencies; furthermore, GCE and GSE scavenged hydroxyl radicals and GSE scavenged singlet oxygen.

superoxide

peroxynitrite

peroxyl

hydroxyl

oxygen


Input: These extracts significantly prevented reduction of neuronal nuclear antigen in the infarcted area, although no improvement in neurological function was observed.


Input: Importantly, GCE and GSE contained S-allylcystein, a compound associated with AGE' s neuroprotective effect against damage induced by cerebral ischemia.

S-allylcystein


Input: Extracts decreased mRNA expression of NR1-and NR2B-NMDA-receptor subunits and prevented ischemia-induced reduction in mitochondrial potential and in ATP synthesis.

NMDA

ATP


Input: These results indicate that antioxidants present in garlic extracts may regulate ROS concentrations during ischemia, favour pro-survival pathways, and attenuate mitochondrial dysfunction.


Input: A calibrator plasmid for quantitative analysis of insect resistant maize (Yieldgard MON 810).


Input: Real-time PCR (RT-PCR) is the preferred method for the quantification of genetically modified organisms (GMOs) and implementation of labeling regulations.


Input: The precision, sensitivity, and reproducibility of RT-PCR data depend on the use of external calibrators.


Input: In this investigation, a dual target plasmid designated pRSETMON-02 comprising of MON 810 maize event specific and endogenous zein gene sequences in 1: 1 ratio in tandem was constructed and validated.


Input: Commutability of plasmid DNA (pDNA) and genomic DNA (gDNA) calibrators for the quantification of MON 810 maize was assessed by employing a TaqMan RT-PCR targeting the P-35S and zein gene.


Input: Higher PCR efficiencies, good linearity and lower relative standard deviation (RSD) values were associated with pRSETMON-02 as opposed to gDNA calibrants.


Input: pDNA calibrants exhibited better performance characteristic in terms of closeness to the expected value of unknown samples than their genomic counterparts.


Input: Short term stability study of the pRSETMON-02 plasmid stored at different temperatures showed that pDNA is stable for 45days at-20, and 4 degrees C.


Input: The results demonstrated that the developed dual target plasmid pRSETMON-02 is fit for the intended use of quantifying MON 810 maize and is a better alternative to conventional seed powder calibrants.


Input: Novel ROS-activated agents utilize a tethered amine to selectively target acute myeloid leukemia.

tethered amine


Input: This study explores the possible use of reactive oxygen-activated DNA modifying agents against acute myeloid leukemia (AML).

oxygen


Input: A key amine on the lead agent was investigated via cytotoxicity assays and was found necessary for potency.

amine


Input: The two best compounds were screened via the NCI-60 cell panel.


Input: These two compounds had potency between 200 and 800nM against many of the leukemia cancer cell types.


Input: Subsequent experiments explored activity against a transformed AML model that mimics the molecular signatures identified in primary AML patient samples.


Input: A lead compound had an IC50 of 760nM against this AML cell line as well as a therapeutic index of 7. 7 +/- 3 between the transformed AML model cell line and non-cancerous human CD34 + blood stem/progenitor cells (UCB).


Input: The selectivity was much greater than the mainstays of AML treatment: doxorubicin and cytarabine.

doxorubicin

cytarabine


Input: This manuscript demonstrates that this novel type of agent may be useful against AML.


Input: Personalized medicine: predicting responses to therapy in patients with RA.


Input: Personalized medicine where each patient receives the right drug and the right intensity of drug treatment for as long as needed or safe is the goal of medicine.


Input: The identification of predictors of response is the first step toward this.


Input: In rheumatoid arthritis (RA), several prediction matrices were designed to predict the risk of rapid radiological progression (RRP) in the first year of treatment, on either disease modifying anti-rheumatic drug (DMARD) monotherapy or combination therapy with prednisone or a biological agent.

prednisone


Input: Both clinical markers and biomarkers of response to either anti-TNF or different mode of action biological agents, and of successful discontinuation of these agents once the treatment goal has been achieved, have been identified in different studies.


Input: Most of these markers need validation in other cohorts.


Input: Research into combining clinical markers and biomarkers of response could lead to identification of risk profiles resulting in a new step toward personalized medicine in RA.


Input: Evaluation of a predictive in vitro Leydig cell assay for anti-androgenicity of phthalate esters in the rat.

phthalate esters


Input: An in vitro assay using the rat Leydig cell line R2C was evaluated for its ability to quantitatively predict inhibition of testosterone synthesis.

testosterone


Input: Results obtained for endocrine active phthalates (MEHP, MBP), and inactive phthalates (MMP and MEP) were highly consistent with in vivo results based on tissue and media concentrations.

phthalates

MEHP

MBP

phthalates

MMP

MEP


Input: Statistically significant inhibition of testosterone synthesis (p < 0. 05, 1-way ANOVA) was observed at 1 mu M MBP and 3 mu M MEHP, while MEP and MMP did not affect inhibition of testosterone synthesis until much higher concentrations (>> 100 mu M).

testosterone

MBP

MEHP

MEP

MMP

testosterone


Input: Concentrations causing 50% inhibition of testosterone synthesis for MBP and MEHP (3 and 6 mu M respectively), were similar to in vivo values (3 and 7 mu M).

testosterone

MBP

MEHP


Input: The R2C assay was used to determine the relative potency of 14 structurally diverse monoesters and oxidative metabolites of MEHP.

monoesters

MEHP


Input: Monoesters with alkyl chains 4-5 carbons in length had the highest potency for testosterone inhibition, while 0-2 carbon alkyl chains were least potent.

Monoesters

carbons

testosterone

carbon


Input: Phase I metabolism did not completely inactivate MEHP, underscoring the need for metabolism data when interpreting in vitro pharmacodynamic data.

MEHP


Input: This steroid inhibition assay provides a predictive in vitro alternative to expensive and timeconsuming developmental rat studies for phthalate-induced antiandrogenicity.

steroid

phthalate


Input: Effects of chronic methylphenidate on cocaine self-administration under a progressive-ratio schedule of reinforcement in rhesus monkeys.

methylphenidate

cocaine


Input: It has been hypothesized that drugs that serve as substrates for dopamine (DA) and norepinephrine (NE) transporters may be more suitable medications for cocaine dependence than drugs that inhibit DA and NE uptake by binding to transporters.

dopamine

norepinephrine

cocaine


Input: Previous studies have shown that the DA/NE releaser d-amphetamine can decrease cocaine self-administration in preclinical and clinical studies.

d-amphetamine

cocaine


Input: The present study examined the effects of methylphenidate (MPD), a DA uptake inhibitor, for its ability to decrease cocaine self-administration under conditions designed to reflect clinically relevant regimens of cocaine exposure and pharmacotherapy.

methylphenidate

MPD

cocaine

cocaine


Input: Each morning, rhesus monkeys pressed a lever to receive food pellets under a fixed-ratio 50 schedule of reinforcement; cocaine was self-administered under a progressiveratio schedule of reinforcement in the evening.

cocaine


Input: After cocaine (0. 003-0. 56 mg/kg per injection, i. v.) dose-response curves were determined, self-administration sessions were suspended and MPD (0. 003-0. 0056 mg/kg per hr, i. v. or 1. 0-9. 0 mg/kg p. o., b. i. d.) was administered for several weeks.

cocaine

MPD


Input: A cocaine self-administration session was conducted every 7 days.

cocaine


Input: When a MPD dose was reached that either persistently decreased cocaine self-administration or produced disruptive effects, the cocaine dose-effect curve was re-determined.

MPD

cocaine

cocaine


Input: In most cases, MPD treatment either produced behaviorally disruptive effects or increased cocaine selfadministration; it took several weeks for these effects to dissipate.

MPD

cocaine


Input: These data are consistent with the largely negative results of clinical trials with MPD.

MPD


Input: In contrast to the positive effects with the monoamine releaser d-amphetamine under identical conditions, these results do not support use of monoamine uptake inhibitors like MPD as a medication for cocaine dependence.

monoamine

d-amphetamine

monoamine

MPD

cocaine


Input: Clinical and Subclinical Macrovascular Disease as Predictors of Cognitive Decline in Older Patients With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study.


Input: OBJECTIVEMacrovascular disease may contribute to increased risk of accelerated cognitive decline in patients with type 2 diabetes.


Input: We aimed to determine associations of measures of macrovascular disease with cognitive change in a cognitively healthy older population with type 2 diabetes. RESEARCH DESIGN AND METHODSEight-hundred thirty-one men and women (aged 60-75 years) attended two waves of the prospective Edinburgh Type 2 Diabetes Study (ET2DS).


Input: At baseline, clinical and subclinical macrovascular disease was measured, including cardiovascular event history, carotid intima-media thickness (cIMT), ankle brachial index (ABI), and serum N-terminal probrain natriuretic peptide (NT-proBNP).

N


Input: Seven neuropsychological tests were administered at baseline and after 4 years; scores were combined to a standardized general ability factor (g).


Input: Adjustment of follow-up g for baseline g assessed 4-year cognitive change.