Input: Alternative splicing (AS) is one of the most significant components of the functional complexity of human UDP-glucuronosyltransferase enzymes (UGTs), particularly for the UGT1A gene, which represents one of the best examples of a drug-metabolizing gene regulated by AS.

UDP


Input: Shorter UGT1A isoforms [isoform 2 (i2)] are deficient in glucuronic acid transferase activity but function as negative regulators of enzyme activity through protein-protein interaction.

glucuronic acid


Input: Their abundance, relative to active UGT1A enzymes, is expected to be a determinant of the global transferase activity of cells and tissues.


Input: Here we tested whether i2-mediated inhibition increases with greater abundance of the i2 protein relative to the isoform 1 (i1) enzyme, using the extrahepatic UGT1A7 as a model and a series of 23 human embryonic kidney 293 clonal cell lines expressing variable contents of i1 and i2 proteins.


Input: Upon normalization for i1, a significant reduction of 7-ethyl-10-hydroxycamptothecin glucuronide formation was observed for i1 + i2 clones (mean of 53%) compared with the reference i1 cell line.

7-ethyl-10-hydroxycamptothecin glucuronide


Input: In these clones, the i2 protein content varied greatly (38-263% relative to i1) and revealed two groups: 17 clones with i2 < i1 (60% +/- 3%) and 6 clones with i2 >= i1 (153% +/- 24%).


Input: The inhibition induced by i2 was more substantial for clones displaying i2 >= i1 (74. 5%; P = 0. 001) compared with those with i2 < i1 (45. 5%).


Input: Coimmunoprecipitation supports a more substantial i1-i2 complex formation when i2 exceeds i1.


Input: We conclude that the relative abundance of regulatory i2 proteins has the potential to drastically alter the local drug metabolism in the cells, particularly when i2 surpasses the protein content of i1.


Input: Understanding photosynthetic light-harvesting: a bottom up theoretical approach.


Input: We discuss a bottom up approach for modeling photosynthetic light-harvesting.


Input: Methods are reviewed for a full structure-based parameterization of the Hamiltonian of pigment-protein complexes (PPCs).


Input: These parameters comprise (i) the local transition energies of the pigments in their binding sites in the protein, the site energies; (ii) the couplings between optical transitions of the pigments, the excitonic couplings; and (iii) the spectral density characterizing the dynamic modulation of pigment transition energies and excitonic couplings by protein vibrations.


Input: Starting with quantum mechanics perturbation theory, we provide a microscopic foundation for the standard PPC Hamiltonian and relate the expressions obtained for its matrix elements to quantities that can be calculated with classical molecular mechanics/electrostatics approaches including the whole PPC in atomic detail and using charge and transition densities obtained with quantum chemical calculations on the isolated building blocks of the PPC.


Input: In the second part of this perspective, the Hamiltonian is utilized to describe the quantum dynamics of excitons.


Input: Situations are discussed that differ in the relative strength of excitonic and exciton-vibrational coupling.


Input: The predictive power of the approaches is demonstrated in application to different PPCs, and challenges for future work are outlined.


Input: Multiple dosing of ephedra-free dietary supplements: hemodynamic, electrocardiographic, and bacterial contamination effects.


Input: Four popular ephedra-free dietary supplements were evaluated for their effects on heart rate (HR), blood pressure (BP), and electrocardiographic (ECG) parameters.


Input: Twelve healthy men participated in a study randomized for product sequence, with a 21-day washout period between supplement-administration phases.


Input: Throughout the study, Holter monitors were used to assess ECG and HR activity.


Input: BP was assessed automatically on multiple occasions.


Input: The supplements were ingested three times daily for 3 days.


Input: Caffeine content, microbial load, and serum caffeine concentrations were determined.

Caffeine

caffeine


Input: Mean systolic (SBP) and diastolic BP (DBP) readings showed significant increases relative to baseline (10. 8 +/- 2. 5 and 5. 3 +/- 3. 1 mm Hg, respectively; P < 0. 05).


Input: All supplements significantly increased HR and decreased bradycardia runs; abnormal atrial/ventricular events were frequently noted.


Input: Gastrointestinal and sympathomimetic symptoms were also common.


Input: Two supplements were heavily contaminated with Bacillus species.


Input: In light of these findings, the use of ephedra-free dietary supplements should be discouraged in individuals with hypertension, diabetes, or other cardiovascular diseases.


Input: Role of diuretics and lipid formulations in the prevention of amphotericin B-induced nephrotoxicity.

amphotericin B


Input: PURPOSE: To collect available clinical data to define the role of diuretics and lipid formulations in the prevention of amphotericin B (AmB)-induced nephrotoxicity (AIN) in human populations.

amphotericin B

AmB


Input: METHOD: A literature search was performed in the following databases: Scopus, Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews.


Input: RESULTS AND CONCLUSION: Co-administration of mannitol failed to show any clinically significant benefit in preventing AIN.

mannitol


Input: Potassium-sparing diuretics, such as amiloride and spironolactone, have been shown to have beneficial effects as an alternative or adjunct to oral/parenteral potassium supplements in preventing hypokalemia due to AmB.

Potassium

amiloride

spironolactone

potassium

AmB


Input: Lipid-based formulations of AmB are clinically effective and safe in preventing AIN.

AmB


Input: However, due to their high cost and limited accessibility, these formulations are generally used as second-line antifungal therapy in cases of conventional AmB refractoriness and/or intolerance or pre-existing renal dysfunction.

AmB


Input: The potential effects of other nephroprotective agents, such as N-acetylcysteine, AIN merit further considerations and investigations.

N-acetylcysteine


Input: Structural and up-conversion properties of Er3 + and Yb3 + co-doped Y2Ti2O7 phosphors.

Er3 +

Yb3 +


Input: Y (2) Ti (2) O (7) (YTO) and Er (3 +)/Yb (3 +) co-doped Y (2) Ti (2) O (7) (EYYTO) phosphors have been prepared by solid-state reaction method.

Y (2) Ti (2) O (7)

YTO

Er (3 +)

Yb (3 +)

Y (2) Ti (2) O (7)

EYYTO


Input: Structures of YTO and EYYTO phosphors are identified as face centered cubic pyrochlores.

YTO

EYYTO


Input: Up-conversion emission spectra of EYYTO under 976 nm excitation is studied, which revealed three prominent emission lines at ~ 524, 548 and 661 nm originating from (2) H (11/2) --> (4) I (15/2), (4) S (3/2) --> (4) I (15/2) and (4) F (9/2) --> (4) I (15/2) electronic transitions of Er (3 +) ion, respectively in green and red regions.

EYYTO

Er (3 +)


Input: The power dependence study suggests that these bands arise due to two photon absorption.


Input: The monodispersed laser ablated colloidal solution of EYYTO shows strong red and green emissions on excitation with 976 nm laser.

EYYTO


Input: The variation of luminescence intensity at different laser excitation powers is observed and thus a color can be tuned.


Input: The photoluminescence lifetime of green band at 548 nm ((4) S (3/2) level) has been found to be ~ 446 mu s.


Input: Anti-aging molecule, Sirt1: a novel therapeutic target for diabetic nephropathy.


Input: Caloric restriction prolongs the lifespan of many species.


Input: Therefore, investigators have researched the usefulness of caloric restriction for healthy lifespan extension.


Input: Sirt1, an NAD (+)-dependent deacetylase, was identified as a molecule necessary for caloric restriction-related anti-aging strategies.

NAD (+)


Input: Sirt1 functions as an intracellular energy sensor to detect the concentration of NAD (+), and controls in vivo metabolic changes under caloric restriction and starvation through its deacetylase activity to many targets including histones, nuclear transcriptional factors, and enzymes.

NAD (+)


Input: During the past decade, investigators have reported the relationship between disturbance of Sirt1 activation and the onset of aging-and obesity-associated diseases such as diabetes, cardiovascular disease and neurodegenerative disorders.


Input: Consequently, a calorie restriction-mimetic action of Sirt1 is now expected as a new therapy for these diseases.


Input: In addition, recent studies have gradually clarified the role of Sirt1 in the onset of kidney disease.


Input: Its activation may also become a new target of treatment in the patients with chronic kidney disease including diabetic nephropathy.


Input: In this article, we would like to review the role of Sirt1 in the onset of kidney disease based on previous studies, and discuss its possibility as the target of treatment in diabetic nephropathy.


Input: [(3) H] UR-PLN196: a selective nonpeptide radioligand and insurmountable antagonist for the neuropeptide Y Y (2) receptor.

[(3) H] UR-PLN196


Input: Radioing in on NPY: Attachment of a [2, 3-(3) H] propionyl group through an appropriate linker to the guanidine group of an (S)-argininamide-type neuropeptide Y (NPY) Y (2) receptor antagonist resulted in a subtype-selective radioligand.

[2, 3-(3) H] propionyl

guanidine

(S)-argininamide


Input: Glycan sequence-dependent Nod2 activation investigated by using a chemically synthesized bacterial peptidoglycan fragment library.


Input: Nucleotide oligomerization domain-containing protein 2 (Nod2), an innate immune receptor, recognizes bacterial cell-wall peptidoglycan (PGN), the minimum ligand of which is muramyl dipeptide (MDP).

Nucleotide

muramyl dipeptide

MDP


Input: Enzymatic digestion of PGN appears to be important for Nod2 recognition.


Input: PGN is degraded by muramidase or glucosamidase through a process that produces two types of glycan sequence; glycans containing GlcNAc beta (1 --> 4) MurNAc or MurNAc beta (1 --> 4) GlcNAc.

GlcNAc beta (1 --> 4) MurNAc

MurNAc beta (1 --> 4) GlcNAc


Input: In this report, a range of disaccharide or tetrasaccharide fragments of each sequence were chemically synthesized, and their activities in stimulating human Nod2 (hNod2) were investigated.

disaccharide

tetrasaccharide


Input: The results reveal that hNod2 recognitions is dependent on the glycan sequence, as demonstrated by comparing the activities of glycans with the same peptide moieties.


Input: (MurNAc beta (1 --> 4) GlcNAc) (2)-containing structures exhibited stronger activity than those containing (GlcNAc beta (1 --> 4) MurNAc) (2).

MurNAc beta (1 --> 4) GlcNAc

GlcNAc beta (1 --> 4) MurNAc


Input: The results suggest that differences in the enzymatic degradation process affect the host' s immunomodulation process.


Input: Ca (2) +-dependent phosphorylation of Ca (2) + cycling proteins generates robust rhythmic local Ca (2) + releases in cardiac pacemaker cells.

Ca (2) +

Ca (2) +

Ca (2) +


Input: The spontaneous beating of the heart is governed by spontaneous firing of sinoatrial node cells, which generate action potentials due to spontaneous depolarization of the membrane potential, or diastolic depolarization.


Input: The spontaneous diastolic depolarization rate is determined by spontaneous local submembrane Ca (2) + releases through ryanodine receptors (RyRs).

Ca (2) +

ryanodine


Input: We sought to identify specific mechanisms of intrinsic Ca (2) + cycling by which sinoatrial node cells, but not ventricular myocytes, generate robust, rhythmic local Ca (2) + releases.

Ca (2) +

Ca (2) +


Input: At similar physiological intracellular Ca (2) + concentrations, local Ca (2) + releases were large and rhythmic in permeabilized sinoatrial node cells but small and random in permeabilized ventricular myocytes.

Ca (2) +

Ca (2) +


Input: Furthermore, sinoatrial node cells spontaneously released more Ca (2) + from the sarcoplasmic reticulum than did ventricular myocytes, despite comparable sarcoplasmic reticulum Ca (2) + content in both cell types.

Ca (2) +

Ca (2) +


Input: This ability of sinoatrial node cells to generate larger and rhythmic local Ca (2) + releases was associated with increased abundance of sarcoplasmic reticulum Ca (2) +-ATPase (SERCA), reduced abundance of the SERCA inhibitor phospholamban, and increased Ca (2) +-dependent phosphorylation of phospholamban and RyR.

Ca (2) +

Ca (2) +

Ca (2) +


Input: The increased phosphorylation of RyR in sinoatrial node cells may facilitate Ca (2) + release from the sarcoplasmic reticulum, whereas Ca (2) +-dependent increase in phosphorylation of phospholamban relieves its inhibition of SERCA, augmenting the pumping rate of Ca (2) + required to support robust, rhythmic local Ca (2) + releases.

Ca (2) +

Ca (2) +

Ca (2) +

Ca (2) +


Input: The differences in Ca (2) + cycling between sinoatrial node cells and ventricular myocytes provide insights into the regulation of intracellular Ca (2) + cycling that drives the automaticity of sinoatrial node cells.

Ca (2) +

Ca (2) +


Input: Physical interaction between MYCN oncogene and polycomb repressive complex 2 (PRC2) in neuroblastoma: functional and therapeutic implications.


Input: CLU (clusterin) is a tumor suppressor gene that we have previously shown to be negatively modulated by the MYCN proto-oncogene, but the mechanism of repression was unclear.


Input: Here, we show that MYCN inhibits the expression of CLU by direct interaction with the non-canonical E box sequence CACGCG in the 5'-flanking region.


Input: Binding of MYCN to the CLU gene induces bivalent epigenetic marks and recruitment of repressive proteins such as histone deacetylases and Polycomb members.


Input: MYCN physically binds in vitro and in vivo to EZH2, a component of the Polycomb repressive complex 2, required to repress CLU.


Input: Notably, EZH2 interacts with the Myc box domain 3, a segment of MYC known to be essential for its transforming effects.


Input: The expression of CLU can be restored in MYCN-amplified cells by epigenetic drugs with therapeutic results.


Input: Importantly, the anticancer effects of the drugs are ablated if CLU expression is blunted by RNA interference.


Input: Our study implies that MYC tumorigenesis can be effectively antagonized by epigenetic drugs that interfere with the recruitment of chromatin modifiers at repressive E boxes of tumor suppressor genes such as CLU.


Input: Biselectivity of isoDGR Peptides for Fibronectin Binding Integrin Subtypes alpha 5 beta 1 and alpha v beta 6: Conformational Control through Flanking Amino Acids.

Amino Acids


Input: Integrins are the major class of cell adhesion proteins.


Input: Their interaction with different ligands of the extracellular matrix is diverse.


Input: To get more insight into these interactions, artificial ligands endowed with a well-defined activity/selectivity profile are necessary.


Input: Herein, we present a library of cyclic pentapeptides, based on our previously reported peptide motif c (-phg-isoDGR-X-), in which high activity toward fibronectin binding integrins alpha 5 beta 1 and alpha v beta 6 and not on vitronectin binding integrins alpha v beta 3 and alpha v beta 5 has been achieved by changing the flanking amino acids.

cyclic pentapeptides

amino acids


Input: The structure of the most promising candidates has been determined using a combined approach of NMR, distance geometry, and molecular dynamics simulations, and docking studies have been further used to elucidate the peptide-integrin interactions at the molecular level.


Input: The peptides' binding affinity has been characterized by enzyme linked immunosorbent assay experiments, and the results have been verified by cell adhesion experiments on specifically functionalized surfaces.


Input: Chiral selective transmembrane transport of amino acids through artificial channels.

amino acids


Input: Peptide-appended pillar [n] arene (n = 5, 6) derivatives have been synthesized.

pillar [n] arene (n = 5, 6)


Input: (1) H NMR and IR studies revealed that the molecules adopt a tubular conformation in solution and lipid bilayer membranes.

(1) H


Input: Kinetic measurements using the fluorescent labeling method with lipid vesicles revealed that these molecules can efficiently mediate the transport of amino acids across lipid membranes at a very low channel-to-lipid ratio (EC (50) = 0. 002 mol%).

amino acids


Input: In several cases, chiral selectivity for amino acid enantiomers was achieved, which is one of the key functions of natural amino acid channels.

amino acid

amino acid


Input: DNA origami nanopillars as standards for three-dimensional superresolution microscopy.


Input: Nanopillars are promising nanostructures composed of various materials that bring new functionalities for applications ranging from photovoltaics to analytics.


Input: We developed DNA nanopillars with a height of 220 nm and a diameter of ~ 14 nm using the DNA origami technique.


Input: Modifying the base of the nanopillars with biotins allowed selective, upright, and rigid immobilization on solid substrates.

biotins


Input: With the help of site-selective dye labels, we visualized the structure and determined the orientation of the nanopillars by three-dimensional fluorescence superresolution microscopy.


Input: Because of their rigidity and nanometer-precise addressability, DNA origami nanopillars qualify as scaffold for the assembly of plasmonic devices as well as for three-dimensional superresolution standards.


Input: Homopolar dihydrogen bonding in alkali metal amidoboranes: crystal engineering of low-dimensional molecular materials.

dihydrogen

alkali metal amidoboranes


Input: Hydrogen bonding is a predominant interaction in supramolecular chemistry.

Hydrogen


Input: The absence of a conventional hydrogen bond donor in LiNMe (2) BH (3) and KNMe (2) BH (3) results in the formation of elaborate M... H-B polymeric arrays supported by heteropolar and homopolar H... H bonding, in a unique synergistic combination of unconventional intermolecular interactions.

hydrogen

LiNMe (2) BH (3)

KNMe (2) BH (3)

H-B

H

H


Input: Base-flipping propensities of unmethylated, hemimethylated, and fully methylated CpG sites.

CpG


Input: Methylation of C5 of cytosines at CpG dinucleotide sites of the DNA is one of the most important factors regulating the expression of genes.

cytosines

CpG dinucleotide


Input: The interactions of these CpG sites with proteins are essential for recognition and catalysis and in many cases are characterized by the flipping of either of the cytosine bases out of the DNA helix.

CpG

cytosine


Input: In this paper, we present results from molecular dynamics simulations indicating that methylation of CpG sites suppresses spontaneous extra-helical conformations of either of the two cytosines.

CpG

cytosines


Input: Thus, cytosines in unmethylated sites flip out easier than in hemimethylated sites and the latter flip out easier than in fully methylated sites.

cytosines


Input: The different propensities for base flipping is observed not only between the cytosines that differ in their methylation states but also between the cytosines on the complementary strand.

cytosines

cytosines


Input: From alchemical mutation calculations, we find that methylation of one of the cytosines increases the free energy of the extra-helical conformation by 10. 3-16. 5 kJ/mol and this increase is additive with respect to the second methylation.

cytosines


Input: Potential of mean force calculations confirm these results and reveal that cytosines in unmethylated sites favor flipping via the major-groove pathway.

cytosines


Input: We perform several analyses to correlate this behavior with structural changes induced by the different methylation states of the CpG site.

CpG


Input: However, we demonstrate that the driving force for these propensities is the change in the electronic distribution around the pyrimidine ring upon methylation.

pyrimidine


Input: In particular, unmethylated cytosine interacts more favorably (primarily via electrostatic forces) with solvent water molecules than methylated cytosine.

cytosine

cytosine


Input: This is observed for, both, extra-helical cytosines and intra-helical cytosines in which the cytosine on the complementary strand flips out and water molecules enter the DNA double-helix and substitute the hydrogen bonds with the orphan guanine.

cytosines

cytosines

cytosine

hydrogen

guanine


Input: On the basis of these results of spontaneous base flipping, we conjecture that the mechanism for base flipping observed in complexes between hemimethylated DNAs and proteins is not likely to be passive.


Input: Highly luminescent and photostable quantum dot-silica monolith and its application to light-emitting diodes.

silica


Input: A highly luminescent and photostable quantum dot-silica monolith (QD-SM) substance was prepared by preliminary surface exchange of the QDs and base-catalyzed sol-gel condensation of silica.

silica


Input: The SM was heavily doped with 6-mercaptohexanol exchanged QDs up to 12 vol% (26 wt%) without particle aggregation.


Input: Propylamine catalyst was important in maintaining the original luminescence of the QDs in the SM during sol-gel condensation.


Input: The silica layer was a good barrier against oxygen and moisture, so that the QD-SM maintained its initial luminescence after high-power UV radiation (~ 1 W) for 200 h and through the 150 degrees C LED encapsulant curing process.

silica

oxygen


Input: Green and red light-emitting QD-SMs were applied as color-converting layers on blue LEDs, and the external quantum efficiency reached up to 89% for the green QD-SM and 63% for the red one.


Input: A white LED made with a mixture of green and red QDs in the SM, in which the color coordinate was adjusted at (0. 23, 0. 21) in CIE1931 color space for a backlight application, showed an efficacy of 47 lm/W, the highest value yet reported.


Input: Silica precipitation by synthetic minicollagens.

Silica


Input: Oligomeric Pro-Hyp-Gly-(POG-) peptides, wherein the collagenous triple helix is supported by C-terminal capping, exhibit silica precipitation properties (O, Hyp = (2S, 4R) hydroxyproline).

Pro-Hyp-Gly

C

silica

Hyp

(2S, 4R) hydroxyproline


Input: As quantified by a molybdate assay, the length of the covalently tethered triple helix (number of POG units) determines the amount of amorphous silica obtained from silicic acid solution.

silica

silicic acid


Input: Although lacking charged side chains, the synthetic collagens precipitate large quantities of silicic acid resulting in micrometer-sized spheres of varying surface morphologies as analyzed by scanning electron microscopy.

silicic acid


Input: Similar precipitation efficiencies on a fast time scale of less than 10 min were previously described only for biogenic diatom proteins and sponge collagen, respectively, which have a considerably higher structural complexity and limited accessibility.


Input: The minicollagens described here provide an unexpected alternative to the widely used precipitation conditions, which generally depend on (poly-) amines in phosphate buffer.

(poly-) amines

phosphate


Input: Collagen can form intimate connections with inorganic matter.


Input: Hence, silica-enclosed collagens have promising perspectives as composite materials.

silica


Input: Purification and characterization of glucose 6-phosphate dehydrogenase enzyme from rainbow trout (Oncorhynchus mykiss) liver and investigation of the effects of some metal ions on enzyme activity.

glucose 6-phosphate


Input: Glucose 6-phosphate dehydrogenase (< sc > d </sc >-glucose 6-phosphate: NADP (+) oxidoreductase, EC 1. 1. 1. 49; G6PD) is a key enzyme that is localized in all mammal tissues, especially in cytoplasmic sections and that catalyzes the first step of pentose phosphate metabolic pathway.

Glucose 6-phosphate

< sc > d </sc >-glucose 6-phosphate

NADP (+)

pentose phosphate


Input: In this study, G6PD enzyme was purified 1444-fold with a yield of 77% from rainbow trout liver using 2', 5'-ADP-sepharose-4B affinity chromatography.

2', 5'-ADP-sepharose-4B


Input: Moreover, a purity check of the enzyme was performed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

sodium dodecyl sulfate

polyacrylamide


Input: Some characteristic features like optimal pH, stable pH, optimal temperature and optimal ionic strength were determined for the purified enzyme.


Input: In addition to this, in vitro effects of ions like silver nitrate (Ag (+)), thallium sulphate (TI (+)), cobalt (II) nitrate (Co (2 +)) and arsenic (V) oxide (As (5 +)) on enzyme activity were researched.

silver nitrate

Ag (+)

thallium sulphate

TI (+)

cobalt (II) nitrate

Co (2 +)

arsenic (V) oxide

As (5 +)


Input: Half-maximal inhibitory concentration (IC (50)) values of Ag (+), Co (2 +) and As (5 +) metal ions, which showed an inhibitory effect, were found to be 0. 0044, 0. 084 and 4. 058 mM, respectively; and their inhibition constants (K (i)) were found to be 0. 0052 +/- 0. 00042, 0. 087 +/- 0. 015700 and 4. 833 +/- 1. 753207 mM, respectively.

Ag (+)

Co (2 +)

As (5 +)


Input: Tl (+) not exhibited inhibitory effect on the enzyme activity.

Tl (+)


Input: Hepatoprotective effect of carob against acute ethanol-induced oxidative stress in rat.

ethanol


Input: The present study was undertaken to determine whether subacute treatment with aqueous extract of carob (Ceratonia siliqua L.) pods (AECPs) protects against ethanol (EtOH)-induced oxidative stress in rat liver.

ethanol

EtOH


Input: Animals were divided into four groups: control, carob, EtOH and EtOH + carob.

EtOH

EtOH


Input: Wistar rats were intraperitoneally pretreated with AECP (600 mg/kg body weight (bw)) during 7 days and intoxicated for 6 h by acute oral administration of EtOH (6 g/kg bw) 24 h after the last injection.

EtOH


Input: We found that acute administration of EtOH leads to hepatotoxicity as monitored by the increase in the levels of hepatic marker aspartate aminotransferase and alanine aminotransferase as well as hepatic tissue injury.

EtOH

aspartate

alanine


Input: EtOH also increased the formation of malondialdehyde in the liver, indicating an increase in lipid peroxidation and depletion of antioxidant enzyme activities as superoxide dismutase, catalase and glutathione peroxidase.

EtOH

malondialdehyde

superoxide

glutathione


Input: Subacute carob pretreatment prevented all the alterations induced by EtOH and returned their levels to near normal.

EtOH


Input: Importantly, we showed that acute alcohol increased hepatic and plasmatic hydrogen peroxide and free iron levels.

hydrogen peroxide


Input: The carob pretreatment reversed EtOH effects to near control levels.

EtOH


Input: These data suggest that carob could have a beneficial effect in inhibiting the oxidative damage induced by acute EtOH administration and that its mode of action may involve an opposite effect on plasma and tissue-free iron accumulation.

EtOH


Input: Indeed, carob can be offered as a food additive to protect against EtOH-induced oxidative damage.

EtOH


Input: Responses of Portulaca oleracea Linn. to selenium exposure.


Input: The present study was investigated to evaluate the uptake and accumulation of selenium (Se) by the stem cuttings of Portulaca oleracea L. grown in alfisol amended with various concentrations of Se.

selenium

Se


Input: P. oleracea accumulated a maximum of 63. 4 micro g g (-1) dry weight in a short growth period of 42 days.


Input: The order of accumulation of Se among the plant parts was leaves (31. 5 mu g g (-1)) > stems (16. 4 mu g g (-1)) > roots (15. 5 mu g g (-1)).

Se


Input: The accumulation potential was fourfold higher than the plant available concentration of 15. 2 mu g g (-1) of Se g (-1) of soil (diethylenetriaminepentaacetic acid extracted).

Se

diethylenetriaminepentaacetic acid


Input: Although the plant was able to accumulate Se in their tissues, increase in Se concentrations in soil caused a concentration-dependent decrease in the growth rate of plants (regeneration of leaves, number of leaves, number of roots, root length, stem length and biomass).

Se

Se


Input: Green approach & #8212; multicomponent production of boron & #8212; containing hantzsch and biginelli esters.

boron


Input: Multicomponent reactions are excellent methods that meet the requirements of green chemistry, by reducing the number of steps, and consequently reducing purification requirements.


Input: Accordingly, in this work, 11 novel hybrid-boron-containing molecules, namely eight 1, 4-dihydropyridines and three 3, 4-dihydropyrimidinones, derived from formylphenylboronic acids (ortho, meta and para), were obtained using a green approach, involving H-4CR and B-3CR practices, in the presence of ethanol, which is a green solvent, and using three comparatively different modes of activation (mantle heating, yield 3%-7% in 24 h, Infrared Radiation (IR) irradiation, yield 12%-17% in 12 h, and microwave irradiation, yield 18%-80%, requiring very low reaction times of 0. 25-0. 33 h).

boron

1, 4-dihydropyridines

3, 4-dihydropyrimidinones

formylphenylboronic acids

ethanol


Input: In addition, as a green-approach is offered, a convenient analysis, of the 12 green chemistry principles for the overall procedure was performed.


Input: Finally, since all the products are new, characterizations were carried out using common analytic procedures (1H, 11B, and 13C NMR, FAB + MS, HRMS, and IR).


Input: The accurate mass data of unexpected ions related to interactions between thioglycerol and the expected products, in the FAB +-mode, enabled unequivocal characterization of the target molecules.

thioglycerol


Input: Adsorption and Self-Assembly of Large Polycyclic Molecules on the Surfaces of TiO2 Single Crystals.


Input: Titanium dioxide is one of the most frequently studied metal oxides, and its (110) rutile surface serves as a prototypical model for the surface science of such materials.

Titanium dioxide

metal oxides


Input: Recent studies have also shown that the (011) surface is relatively easy for preparation in ultra-high vacuum (UHV) and that both the (110) and (011) surfaces could be precisely characterized using scanning tunneling microscopy (STM).


Input: The supramolecular self-assembly of organic molecules on the surfaces of titanium dioxide plays an important role in nanofabrication, and it can control the formation and properties of nanostructures, leading to wide range of applications covering the fields of catalysis, coatings and fabrication of sensors and extends to the optoelectronic industry and medical usage.

titanium dioxide


Input: Although the majority of experiments and theoretical calculations are focused on the adsorption of relatively small organic species, in recent years, there has been increasing interest in the properties of larger molecules that have several aromatic rings in which functional units could also be observed.


Input: The purpose of this review is to summarize the achievements in the study of single polycyclic molecules and thin layers adsorbed onto the surfaces of single crystalline titanium dioxide over the past decade.

titanium dioxide


Input: Anti-inflammatory activity of Bromelia hieronymi: comparison with bromelain.


Input: Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators.


Input: Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus.

cysteine


Input: In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented.

cysteine


Input: Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model.

serotonine


Input: Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses.


Input: Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action.


Input: Primary hepatocyte cultures as prominent in vitro tools to study hepatic drug transporters.


Input: Abstract Before any drug can be placed on the market, drug efficacy and safety must be ensured through rigorous testing.


Input: Animal models are used for this purpose, though currently increasing attention goes to the use of alternative in vitro systems.


Input: In particular, liver-based testing platforms that allow the prediction of pharmacokinetic (PK) and pharmacotoxicological properties during the early phase of drug development are of interest.


Input: They also enable the screening of potential effects on hepatic drug transporters.


Input: The latter are known to affect drug metabolism and disposition, thereby possibly underlying drug-drug interactions, which, in turn, may result in liver toxicity.


Input: Clearly, stable in vivo-like functional expression of drug transporters in hepatic in vitro settings is a prerequisite to be applicable in routine PK and pharmacotoxicological testing.


Input: In the first part of the article, an updated overview of hepatic drug transporters is provided, followed by a state-of-the-art review of drug-transporter production and activity in primary hepatocyte cultures (PHCs), being the gold-standard in vitro system.


Input: Specific focus is hereby put on strategies to maintain long-term functional expression, in casu of drug transporters, in these systems.


Input: In the second part, the use of PHCs to assess hepatobiliary transport and transporter-mediated interactions is outlined.


Input: Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin.

metformin


Input: AIM: Assess the pharmacodynamics of lixisenatide once daily (QD) versus liraglutide QD in type 2 diabetes insufficiently controlled on metformin.

metformin


Input: METHODS: In this 28-day, randomized, open-label, parallel-group, multicentre study (NCT01175473), patients (mean HbA1c 7. 3%) received subcutaneous lixisenatide QD (10 micro g weeks 1-2, then 20 micro g; n = 77) or liraglutide QD (0. 6 mg week 1, 1. 2 mg week 2, then 1. 8 mg; n = 71) 30 min before breakfast.


Input: Primary endpoint was change in postprandial plasma glucose (PPG) exposure from baseline to day 28 during a breakfast test meal.

glucose


Input: RESULTS: Lixisenatide reduced PPG significantly more than liraglutide [mean change in AUC (0) (: 30-4: 30h):-12. 6 vs.-4. 0 h/mmol/l, respectively; p < 0. 0001 (0: 30 h = start of meal)].


Input: Change in maximum PPG excursion was-3. 9 mmol/l vs.-1. 4 mmol/l, respectively (p < 0. 0001).


Input: More lixisenatide-treated patients achieved 2-h PPG < 7. 8 mmol/l (69% vs. 29%).


Input: Changes in fasting plasma glucose were greater with liraglutide (-0. 3 vs.-1. 3 mmol/l, p < 0. 0001).


Input: Lixisenatide provided greater decreases in postprandial glucagon (p < 0. 05), insulin (p < 0. 0001) and C-peptide (p < 0. 0001).


Input: Mean HbA1c decreased in both treatment groups (from 7. 2% to 6. 9% with lixisenatide vs. 7. 4% to 6. 9% with liraglutide) as did body weight (-1. 6 kg vs.-2. 4 kg, respectively).


Input: Overall incidence of adverse events was lower with lixisenatide (55%) versus liraglutide (65%), with no serious events or hypoglycaemia reported.


Input: CONCLUSIONS: Once daily prebreakfast lixisenatide provided a significantly greater reduction in PPG (AUC) during a morning test meal versus prebreakfast liraglutide.


Input: Lixisenatide provided significant decreases in postprandial insulin, C-peptide (vs. an increase with liraglutide) and glucagon, and better gastrointestinal tolerability than liraglutide.


Input: Anti-M u llerian hormone trend after laparoscopic surgery in women with ovarian endometrioma.


Input: Abstract Operative laparoscopy is the gold standard in the treatment of endometriotic ovarian cysts.


Input: Excisional surgery is the best technique to prevent recurrences and improve symptoms but it may result in ovarian reserve damage due to the removal of healthy ovarian cortex.


Input: The aim of this study was to investigate the extent of the ovarian reserve damage after stripping technique of unilateral endometriomas, by dosing the Anti-M u llerian Hormone (AMH).


Input: This prospective study was conducted at the Center of Minimally Invasive Pelvic Surgery of the Department of Health of Woman and Child, University of Padua, from October 2010 to June 2012.


Input: Twenty-five women underwent excision of monolateral endometriosis ovarian cyst by stripping without accessing a bipolar coagulation and performing an intracortical suture.


Input: The AMH serum levels were estimated in the early proliferative phase of the cycle, before surgery (time 0), 24 h after surgery (time 1), the first menstrual cycle after surgery (time 2) and the third menstrual cycle after surgery (time 3).


Input: We found a nonstatistically significant decreases in serum AMH levels after surgical excision of the cysts.


Input: Our results suggest that an appropriate surgical technique, without the use of the bipolar coagulation of ovarian border, does not determine a significant reduction of ovarian reserve.


Input: Eukaryotic initiation factor 5A dephosphorylation is required for translational arrest in stationary phase cells.


Input: The protein known as eIF5A (eukaryotic initiation factor 5A) has an elusive role in translation.


Input: It has a unique and essential hypusine modification at a conserved lysine residue in most eukaryotes.

lysine


Input: In addition, this protein is modified by phosphorylation with unknown functions.


Input: In the present study we show that a phosphorylated state of eIF5A predominates in exponentially growing Trypanosoma cruzi cells, and extensive dephosphorylation occurs in cells in stationary phase.


Input: Phosphorylation occurs mainly at Ser (2), as shown in yeast eIF5A.

Ser


Input: In addition, a novel phosphorylation site was identified at Tyr (21).

Tyr


Input: In exponential cells, T. cruzi eIF5A is partially associated with polysomes, compatible with a proposed function as an elongation factor, and becomes relatively enriched in polysomal fractions in stationary phase.


Input: Overexpression of the wild-type eIF5A, or eIF5A with Ser (2) replaced by an aspartate residue, but not by alanine, increases the rate of cell proliferation and protein synthesis.

Ser

aspartate

alanine


Input: However, the presence of an aspartate residue instead of Ser (2) is toxic for cells reaching the stationary phase, which show a less-pronounced protein synthesis arrest and a decreased amount of eIF5A in dense fractions of sucrose gradients.

aspartate

Ser

sucrose


Input: We conclude that eIF5A phosphorylation and dephosphorylation cycles regulate translation according to the growth conditions.


Input: Potent and Selective Inhibition of Histone Deacetylase 6 (HDAC6) Does Not Require a Surface-Binding Motif.


Input: Hydroxamic acids were designed, synthesized, and evaluated for their ability to selectively inhibit human histone deacetylase 6 (HDAC6).

Hydroxamic acids


Input: Several inhibitors, including compound 14 (BRD9757), exhibited excellent potency and selectivity despite the absence of a surface-binding motif.


Input: The binding of these highly efficient ligands for HDAC6 is rationalized via structure-activity relationships.


Input: These results demonstrate that high selectivity and potent inhibition of HDAC6 can be achieved through careful choice of linker element only.


Input: Left, right, or both?


Input: On the configuration of the phenanthroindolizidine alkaloid tylophorine from Tylophora indica.

phenanthroindolizidine alkaloid


Input: The alkaloid (-)-tylophorine was isolated from a sample of Tylophora indica, and the crude extract was analyzed by HPLC/MS (n) and chiral HPLC/MS.

(-)-tylophorine


Input: While the literature states that the naturally occurring form of this alkaloid is the R-enantiomer and that its S-antipode is usually not found in nature, we confirmed the hypothesis of Govindachari and Nagarajan that natural levorotatory tylophorine is indeed a nearly racemic mixture with a slight excess of the R-enantiomer.

levorotatory tylophorine


Input: Evaluation of in vivo anti-hyperglycemic and antioxidant potentials of alpha-santalol and sandalwood oil.

alpha-santalol


Input: Sandalwood finds numerous mentions across diverse traditional medicinal systems in use worldwide.


Input: The objective of this study was to evaluate the in vivo anti-hyperglycemic and antioxidant potential of sandalwood oil and its major constituent alpha-santalol.

alpha-santalol


Input: The in vivo anti-hyperglycemic experiment was conducted in alloxan-induced diabetic male Swiss albino mice models.

alloxan


Input: The in vivo antioxidant experiment was performed in d-galactose mediated oxidative stress induced male Swiss albino mice models.

d-galactose


Input: Intraperitoneal administration of alpha-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for an week modulated parameters such as body weight, blood glucose, serum bilirubin, liver glycogen, and lipid peroxides contents to normoglycemic levels in the alloxan-induced diabetic mice.

alpha-santalol

glucose

bilirubin

peroxides

alloxan


Input: Similarly, intraperitoneal administration of alpha-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for two weeks modulated parameters such as serum aminotransferases, alkaline phosphatase, bilirubin, superoxide dismutase, catalase, free sulfhydryl, protein carbonyl, nitric oxide, liver lipid peroxide contents, and antioxidant capacity in d-galactose mediated oxidative stress induced mice.

alpha-santalol

bilirubin

superoxide

sulfhydryl

carbonyl

nitric oxide

peroxide

d-galactose


Input: Besides, it was observed that the beneficial effects of alpha-santalol were well complimented, differentially by other constituents present in sandalwood oil, thus indicating synergism in biological activity of this traditionally used bioresource.

alpha-santalol


Input: Endothelium-dependent vasodilatation effects of the essential oil from Fructus alpiniae zerumbet (EOFAZ) on rat thoracic aortic rings in vitro.


Input: Fructus Alpiniae Zerumbet (FAZ) is an herb widely used to treat vascular disorders in Guizhou province, China, the essential oil has been identified as one of it vasodilation effect active components, and especial, the composition was significantly difference from the leaves.


Input: Vasodilation effects and mechanism of essential oil from FAZ (EOFAZ) were investigated.


Input: The EOFAZ showed significant vasodilation effect on endothelium-with rat thoracic aortic rings preincubated with norepinephrine (NE, 1. 0 mu M) or KCl (60mM) in a concentration-dependent manner (1. 14-72. 96 mu g/ml).


Input: The non-selective nitric oxide synthase inhibitor l-NAME, as well as the soluble guanylate cyclase inhibitor MB, attenuated the relaxation of EOFAZ in endothelium-intact rat thoracic aortic rings.

nitric oxide

l-NAME

guanylate


Input: However, there were not significantly affected the vasodilation effects pretreated with cyclooxygenase inhibition by indomethacin (Indo) or beta-noradrenergic inhibition by propranolol (Prop).

indomethacin

Indo

propranolol

Prop


Input: The present results first demonstrated that vasodilation effect of EOFAZ depending upon the endothelium and concentration, and the mechanism involvement of NOS-cGMP system.

cGMP


Input: In contrast, prostacyclin and beta-adrenoceptor may not be associated with EOFAZ-induced vasorelaxation.

prostacyclin


Input: Syntheses of lipophilic chalcones and their conformationally restricted analogues as antitubercular agents.

chalcones


Input: Lipophilic chalcones and their conformationally restricted analogues were synthesized and evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv strain.


Input: Compounds 16, 24, 25a and 25c were found to be active MIC at 60, 30, 3. 5 and 7. 5 mu g-mL (-1).


Input: In vitro cytotoxicity of compounds 16, 24, 25a, 25c and 26 in non-cancerous human epithelial kidney cell line (HEK-293) showed that most active compound 25a was approximately 2. 85 times selective towards tubercular versus healthy cells whereas compound 24 was found to be 16 times selective.


Input: Transformation of paralytic shellfish poisoning toxins in UK surf clams (Spisula solida) for targeted production of reference materials.


Input: The periodic occurrence of Paralytic Shellfish Poisoning (PSP) toxins in UK surf clams and the recent move away from biological assays for PSP testing resulted in the need to determine method performance characteristics for the replacement analytical method in this species.


Input: With the requirement for laboratory reference materials to aid this validation together with known issues relating to toxin transformation in live clams and homogenised tissue, there was the need to assess the toxin transformation characteristics of PSP toxins in surf clam tissue.


Input: Initial work examined the rates of toxin transformation in UK surf clam tissue incubated with toxin standards, showing rapid transformation of N-sulfocarbamoyl toxins with slower transformation of carbamate toxins.

N-sulfocarbamoyl

carbamate


Input: Full transformational pathways were determined using a combination of three different analytical methods and confirmed the major expected transformations involving decarbamoylation, with some evidence for additional reaction pathways.


Input: Results obtained from the analysis of surf clam and oyster tissues incubated with varying concentrations of toxic Alexandrium algae highlighted expected transformation reactions, although significant differences were observed in the extent of the transformations amongst the range of toxins studied, with less efficient transformation of N-hydroxylated toxins as compared with other carbamate and N-sulfocarbamoyl toxins.

N

carbamate and N-sulfocarbamoyl


Input: Analysis of PSP-toxic incurred oyster, scallop and mussel tissues incubated with variable proportions of surf clam tissue showed large differences in the extent of the transformations.


Input: Total conversion of N-sulfocarbamoyl toxins was confirmed at low relative proportions of surf clam tissue in all three species, whereas transformation of carbamate toxins was found to occur only in the presence of higher proportions of surf clam tissue in oysters and mussels in comparison with scallops.

N

carbamate


Input: Results enabled the production of three laboratory reference materials prepared following incubation of incurred homogenates with optimum proportions of surf clam tissue, resulting in materials containing a large number of PSP toxins.


Input: Stability experiments provided good preliminary evidence for the stability of these targeted materials under storage conditions.


Input: The work therefore provides both additional information relating to the transformational activity in UK surf clams and highlights a good potential method for the targeted production of reference materials which include a wider range of toxins than normally present in naturally incurred shellfish.


Input: Mercuric chloride-induced testicular toxicity in rats and the protective role of sodium selenite and vitamin E.

Mercuric chloride

sodium selenite

vitamin E


Input: Mercury has been recognized as an environmental pollutant that adversely affects male reproductive systems of animals.

Mercury


Input: This study examined the effects of mercuric chloride on the antioxidant system and histopathological changes and also evaluated the ameliorating effects of sodium selenite and/or vitamin E in the rat testis tissues.

mercuric chloride

sodium selenite

vitamin E


Input: Sexually mature male Wistar rats (weighing 300-320g and each group six animals) were given mercuric chloride (1mg/kg bw) and/or sodium selenite (0. 25mg/kg bw) + vitamin E (100mg/kg) daily via gavage for 4weeks.

mercuric chloride

sodium selenite

vitamin E


Input: In the present study, mercuric chloride exposure resulted in an increase in the TBARS level and a decrease in the SOD, CAT, GPx activities, with respect to the control.

mercuric chloride


Input: Further, light microscopic investigation revealed that mercury exposure induced histopathological alterations in the testis tissues.

mercury


Input: Supplementation of sodium selenite and/or vitamin E to mercury-induced groups declined lipid peroxidation, increased SOD, CAT, GPx activities.

sodium selenite

vitamin E

mercury


Input: While some histopathological changes were detected in mercuric chloride treated group, milder histopathological changes were observed in animal co-treated with sodium selenite and/or vitamin E supplementation to mercuric chloride-treated rats.

mercuric chloride

sodium selenite

vitamin E

mercuric chloride


Input: As a result, mercuric chloride induced testicular toxicity is reduced by sodium selenite and/or vitamin E, but not ameliorate completely.

mercuric chloride

sodium selenite

vitamin E


Input: Biomonitoring a human population inhabiting nearby a deactivated uranium mine.

uranium


Input: Environmental exposure to uranium and its daughter radionuclides, has been linked to several negative effects such as those related with important physiological processes, like hematopoiesis, and may also be associated with genotoxicity effects.

uranium


Input: Herein, genotoxic effects, immunotoxicity, trace elements and C reactive protein (CRP) analyses, were performed in peripheral blood samples collected from individuals of a population living near a deactivated uranium mine.

uranium


Input: C reactive protein analysis was performed to exclude candidates with active inflammatory processes from further evaluations.


Input: DNA damage and immunotoxicity (immunophenotyping and immune cell counts) were evaluated by comet assay and flow cytometry, respectively.


Input: Significant DNA damage was observed in the peripheral blood samples from volunteers living in the Cunha Baixa village.


Input: A significant decrease of NK and T lymphocytes counts were observed in the individuals from the Cunha Baixa village, when compared with individuals from the reference site.


Input: Uranium and manganese levels were significantly higher in the Cunha Baixa village inhabitants.

Uranium

manganese


Input: On the other hand, zinc levels were significantly lower in those individuals when compared with the volunteers from the control village.

zinc


Input: Results suggest that inhabitants from Cunha Baixa have a higher risk of suffering from serious diseases such as cancer, since high DNA damages were observed in peripheral blood leukocytes and also decreased levels of NK and T cells, which play an essential role in the defense against tumor growth.


Input: Nonhuman primate models of polycystic ovary syndrome.


Input: With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention.


Input: Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS.

testosterone


Input: Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment.


Input: Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming.

dihydrotestosterone

DHT

diethylstilbestrol

DES


Input: Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T).


Input: Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction.


Input: Eight New Diterpenoids and Two New Nor-Diterpenoids from the Stems of Croton cascarilloides.

Diterpenoids

Nor-Diterpenoids


Input: From the stems of Croton cascarilloides, eight new diterpenoids, named crotocascarins A-H (1-8), having a crotofolane skeleton were isolated along with two new nor-diterpenoids (9 and 10), named crotocascarins alpha and beta, derived through rearrangement of the crotofolane skeleton.

diterpenoids

crotocascarins A-H

crotofolane

nor-diterpenoids

crotofolane


Input: The structures of these compounds were elucidated by means of extensive one-and two-dimensional NMR spectroscopic analyses.


Input: The absolute structures of the diterpene moiety were determined by application of the circular dichroism (CD) rule for the gamma-lactone ring.

diterpene

gamma-lactone


Input: The relative structures of the two crotofolanes (1 and 2) and one rearranged compound (9) were confirmed by X-ray crystallographic analyses.

crotofolanes


Input: Compounds 1, 2 and 9 possessed 2-methylbutyric acid in their molecules, the absolute configuration of which was found to be 2S by comparison of its HPLC behavior with that of an authentic sample.

2-methylbutyric acid


Input: Therefore, the absolute structures of these crotocascarins (1, 2 and 9) were unambiguously determined.

crotocascarins


Input: The absolute structures of crotofolanes are reported for the first time in this paper.

crotofolanes


Input: Silencing of RB1 but not of RB2/P130 induces cellular senescence and impairs the differentiation potential of human mesenchymal stem cells.


Input: Stem cell senescence is considered deleterious because it may impair tissue renewal and function.


Input: On the other hand, senescence may arrest the uncontrolled growth of transformed stem cells and protect organisms from cancer.


Input: This double function of senescence is strictly linked to the activity of genes that the control cell cycle such as the retinoblastoma proteins RB1, RB2/P130, and P107.


Input: We took advantage of the RNA interference technique to analyze the role of these proteins in the biology of mesenchymal stem cells (MSC).


Input: Cells lacking RB1 were prone to DNA damage.


Input: They showed elevated levels of p53 and p21 (cip1) and increased regulation of RB2/P130 and P107 expression.


Input: These cells gradually adopted a senescent phenotype with impairment of self-renewal properties.


Input: No significant modification of cell growth was observed as it occurs in other cell types or systems.


Input: In cells with silenced RB2/P130, we detected a reduction of DNA damage along with a higher proliferation rate, an increase in clonogenic ability, and the diminution of apoptosis and senescence.


Input: Cells with silenced RB2/P130 were cultivated for extended periods of time without adopting a transformed phenotype.


Input: Of note, acute lowering of P107 did not induce relevant changes in the in vitro behavior of MSC.


Input: We also analyzed cell commitment and the osteo-chondro-adipogenic differentiation process of clones derived by MSC cultures.


Input: In all clones obtained from cells with silenced retinoblastoma genes, we observed a reduction in the ability to differentiate compared with the control clones.


Input: In summary, our data show evidence that the silencing of the expression of RB1 or RB2/P130 is not compensated by other gene family members, and this profoundly affects MSC functions.


Input: Parallel buprenorphine phMRI responses in conscious rodents and healthy human subjects.

buprenorphine


Input: Pharmacological magnetic resonance imaging (phMRI) is one method by which a drug' s pharmacodynamic effects in the brain can be assessed.


Input: Although phMRI has been frequently used in preclinical and clinical settings, the extent to which a phMRI signature for a compound translates between rodents and humans has not been systematically examined.


Input: In the current investigation, we aimed to build on recent clinical work in which the functional response to 0. 1 and 0. 2 mg/70 kg i. v. buprenorphine (partial micro-opioid receptor agonist) was measured in healthy humans.

buprenorphine


Input: Here, we measured the phMRI response to 0. 04 and 0. 1 mg/kg i. v. buprenorphine in conscious, naive rats to establish the parallelism of the phMRI signature of buprenorphine across species.

buprenorphine

buprenorphine


Input: PhMRI of 0. 04 and 0. 1 mg/kg i. v. buprenorphine yielded dose-dependent activation in a brain network composed of the somatosensory cortex, cingulate, insula, striatum, thalamus, periaqueductal gray, and cerebellum.

buprenorphine


Input: Similar dose-dependent phMRI activation was observed in the human phMRI studies.


Input: These observations indicate an overall preservation of pharmacodynamic responses to buprenorphine between conscious, naive rodents and healthy human subjects, particularly in brain regions implicated in pain and analgesia.

buprenorphine


Input: This investigation further demonstrates the usefulness of phMRI as a translational tool in neuroscience research that can provide mechanistic insight and guide dose selection in drug development.


Input: Resistance to conventional insecticides in Pakistani populations of Musca domestica L.


Input: (Diptera: Muscidae): a potential ectoparasite of dairy animals.


Input: The house fly, Musca domestica L., is an important hygienic pest of humans and dairy animals with the potential to develop resistance to most chemical classes of insecticides.


Input: Six adult house fly strains from dairy farms in Punjab, Pakistan were evaluated for resistance to selected insecticides from organochlorine, organophosphate, carbamate and pyrethroid classes.

organochlorine

organophosphate

carbamate

pyrethroid


Input: For a chlorocyclodiene and two organophosphates tested, the resistance ratios (RR) at LC50 were in the range of 5. 60-22. 02 fold for endosulfan, 7. 66-23. 24 fold for profenofos and 2. 47-7. 44 fold for chlorpyrifos.

chlorocyclodiene

organophosphates

endosulfan

chlorpyrifos


Input: For two pyrethroids and one carbamate, the RR values at LC50 were 30. 22-70. 02 for cypermethrin, 5. 73-18. 31 for deltamethrin, and 4. 39-15. 50 for methomyl.

pyrethroids

carbamate

cypermethrin

deltamethrin

methomyl


Input: This is the first report of resistance to different classes of insecticides in Pakistani dairy populations of house flies.


Input: Regular insecticide resistance monitoring programs on dairy farms are needed to prevent field control failures.


Input: Moreover, integrated approaches including the judicious use of insecticides are needed to delay the development of insecticide resistance in house flies.


Input: In obese postmenopausal women, bone microarchitecture and strength are not commensurate to greater body weight.


Input: The OFELY study.


Input: Obesity is associated with higher areal bone density (aBMD) but its protective effect on the risk of fracture is controversial.


Input: We aimed to analyse bone microarchitecture and biomechanical properties in obese (OB) postmenopausal French women compared with normal weight (NW) women.


Input: A matched case-control study from the OFELY cohort was conducted in 63 OB women (BMI > 30, mean age69 +/- 8 years) age-matched with 126 NW women (19 < BMI < 25).


Input: Bone architecture was measured with high-resolution pQCT at the distal radius and tibia and bone strength was assessed by micro-finite element analysis (micro FEA).


Input: aBMD, total body fat (FM) and lean (LM) masses were measured by DXA.


Input: aBMD was 15% higher at the total hip in OB compared with NW.


Input: At the radius, OB had 13 and 14% higher volumetric total and trabecular bone densities, 11% higher cortical thickness, 13% greater trabecular number, and 22% lower distribution of trabecular separation compared with NW (p adjusted for height, physical activity and medication use < 0. 01 for all).


Input: Differences of a similar magnitude were found at the distal tibia.


Input: At both sites, micro FEA showed significant higher values of bone strength in OB compared to controls.


Input: After normalizing values for individual body weight, we observed that all the parameters were relatively lower in OB compared to NW women.


Input: The increase of FM was four fold greater than the increase of LM in OB.


Input: The effect of FM on bone parameters was more pronounced at the tibia than compared to the non-weight bearing site.


Input: Nevertheless, the coefficients of correlation were about half of those of LM for the biomechanical parameters.


Input: We conclude that higher absolute values of bone densities, cortical and trabecular architecture and strength indices were not in proportion to the excess of BMI and particularly of FM in obese postmenopausal French women.


Input: (c) 2013 American Society for Bone and Mineral Research.


Input: Ceftazidime-avibactam: a novel cephalosporin/beta-lactamase inhibitor combination.

Ceftazidime

avibactam

cephalosporin


Input: Avibactam (formerly NXL104, AVE1330A) is a synthetic non-beta-lactam, beta-lactamase inhibitor that inhibits the activities of Ambler class A and C beta-lactamases and some Ambler class D enzymes.

Avibactam

beta-lactam


Input: This review summarizes the existing data published for ceftazidime-avibactam, including relevant chemistry, mechanisms of action and resistance, microbiology, pharmacokinetics, pharmacodynamics, and efficacy and safety data from animal and human trials.

ceftazidime

avibactam


Input: Although not a beta-lactam, the chemical structure of avibactam closely resembles portions of the cephem bicyclic ring system, and avibactam has been shown to bond covalently to beta-lactamases.

beta-lactam

avibactam

cephem

avibactam


Input: Very little is known about the potential for avibactam to select for resistance.

avibactam


Input: The addition of avibactam greatly (4-1024-fold minimum inhibitory concentration [MIC] reduction) improves the activity of ceftazidime versus most species of Enterobacteriaceae depending on the presence or absence of beta-lactamase enzyme (s).

avibactam

ceftazidime


Input: Against Pseudomonas aeruginosa, the addition of avibactam also improves the activity of ceftazidime (~ fourfold MIC reduction).

avibactam

ceftazidime


Input: Limited data suggest that the addition of avibactam does not improve the activity of ceftazidime versus Acinetobacter species or most anaerobic bacteria (exceptions: Bacteroides fragilis, Clostridium perfringens, Prevotella spp. and Porphyromonas spp.).

avibactam

ceftazidime


Input: The pharmacokinetics of avibactam follow a two-compartment model and do not appear to be altered by the co-administration of ceftazidime.

avibactam

ceftazidime


Input: The maximum plasma drug concentration (C (max)) and area under the plasma concentration-time curve (AUC) of avibactam increase linearly with doses ranging from 50 mg to 2, 000 mg.

avibactam


Input: The mean volume of distribution and half-life of 22 L (~ 0. 3 L/kg) and ~ 2 hours, respectively, are similar to ceftazidime.

ceftazidime


Input: Like ceftazidime, avibactam is primarily renally excreted, and clearance correlates with creatinine clearance.

ceftazidime

avibactam

creatinine


Input: Pharmacodynamic data suggest that ceftazidime-avibactam is rapidly bactericidal versus beta-lactamase-producing Gram-negative bacilli that are not inhibited by ceftazidime alone. Clinical trials to date have reported that ceftazidime-avibactam is as effective as standard carbapenem therapy in complicated intra-abdominal infection and complicated urinary tract infection, including infection caused by cephalosporin-resistant Gram-negative isolates.

ceftazidime

avibactam

ceftazidime

ceftazidime

avibactam

carbapenem

cephalosporin


Input: The safety and tolerability of ceftazidime-avibactam has been reported in three phase I pharmacokinetic studies and two phase II clinical studies.

ceftazidime

avibactam


Input: Ceftazidime-avibactam appears to be well tolerated in healthy subjects and hospitalized patients, with few serious drug-related treatment-emergent adverse events reported to date. In conclusion, avibactam serves to broaden the spectrum of ceftazidime versus beta-lactamase-producing Gram-negative bacilli.

Ceftazidime

avibactam

avibactam

ceftazidime


Input: The exact roles for ceftazidime-avibactam will be defined by efficacy and safety data from further clinical trials.

ceftazidime

avibactam


Input: Potential future roles for ceftazidime-avibactam include the treatment of suspected or documented infections caused by resistant Gram-negative-bacilli producing extended-spectrum beta-lactamase (ESBL), Klebsiella pneumoniae carbapenemases (KPCs) and/or AmpC beta-lactamases.

ceftazidime

avibactam


Input: In addition, ceftazidime-avibactam may be used in combination (with metronidazole) for suspected polymicrobial infections.

ceftazidime

avibactam

metronidazole


Input: Finally, the increased activity of ceftazidime-avibactam versus P. aeruginosa may be of clinical benefit in patients with suspected or documented P. aeruginosa infections.

ceftazidime

avibactam


Input: Increased human dermal microvascular endothelial cell survival induced by cysteamine.

cysteamine


Input: BACKGROUND: Cystinosis is an autosomal recessive disease caused by intralysosomal cystine accumulation, treated with cysteamine.

cysteamine


Input: Recently, new adverse effects of cysteamine were reported.

cysteamine


Input: Skin biopsies showed microvascular proliferation (angioendotheliomatosis).


Input: To examine the mechanism of angioendotheliomatosis associated with cysteamine toxicity, we examined the effect of cysteamine on human dermal microvascular endothelial cells (HDMVEC).

cysteamine

cysteamine


Input: METHODS: After cysteamine exposure (range 0-3. 0 mM) during 24 h, cell viability was measured using water soluble tetrazolium salt-1 (WST-1) in both control HDMVEC and fibroblasts.

cysteamine

tetrazolium salt-1


Input: Cell proliferation and apoptosis rate were measured in HDMVEC by bromodeoxyuridine (BrdU) incorporation and caspase 3 and caspase 7 activity, respectively.

bromodeoxyuridine

BrdU


Input: Intracellular glutathione (GSH) was measured in HDMVEC after cysteamine exposure of 0, 0. 1 or 1. 0 mM.

glutathione

GSH

cysteamine


Input: Medium and cysteamine were refreshed every 6 h to mimic the in vivo situation.

cysteamine


Input: Next, cell viability in HDMVEC was measured after 24 h of GSH exposure (range 0-10. 0 mM).

GSH


Input: RESULTS: HDMVEC viability and proliferation increased after cysteamine exposure 0. 03-3. 0 mM (p < 0. 01) and 0. 03-1. 0 mM (p = 0. 01) respectively; cell viability in fibroblasts was not affected by incubation with cysteamine.

cysteamine

cysteamine


Input: Apoptosis remained unaffected by incubation with 0-1. 0 mM cysteamine, 3. 0 mM caused increased apoptosis.

cysteamine


Input: Intracellular GSH was significantly increased after incubation with cysteamine 0. 1 mM (p = 0. 02) and 1. 0 mM (p < 0. 01).

GSH

cysteamine


Input: HDMVEC viability increased after exposure to GSH 1. 0-5. 0 mM (p < 0. 01).

GSH


Input: CONCLUSION: Cysteamine concentrations, similar to those described in plasma of cystinosis patients, stimulate HDMVEC viability and proliferation and increase intracellular GSH content.

Cysteamine

GSH


Input: We postulate that this mechanism might underlie angioendotheliomatosis induced by cysteamine.

cysteamine


Input: Effect of wheel-running during abstinence on subsequent nicotine-seeking in rats.

nicotine


Input: RATIONALE: Exercise appears to be a promising non-pharmacological treatment for nicotine addiction that may be useful for the vulnerable adolescent population.

nicotine


Input: OBJECTIVES: The aim of this study is to determine if wheel-running, an animal model of aerobic exercise, during an abstinence period would decrease subsequent nicotine-seeking in rats that had extended access to nicotine self-administration during adolescence.

nicotine


Input: METHODS: Male adolescent rats (n = 55) were trained to self-administer saline or nicotine infusions (5 or 10 mu g/kg) under a fixed ratio 1 schedule with a maximum of 20 infusions/day beginning on postnatal day 30.

nicotine


Input: After 5 days, access was extended to 23 h/day with unlimited infusions for a total of 10 days.


Input: After the last self-administration session, rats were moved to polycarbonate cages for a 10-day abstinence period where they either had access to a locked or unlocked running wheel for 2 h/day.

polycarbonate


Input: Nicotine-seeking was examined following the 10th day of abstinence under a within-session extinction/cue-induced reinstatement paradigm.

Nicotine


Input: RESULTS: Intake was higher at the 10 mu g/kg dose as compared to the 5 mu g/kg dose; however, intake did not differ within doses prior to wheel assignment.


Input: Compared to saline controls, rats that self-administered nicotine at either dose showed a significant increase in drug-seeking during extinction, and consistent with our hypothesis, exercise during abstinence attenuated this effect.

nicotine


Input: Nicotine led to modest but significant levels of cue-induced reinstatement; however, in this adolescent-onset model, levels were variable and not affected by exercise.

Nicotine


Input: CONCLUSIONS: Exercise may effectively reduce relapse vulnerability for adolescent-onset nicotine addiction.

nicotine


Input: Mephedrone and methylenedioxypyrovalerone (MDPV), major constituents of " bath salts, " produce opposite effects at the human dopamine transporter.

Mephedrone

methylenedioxypyrovalerone

MDPV

dopamine


Input: RATIONALE: Psychoactive " bath salts " represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011.


Input: Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV).

cathinone

mephedrone

methylenedioxypyrovalerone

MDPV


Input: The mechanism of action of these synthetic cathinone analogs has not been well investigated.

cathinone


Input: MATERIALS AND METHODS: Because cathinone and methcathinone are known to act as releasing agents at the human dopamine transporter (hDAT), mephedrone and MDPV were investigated at hDAT expressed in Xenopus oocytes.

cathinone

methcathinone

dopamine

mephedrone

MDPV


Input: RESULTS: Whereas mephedrone was found to have the signature of a dopamine-releasing agent similar to methamphetamine or methcathinone, MDPV behaved as a cocaine-like reuptake inhibitor of dopamine.

mephedrone

dopamine

methamphetamine

methcathinone

MDPV

cocaine

dopamine


Input: CONCLUSIONS: Mephedrone and MDPV produce opposite electrophysiological signatures through hDAT expressed in oocytes.

Mephedrone

MDPV


Input: Implications are that the combination (as found in bath salts) might produce effects similar to a combination of methamphetamine and cocaine.

methamphetamine

cocaine


Input: Resin acid conversion with CYP105A1: an enzyme with potential for the production of pharmaceutically relevant diterpenoids.

Resin acid

diterpenoids


Input: Cytochrome P450s are very versatile enzymes with great potential for biotechnological applications because of their ability to oxidize unactivated C <F8FF> H bonds.

C <F8FF> H


Input: CYP105A1 from Streptomyces griseolus was first described as a herbicide-inducible sulfonylurea hydroxylase, but it is also able to convert other substrates such as vitamin D (3).

sulfonylurea

vitamin D (3)


Input: To extend the substrate pool of this interesting enzyme further, we screened a small diterpenoid compound library and were able to show the conversion of several resin acids.

diterpenoid

resin acids


Input: Binding of abietic acid, dehydroabietic acid, and isopimaric acid to the active site was assayed, and V (max) and K (m) values were calculated.

abietic acid

dehydroabietic acid

isopimaric acid


Input: The products were analyzed by NMR spectroscopy and identified as 15-hydroxyabietic acid, 15-hydroxydehydroabietic acid, and 15, 16-epoxyisopimaric acid.

15-hydroxyabietic acid

15-hydroxydehydroabietic acid

15, 16-epoxyisopimaric acid


Input: As the observed products are difficult to obtain by chemical synthesis, CYP105A1 has proved to be a promising candidate for biotechnological applications that combine bioconversion and chemical synthesis to obtain functionalized resin acids.

resin acids


Input: Anisotropically Luminescent Hydrogels Containing Magnetically-Aligned MWCNTs-Eu (III) Hybrids.

Eu (III)


Input: The anisotropic emission properties of an Eu (III)-MWCNTs-based nanocomposite PNIPAAm hydrogel is induced upon application of a 10 T magnetic field, the latter dictating the alignment of the carbon nanotubes.

Eu (III)

carbon


Input: This structuration creates directional highways for light to be preferentially absorbed, giving rise to orientation-dependent light emission intensity.


Input: Thermal control of the transparency of the aqueous matrix also allowed a stimulus-induced switching of the materials' emission properties.


Input: The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation.

phenethyl isothiocyanate


Input: Phenethylisothiocyanate (PEITC), a naturally occurring isothiocyanate and potent cancer chemopreventive agent, works by multiple mechanisms, including the inhibition of cytochrome P450 (P450) enzymes, such as CYP2E1, that are involved in the bioactivation of carcinogens.

Phenethylisothiocyanate

PEITC

isothiocyanate


Input: PEITC has been reported to be a mechanism-based inactivator of some P450s.

PEITC


Input: We describe here the possible mechanism for the inactivation of human CYP2E1 by PEITC, as well as the putative intermediate that might be involved in the bioactivation of PEITC.

PEITC

PEITC


Input: PEITC inactivated recombinant CYP2E1 with a partition ratio of 12, and the inactivation was not inhibited in the presence of glutathione (GSH) and not fully recovered by dialysis.

PEITC

glutathione

GSH


Input: The inactivation of CYP2E1 by PEITC is due to both heme destruction and protein modification, with the latter being the major pathway for inactivation.

PEITC


Input: GSH-adducts of phenethyl isocyanate (PIC) and phenethylamine were detected during the metabolism by CYP2E1, indicating formation of PIC as a reactive intermediate following P450-catalyzed desulfurization of PEITC.

GSH

phenethyl isocyanate

PIC

phenethylamine

PIC

PEITC


Input: Surprisingly, PIC bound covalently to CYP2E1 to form protein adducts but did not inactivate the enzyme.

PIC


Input: Liquid chromatography mass spectroscopy analysis of the inactivated CYP2E1 apo-protein suggests that a reactive sulfur atom generated during desulfurization of PEITC is involved in the inactivation of CYP2E1.

sulfur

PEITC


Input: Our data suggest that the metabolism of PEITC by CYP2E1 that results in the inactivation of CYP2E1 may occur by a mechanism similar to that observed with other sulfur-containing compounds, such as parathion.

PEITC

sulfur

parathion


Input: Digestion of the inactivated enzyme and analysis by SEQUEST showed that Cys 268 may be the residue modified by PIC.

Cys

PIC


Input: Metal-enzyme frameworks: role of metal ions in promoting enzyme self-assembly on alpha-zirconium (IV) phosphate nanoplates.

alpha-zirconium (IV) phosphate


Input: Previously, an ion-coupled protein binding (ICPB) model was proposed to explain the thermodynamics of protein binding to negatively charged alpha-Zr (IV) phosphate (alpha-ZrP).

alpha-Zr (IV) phosphate

alpha-ZrP


Input: This model is tested here using glucose oxidase (GO) and met-hemoglobin (Hb) and several cations (Zr (IV), Cr (III), Au (III), Al (III), Ca (II), Mg (II), Zn (II), Ni (II), Na (I), and H (I)).

glucose

Zr (IV)

Cr (III)

Au (III)

Al (III)

Ca (II)

Mg (II)

Zn (II)

Ni (II)

Na (I)

H (I)


Input: The binding constant of GO with alpha-ZrP was increased ~ 380-fold by the addition of either 1 mM Zr (IV) or 1 mM Ca (II), and affinities followed the trend Zr (IV) ~ Ca (II) > Cr (III) > Mg (II) >> H (I) > Na (I).

alpha-ZrP

Zr (IV)

Ca (II)

Zr (IV)

Ca (II)

Cr (III)

Mg (II)

H (I)

Na (I)


Input: Binding studies could not be conducted with Au (III), Al (III), Zn (II), Cu (II), and Ni (II), as these precipitated both proteins.

Au (III)

Al (III)

Zn (II)

Cu (II)

Ni (II)


Input: Zr (IV) increased Hb binding constant to alpha-ZrP by 43-fold, and affinity enhancements followed the trend Zr (IV) > H (I) > Mg (II) > Na (I) > Ca (II) > Cr (III).

Zr (IV)

alpha-ZrP

Zr (IV)

H (I)

Mg (II)

Na (I)

Ca (II)

Cr (III)


Input: Zeta potential studies clearly showed metal ion binding to alpha-ZrP and affinities followed the trend, Zr (IV) >> Cr (III) > Zn (II) > Ni (II) > Mg (II) > Ca (II) > Au (III) > Na (I) > H (I).

alpha-ZrP

Zr (IV)

Cr (III)

Zn (II)

Ni (II)

Mg (II)

Ca (II)

Au (III)

Na (I)

H (I)


Input: Electron microscopy showed highly ordered structures of protein/metal/alpha-ZrP intercalates on micrometer length scales, and protein intercalation was also confirmed by powder X-ray diffraction.

alpha-ZrP


Input: Specific activities of GO/Zr (IV)/alpha-ZrP and Hb/Zr (IV)/alpha-ZrP ternary complexes were 2. 0 x 10 (-3) and 6. 5 x 10 (-4) M (-1) s (-1), respectively.

Zr (IV)

alpha-ZrP

Zr (IV)

alpha-ZrP


Input: While activities of all GO/cation/alpha-ZrP samples were comparable, those of Hb/cation/alpha-ZrP followed the trend Mg (II) > Na (I) > H (I) > Cr (III) > Ca (II) ~ Zr (IV).

alpha-ZrP

alpha-ZrP

Mg (II)

Na (I)

H (I)

Cr (III)

Ca (II)

Zr (IV)


Input: Metal ions enhanced protein binding by orders of magnitude, as predicted by the ICPB model, and binding enhancements depended on charge as well as the phosphophilicity/oxophilicity of the cation.


Input: Reaction-diffusion framework: the mechanism of the polymorphic transition of alpha-to beta-cobalt hydroxide.

alpha-to beta-cobalt hydroxide


Input: A new and simple method is proposed to explore the mechanism of the intercalation/deintercalation of a variety of anions throughout the formation of alpha-Co (OH) 2 crystals and their polymorphic conversion to beta-Co (OH) 2.

alpha-Co (OH) 2

beta-Co (OH) 2


Input: This method is based on the reaction-diffusion of hydroxide ions in a gel matrix containing the cobalt salt.

hydroxide

cobalt


Input: The spatiotemporal evolution of each polymorph and their interaction is revealed by tracking the location of the two sharp interfaces between the two polymorphs (conversion zone) and between the gel and alpha-Co (OH) 2 (formation zone) and by measuring the weight composition of each zone.

alpha-Co (OH) 2


Input: We thereby find that the dynamics of the transformation reaction are correctly described by the two-dimensional Avrami-Erofe' ev equation at different temperatures.


Input: The data suggest that the structural redistribution of the atoms inside the alpha-Co (OH) 2 particles plays the fundamental role in establishing the overall rate of the reaction.

alpha-Co (OH) 2


Input: On the other hand, we notice that other factors such as the nature of the intercalated anions and the concentration of the polymer matrix alter considerably the final rate of the transition reaction through increasing the stability of the alpha phase.


Input: Investigation of the conformational changes of a conducting polymer in gas sensor active layers by means of polarization-modulation infrared reflection absorption spectroscopy (PM-IRRAS).


Input: Polarization-Modulation Infrared Reflection Absorption Spectroscopy (PM-IRRAS) was employed to observe the changes in the molecular conformation of poly (2-phenyl-1, 4-xylylene) (PPPX) films that occurred after exposure to organic solvent vapors.

poly (2-phenyl-1, 4-xylylene)

PPPX


Input: The PPPX films were supported on solid matrixes by casting, spin-coating, and Langmuir-Blodgett (LB) techniques.

PPPX


Input: The results show that the polymer is sensitive to the solvent vapors, which affect some of the vibration dipole moments, as detected by PM-IRRAS.


Input: The sensitivity depends on the method employed to immobilize the polymer, with more significant changes in films formed using techniques that result in a less systematically organized conformation.


Input: This feature enables the use of surface vibration spectroscopy to detect organic solvent vapors and may be applied in an artificial nose.


Input: Schisandra lignans-loaded enteric nanoparticles: preparation, characterization, and in vitro-in vivo evaluation.

lignans


Input: Schisandrae lignans (SL) have been well proven to possess hepatoprotective effect against the hepatic dysfunction induced by various chemical hepatotoxins.

lignans


Input: Deoxyschisandrin (DA) and schisantherin A (SA) are both considered as the major active components in SL.

Deoxyschisandrin

schisantherin A


Input: The objective of the study was to prepare and evaluate Schisandra lignans (composed of DA and SA)-loaded enteric nanoparticles produced by a novel toxic solvent-free modified spontaneous emulsification solvent diffusion (SESD) method.

lignans


Input: An organic Schisandra lignans/Eudragit ((R)) S100 solution was injected into an aqueous poloxamer 188 solution under a agitation.

lignans

Eudragit

poloxamer 188


Input: The nanoparticles were characterized with respect to particle size distribution, morphology, encapsulation efficiency (EE) and physical stability of the drug, wettability, in vitro release and in vivo bioavailability.


Input: Nanoparticles with a smooth surface and dense structure were obtained with high EE (EE (DA) > 90%; EE (SA) > 85%).


Input: The drug was in a noncrystalline state in the matrix and physically stable for 120 days at room temperature.


Input: In vitro drug release study, the drug dissolution rate from the nanoparticles was significantly enhanced compared to the physical mixture and to the pure drug; the release profile of the nanoparticles was stable after 120 days.


Input: The appropriate size of nanoparticles (~ 93 nm), the solubilization of the surfactant, the noncrystalline state of the drug in the matrix and the fast dissolution rate contributed to a significantly enhanced oral bioavailability from the nanoparticles when compared to pure drug suspension.


Input: Stabilization of iron oxide nanoparticles in high sodium and calcium brine at high temperatures with adsorbed sulfonated copolymers.

iron oxide

sodium

calcium


Input: A series of sulfonated random and block copolymers were adsorbed on the surface of ~ 100 nm iron oxide (IO) nanoparticles (NPs) to provide colloidal stability in extremely concentrated brine composed of 8% wt NaCl + 2% wt CaCl2 (API brine; 1. 4 M NaCl + 0. 2 M CaCl2) at 90 degrees C.

iron oxide

NaCl

NaCl


Input: A combinatorial materials chemistry approach, which employed Ca (2 +)-mediated adsorption of anionic acrylic acid-containing sulfonated polymers to preformed citrate-stabilized IO nanoclusters, enabled the investigation of a large number of polymer coatings.

Ca (2 +)

acrylic acid

citrate


Input: Initially a series of poly (2-methyl-2-acrylamidopropanesulfonate-co-acrylic acid) (poly (AMPS-co-AA)) (1: 8 to 1: 1 mol: mol), poly (styrenesulfonate-block-acrylic acid) (2. 4: 1 mol: mol), and poly (styrenesulfonate-alt-maleic acid) (3: 1 mol: mol) copolymers were screened for solubility in API brine at 90 degrees C.

poly (2-methyl-2-acrylamidopropanesulfonate-co-acrylic acid)

poly (AMPS-co-AA)

poly (styrenesulfonate-block-acrylic acid)

poly (styrenesulfonate-alt-maleic acid)


Input: The ratio of AMPS to AA groups was varied to balance the requirement of colloid dispersibility at high salinity (provided by AMPS) against the need for anchoring of the polymers to the iron oxide surface (via the AA).

AMPS

AMPS

iron oxide


Input: Steric stabilization of IO NPs coated with poly (AMPS-co-AA) (1: 1 mol: mol) provided colloidal stability in API brine at room temperature and 90 degrees C for up to 1 month.

poly (AMPS-co-AA)


Input: The particles were characterized before and after coating at ambient and elevated temperatures by a variety of techniques including colloidal stability experiments, dynamic light scattering, zeta potential, and thermogravimetric analysis.


Input: Pulsed magnetic field improves the transport of iron oxide nanoparticles through cell barriers.

iron oxide


Input: Understanding how a magnetic field affects the interaction of magnetic nanoparticles (MNPs) with cells is fundamental to any potential downstream applications of MNPs as gene and drug delivery vehicles.


Input: Here, we present a quantitative analysis of how a pulsed magnetic field influences the manner in which MNPs interact with and penetrate across a cell monolayer.


Input: Relative to a constant magnetic field, the rate of MNP uptake and transport across cell monolayers was enhanced by a pulsed magnetic field.


Input: MNP transport across cells was significantly inhibited at low temperature under both constant and pulsed magnetic field conditions, consistent with an active mechanism (i. e., endocytosis) mediating MNP transport.


Input: Microscopic observations and biochemical analysis indicated that, in a constant magnetic field, transport of MNPs across the cells was inhibited due to the formation of large (> 2 mu m) magnetically induced MNP aggregates, which exceeded the size of endocytic vesicles.


Input: Thus, a pulsed magnetic field enhances the cellular uptake and transport of MNPs across cell barriers relative to a constant magnetic field by promoting accumulation while minimizing magnetically induced MNP aggregation at the cell surface.


Input: Recent advancements in small molecule inhibitors of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase as anticancer agents.

tyrosine


Input: Advancements in understanding of the genetics, genomics, biochemistry and the pharmacology of cancer inhuman, have driven the current cancer chemotherapy to intently focus on development of target-based approaches rather than conventional approaches.


Input: From among the various targets identified, validated and inhibited at different hallmarks of cancer, protein tyrosine kinases (PTKs) have been exploited the most.

tyrosine


Input: Insulin receptors (IRs), insulin like growth factor receptors (IGF-1R) and their hybrid receptors belong to tyrosine kinase receptor (TKR) family, constitute a structural homology among them and generate a growth promoting IGF system on binding with either insulin, IGF-1 or IGF-2.

tyrosine


Input: The system induces the mitogenic effects through a torrent of cell signals produced as a result of cross talk with other growth promoting peptides and steroidal hormones, ultimately resulting in hijacking apoptosis and increasing cell proliferation and cell survival in cancer cells.

steroidal hormones


Input: Various strategies such as anti-IGF-1R antibodies, IGF-1 mimetic peptides, antisense strategies, IGF-1R specific peptide aptamers, targeted degradation of IGF-1R and expression of dominant negative IGF-1R mutants have been explored to inhibit the IGF-1R signaling.


Input: However, targeting IGF-1R with small molecules has gained considerable attention in last few years due to their ease of synthesis, ease of optimization of absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters, oral route of administration, lesser side effects and cost effectiveness.


Input: The present review provides a broad overview and discusses the highlights on discoveries, SAR studies and binding interactions of small molecules with either IGF-1R active or allosteric sites reported till date.


Input: Enhancing the efficacy of Ara-C through conjugation with PAMAM dendrimer and linear PEG: a comparative study.

Ara-C

PAMAM

PEG


Input: 1 beta-d-Arabinofuranosylcytosine (Cytarabine, Ara-C) is a key drug in the treatment of acute myeloid leukemia.

1 beta-d-Arabinofuranosylcytosine

Cytarabine

Ara-C


Input: Ara-C has a number of limitations such as a rapid deactivation by cytidine deaminase leading to the formation of a biologically inactive metabolite, Ara-U (1 beta-d-arabinofuranosyluracil), a low lipophilicity, and fast clearance from the body.

Ara-C

cytidine

Ara-U

1 beta-d-arabinofuranosyluracil


Input: To address these problems, we developed a conjugate in which hydroxyl-terminated PAMAM dendrimer, G4-OH [" D "] and PEG were used as carriers for the drug (Ara-C).

hydroxyl

PAMAM

OH

PEG

Ara-C


Input: The conjugates were synthesized using an efficient multistep protection/deprotection method resulting in the formation of a covalent bond between the primary hydroxyl group of Ara-C and dendrimer/PEG.

hydroxyl

Ara-C

PEG


Input: The structure, physicochemical properties, and drug release kinetics were characterized extensively.


Input: (1) H NMR and MALDI-TOF mass spectrometry suggested covalent attachment of 10 Ara-C molecules to the dendrimer.

(1) H

Ara-C


Input: The release profile of Ara-C in human plasma and in PBS buffer (pH 7. 4) showed that the conjugates released the drug over 14 days in PBS, with the release sped up in plasma.

Ara-C


Input: In PBS, while most of the drug is released from PEG-Ara-C, the dendrimer continues to release the drug in a sustained fashion.

PEG

Ara-C


Input: The results also suggested that the formation of the inactive form of Ara-C (Ara-U) was delayed upon conjugation of Ara-C to the polymers.

Ara-C

Ara-U

Ara-C


Input: The inhibition of cancer growth by the dendrimer-Ara-C and PEG-Ara-C conjugates was evaluated in A549 human adenocarcinoma epithelial cells.

Ara-C

PEG

Ara-C


Input: Both dendrimer-and PEG-Ara-C conjugates were 4-fold more effective in inhibition of A549 cells compared to free Ara-C after 72 h of treatment.

PEG

Ara-C

Ara-C


Input: Catalytic hydrotrifluoromethylation of unactivated alkenes.

alkenes


Input: A visible-light-mediated hydrotrifluoromethylation of unactivated alkenes that uses the Umemoto reagent as the CF (3) source and MeOH as the reductant is disclosed.

alkenes

CF (3)

MeOH


Input: This effective transformation operates at room temperature in the presence of 5 mol% Ru (bpy) (3) Cl (2); the process is characterized by its operational simplicity and functional group tolerance.

Ru (bpy) (3) Cl (2)


Input: Discovery of a potential anti-inflammatory agent: 3-oxo-29-noroleana-1, 9 (11), 12-trien-2, 20-dicarbonitrile.

3-oxo-29-noroleana-1, 9 (11), 12-trien-2, 20-dicarbonitrile


Input: Fifteen novel derivatives of glycyrrhetinic acid (GA) were synthesized and evaluated for anti-inflammatory activities.

glycyrrhetinic acid


Input: It was found that the introduction of 1-en-3-one and 9 (11), 12-diene and 2, 20-dinitrile functionalities into the scaffold of GA led to the discovery of potent compound 19 for inhibition of LPS-induced NO production.

9 (11), 12-diene

2, 20-dinitrile

NO


Input: Furthermore, 19 effectively inhibited the protein and mRNA expression of inducible NO synthase (iNOS) and the mRNA expression of TNF-alpha, IL-6, and IL-1 beta in LPS-stimulated RAW 264. 7 macrophages.

NO


Input: Mechanistically, 19 exerted inhibitory effects on the activation of the three main MAPKs and phosphorylation and degradation of I kappa B-alpha, as well as the ratio of nuclear/cytosolic content of p65.


Input: Importantly, 19 significantly decreased the mortality rate in the mouse model of LPS-induced sepsis shock.


Input: It is noteworthy that inhibitory effect of 19 on NO production was not blocked by the glucocorticoid receptor antagonist mifepristone, indicating that it does not act through the glucocorticoid receptor.

NO


Input: Synthesis and micellar mimic properties of bile acid trimers.

bile acid


Input: Two fan-shaped bile acid trimers have been synthesized via Cu (I)-catalyzed azide-alkyne cycloaddition (CuAAC)' click chemistry', and their extraction experiments of cresol red sodium (CR) and pyrene were investigated in the polar and non-polar solvents, respectively.

bile acid

Cu (I)

azide-alkyne

cresol red sodium

pyrene


Input: The transmission electron microscopy (TEM) results showed that the homogenous hollow capsules formed with the diameter size range of 40-70 nm in a solution of water and acetone.

acetone


Input: Thus the amphiphilicity of fan-shaped bile acid trimers might be used as the promising candidate in biological and drug delivery applications.

bile acid


Input: 1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl) ethanones as novel CCR1 antagonists.

1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl) ethanones


Input: A novel series of CCR1 antagonists based on the 1-(4-phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl) ethanone scaffold was identified by screening a compound library utilizing CCR1-expressing human THP-1 cells.

1-(4-phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl) ethanone


Input: SAR studies led to the discovery of the highly potent and selective CCR1 antagonist 14 (CCR1 binding IC (50) = 4 nM using [(125) I]-CCL3 as the chemokine ligand).

[(125) I]-CCL3


Input: Compound 14 displayed promising pharmacokinetic and toxicological profiles in preclinical species.


Input: Inhibition of monoamine oxidase by phthalide analogues.

monoamine

phthalide


Input: Based on recent reports that the small molecules, isatin and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase (MAO) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1 (3H)-one] analogues.

isatin

phthalimide

monoamine

phthalide

2-benzofuran-1 (3H)-one


Input: Phthalide is structurally related to isatin and phthalimide and it is demonstrated here that substitution at C6 of the phthalide moiety yields compounds endowed with high binding affinities to both human MAO isoforms.

Phthalide

isatin

phthalimide

phthalide


Input: Among the nineteen homologues evaluated, the lowest IC (50) values recorded for the inhibition of MAO-A and-B were 0. 096 and 0. 0014 mu M, respectively.


Input: In most instances, C6-substituted phthalides exhibit MAO-B specific inhibition.

phthalides


Input: Among a series of 6-benzyloxyphthalides bearing substituents on the para position of the phenyl ring the general order of potency was CF (3) > I > Br > Cl > F > CH (3) > H.

phenyl

CF (3)

I

Br

Cl

F

CH (3)

H


Input: The results also show that the binding modes of representative phthalides are reversible and competitive at both MAO isoforms.

phthalides


Input: Based on these data, C6-substituted phthalides may serve as leads for the development of therapies for neurodegenerative disorders such as Parkinson' s disease.

phthalides


Input: Synthesis, crystal structure and antibacterial activity of new highly functionalized ionic compounds based on the imidazole nucleus.

imidazole


Input: Several new highly functionalized imidazolium derivatives were synthesized, via appropriate synthetic routes, using imidazole, 1-methylimidazole and 2-phenyl-1-methylimidazole as key intermediates.

imidazolium

imidazole


Input: The antibacterial activity of the prepared compounds was evaluated against: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella thipymurium using disk-diffusion and MIC methods.


Input: Crystal X-ray structures are reported for six compounds.


Input: Potent and selective tariquidar bioisosters as potential PET radiotracers for imaging P-gp.

tariquidar


Input: Compounds 8a-d have been designed as bioisosters of tariquidar for imaging P-gp expression and density by PET.

tariquidar


Input: The results displayed that compounds 8b and 8d could be considered potential P-gp/BCRP ligands suitable as (11) C and (18) F radiotracers, respectively.

(11) C

(18) F


Input: Chemometrics-Based Approach to Feature Selection of Chromatographic Profiles and its Application to Search Active Fraction of Herbal Medicine.


Input: In our previous report (J Pharmaceut Biomed 56 (2011) 443-447), a support vector machine (SVM)-based pharmacodynamic model was established for predicting active fractions of herbal medicines (HMs), where information contents embedded in the chromatograms of the fractions were represented with the peak areas.


Input: However, in this representation the global characteristics of the chromatograms were completely missed, which is definitely contrary to the global and holistic views in theories of HMs and undoubtedly reduce the success rate of this model.


Input: To deal with the challenge, two chemometrics methods, that is, minimum redundancy maximum relevance (mRMR) and particle swarm optimizer (PSO), were applied in this article for feature selection of the whole chromatograms, and the PSO was also used to tune the SVM parameters.


Input: As a case, a sample HM, that is, Xiangdan injection, was investigated.


Input: The predictive accuracy was fully evaluated and compared with those by other popular and reported methods.


Input: Furthermore, the confirmation on the independent predicting set exhibited that the predicted bioactivities were well consistent with the experimental values.


Input: The important potential application of the present model is to be extended to help search active fractions of other HMs.


Input: Activity cliffs: facts or artifacts?


Input: The fact that similar compounds may have very different properties has a large impact in several areas of chemistry.


Input: In drug discovery, almost every medicinal chemist working on lead optimization has faced unexpected large' jumps' in activity due to small changes in structure, that is, activity cliffs.


Input: A number of computational approaches have been developed to detect and quantify activity cliffs and help to understand, and eventually predict, structure-activity relationships (SAR) in compound data sets.


Input: Although activity cliffs do exist, the identification and quantification of cliffs have to proceed with caution because one may identify' false positive cliffs'.