Input: After 30min of treatment, antofine induced a rapid increase in the intracellular Ca (2 +) concentration and activation of protein kinase C (PKC) alpha/beta II, which was maintained for at least 6h.

Ca (2 +)


Input: Co-treatment of astrocytes with antofine and the intracellular Ca (2 +) chelator BAPTA-AM prevented downregulation of Cx43 and inhibition of GJIC.

antofine

Ca (2 +)

BAPTA-AM


Input: Moreover, co-treatment with antofine and a specific PKC beta inhibitor prevented endocytosis of gap junctions, downregulation of Cx43, and inhibition of GJIC.

antofine


Input: Taken together, these findings indicate that antofine induces Cx43 gap junction disassembly by the PKC beta signaling pathway.

antofine


Input: Inhibition of GJIC by antofine may undermine the neuroprotective effect of astrocytes in CNS.

antofine


Input: HIV protease inhibitors in pregnancy: pharmacology and clinical use.


Input: The impact of antiretroviral therapy (ART) on the natural history of HIV-1 infection has resulted in dramatic reductions in disease-associated morbidity and mortality.


Input: Additionally, the epidemiology of HIV-1 infection worldwide is changing, as women now represent a substantial proportion of infected adults.


Input: As more highly effective and tolerable antiretroviral regimens become available, and as the prevention of mother-to-child transmission becomes an attainable goal in the management of HIV-infected individuals, more and more HIV-positive women are choosing to become pregnant and have children.


Input: Consequently, it is important to consider the efficacy and safety of antiretroviral agents in pregnancy.


Input: Protease inhibitors are a common class of medication used in the treatment of HIV-1 infection and are increasingly being used in pregnancy.


Input: However, several studies have raised concerns regarding pharmacokinetic alterations in pregnancy, particularly in the third trimester, which results in suboptimal drug concentrations and a theoretically higher risk of virologic failure and perinatal transmission.


Input: Drug level reductions have been observed with each individual protease inhibitor and dose adjustments in pregnancy are suggested for certain agents.


Input: Furthermore, studies have also raised concerns regarding the safety of protease inhibitors in pregnancy, particularly as they may increase the risk of pre-term birth and metabolic disturbances.


Input: Overall, protease inhibitors are safe and effective for the treatment of HIV-infected pregnant women.


Input: Specifically, ritonavir-boosted lopinavir-and atazanavir-based regimens are preferred in pregnancy, while ritonavir-boosted darunavir-and saquinavir-based therapies are reasonable alternatives.

ritonavir

lopinavir

atazanavir

ritonavir

darunavir

saquinavir


Input: This paper reviews the use of protease inhibitors in pregnancy, focusing on pharmacokinetic and safety considerations, and outlines the recommendations for use of this class of medication in the HIV-1-infected pregnant woman.


Input: Predicting Macro-and Microvascular Complications in Type 2 Diabetes: The Japan Diabetes Complications Study/the Japanese Elderly Diabetes Intervention Trial risk engine.


Input: OBJECTIVE To develop and validate a risk engine that calculates the risks of macro-and microvascular complications in type 2 diabetes.


Input: RESEARCH DESIGN AND METHODS We analyzed pooled data from two clinical trials on 1, 748 Japanese type 2 diabetic patients without diabetes complications other than mild diabetic retinopathy with a median follow-up of 7. 2 years.


Input: End points were coronary heart disease (CHD), stroke, noncardiovascular mortality, overt nephropathy defined by persistent proteinuria, and progression of retinopathy.


Input: We fit a multistate Cox regression model to derive an algorithm for prediction.


Input: The predictive accuracy of the calculated 5-year risks was cross-validated.


Input: RESULTS Sex, age, HbA1c, years after diagnosis, BMI, systolic blood pressure, non-HDL cholesterol, albumin-to-creatinine ratio, atrial fibrillation, current smoker, and leisure-time physical activity were risk factors for macro-and microvascular complications and were incorporated into the risk engine.

cholesterol

creatinine


Input: The observed-to-predicted (O/P) ratios for each event were between 0. 93 and 1. 08, and Hosmer-Lemeshow tests showed no significant deviations between observed and predicted events.


Input: In contrast, the UK Prospective Diabetes Study (UKPDS) risk engine overestimated CHD risk (O/P ratios: 0. 30 for CHD and 0. 72 for stroke).


Input: C statistics in our Japanese patients were high for CHD, noncardiovascular mortality, and overt nephropathy (0. 725, 0. 696, and 0. 767) but moderate for stroke and progression of retinopathy (0. 636 and 0. 614).


Input: By combining macro-and microvascular risks, the classification of low-and high-risk patients was improved by a net reclassification improvement of 5. 7% (P = 0. 02).


Input: CONCLUSIONS The risk engine accurately predicts macro-and microvascular complications and would provide helpful information in risk classification and health economic simulations.


Input: MRI morphometric characterisation of the paediatric cervical spine and spinal cord in children with MPS IVA (Morquio-Brailsford syndrome).


Input: Nearly all children with MPS IVA develop skeletal deformities affecting the spine.


Input: At the atlanto-axial spine, odontoid hypoplasia occurs.


Input: GAG deposition around the dens, leads to peri-odontoid infiltration.


Input: Transverse/alar ligament incompetence causes instability.


Input: Atlanto-axial instability is associated with cord compression and myelopathy, leading to major morbidity and mortality.


Input: Intervention is often required.


Input: Does the presence of widened bullet shaped vertebra in platyspondily encroach on the spinal canal and cause spinal stenosis in MPS IVA?


Input: So far, there have been no standardised morphometric measurements of the paediatric MPS IVA cervical spine to evaluate whether there is pre-existing spinal stenosis predisposing to compressive myelopathy or whether this is purely an acquired process secondary to instability and compression.


Input: This study provides the first radiological quantitative analysis of the cervical spine and spinal cord in a series of affected children.


Input: MRI morphometry indicates that the MPS IVA spine is narrower at C1-2 level giving an inverted funnel shape.


Input: There is no evidence of a reduction in the Torg ratio (canal-body ratio) in the cervical spine.


Input: The spinal canal does not exceed 11 mm at any level, significantly smaller than normal historical cohorts (14 mm).


Input: The sagittal diameter and axial surface area of both spinal canal and cord are reduced.


Input: C1-2 level cord compression was evident in the canal-cord ratio but the Torg ratio was not predictive of cord compression.


Input: In MPS IVA the reduction in the space available for the cord (SAC) is multifactorial rather than due to congenital spinal stenosis.


Input: A pathophysiologic role for epidermal growth factor receptor in pemphigus acantholysis.


Input: The pemphigus family of autoimmune bullous disorders is characterized by autoantibody binding to desmoglein 1 and/or 3 (dsg1/dsg3).


Input: In this study we show that EGF receptor (EGFR) is activated following pemphigus vulgaris (PV) IgG treatment of primary human keratinocytes and that EGFR activation is downstream of p38 mitogen-activated protein kinase (p38).


Input: Inhibition of EGFR blocked PV IgG-triggered dsg3 endocytosis, keratin intermediate filament retraction, and loss of cell-cell adhesion in vitro.


Input: Significantly, inhibiting EGFR prevented PV IgG-induced blister formation in the passive transfer mouse model of pemphigus.


Input: These data demonstrate cross-talk between dsg3 and EGFR, that this cross-talk is regulated by p38, and that EGFR is a potential therapeutic target for pemphigus.


Input: Small-molecule inhibitors and monoclonal antibodies directed against EGFR are currently used to treat several types of solid tumors.


Input: This study provides the experimental rationale for investigating the use of EGFR inhibitors in pemphigus.


Input: The propeptides of VEGF-D determine heparin binding, receptor heterodimerization, and effects on tumor biology.


Input: VEGF-D is an angiogenic and lymphangiogenic glycoprotein that can be proteolytically processed generating various forms differing in subunit composition due to the presence or absence of N-and C-terminal propeptides.

N

C


Input: These propeptides flank the central VEGF homology domain, that contains the binding sites for VEGF receptors (VEGFRs), but their biological functions were unclear.


Input: Characterization of propeptide function will be important to clarify which forms of VEGF-D are biologically active and therefore clinically relevant.


Input: Here we use VEGF-D mutants deficient in either propeptide, and in the capacity to process the remaining propeptide, to monitor the functions of these domains.


Input: We report for the first time that VEGF-D binds heparin, and that the C-terminal propeptide significantly enhances this interaction (removal of this propeptide from full-length VEGF-D completely prevents heparin binding).

C


Input: We also show that removal of either the N-or C-terminal propeptide is required for VEGF-D to drive formation of VEGFR-2/VEGFR-3 heterodimers which have recently been shown to positively regulate angiogenic sprouting.

N

C


Input: The mature form of VEGF-D, lacking both propeptides, can also promote formation of these receptor heterodimers.


Input: In a mouse tumor model, removal of only the C-terminal propeptide from full-length VEGF-D was sufficient to enhance angiogenesis and tumor growth.

C


Input: In contrast, removal of both propeptides is required for high rates of lymph node metastasis.


Input: The findings reported here show that the propeptides profoundly influence molecular interactions of VEGF-D with VEGF receptors, co-receptors, and heparin, and its effects on tumor biology.


Input: Increased immunoreactive 11-ketotestosterone concentrations in sheep feces after acth challenge.


Input: 11-Oxoetiocholanolone and related substances are important metabolites of cortisol and are excreted via feces in ruminants.

cortisol


Input: To investigate whether 11-ketotestosterone (11-KT) or its immunoreactive metabolites are formed and excreted in ruminant feces, an enzyme immunoassay (EIA) was developed and validated.


Input: The antibody was raised in rabbits against 11-KT-3-CMO: bovine serum albumin with biotinylated 11-KT as a label.

biotinylated 11-KT


Input: The assay showed a sensitivity of 0. 3 pg/well.


Input: To validate the assay biologically, 6 rams were injected with a synthetic analogue of the adrenocorticotropic hormone (Synacthen, 2 micro g/kg body wt).


Input: An aliquot was collected of each fecal portion spontaneously defecated 8 h before Synacthen injection to 24 h after injection and stored at-20 degrees C until analysis.


Input: Samples (0. 5 g) were extracted using 80% methanol and immunoreactive metabolites measured using the 11-KT EIA and an already established 11, 17-dioxoandrostane (11, 17-DOA) EIA.

methanol

11, 17-dioxoandrostane

11, 17-DOA


Input: High-performance liquid chromatography separation revealed no peak in the same elution position as authentic 11-KT; therefore, reacting substances were referred to as 11-KT equivalents.


Input: In the case of 11-KT immunoreactive substances, the values increased from baseline (median, 136 ng/g feces) to a peak concentration (median, 424 ng/g) 10 to 14 h after Synacthen injection and declined afterwards.


Input: Concentrations of 11, 17-DOA showed the same pattern, but the values were 2 to 4 times higher.

11, 17-DOA


Input: From this data, the authors conclude that 11-KT-like substances, specifically C19 O3-androgens with a 17 beta-hydroxy group, were present in the feces.

C19 O3-androgens

17 beta-hydroxy


Input: These substances originate from the adrenals and are most likely cortisol metabolites.

cortisol


Input: Environ Toxicol Chem 2013; 32: 1332-1336.


Input: (c) 2013 SETAC.


Input: Fractionation of organosolv lignin from olive tree clippings and its valorization to simple phenolic compounds.

phenolic


Input: Lignin valorization practices have attracted a great deal of interest in recent years due to the large excess of lignin produced by the pulp and paper industry, together with second-generation bioethanol plants.


Input: In this work, a new lignin valorization approach is proposed.


Input: It involves ultrafiltration as a fractionation process to separate different molecular weight lignin fractions followed by a hydrogen-free, mild, hydrogenolytic, heterogeneously catalyzed methodology assisted by microwave irradiation to obtain simple phenolic, monomeric products by depolymerization using a nickel-based catalyst.

hydrogen

phenolic


Input: The main products obtained were desaspidinol, syringaldehyde, and syringol; this proves the efficiency of the depolymerization conditions applied.

desaspidinol

syringaldehyde

syringol


Input: The concentration of these observed compounds increased when the molecular weights of the lignin fractions increased.


Input: The applied depolymerization conditions, which take advantage of the use of formic acid as a hydrogen-donating solvent, did not generate any biochar in the systems.

formic acid

hydrogen


Input: Searching the coding region for microRNA targets.


Input: Finding microRNA targets in the coding region is difficult due to the overwhelming signal encoding the amino acid sequence.

amino acid


Input: Here, we introduce an algorithm (called PACCMIT-CDS) that finds potential microRNA targets within coding sequences by searching for conserved motifs that are complementary to the microRNA seed region and also overrepresented in comparison with a background model preserving both codon usage and amino acid sequence.

amino acid


Input: Precision and sensitivity of PACCMIT-CDS are evaluated using PAR-CLIP and proteomics data sets.


Input: Thanks to the properly constructed background, the new algorithm achieves a lower rate of false positives and better ranking of predictions than do currently available algorithms, which were designed to find microRNA targets within 3' UTRs.


Input: A nonionic inhibitor with high specificity for the UDP-Gal donor binding site of human blood group B galactosyltransferase: design, synthesis, and characterization.

UDP-Gal


Input: 9-(5-O-alpha-D-galactopyranosyl)-D-arabinityl-1, 3, 7-trihydropurine-2, 6, 8-trione (1) was designed and synthesized as a nonionic inhibitor for the donor binding site of human blood group B galactosyltransferase (GTB).

9-(5-O-alpha-D-galactopyranosyl)-D-arabinityl-1, 3, 7-trihydropurine-2, 6, 8-trione


Input: Enzymatic characterization showed 1 to be extremely specific, as the highly homologous human N-acetylgalactosaminyltransferase (GTA) is not inhibited.

N


Input: The binding epitope of 1 demonstrates a high involvement of the arabinityl linker, whereas the galactose residue is only making contact to the protein via its C-2 site, which is very important for the discrimination between galactose and N-acetylgalactosamine, the substrate transferred by GTA.

arabinityl

galactose

galactose

N-acetylgalactosamine


Input: The approach can generate highly specific glycosyltransferase inhibitors.


Input: Switchable Elastin-Like Polypeptides that Respond to Chemical Inducers of Dimerization.


Input: Elastin-like polypeptides (ELPs) are protein polymers that reversibly phase separate in response to increased temperature, pressure, concentration, ionic strength, and molecular weight.


Input: If it were possible to engineer their phase separation to respond to specific molecular substrates, ELP fusion proteins might be engineered as biosensors, smart biomaterials, diagnostic imaging agents, and targeted therapies.


Input: What has been lacking is a strategy to design ELPs to respond to specific substrates.


Input: To address this deficiency, we report that ELP fusion proteins phase separate in response to chemical inducers of dimerization (CID).


Input: The rationale is that ELP phase separation depends on molecular weight, concentration, and local hydrophobicity; therefore, processes that affect these properties, including noncovalent dimerization, can be tuned to produce isothermal phase separation.


Input: To test this hypothesis, constructs were evaluated consisting of an immunophilin: human FK-506 binding protein 12 (FKBP) attached to an ELP.


Input: Under stoichiometric binding of a CID, the fusion protein homodimerizes and triggers phase separation.


Input: This dimerization is reversible upon saturation with excess CID or competitive binding of a small lipophilic macrolide to FKBP.


Input: By modulating the ELP molecular weight, phase separation was tuned for isothermal response to CID at physiological ionic strength and temperature (37 degrees C).


Input: To interpret the relationship between transition temperature and equilibrium binding constants, an empirical mathematical model was employed.


Input: To the best of our knowledge, this report is the first demonstration of reversible ELP switching in response to controlled dimerization.


Input: Due to its simplicity, this strategy may be useful to design ELP fusion proteins that respond to specific dimeric biological entities.


Input: Cause and prevention of moisture-induced degradation of resistance random access memory nanodevices.


Input: Dielectric thin films in nanodevices may absorb moisture, leading to physical changes and property/performance degradation, such as altered data storage and readout in resistance random access memory.


Input: Here we demonstrate using a nanometallic memory that such degradation proceeds via nanoporosity, which facilitates water wetting in otherwise nonwetting dielectrics.


Input: Electric degradation only occurs when the device is in the charge-storage state, which provides a nanoscale dielectrophoretic force directing H2O to internal field centers (sites of trapped charge) to enable bond rupture and charged hydroxyl formation.

hydroxyl


Input: While these processes are dramatically enhanced by an external DC or AC field and electron-donating electrodes, they can be completely prevented by eliminating nanoporosity, depositing a barrier layer, or using an oxidation-resistant electrode.


Input: These findings provide insight for understanding high-performance memory and field-assisted degradation of nanodevices.


Input: Evaluation of oxidant-antioxidant status in oral toxicity of fish oil methyl esters and diesel fuel in male rats.

methyl esters


Input: This study was conducted to compare the effects of oral toxicity induced by fish oil biodiesel and diesel fuel.


Input: Diesel and fish oil biodiesel were administered by oral gavage to rats.


Input: For this purpose, 35 rats were divided into five groups.


Input: Sunflower oil of 250 mg kg (-1) was administered to the rats in the control group by oral gavage.


Input: The rats in the D250 and D500 groups were administered by oral gavage 250 mg kg (-1) and 500 mg kg (-1) of diesel fuel dissolved in equal amounts of sunflower oil, respectively.


Input: The rats in the F250 and F500 groups were administered by oral gavage 250 mg kg (-1) and 500 mg kg (-1) of fish oil biodiesel dissolved in equal amounts of sunflower oil, respectively.


Input: At the end of the study, malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured in the whole blood; catalase (CAT) activity level was measured in erythrocytes; and nitrite (NO (2)) and nitrate (NO (3)) levels were measured in the serum.

malondialdehyde

MDA

reduced glutathione

GSH

nitrite

NO (2)

nitrate

NO (3)


Input: It was observed that the whole blood MDA levels of the diesel groups were considerably different from those in the control and fish oil biodiesel groups (p < 0. 001).

MDA


Input: GSH levels in the control group were observed to be considerably different from those in all other groups (p < 0. 001).

GSH


Input: Serum NO (3) concentrations in the diesel groups were found to be considerably different from those in the control and biodiesel groups.

NO (3)


Input: Serum NO (2) concentrations in one of the diesel groups were significantly different from those in the control and biodiesel groups (p < 0. 01 and p < 0. 05, respectively).

NO (2)


Input: The CAT activity of the control group was observed to be different from that in the other groups.


Input: According to these results, both fish oil biodiesel and diesel fuel are thought to cause lipid peroxidation.


Input: It was observed that fish oil biodiesel does not induce as much oxidative damage as does the diesel fuel.


Input: It is suggested that fish oil biodiesel should be preferred as an alternative to the diesel.


Input: Effect of tocopherol on biochemical blood parameters in pleuritis-induced rats treated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin.

tocopherol

2, 3, 7, 8-tetrachlorodibenzo-p-dioxin


Input: The aim of this study was to evaluate the effect of tocopherol on pleuritis-induced rats exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).

tocopherol

2, 3, 7, 8-tetrachlorodibenzo-p-dioxin

TCDD


Input: Rats were treated with a single TCDD dose of 5 mu g/kg body weight (b. w.) and then for 3 weeks they were daily supplemented with tocopherol at a dose of 30 mg/kg b. w.

TCDD

tocopherol


Input: The inflammation was initiated by intrapleural injection of a single dose of 1% carrageenin solution in a volume of 0. 15 ml.


Input: Changes in biochemical blood parameters were measured three times at the 24th, 72nd and 120th hour of pleuritis and the blood was collected from 20 animals of each group of rats (group with the control inflammation; group treated with TCDD and with control inflammation; group treated with TCDD, supplemented with tocopherol and with the inflammation).

TCDD

TCDD


Input: The following biochemical parameters were measured: tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, IL-4, IL-6, procollagen, telopeptide, fibrinogen, cholesterol, urea, creatinine, aspartate aminotransferase (AspAT) and alanine aminotransferase (AlAT).

cholesterol

urea

creatinine

aspartate

alanine


Input: Daily supplementation of tocopherol caused significant changes in the level of TNF, IL-1, IL-4, IL-6, urea, creatinine, AspAT and AlAT.

tocopherol

urea

creatinine


Input: According to the results of these studies, we suggest that tocopherol supplementation in high doses could act as a protective treatment to improve liver metabolism.

tocopherol


Input: Cytotoxic and phytotoxic actions of Heliotropium strigosum.


Input: This study describes the cytotoxic and phytotoxic activities of the crude extract of Heliotropium strigosum and its resultant fractions.


Input: In brine shrimp toxicology assays, profound cytotoxicity was displayed by ethyl acetate (LD (50) 8. 3 mu g/ml) and chloroform (LD (50) 8. 8 mu g/ml) fractions, followed by relatively weak crude methanolic extract of H. strigosum (LD (50) 909 mu g/ml) and n-hexane fraction (LD (50) 1000 mu g/ml).

ethyl acetate

chloroform

n-hexane


Input: In case of phytotoxicity activity against Lemna acquinoctialis, highest phytotoxic effect was showed by ethyl acetate fraction (LD (50) 91. 0 mu g/ml), while chloroform fraction, plant crude extract and n-hexane, respectively, caused 50%, 30. 76 +/- 1. 1% and 30. 7 +/- 1. 1% inhibitory action at maximum concentration used, that is, 1000 mu g/ml.

ethyl acetate

chloroform

n-hexane


Input: These data indicates that H. strigosum exhibits cytotoxic and phytotoxic potential, which explore its use as anticancer and herbicidal medicine.


Input: The ethyl acetate and chloroform fractions were more potent for the evaluated toxicity effects, thus recommended for isolation and identification of the active compounds.

ethyl acetate

chloroform


Input: Follistatin-like 3 (FSTL3) mediated silencing of transforming growth factor beta (TGF beta) signaling is essential for testicular aging and regulating testis size.


Input: Follistatin-like 3 (FSTL3) is a glycoprotein that binds and inhibits the action of TGF beta ligands such as activin.


Input: The roles played by FSTL3 and activin signaling in organ development and homeostasis are not fully understood.


Input: The authors show mice deficient in FSTL3 develop markedly enlarged testes that are also delayed in their age-related regression.


Input: These FSTL3 knockout mice exhibit increased Sertoli cell numbers, allowing for increased spermatogenesis but otherwise showing normal testicular function.


Input: The data show that FSTL3 deletion leads to increased AKT signaling and SIRT1 expression in the testis.


Input: This demonstrates a cross-talk between TGF beta ligand and AKT signaling and leads to a potential mechanism for increased cellular survival and antiaging.


Input: The findings identify crucial roles for FSTL3 in limiting testis organ size and promoting age-related testicular regression.


Input: Ruthenium (II) polypyridyl complexes as G-quadruplex inducing and stabilizing ligands in telomeric DNA.

Ruthenium (II) polypyridyl


Input: Two ruthenium (ii) polypyridyl complexes [Ru (phen) 2 (4idip)] (ClO4) 2 () and [Ru (bpy) 2 (4idip)] (ClO4) 2 () (phen = 1, 10-phenanthroline, bpy = 2, 2'-bipyridine, 4idip = 4-indoleimidazo [4, 5-f] [1, 10] phenanthroline) designed as telomeric G-quadruplex ligands have been synthesized and characterized.

ruthenium (ii) polypyridyl

[Ru (phen) 2 (4idip)] (ClO4) 2

[Ru (bpy) 2 (4idip)] (ClO4) 2

phen

1, 10-phenanthroline

bpy

2, 2'-bipyridine

4-indoleimidazo [4, 5-f] [1, 10] phenanthroline


Input: The interaction of human telomeric G-quadruplex DNA (HTG21) with the designed ligands was explored by fluorescence analysis, absorption spectroscopy, continuous variation, circular dichroism spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, telomerase repeat amplification protocol (TRAP), and visual studies.


Input: The results showed that both complexes could induce and stabilize different G-quadruplex structures by using a 1: 1 [quadruplex]/[complex] binding mode ratio.


Input: Complex exhibited higher interaction ability and better G-quadruplex selectivity than duplex DNA.


Input: Furthermore, both ruthenium complexes led to the inhibition of the enzyme telomerase, and complex was the significantly better inhibitor.

ruthenium


Input: Characterization of the head-twitch response induced by hallucinogens in mice: Detection of the behavior based on the dynamics of head movement.


Input: RATIONALE: The head-twitch response (HTR) is a rapid side-to-side rotational head movement that occurs in rats and mice after administration of serotonergic hallucinogens and other 5-HT (2A) agonists.


Input: The HTR is widely used as a behavioral assay for 5-HT (2A) activation and to probe for interactions between the 5-HT (2A) receptor and other transmitter systems.


Input: OBJECTIVE: High-speed video recordings were used to analyze the head movement that occurs during head twitches in C57BL/6J mice.


Input: Experiments were also conducted in C57BL/6J mice to determine whether a head-mounted magnet and a magnetometer coil could be used to detect the HTR induced by serotonergic hallucinations based on the dynamics of the response.


Input: RESULTS: Head movement during the HTR was highly rhythmic and occurred within a specific frequency range (mean head movement frequency of 90. 3 Hz).


Input: Head twitches produced wave-like oscillations of magnetometer coil voltage that matched the frequency of head movement during the response.


Input: The magnetometer coil detected the HTR induced by the serotonergic hallucinogens 2, 5-dimethoxy-4-iodoamphetamine (DOI; 0. 25, 0. 5, and 1. 0 mg/kg, i. p.) and lysergic acid diethylamide (LSD; 0. 05, 0. 1, 0. 2, and 0. 4 mg/kg, i. p.) with extremely high sensitivity and specificity.

2, 5-dimethoxy-4-iodoamphetamine

DOI

lysergic acid diethylamide

LSD


Input: Magnetometer coil recordings demonstrated that the non-hallucinogenic compounds (+)-amphetamine (2. 5 and 5. 0 mg/kg, i. p.) and lisuride (0. 8, 1. 6, and 3. 2 mg/kg, i. p.) did not induce the HTR.

(+)-amphetamine

lisuride


Input: CONCLUSIONS: These studies confirm that a magnetometer coil can be used to detect the HTR induced by hallucinogens.


Input: The use of magnetometer-based HTR detection provides a high-throughput, semi-automated assay for this behavior, and offers several advantages over traditional assessment methods.


Input: Faecal Excretion Dynamic during Subacute Oral Exposure to Different Pb Species in Rattus norvegicus.

Pb


Input: Faecal excretion is a basic means of detoxification upon ingestion of Pb-contaminated feed.

Pb


Input: In order to determine a time course of Pb elimination after oral exposure to two different forms of this heavy metal (lead acetate vs. phyto-bound Pb), a feeding study was carried out in experimental rats using the Pb phyto-hyperaccumulator Pistia stratiotes as a model diet.

Pb

lead acetate

Pb

Pb


Input: The effect of starvation on Pb excretion was further studied in rats that were fed plant material.

Pb


Input: Twelve Pb doses (7 mu g Pb/1 g BW) were administered orally over a 5-week period.

Pb

Pb


Input: Faeces samples were collected 24 and 72 h post-exposure.


Input: Inductively coupled plasma optical emission spectrometry and electrothermal absorption spectrometry methods were used for determination of heavy metal concentrations.


Input: Up to 53% of ingested Pb was rapidly eliminated from the exposed rats via faeces within 24 h after exposure.

Pb


Input: Faecal excretion in exposed rats differed significantly when compared to that of the control group.


Input: Fasting before exposure reduced Pb excretion by up to 50%.

Pb


Input: Faecal excretions of both examined Pb forms exhibited almost identical patterns.

Pb


Input: Considerable differences were revealed concerning total excretion levels; lead acetate was excreted in amount greater extent than those of phytobound Pb.

lead acetate

Pb


Input: Results of our study suggest that Pb forms occurring in the P. stratiotes tissues are absorbed through the gastrointestinal tract to a greater extent than Pb from lead acetate.

Pb

Pb

lead acetate


Input: Therefore, higher portions of ingested Pb can be available for potential accumulation in tissues of exposed subjects.

Pb


Input: Echinacea sanguinea and Echinacea pallida extracts stimulate glucuronidation and basolateral transfer of Bauer alkamides 8 and 10 and ketone 24 and inhibit P-glycoprotein transporter in Caco-2 cells.

alkamides

ketone


Input: The use of Echinacea as a medicinal herb is prominent in the United States, and many studies have assessed the effectiveness of Echinacea as an immunomodulator.


Input: We hypothesized that Bauer alkamides 8, 10, and 11 and ketone 24 were absorbed similarly either as pure compounds or from Echinacea sanguinea and Echinacea pallida ethanol extracts, and that these Echinacea extracts could inhibit the P-glycoprotein transporter in Caco-2 human intestinal epithelial cells.

alkamides

ketone

ethanol


Input: Using HPLC analysis, the permeation rate of Bauer alkamides by passive diffusion across Caco-2 cells corresponded with compound hydrophilicity (alkamide 8 > 10 > 11), independent of the plant extract matrix.

alkamides

alkamide


Input: Both Echinacea ethanol extracts stimulated apparent glucuronidation and basolateral efflux of glucuronides of alkamides 8 and 10 but not alkamide 11.

ethanol

alkamides

alkamide


Input: Bauer ketone 24 was totally metabolized to more hydrophilic metabolites when administered as a single compound, but was also glucuronidated when present in Echinacea extracts.

ketone


Input: Bauer alkamides 8, 10, and 11 (175-230 micro M) and ethanol extracts of E. sanguinea (1 mg/mL, containing ~ 90 micro M total alkamides) and E. pallida (5 mg/mL, containing 285 micro M total alkamides) decreased the efflux of the P-glycoprotein transporter probe calcein-AM from Caco-2 cells.

alkamides

ethanol

alkamides


Input: These results suggest that other constituents in these Echinacea extracts facilitated the metabolism and efflux of alkamides and ketones, which might improve therapeutic benefits.

alkamides

ketones


Input: Alkamides and Echinacea extracts might be useful in potentiating some chemotherapeutics, which are substrates for the P-glycoprotein transporter.

Alkamides


Input: Concentrations and trends of halogenated flame retardants in the pooled serum of residents of Laizhou Bay, China.


Input: The south coast of Laizhou Bay, in northeastern China, is a production area for halogenated flame retardants (HFR).


Input: In 2007, the authors measured serum concentrations of polybrominated diphenyl ethers (PBDEs) in Laizhou Bay residents.

polybrominated diphenyl ethers

PBDEs


Input: To assess the PBDE concentration trend, and determine the concentrations of the emerging flame retardants Dechlorane Plus (DP) and bis (2-ethylhexyl)-3, 4, 5, 6-tetrabromophthalate (TBPH), the authors measured the concentrations of 8 PBDE congeners, 2 DP isomers, and TBPH in 10 composite samples, which were pooled from the serum collected from 305 Laizhou Bay residents in October 2011.

PBDE

Dechlorane Plus

bis (2-ethylhexyl)-3, 4, 5, 6-tetrabromophthalate

TBPH

PBDE

TBPH


Input: The average concentration of the total PBDE (sum 8 PBDE) concentration in all serum pools was 240 ng/g lipid weight, and the highest serum pool concentration (in the 30-to 39-yr-old male group) was 780 ng/g lipid weight.

PBDE

PBDE


Input: Brominated diphenyl ether-209 was the dominant congener, accounting for 87% of sum 8 PBDE.

Brominated diphenyl ether-209

PBDE


Input: Compared with a previous study, sum 8 PBDE serum concentrations in the present study showed no change in order of magnitude, but the relative contribution of BDE-209 to sum 8 PBDE was higher.

PBDE

PBDE


Input: The average concentration of sum DP in all serum pools was 3. 6 ng/g lipid weight, ranging from 1. 4 ng/g lipid weight (in the 50-to 59-yr-old male group) to 11 ng/g lipid weight (in the 20-to 29-yr-old male group).


Input: The concentration of DP was lower than in other reported studies.


Input: The study also detected TBPH in the 30-to 39-yr-old female group, suggesting that TBPH, as an emerging HFR, requires further monitoring.

TBPH

TBPH


Input: Environ Toxicol Chem 2013; 32: 1242-1247.


Input: (c) 2013 SETAC.


Input: Synthesis and NMR studies of novel chromone-2-carboxamide derivatives.


Input: Chromones are heterocyclic compounds of natural or synthetic origin that possess relevant pharmacological activities.

Chromones


Input: Versatile functionalization of the chromone nucleus allows attaining of a chemical diversity suitable to perform structure-activity relationships in drug discovery and development programs.

chromone


Input: Accordingly, the synthesis and identification of novel chromone carboxamide derivatives with electron-donating and electron-withdrawing substituents in different positions of the exocyclic ring are reported in this work.

chromone carboxamide


Input: Their complete structural characterization was performed using one-dimensional and two-dimensional resonance techniques.


Input: The data acquired are useful for a prompt analysis of related compounds that encompass our integrated medicinal chemistry sketch.


Input: Correlates of bone microarchitectural parameters and serum sclerostin levels in men-the STRAMBO study.


Input: Sclerostin is predominantly expressed by osteocytes.


Input: Serum sclerostin levels are positively correlated with areal bone mineral density (aBMD) measured by DXA and bone microarchitecture assessed by high resolution peripheral quantitative computed tomography (HR-pQCT) in small studies.


Input: We assessed the relation of serum sclerostin levels with aBMD and microarchitectural parameters based on HR-pQCT in 1134 men aged 20-87 years using multivariable models adjusted for confounders (age, body size, lifestyle, co-morbidities, hormones regulating bone metabolism, muscle mass and strength).


Input: The apparent age-related increase in serum sclerostin levels was faster before the age of 63 than afterwards (0. 43SD vs 0. 20SD per decade).


Input: In 446 men aged <= 63, aBMD (spine, hip, whole body), trabecular volumetric BMD (Tb. vBMD) and trabecular number (Tb. N) at the distal radius and tibia were higher in the highest sclerostin quartile vs the three lower quartiles combined.


Input: After adjustment for aBMD, men in the highest sclerostin quartile had higher Tb. vBMD (mainly in the central compartment) and Tb. N at both skeletal sites (p < 0. 05-0. 001).


Input: In 688 men aged > 63, aBMD was positively associated with serum sclerostin levels at all skeletal sites.


Input: Cortical vBMD (Ct. vBMD) and cortical thickness (Ct. Th) were lower in the first sclerostin quartile vs the three higher quartiles combined.


Input: Tb. vBMD increased across the sclerostin quartiles which was associated with lower Tb. N and more heterogeneous trabecular distribution (higher Tb. Sp. SD) in men in the lowest sclerostin quartile.


Input: After adjustment for aBMD, men in the lowest sclerostin quartile had lower Tb. vBMD and Tb. N, but higher Tb. Sp. SD (p < 0. 05-0. 001) at both the skeletal sites.


Input: In conclusion, serum sclerostin levels in men are strongly positively associated with better bone microarchitectural parameters, mainly trabecular architecture, regardless of the potential confounders.


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


Input: MMP driven endochondral fracture union proceeds independently of osteoclast activity.


Input: As new insights into the complexities of endochondral fracture repair emerge, the temporal role of osteoclast activity remains ambiguous.


Input: With numerous anti-resorptive agents available to treat bone disease, understanding their impact on bone repair is vital.


Input: Further, in light of recent work suggesting osteoclast activity may not be necessary during early endochondral fracture union, we hypothesize instead a pivotal role of MMP secreting cells in driving this process.


Input: While the role of MMPs in fracture healing has been examined, no directly comparative experiments exist.


Input: We examined a number of anti-resorptive treatments to either block osteoclast activity, including the potent bisphosphonates zoledronic acid (ZA) and clodronate (CLOD), which work via differing mechanisms, or antagonize osteoclastogenesis with recombinant OPG (HuOPG-Fc), comparing these directly to an inhibitor of matrix metalloproteinase (MMP) activity (MMI270).

bisphosphonates zoledronic acid

clodronate

CLOD


Input: Endochondral ossification to union occurred normally in all anti-resorptive groups.


Input: In contrast, MMP inhibition greatly impaired endochondral union, significantly delaying cartilage callus removal.


Input: MMP inhibition also produced smaller, denser hard calluses.


Input: Hard callus remodeling was, as expected, delayed with ZA, CLOD and OPG treatment at 4 and 6 weeks, resulting in larger more mineralized calluses at 6 weeks.

CLOD


Input: As a result of reduced hard callus turnover, bone formation was reduced with anti-resorptive agents at these time points.


Input: These results confirm that the achievement of endochondral fracture union occurs independently of osteoclast activity.


Input: Alternatively, MMP secretion by invading cells is obligatory to endochondral union.


Input: This study provides new insight into cellular contributions to bone repair and may abate concerns regarding anti-resorptive therapies impeding initial fracture union.


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


Input: Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: A systematic review and meta-analysis.

Bisphosphonates


Input: While there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that these medications may be associated with rare atypical femoral fractures (AFF).

bisphosphonates


Input: Recent published studies examining this potential association are conflicting in regards to the existence and strength of this association.


Input: We conducted a systematic review and meta-analysis of published studies examining the association of bisphosphonates with subtrochanteric, femoral shaft, and AFF.

bisphosphonates


Input: The random-effects model was used to calculate the pooled estimates of adjusted risk ratios (RR).


Input: Subgroup analysis was performed by study design, for studies that used validated outcome definitions for AFF, and for studies reporting on duration of bisphosphonate use.

bisphosphonate


Input: Eleven studies were included in the meta-analysis: five case-control and six cohort studies.


Input: Bisphosphonate exposure was associated with an increased risk of subtrochanteric, femoral shaft, and AFF with adjusted RR of 1. 70 (95% CI 1. 22-2. 37).

Bisphosphonate


Input: Subgroup analysis of studies using the ASBMR-criteria to define AFF suggests a higher risk of AFF with bisphosphonate use with RR of 11. 78 (95% CI 0. 39-359. 69) as compared to studies using mainly diagnosis codes (RR 1. 62, 95% CI 1. 18-2. 22), although there is a wide confidence interval and severe heterogeneity (I (2) = 96. 15%) in this subgroup analysis.

bisphosphonate


Input: Subgroup analysis of studies examining at least 5 years of bisphosphonate use showed adjusted RR of 1. 62 (95% CI 1. 29-2. 04).

bisphosphonate


Input: This meta-analysis suggests there is an increased risk of subtrochanteric, femoral shaft, and AFF among bisphosphonate users.

bisphosphonate


Input: Further research examining the risk of AFF with long-term use of bisphosphonates is indicated as there was limited data in this subgroup.

bisphosphonates


Input: The public health implication of this observed increase in AFF risk is not clear.


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


Input: Novel inhibition of archaeal family-D DNA polymerase by uracil.

uracil


Input: Archaeal family-D DNA polymerase is inhibited by the presence of uracil in DNA template strands.

uracil


Input: When the enzyme encounters uracil, following three parameters change: DNA binding increases roughly 2-fold, the rate of polymerization slows by a factor of ~ 5 and 3'-5' proof-reading exonuclease activity is stimulated by a factor of ~ 2.

uracil


Input: Together these changes result in a significant decrease in polymerization activity and a reduction in net DNA synthesis.


Input: Pol D appears to interact with template strand uracil irrespective of its distance ahead of the replication fork.

uracil


Input: Polymerization does not stop at a defined location relative to uracil, rather a general decrease in DNA synthesis is observed.

uracil


Input: ' Trans' inhibition, the slowing of Pol D by uracil on a DNA strand not being replicated is also observed.

uracil


Input: It is proposed that Pol D is able to interact with uracil by looping out the single-stranded template, allowing simultaneous contact of both the base and the primer-template junction to give a polymerase-DNA complex with diminished extension ability.

uracil


Input: The renin-angiotensin system: new insight into old therapies.


Input: Although the renin-angiotensin system (RAS) is already an old acquaintance, there are often exciting discoveries that improve our knowledge of it and open new therapeutic possibilities.


Input: Moreover, well-established drugs, such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), or beta-blockers, show that their mechanism of action may be the result of parallel pathways other than the ones initially established.


Input: A detailed analysis of the RAS can be carried out in part through the study of the enzymes, named angiotensinases, involved in its cascade, whose activity is a reflection of the functionality of their peptide substrates.


Input: The study of these enzymes offers the possibility of controlling the effects of angiotensins through various pharmacological manipulations.


Input: For example, angiotensinase inhibitors or activators are being used or have been proposed as antihypertensive agents.


Input: They have also been suggested as analgesic and antidepressant drugs or targets for drug development against different pathologies such as Alzheimer' s disease, epilepsy or ischemia.


Input: On the other hand, the analysis of brain asymmetry has revealed surprising results about the laterality of central and peripheral components of the RAS.


Input: Such studies indicate that the neurovisceral integration, already proposed by Claude Bernard (1867) should also be analyzed from a bilateral perspective.


Input: In this review, the RAS and the role of various angiotensinases implicated in the cascade are revisited.


Input: Therapeutic strategies involving some components of the RAS with an unusual vision resulting from a bilateral perspective added to their study are discussed.


Input: Myeloid derived suppressor cells and their role in diseases.


Input: Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitors that can play a major role in tumour development and chronic inflammation.


Input: The importance of the suppressive function ofMDSCs was first suggested by studies involving cancer patients and cancer-bearing mice.


Input: In addition, recent studies have demonstrated that MDSCs can also be involved in many other pathological conditions.


Input: MDSCs have unique ways of abrogatingan immune response in addition to those utilised by other immune-suppressive cell types, for example via the induction of arginase-1 and consequent upregulation in reactive oxygen species (ROS) production.

oxygen


Input: Due to their heterogeneity, they further can express a variety of lineage markers, which overlap with other myeloid cell types such as Gr1, CD11b, MHCIIlo, Ly6C and Ly6G, making it difficult to identify them by surface phenotype alone.


Input: The disparity between mouse and human MDSCs further complicates the identification of these elusive cell populations.


Input: In this review, we will summarise the recent updates on the methods for eliciting and studying different MDSC subsets, including newly proposed surface phenotypes, as well as insights into how their function is being characterised in both mice and humans.


Input: In addition, exciting new discoveries suggesting their involvement across a number of different pathological settings, such as sepsis, autoimmunity and Leishmaniasis, will be discussed.


Input: Developing FGFR4 inhibitors as potential anti-cancer agents via in silico design, supported by in vitro and cell-based testing.


Input: Fibroblast growth factor receptor-4 (FGFR4) is a tyrosine kinase with a range of important physiological functions.

tyrosine


Input: However, it is also frequently mutated in various cancers and is now generating significant interest as a potential therapeutic target.


Input: Unfortunately, biochemical characterization of its role in disease, and further evaluation as a drug target is hampered by lack of a specific inhibitor.


Input: We aimed to discover new inhibitors for FGFR4 ab initio using a strategy combining in silico, in vitro and cell-based assays.


Input: We used the homologous FGFR1 to calculate docking scores of a chemically-diverse library of approximately 2000 potential kinase inhibitors.


Input: Nineteen potential inhibitors and ten randomly-selected negative controls were taken forward for in vitro FGFR4 kinase assays.


Input: All compounds with good docking scores significantly inhibited FGFR4 kinase activity, some with sub-micromolar (most potent being V4-015 with an IC (50) of 0. 04 mu M).


Input: Four of these compounds also demonstrated substantial activity in cellular assays using the FGFR4-overexpressing breast carcinoma cell line, MDA-MB453.


Input: Through immunoblot assays, these compounds were shown to block the phosphorylation of the FGFR4 adaptor protein, FGFR substrate protein-2 alpha (FRS2 alpha).


Input: The most potent compound to date, V4-015, suppressed proliferation of MDA-MB453 cells at sub-micromolar concentrations, activated the pro-apoptotic caspases 3/7 and inhibited cellular migration.


Input: While achieving complete selectivity of this compound for FGFR4 will require further lead optimization, this study has successfully identified new chemical scaffolds with unprecedented FGFR4 inhibition capacities that will support mechanism of action studies and future anti-cancer drug design.


Input: Long-Acting Beta-Agonists and their Association with Inhaled Corticosteroids in COPD.


Input: Inhaled bronchodilators, including beta2-agonists and antimuscaric receptor antagonists, are the mainstay of pharmacotherapy in chronic obstructive pulmonary disease (COPD).


Input: The short-acting beta2-agonists, including salbutamol, and fenoterol, have a rapid onset of action, a bronchodilating effect for 3-6 h and are used on demand.

salbutamol

fenoterol


Input: The longacting beta2-agonists (LABAs), including salmeterol and formoterol, have 12-hour duration of action and are used with a twice-daily dosing regimen for long-term COPD treatment.

salmeterol

formoterol


Input: Unlike salmeterol, formoterol has a rapid onset of action.

salmeterol

formoterol


Input: Pharmacological characteristics required by novel inhaled LABAs include 24 h bronchodilator effect in vivo which would make them suitable for once daily administration (ultra-LABA), high potency and selectivity for beta2-adrenoceptors, rapid onset of action, low oral bioavailability (< 5%) after inhalation, and high systemic clearance.


Input: Indacaterol, which has been approved for long-term treatment of COPD in Europe and in the USA, has a 24-h duration of action and a once-daily dosing regimen.

Indacaterol


Input: Newer ultra-LABAs, including olodaterol, vilanterol, milveterol, carmoterol, and abediterol, are in development.

olodaterol

vilanterol

milveterol

carmoterol

abediterol


Input: Combination with ICS (fluticasone/salmeterol, budesonide/formoterol, beclomethasone/formoterol) appears to provide an additional benefit over the monocomponent therapy, although the extent of this benefit is variable and often not clinically significant in all the endpoints assessed.

fluticasone

salmeterol

budesonide

formoterol

beclomethasone

formoterol


Input: In patients with COPD, treatment with ICS is associated with increased risk of pneumonia which should be carefully considered when assessing the risk/benefit ratio of ICS/LABA combinations.


Input: Subphenotyping of patients with COPD (e. g., frequent exacerbations, sputum eosinophilia, mixed asthma/COPD phenotype) might help identify those patients who are most likely to benefit from addition of ICS to bronchodilating treatment.


Input: Ultra-LABA/long-acting muscarinic receptor antagonist (LAMA) combination treatment is under development and is likely to become a standard pharmacological strategy for COPD.


Input: Dual-pharmacology inhaled muscarinic antagonist-beta2 agonist (MABA) molecules provide a new approach to the treatment of COPD.


Input: The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs.

fatty acid


Input: G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets.


Input: Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential.


Input: One in particular that has been gaining attention in recent times is that of GPCR ligands that bind to allosteric sites on the receptor distinct from the orthosteric site of the endogenous ligand.


Input: As therapeutics, allosteric ligands possess many theoretical advantages over their orthosteric counterparts, including more complex modes of action, improved safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis.


Input: Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge of identifying allosteric leads and their often flat or confusing SAR.


Input: The present review will consider the advantages and challenges associated with allosteric GPCR ligands, and examine how the particular properties of these ligands may be exploited to uncover the therapeutic potential for free fatty acid sensitive GPCRs.

fatty acid


Input: Dynamics of site switching in DNA polymerase.


Input: DNA polymerases replicate DNA by catalyzing the template-directed polymerization of deoxynucleoside triphosphate (dNTP) substrates onto the 3' end of a growing DNA primer strand.

deoxynucleoside triphosphate

dNTP


Input: Many DNA polymerases also possess a separate 3'-5' exonuclease activity that is used to remove misincorporated nucleotides from the nascent DNA (proofreading).

nucleotides


Input: The polymerase (pol) and exonuclease (exo) activities are spatially separated in different enzyme domains, indicating that a mechanism must exist to transfer the growing primer terminus from one site to the other.


Input: Here we report a single-molecule F o rster resonance energy transfer (smFRET) system that directly monitors the movement of a DNA substrate between the pol and exo sites of DNA polymerase I Klenow fragment (KF).


Input: FRET trajectories recorded during the encounter between single polymerase and DNA molecules reveal that DNA can channel between the pol and exo sites in both directions while remaining closely associated with the enzyme (intramolecular transfer).


Input: In addition, it is evident from the trajectories that DNA can also dissociate from one site and subsequently rebind at the other (intermolecular transfer).


Input: Rate constants for each pathway have been determined by dwell-time analysis, revealing that intramolecular transfer is the faster of the two pathways.


Input: Unexpectedly, a mispaired primer terminus accesses the exo site more frequently when dNTP substrates are also present in solution, which is expected to enhance proofreading.

dNTP


Input: Together, these results explain how the separate pol and exo activities of KF are physically coordinated to achieve efficient proofreading.


Input: Novel HldE-K Inhibitors Leading to Attenuated Gram Negative Bacterial Virulence.


Input: We report here the optimization of an HldE kinase inhibitor to low nanomolar potency, which resulted in the identification of the first reported compounds active on selected E. coli strains.


Input: One of the most interesting candidates, compound 86, was shown to inhibit specifically bacterial LPS heptosylation on efflux pump deleted E. coli strains.


Input: This compound did not interfere with E. coli bacterial growth (MIC > 32 mu g/mL) but sensitized this pathogen to hydrophobic antibiotics like macrolides normally inactive on Gram-negative bacteria.


Input: In addition, 86 could sensitize E. coli to serum complement killing.


Input: These results demonstrate that HldE kinase is a suitable target for drug discovery.


Input: They also pave the way toward novel possibilities of treating or preventing bloodstream infections caused by pathogenic Gram negative bacteria by inhibiting specific virulence factors.


Input: Compound and compositions as TGR5 agonists: WO2012082947.


Input: The patent application WO2012082947 claims novel compounds as agonists of a plasma membrane-bound bile acid receptor TGR5.


Input: By activating TGR5, the agonists improve glycemic control and enhance energy expenditure.


Input: The basic generic claim of the patent covers pyrazole derivatives, different permutations on the core pyrazole ring are covered in the subsidiary claims.

pyrazole

pyrazole


Input: The claimed compounds are human TGR5 agonists having potency in the nM range.


Input: Synthesis and structure-activity relationships of indazole arylsulfonamides as allosteric CC-chemokine receptor 4 (CCR4) antagonists.

indazole arylsulfonamides


Input: A series of indazole arylsulfonamides were synthesized and examined as human CCR4 antagonists.

indazole arylsulfonamides


Input: Methoxy-or hydroxyl-containing groups were the more potent indazole C4 substituents.

Methoxy

hydroxyl

indazole


Input: Only small groups were tolerated at C5, C6, or C7, with the C6 analogues being preferred.


Input: The most potent N3-substituent was 5-chlorothiophene-2-sulfonamide.


Input: N1 meta-substituted benzyl groups possessing an alpha-amino-3-[(methylamino) acyl]-group were the most potent N1-substituents.

benzyl

3-[(methylamino) acyl]


Input: Strongly basic amino groups had low oral absorption in vivo.

amino


Input: Less basic analogues, such as morpholines, had good oral absorption; however, they also had high clearance.

morpholines


Input: The most potent compound with high absorption in two species was analogue 6 (GSK2239633A), which was selected for further development.


Input: Aryl sulfonamide antagonists bind to CCR4 at an intracellular allosteric site denoted site II.

Aryl sulfonamide


Input: X-ray diffraction studies on two indazole sulfonamide fragments suggested the presence of an important intramolecular interaction in the active conformation.

indazole sulfonamide


Input: Structure-based discovery of pyrazolobenzothiazine derivatives as inhibitors of hepatitis C virus replication.

pyrazolobenzothiazine


Input: The NS5B RNA-dependent RNA polymerase is an attractive target for the development of novel and selective inhibitors of hepatitis C virus replication.


Input: To identify novel structural hits as anti-HCV agents, we performed structure-based virtual screening of our in-house library followed by rational drug design, organic synthesis, and biological testing.


Input: These studies led to the identification of pyrazolobenzothiazine scaffold as a suitable template for obtaining novel anti-HCV agents targeting the NS5B polymerase.

pyrazolobenzothiazine


Input: The best compound of this series was the meta-fluoro-N-1-phenyl pyrazolobenzothiazine derivative 4a, which exhibited an EC50 = 3. 6 mu M, EC90 = 25. 6 mu M, and CC50 > 180 mu M in the Huh 9-13 replicon system, thus providing a good starting point for further hit evolution.

meta-fluoro-N-1-phenyl pyrazolobenzothiazine


Input: Acute arsenic treatment alters cytochrome P450 expression and arachidonic acid metabolism in lung, liver and kidney of C57Bl/6 mice.

arsenic

arachidonic acid


Input: Abstract 1. Arsenic (As (III)) toxicity has received increasing attention as human exposure to arsenic is associated with pulmonary, hepatic and renal toxicities.

Arsenic

As (III)

arsenic


Input: Therefore, in the present study, we investigated the effect of acute As (III) treatment on pulmonary, hepatic and renal cytochrome (CYP) P450-mediated arachidonic acid metabolism.

As (III)

arachidonic acid


Input: 2. Our results demonstrated that acute As (III) treatment (12. 5 mg/kg) altered CYP epoxygenases, CYP omega-hydroxylases and EPHX2 mRNA levels that were isozyme and tissue specific.

As (III)


Input: 3. Furthermore, As (III) increased the formation of epoxyeicosatrienoic acids (EETs) in the kidney without affecting their levels in the lung or liver.

As (III)

epoxyeicosatrienoic acids

EETs


Input: In addition, acute As (III) treatment increased dihydroxyeicosatrienoic acid (DHETs) formation in the lung, while it did not affect liver DHETs formation and decreased kidney DHETs formation.

As (III)

dihydroxyeicosatrienoic acid

DHETs

DHETs

DHETs


Input: 4. As (III) also increased total epoxygenases activity in the lung while it decreased its levels in the kidney and had no effect on the liver.

As (III)


Input: Furthermore, As (III) increased 20-hydroxyeicosatetraenoic acid formation in the liver while it decreased its formation in the kidney.

As (III)

20-hydroxyeicosatetraenoic acid


Input: 5. Lastly, As (III) increased soluble epoxide hydrolase activity in the lung, while it decreased its levels in the kidney and had no effect on the liver.

As (III)

epoxide


Input: In conclusion, this is the first demonstration that As (III) alters arachidonic acid metabolism in a tissue specific manner.

As (III)

arachidonic acid


Input: Protein recognition of the S23906-1-DNA adduct by nuclear proteins: direct involvement of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) 1.


Input: In a view to develop new DNA alkylating antitumour drugs, evaluating the precise mechanism of action and the molecular/cellular consequences of the alkylation is a point of major interest.


Input: The benzo-b-acronycine derivative S23906-1 alkylates guanine nucleobases in the minor groove of the DNA helix and presents an original ability to locally open the double helix of DNA, which appears to be associated with its cytotoxic activity.

benzo-b-acronycine

guanine nucleobases


Input: However, the molecular mechanism linking adduct formation to cellular consequences is not precisely known.


Input: The objective of the present study was to identify proteins involved in the recognition and mechanism of action of S23906-DNA adducts.


Input: We found that GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is a protein that binds to S23906-alkylated single-stranded, double-stranded and telomeric sequences in a drug-dependent and DNA sequence/structure-dependent manner.


Input: We used the CASTing (cyclic amplification of sequence targeting) method to identify GAPDH DNA-binding selectivity and then evaluated its binding to such selected S23906-alkylated sequences.


Input: At the cellular level, alkylation of S23906-1 results in an increase in the binding of GAPDH and its protein partner HMG (high-mobility group) B1 to the chromatin.


Input: Regarding the multiple roles of GAPDH in apoptosis and DNA repair, the cytotoxic and apoptotic activities of GAPDH were evaluated and present opposite effects in two different cellular models.


Input: Synthesis and cancer stem cell-based activity of substituted 5-morpholino-7H-thieno [3, 2-b] pyran-7-ones designed as next generation PI3K inhibitors.

5-morpholino-7H-thieno [3, 2-b] pyran-7-ones


Input: Dysregulation of the phosphatidylinositol-3-kinase (PI3K) pathway in a wide range of tumors has made PI3K a consensus target to inhibit as illustrated by more than 15 inhibitors now in clinical trials.


Input: Our previous work, built on the early pioneering multikinase inhibitor LY294002, resulted in the only PI3K vascular-targeted PI3K inhibitor prodrug, SF1126, which has now completed Phase I clinical trials.


Input: This inhibitor has properties that impart more in vivo activity than should be warranted by its enzymatic potency, which in general is much lower than other clinical stage PI3K inhibitors.


Input: We embarked on the exploration of scaffolds that retained such properties while simultaneously exhibiting an increased potency toward PI3K.


Input: This work resulted in the discovery of the 5-morpholino-7H-thieno [3, 2-b] pyran-7-one system as the foundation of a new compound class of potential PI3K inhibitors having improved potency toward PI3K.

5-morpholino-7H-thieno [3, 2-b] pyran-7-one


Input: The synthesis and cancer stem cell-based activity of these compounds are reported herein.


Input: Injectable superparamagnets: highly elastic and degradable poly (N-isopropylacrylamide)-superparamagnetic iron oxide nanoparticle (SPION) composite hydrogels.

poly (N-isopropylacrylamide)

iron oxide


Input: Injectable, in situ-gelling magnetic composite materials have been fabricated by using aldehyde-functionalized dextran to cross-link superparamagnetic nanoparticles surface-functionalized with hydrazide-functionalized poly (N-isopropylacrylamide) (pNIPAM).

aldehyde

hydrazide

poly (N-isopropylacrylamide)

pNIPAM


Input: The resulting composites exhibit high water contents (82-88 wt.%) while also displaying significantly higher elasticities (G' > 60 kPa) than other injectable hydrogels previously reported.


Input: The composites hydrolytically degrade via slow hydrolysis of the hydrazone cross-link at physiological temperature and pH into degradation products that show no significant cytotoxicity.

hydrazone


Input: Subcutaneous injections indicate only minor chronic inflammation associated with material degradation, with no fibrous capsule formation evident.


Input: Drug release experiments indicate the potential of these materials to facilitate pulsatile, " on-demand " changes in drug release upon the application of an external oscillating magnetic field.


Input: The injectable but high-strength and externally triggerable nature of these materials, coupled with their biological degradability and inertness, suggest potential biological applications in tissue engineering and drug delivery.


Input: Identification of Novel Drug Targets in HpB38, HpP12, HpG27, Hpshi470, HpSJM180 Strains of Helicobacter pylori: An In Silico Approach for Therapeutic Intervention.


Input: Helicobacter species colonizes the stomach and are associated with the development of gastritis disease.


Input: Drugs for treatment of Helicobacter infection relieve pain or gastritis symptoms but they are not targeted specifically to Helicobacter pylori.


Input: Therefore, there is dire need for discovery of new drug targets and drugs for the treatment of H. pylori.


Input: The main objective of this study is to screen the potential drug targets by in silico analysis for the potent strains of H. pylori which include HpB38, HpP12, HpG27, Hpshi470 and HpSJM180.


Input: Genome and metabolic pathways of pathogen H. pylori and the host Homosapien sapiens are compared and genes which were unique to H. pylori were filtered and catalogued.


Input: These unique genes were subjected to gene property analysis to identify the potentiality of the drug targets.


Input: Among the total number of genes analysed in different strains of H. pylori nearly 558, 569, 539, 569, 567 number of genes in HpB38, HpP12, HpG27, Hpshi470 and HpSJM180 found qualified as unique molecules and among them 17 qualified as potential drug targets.


Input: Membrane fusion protein of hefABC efflux system, 50 S ribosomal protein L33, Hydrogenase expression protein/formation of HypD, Cag pathogenecity island protein X, Apolipoprotein N acyl transferase, DNA methyalse, Histone like binding protein, Peptidoglycan-associated lipoprotein OprL were found to be critical drug targets to H. pylori.

N acyl


Input: Three (hefABC efflux system, Hydrogenase expression protein/formation of HypD, Cag pathogenecity island protein X) of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lending credence to our unique approach.


Input: Profiling the structural determinants of heteroarylnitrile scaffold-based derivatives as falcipain-2 inhibitors by in silico methods.

heteroarylnitrile


Input: Evidence indicates that cysteine protease falcipain-2 plays essential role in malaria parasites; therefore the potent and selective inhibitors of falcipain-2 may be therapeutically useful drugs for treatment of various forms of malaria parasite plasmodium.

cysteine


Input: In order to understand the structure-activity correlation of falcipain-2 inhibitors, a set of ligand-and receptor-based 3D-QSAR models were, for the first time, developed in the present work employing Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA) for 240 promising molecules.


Input: Based on the ligand-based alignment, an optimal 3D-QSAR model was obtained with good predictive power of Q (2) = 0. 501, R (2) ncv = 0. 890, SEE = 0. 282, F = 153. 522 and R (2) pred = 0. 768.


Input: And the contour maps intuitively suggest where to modify the molecular structures in order to improve the binding affinity.


Input: In addition, docking analysis and molecular dynamics simulation (MD) study were also carried out on the dataset with purpose of exploring the detailed binding modes of ligand in the falcipain-2 binding pocket.


Input: The combination of docking analysis and MD simulation shows that Gly83, Trp43 and Ala175 which formed several H-bonds are crucial for falcipain-2 inhibitors.

H


Input: The analysis of the best QSAR model reveals the structural features related to the activity, and provides an insight into molecular mechanisms of inhibition and possible modification of the molecules for better activity.


Input: Multitarget drugs of plants origin acting on Alzheimer' s disease.


Input: The etiopathology of Alzheimer' s disease (AD) is extremely complex and heterogeneous, often associated with comorbidities.


Input: As a result it may be unlikely that AD may be mitigated by drug acting on a single specific target.


Input: The current tendency in drug design and discovery in AD is the rational design or " serendipitous " discovery of new drug entities challenging multiple targets.


Input: Since two of the presently approved drugs for AD are based on natural products (galantamine and the physostigmine-derivative rivastigmine), many plants are now under investigation as a potential source of new drugs.

galantamine

physostigmine

rivastigmine


Input: Multifunctional drugs often have their origin in natural sources.


Input: This review is limited to plant chemicals having different targets with actual (galantamine) or promising (drugs from Crocus sativus, Ginkgo biloba, Salvia species, and Huperzia serrata) clinical evidence in people with dementia or AD.

galantamine


Input: Hedgehog Signaling in Medullary Thyroid Carcinoma: A Novel Signaling Pathway.


Input: Background: Locally or widely metastatic medullary thyroid carcinoma (MTC) is difficult to treat and therapeutic options are limited.


Input: Recently, kinase inhibitors have shown partial efficacy in this cancer, but there is a continued need for the development of novel therapeutics.


Input: Within this context, the Hedgehog (Hh) pathway has been implicated in several types of human tumors, and early clinical trials with Hh antagonists have validated Hh as a novel therapeutic target.


Input: For the first time, we evaluated Hh pathway activity in MTC and examined the effect of Hh pathway perturbation in highly characterized MTC cell lines.


Input: Methods: We examined immunohistochemical expression of Hh signaling mediators Sonic Hedgehog (Shh) and Glioblastoma (Gli) 2 in paraffin-embedded normal versus histologically characterized human MTC tissue.


Input: We examined pharmacologic disruption of Hh signaling in vitro using two established MTC cell lines (TT and MZ-CRC-1).


Input: Hh signaling was either pharmacologically activated (SAG) or inhibited (GDC-0449) in MTC cell lines; Hh activity was assessed by qRT-PCR, Western blot analysis, and quantification of cellular growth and apoptotic activity.


Input: Results: Our data showed increased expression of Hh signaling factors in human MTC compared to normal tissue.


Input: In vitro, activation of the Hh pathway resulted in increased expression of key Hh signaling components Smoothened (Smo) and Gli2.


Input: Conversely, inhibition of the Hh pathway decreased expression of these genes, leading to significantly reduced cellular growth and increased apoptosis.


Input: Conclusions: Hedgehog signaling components are markedly upregulated in MTC.


Input: Hh pathway inhibitors have potential as novel therapeutic options in patients with metastatic and/or surgically unresectable MTC.


Input: High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice.


Input: Dynamic epigenetic reprogramming occurs during mammalian germ cell development, although the targets of this process, including DNA demethylation and de novo methylation, remain poorly understood.


Input: We performed genome-wide DNA methylation analysis in male and female mouse primordial germ cells at embryonic days 10. 5, 13. 5, and 16. 5 by whole-genome shotgun bisulfite sequencing.

bisulfite


Input: Our high-resolution DNA methylome maps demonstrated gender-specific differences in CpG methylation at genome-wide and gene-specific levels during fetal germline progression.

CpG


Input: There was extensive intra-and intergenic hypomethylation with erasure of methylation marks at imprinted, X-linked, or germline-specific genes during gonadal sex determination and partial methylation at particular retrotransposons.


Input: Following global demethylation and sex determination, CpG sites switched to de novo methylation in males, but the X-linked genes appeared resistant to the wave of de novo methylation.

CpG


Input: Significant differential methylation at a subset of imprinted loci was identified in both genders, and non-CpG methylation occurred only in male gonocytes.

CpG


Input: Our data establish the basis for future studies on the role of epigenetic modifications in germline development and other biological processes.


Input: Aspulvinones from a mangrove rhizosphere soil-derived fungus Aspergillus terreus Gwq-48 with anti-influenza A viral (H1N1) activity.

Aspulvinones


Input: A new butenolide isoaspulvinone E (1), together with two known butenolides aspulvinone E (2) and pulvic acid (3) were isolated from the marine-derived fungus, Aspergillus terreus Gwq-48.

butenolide isoaspulvinone E

butenolides aspulvinone E

pulvic acid


Input: They showed significant anti-influenza A H1N1 virus activities, with IC50 values of 32. 3, 56. 9, and 29. 1 mu g/mL, respectively.


Input: Moreover, only compound 1 exhibited effective inhibitory activity against H1N1 viral neuraminidase (NA), and docking of two isomers (1-2) into the active sites of NA showed that the E double bond Delta (5 (10)) was essential to achieve activity.


Input: A novel fluorogenic substrate for dinuclear Zn (II)-containing metallo-beta-lactamases.

Zn (II)


Input: In an effort to prepare a fluorogenic substrate to be used in activity assays with metallo-beta-lactamases, (6R, 7R)-8-oxo-7-(2-oxo-2H-chromene-3-carboxamido)-3-((4-(2-oxo-2H-chromene-3-carboxamido)-phenylthio) methyl)-5-thia-1-azabicyclo [4. 2. 0] oct-2-ene-2-carboxylic acid (CA) was synthesized and characterized.

(6R, 7R)-8-oxo-7-(2-oxo-2H-chromene-3-carboxamido)-3-((4-(2-oxo-2H-chromene-3-carboxamido)-phenylthio) methyl)-5-thia-1-azabicyclo [4. 2. 0] oct-2-ene-2-carboxylic acid


Input: CA exhibited a fluorescence quantum yield (phi) of 0. 0059, two fluorescence lifetimes of 3. 63 x 10 (-10) and 5. 38 x 10 (-9) s, and fluorescence intensity that is concentration-dependent.


Input: Steady-state kinetic assays revealed that CA is a substrate for metallo-beta-lactamases (M beta Ls) L1 and CcrA, exhibiting Km and kcat values of 18 mu M and 5s (-1) and 11 mu M and 17s (-1), respectively.


Input: Synthesis and physicochemical properties of new tripodal amphiphiles bearing fatty acids as a hydrophobic group.

fatty acids


Input: Saturated fatty acids (FA) were grafted using tyrosine as a spacer group to the cyclotriphosphazene ring along with equimolar hydrophilic methoxy poly (ethylene glycol) (MPEG) in cis-nongeminal way.

Saturated fatty acids

tyrosine

cyclotriphosphazene

methoxy poly (ethylene glycol)

MPEG


Input: Seven new cyclotriphosphazene amphiphiles were prepared from combinations of hydrophilic MPEGs with different molecular weights of 350, 550, 750 and 1000 and four different fatty acids of different hydrophobicity including lauric, myristic, palmitic and stearic acids.

cyclotriphosphazene

MPEGs

fatty acids

lauric, myristic, palmitic and stearic acids


Input: These steric amphiphiles bearing fatty acids as a hydrophobic group were found to form more stable micelles with very low critical micelle concentrations (CMC) (2. 95-7. 80mg/L) compared with oligopeptide analogues, and their highly hydrophobic core environment is unique and potentially useful for various biomedical applications.

fatty acids


Input: Electrochemical determination of Sudan I in food samples at graphene modified glassy carbon electrode based on the enhancement effect of sodium dodecyl sulphonate.

Sudan I

graphene

carbon

sodium dodecyl sulphonate


Input: This paper describes a novel electrochemical method for the determination of Sudan I in food samples based on the electrochemical catalytic activity of graphene modified glassy carbon electrode (GMGCE) and the enhancement effect of an anionic surfactant: sodium dodecyl sulphonate (SDS).

Sudan I

graphene

carbon

sodium dodecyl sulphonate

SDS


Input: Using pH 6. 0 phosphate buffer solution (PBS) as supporting electrolyte and in the presence of 1. 5 x 10 (-4) mol L (-1) SDS, Sudan I yielded a well-defined and sensitive oxidation peak at a GMGCE.

phosphate

SDS

Sudan I


Input: The oxidation peak current of Sudan I remarkably increased in the presence of SDS.

Sudan I

SDS


Input: The experimental parameters, such as supporting electrolyte, concentration of SDS, and accumulation time, were optimised for Sudan I determination.

SDS

Sudan I


Input: The oxidation peak current showed a linear relationship with the concentrations of Sudan I in the range of 7. 50 x 10 (-8)-7. 50 x 10 (-6) mol L (-1), with the detection limit of 4. 0 x 10 (-8) mol L (-1).

Sudan I


Input: This new voltammetric method was successfully used to determine Sudan I in food products such as ketchup and chili sauce with satisfactory results.

Sudan I


Input: Pterostilbene inhibits dimethylnitrosamine-induced liver fibrosis in rats.

Pterostilbene

dimethylnitrosamine


Input: Pterostilbene, found in grapes and berries, exhibits pleiotropic effects, including anti-inflammatory, antioxidant, and anti-proliferative activities.

Pterostilbene


Input: This study was conducted to investigate the effect of pterostilbene on liver fibrosis and the potential underlying mechanism for such effect.

pterostilbene


Input: Sprague-Dawley rats were intraperitoneally given dimethyl n-nitrosamine (DMN) (10mg/kg) 3 days per week for 4 weeks.

dimethyl n-nitrosamine

DMN


Input: Pterostilbene (10 or 20mg/kg) was administered by oral gavage daily.

Pterostilbene


Input: Liver function, morphology, histochemistry, and fibrotic parameters were examined.


Input: Pterostilbene supplementation alleviated the DMN-induced changes in the serum levels of alanine transaminase and aspartate transaminase (p < 0. 05).

Pterostilbene

DMN


Input: Fibrotic status and the activation of hepatic stellate cells were improved upon pterostilbene supplementation as evidenced by histopathological examination as well as the expression of alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta 1 (TGF-beta 1), and matrix metalloproteinase 2 (MMP2).

pterostilbene


Input: These data demonstrated that pterostilbene exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-beta 1/Smad signaling.

pterostilbene


Input: Thermal-induced changes of kale' s antioxidant activity analyzed by HPLC-UV/Vis-online-TEAC detection.


Input: Generally, boiling of vegetables is assumed leading to lower nutritional values because of leaching effects and activity loss of bioactive compounds.


Input: Kale (Brassica oleracea var. sabellica) reveals a great diversity of flavonoids, which have been shown to be good antioxidants.

flavonoids


Input: As Brassica vegetables are mainly consumed cooked, the influence of boiling on kale' s flavonoids and their antioxidant activity was investigated.

flavonoids


Input: Therefore, three kale cultivars were cooked at 100 degrees C for 2 and 4h prior to analysis.


Input: The total phenolic content (TPC) and the total antioxidant activity (TEAC assay and EPR spectrometry) of each cultivar were determined and revealed no change, independent of cooking time, although kale samples visually altered.


Input: Using the HPLC-UV/Vis-online-TEAC approach, distinct changes in composition and antioxidant activity of the flavonoids were detectable.

flavonoids


Input: Thus, it was observable, that the antioxidant activities of the reaction products compensated the " loss " of the antioxidant activity of the original compounds of the uncooked material.


Input: Dispersive liquid-liquid microextraction combined with field-amplified sample stacking in capillary electrophoresis for the determination of non-steroidal anti-inflammatory drugs in milk and dairy products.

steroidal


Input: Dispersive liquid-liquid microextraction (DLLME) was coupled with field-amplified sample stacking in capillary electrophoresis (FASS) for the determination of five non-steroidal anti-inflammatory drugs (NSAIDs) in bovine milk and dairy products.

steroidal


Input: After extraction, the enriched analytes were back-extracted into a basic aqueous solution for injection into CE.


Input: Under optimum conditions, enrichment factors were in the range 46-229.


Input: Limits of detection of the analytes ranged from 3. 0 to 13. 1 mu g kg (-1) for all matrices analysed.


Input: Calibration graphs showed good linearity with coefficients of determination (R (2)) >= 0. 9915 and relative standard deviations (RSD%) of the analyses in the range of 0. 6-6. 2% (n = 5).


Input: Recoveries of all NSAIDs from bottled milk, raw milk, yogurt and white cheese samples were in the ranges of 86. 6-109. 3%, 84. 3-100. 5%, 77. 4-107. 3%, and 90. 9-101. 6%, respectively.


Input: DLLME-FASS-CE was demonstrated to be a rapid and convenient method for the determination of NSAIDs in milk and dairy products.


Input: Antioxidant activities of the synthesized thiol-contained peptides derived from computer-aided pepsin hydrolysis of yam tuber storage protein, dioscorin.

thiol

dioscorin


Input: Our previous report showed that yam dioscorin and its peptic hydrolysates exhibit radical scavenging activities; however, the functions of these peptic hydrolases are still under investigation.

dioscorin


Input: In this study, the thiol-containing peptides derived from computer-aided simulation of pepsin hydrolysis of dioscorin, namely, KTCGNGME (diotide1), PPCSE (diotide2), CDDRVIRTPLT (diotide3), KTCGY (diotide4), and PPCTE (diotide5) were synthesized to compare their antioxidant activities with GSH and/or carnosine by examining hydroxyl radical scavenging activity by electron spin resonance spectrometry, anti-low-density lipoprotein peroxidation, anti-AAPH-induced hemolysis, and oxygen radical absorbance capacity activity.

thiol

dioscorin

GSH

carnosine

hydroxyl

AAPH

oxygen


Input: We found that while all the synthesized diotides showed antioxidant activity, diotide4 exhibited the highest levels.


Input: Moreover, all diotides (100 mu M) showed protective effects against methylglyoxal-induced human umbilical vein endothelial cell death.

methylglyoxal


Input: These results suggest that thiol-containing diotides derived from dioscorin hydrolysis exhibit antioxidant activities and reveal the benefits of yam tuber as an antioxidant-rich food.

thiol

dioscorin


Input: Winter wheat hull (husk) is a valuable source for tricin, a potential selective cytotoxic agent.

tricin


Input: The flavone, tricin (5, 7, 4'-trihydroxy-3', 5'-dimethoxyflavone) has great potential as an anticancer agent, due to its specific chemopreventive activity.

flavone

tricin

5, 7, 4'-trihydroxy-3', 5'-dimethoxyflavone


Input: In spite of these characteristics, its use in preclinical studies is still limited, mainly because of its limited availability and high production cost.


Input: Tricin is found mainly in cereal grains, such as wheat, rice, barley, oat and maize.

Tricin


Input: However, its concentration in these plants is not sufficient for commercial use.


Input: To find a reliable, rich source of tricin, we investigated its distribution in different parts of wheat (Triticum aestivum) and designed an efficient method for its isolation and purification.

tricin


Input: The highest amount (770 +/- 157 mg/kg dry weight) was found in the husks of winter wheat.


Input: This concentration is one of the highest in any plant species and is considered as a cheap source of natural tricin.

tricin


Input: The purified wheat husks tricin was found to be a selective potent inhibitor of two cancer cell lines of liver and pancreas, while having no side effects on normal cells.

tricin


Input: This selective action suggests that tricin could be considered as a potential candidate for pre-clinical trials as a chemopreventive agent.

tricin


Input: In addition, fibre-rich crude wheat husk could be used as a natural chemopreventive agent in food supplement.


Input: Glycosidic aroma precursors of Syrah and Chardonnay grapes after an oak extract application to the grapevines.


Input: Syrah and Chardonnay grapevines were treated with an oak extract in order to determine the effect on glycosidic aroma precursors.


Input: Grapevines were treated at three different timings of the veraison (treatment 1, 2 and 3).


Input: Aglycons were obtained by enzymatic hydrolysis, and these were identified and quantified by means of gas chromatography-mass spectrometry (GC-MS).


Input: Results suggest that after the applications the majority of compounds from the oak extract were assimilated and stored as glycosidic forms in both cultivars.


Input: Also, other compounds not present in the extract were affected, with a different behaviour observed depending on the timing of application and the variety.


Input: In general, C6 compounds, alcohols, terpenes, phenols and C13-norisoprenoids in Syrah showed a decrease and in Chardonnay an increase.

alcohols

terpenes

phenols


Input: Thus, this study proved a change in the glycosidic aroma profile in grapes after the oak application, so these treated grapes could produce wines with different aromatic quality.


Input: 1H NMR-based metabolic fingerprinting of urine metabolites after consumption of lingonberries (Vaccinium vitis-idaea) with a high-fat meal.


Input: The use of NMR metabolomics in clinical trials is growing; however, reports of postprandial experiments in humans are scarce.


Input: The present study investigated whether consumption of lingonberries as a supplement to an oil-rich meal modifies the postprandial fingerprints of human urine.


Input: Urine samples were analysed by (1) H NMR, and untargeted multivariate analysis was applied to the data for comprehensive fingerprinting.

(1) H


Input: A clear separation of postprandial lingonberry meal samples was revealed.


Input: To evaluate statistical differences, a targeted approach was applied for the informative spectral areas.


Input: Significantly (p < 0. 05) increased levels of polyphenol metabolites, hippuric acid and 4-hydroxyhippuric acid, and decreased creatinine and dimethylamine levels were the major explanations for the grouping of the postprandial samples after the different meals.

polyphenol

hippuric acid

4-hydroxyhippuric acid

creatinine

dimethylamine


Input: Thus, inclusion of polyphenol-rich lingonberry powder in a rapeseed oil-rich meal modifies the metabolic profile of urine which may be used to reveal both consumption of berries and health-promoting changes in the common metabolism.

polyphenol


Input: Simultaneous determination of Mn2 + and Fe3 + as 4, 4' [(4-cholorophenyl) methylene] bis (3-methyl-1-phenyl-1H-pyrazol-5-ol) complexes in some foods, vegetable and water samples by artificial neural networks.

Mn2 +

Fe3 +

4, 4' [(4-cholorophenyl) methylene] bis (3-methyl-1-phenyl-1H-pyrazol-5-ol)


Input: A simple and sensitive spectrophotometric method to the simultaneous determination of Mn (2 +) and Fe (3 +) in foods, vegetable and water sample with the aid of artificial neural networks (ANNs) is described.

Mn (2 +)

Fe (3 +)


Input: It relies on the complexation of analytes with recently synthesised bis pyrazol base ligand as 4, 4' [(4-cholorophenyl) methylene] bis (3-methyl-1-phenyl-1H-pyrazol-5-ol) (CMBPP).

pyrazol

4, 4' [(4-cholorophenyl) methylene] bis (3-methyl-1-phenyl-1H-pyrazol-5-ol)

CMBPP


Input: The analytical data show that the ratio of ligand to metal in metal complexes is 1: 1 and 1: 2 for Fe (3 +) and Mn (2 +), respectively.

Fe (3 +)

Mn (2 +)


Input: It was found that the complexation reactions are completed at pH 6. 7 and 5 min after mixing.


Input: The results showed that Mn (2 +) and Fe (3 +) could be determined simultaneously in the range of 0. 20-7. 5 and 0. 30-9. 0 mgl (-1), respectively.

Mn (2 +)

Fe (3 +)


Input: The analytical characteristics of the method such as the detection limit and the relative standard error predictions were calculated.


Input: The data obtained from synthetic mixtures of the metal ions were processed by radial basis function networks (RBFNs) and feed forward neural networks (FFNNs).


Input: The optimal conditions of the neural networks were obtained by adjusting various parameters by trial-and-error.


Input: Under the working conditions, the proposed methods were successfully applied to the simultaneous determination of elements in different water, tablet, rice, tea leaves, tomato, cabbage and lettuce samples.


Input: The influence of cation exchange treatment on the final characteristics of red wines.


Input: Ion exchange technology has been applied to adjust the pH of red wine and improve its tartaric and oxidative stability.


Input: Ion exchange appears to be a useful technique to achieve these objectives.


Input: Regarding the effect of ion exchange on organoleptic characteristics and the quality of the obtained wines, a slight decrease in both anthocyanin and tannin contents was observed along with a small drop in the aromatic content.

anthocyanin

tannin


Input: However, the treated wines had lower hue and higher colour intensity and gave better punctuations in the sensory evaluation.


Input: These results confirm that ion exchange is an interesting technique for application in red winemaking.


Input: Multidisciplinary analytical investigation of phospholipids and triglycerides in offshore farmed gilthead sea bream (Sparus aurata) fed commercial diets.

triglycerides


Input: In this work, a quantitative characterisation of lipid (both triglycerides and phospholipids) rearrangements in the muscle of offshore-raised gilthead sea bream was carried out as a function of fish growth between April and September.

triglycerides


Input: Relative percentages of lipid classes and fatty acids/acyls composition of the commercial feeds and fish dorsal muscles were assessed by means of an interdisciplinary analytical approach.

fatty acids

acyls


Input: A combination of preparative chemistry and experimental results from NMR spectroscopy, GC, 3D-TLC as well as proximate analysis permitted the observed growth parameters in key metabolic events to be linked with fish fattening and lipid turnover.


Input: While defined effects of feed composition on fatty acid profiles of fillets were ascertained, the relative increase of fatty acyls in triglycerides and phospholipids were also estimated enabling detailed evaluation of TAG: PL ratio in adult offshore-farmed gilthead sea bream.

fatty acid

fatty acyls

triglycerides


Input: NMR was also used to quantify PUFA regiospecific distribution in TAG and PL.

PUFA

TAG


Input: Non-destructive determination of chemical composition in intact and minced pork using near-infrared hyperspectral imaging.


Input: In this study a near-infrared (NIR) hyperspectral imaging technique was investigated for non-destructive determination of chemical composition of intact and minced pork.


Input: Hyperspectral images (900-1700 nm) were acquired for both intact and minced pork samples and the mean spectra were extracted by automatic segmentation.


Input: Protein, moisture and fat contents were determined by traditional methods and then related with the spectral information by partial least-squares (PLS) regression models.


Input: The coefficient of determination obtained by cross-validated PLS models indicated that the NIR spectral range had an excellent ability to predict the content of protein (R (2) (cv) = 0. 88), moisture (R (2) (cv) = 0. 87) and fat (R (2) (cv) = 0. 95) in pork.


Input: Regression models using a few selected feature-related wavelengths showed that chemical composition could be predicted with coefficients of determination of 0. 92, 0. 87 and 0. 95 for protein, moisture and fat, respectively.


Input: Prediction of chemical contents in each pixel of the hyperspectral image using these prediction models yielded spatially distributed visualisations of the sample composition.


Input: Simple, fast, and efficient process for producing and purifying trehalulose.

trehalulose


Input: A new property of recombinant trehalose synthase (GTase) from Thermus thermophilus HB-8 (ATCC 27634) was found and described in this study.

trehalose


Input: GTase can act on sucrose and catalyze trehalulose formation without isomaltose, isomaltulose, or isomelezitose, releasing small amounts of glucose and fructose as byproducts.

sucrose

trehalulose

isomaltose

isomaltulose

isomelezitose

glucose

fructose


Input: Maximum trehalulose yield (approximately 81%) was obtained at an optimum temperature of 65 degrees C and was independent of substrate concentration.

trehalulose


Input: A simple, fast, and efficient method of producing and purifying trehalulose is then described.

trehalulose


Input: In the first step, GTase catalyzed trehalulose formation using a 20% sucrose substrate.

trehalulose

sucrose


Input: Miscellaneous sugars were then rapidly removed, while trehalulose was completely preserved by Saccharomyces cerevisiae cells.

sugars

trehalulose


Input: Finally, the cells were separated by centrifugation, and salt ions were removed by an ion-exchange resin, subsequently obtaining a high-purity trehalulose solution.

trehalulose


Input: A trehalulose recovery rate of over 95% was achieved using this process.

trehalulose


Input: This method has a simple process, fast separation efficiency, and low investment in production equipment, so greatly to improve production efficiency and reduce production costs.


Input: Effect of peeling and three cooking methods on the content of selected phytochemicals in potato tubers with various colour of flesh.


Input: The impact of peeling and three cooking treatments (boiling, baking and microwaving) on the content of selected phytochemicals in white-, yellow-, red-and purple-fleshed potatoes was investigated.


Input: Ascorbic acid and chlorogenic acid contents were determined by HPLC-DAD, total anthocyanin content by pH-differential spectrophotometry, glycoalkaloid, alpha-chaconine and alpha-solanine contents by HPLC-ESI/MS/MS.

Ascorbic acid

chlorogenic acid

anthocyanin

glycoalkaloid

alpha-chaconine

alpha-solanine


Input: All cooking treatments reduced ascorbic and chlorogenic acid contents, total glycoalkaloids, alpha-chaconine and alpha-solanine with the exception of total anthocyanins.

ascorbic and chlorogenic acid

glycoalkaloids

alpha-chaconine

alpha-solanine

anthocyanins


Input: The losses of ascorbic and chlorogenic acids were minimised with boiling and total anthocyanin levels retained the highest.

ascorbic and chlorogenic acids

anthocyanin


Input: Boiling of peeled tubers decreased contents of total glycoalkaloids (alpha-chaconine and alpha-solanine) and appeared as the most favourable among the three tested methods.

glycoalkaloids

alpha-chaconine and alpha-solanine


Input: Moreover, due to higher initial levels, red-and purple-fleshed cultivars retained higher amounts of antioxidants (ascorbic acid, chlorogenic acid and total anthocyanin) after boiling and may be healthier as compared with white or yellow cultivars.

ascorbic acid

chlorogenic acid

anthocyanin


Input: A multi-residue method for the determination of 124 pesticides in rice by modified QuEChERS extraction and gas chromatography-tandem mass spectrometry.


Input: A modified QuEChERS method for simultaneous determination of 124 pesticide residues in rice was established and validated.


Input: The rice samples were initially extracted with acetonitrile (MeCN), and the targeted pesticides were purified following the dispersive solid phase extraction (d-SPE) cleanup method and detected by gas chromatography-tandem mass spectrometry (GC-MS/MS).

acetonitrile

MeCN


Input: The efficiency of citrate-buffered and unbuffered method in liquid extraction procedure was compared; the amount of primary secondary amine (PSA) was optimised.

citrate

primary secondary amine

PSA


Input: In the method validation, correlation coefficients (r (2)) were higher than 0. 990 with the linear ranging from 10 to 200 mu g kg (-1).


Input: At the fortification levels of 20-200 mu g kg (-1), average recoveries ranged from 70% to 122. 7% with the RSD < 20%.


Input: Antioxidant activity of phytosteryl phenolates in different model systems.

phytosteryl phenolates


Input: As part of a comprehensive study of the physiochemical and biological properties of phytosteryl phenolates, successfully synthesized chemoenzymatically in our lab, their antioxidant activity was evaluated using three different in vitro model systems, namely bulk oil model system, beta-carotene-linoleate model system and low-density lipoprotein cholesterol (LDL-C) oxidation assay.

phytosteryl phenolates

beta-carotene

linoleate

cholesterol


Input: In the bulk oil system, phytosteryl phenolates showed similar or lower antioxidant activity compared with those of phenolic acids.

phytosteryl phenolates

phenolic acids


Input: However, in beta-carotene-linoleate assay, an emulsion model system, phytosteryl phenolates showed enhanced antioxidant activity except phytosteryl ferulates.

beta-carotene

linoleate

phytosteryl phenolates

phytosteryl ferulates


Input: Moderate inhibitory effect of LDL-C oxidation by phytosteryl phenolates was observed.

phytosteryl phenolates


Input: These findings demonstrate that use of multidimensional antioxidant activity determinations with differing reaction mechanisms is necessary to provide an overall understanding of the mechanisms of antioxidant action of phytosteryl phenolates.

phytosteryl phenolates


Input: A nanosilver-based spectrophotometry method for sensitive determination of tartrazine in food samples.

tartrazine


Input: A new method is reported for sensitive determination of tartrazine in the food samples.

tartrazine


Input: The method is based on the catalytic effect of silver nanoparticle (AgNPs) on the oxidation reaction of tartrazine by potassium iodate in the acetate buffer medium.

silver

tartrazine

potassium iodate

acetate