Input: Cyclic tetrapeptides are an important class of biologically active molecules that exhibit interesting conformational dynamics, with slow interconversion of several different structures.

Cyclic tetrapeptides


Input: We present calculations on their energy landscapes using discrete path sampling.


Input: In acyclic peptides and large cyclic peptides, isomers containing cis-peptide groups are much less stable than the all-trans isomers and separated from them by large barriers.


Input: Strain in small cyclic peptides causes the cis and trans isomers to be closer in energy and separated by much lower barriers.


Input: If d-amino acids or proline residues are introduced, isomers containing cis-peptides become more stable than the all-trans structures.

d-amino acids

proline


Input: We also show that changing the polarity of the solvent has a significant effect on the energy landscapes of cyclic tetrapeptides, causing changes in the orientations of the peptide groups and in the degree of intramolecular hydrogen bonding.

cyclic tetrapeptides

hydrogen


Input: Effect of moisture content, temperature and exposure time on the physical stability of chitosan powder and tablets.


Input: Abstract Context: Chitosan does not rank highly regarding its employment as tablet filler due to certain limitations.


Input: Undesirable properties that limit its utilization as excipient in solid dosage forms include its hydration propensity that negatively affects tablet stability, strength and disintegration.


Input: Objective: The objective of this study was to investigate the physical stability of chitosan powder, mixtures, granules and tablets under accelerated conditions such as elevated temperatures and humidity over different periods of time.


Input: Methods: Selected physico-chemical properties of pure chitosan powder, physical mixtures of chitosan with Kollidon (R) VA64 (BASF, Ludwigshafen, Germany), chitosan granules, as well as tablets were evaluated under conditions of elevated humidity and temperature.


Input: Results and discussion: The physical stability of chitosan tablets exhibited sensitivity towards varying exposure conditions.


Input: It was furthermore evident that the presence of moisture (sorbed water) had a marked influence on the physical stability of chitosan powder and tablets.


Input: It was evident that the presence of Kollidon (R) VA64 as well as the method of inclusion of this binder influenced the properties of chitosan tablets.


Input: The physical stability of chitosan powder deteriorated to a greater extent compared to that of the chitosan tablets, which were subjected to the same conditions.


Input: Conclusion: It is recommended that tablets containing chitosan should be stored at a temperature not exceeding 25 degrees C as well as at a relatively low humidity (< 60%) to prevent deterioration of physical properties.


Input: Direct compression of chitosan granules which contained 5% w/w Kollidon (R) VA64 produced the best formulation in terms of physical stability at the different conditions.


Input: 2012 Philip S. Portoghese Medicinal Chemistry Lectureship: Structure-Based Approaches to Ligands for G Protein-Coupled Adenosine and P2Y Receptors, From Small Molecules to Nanoconjugates.

Adenosine


Input: Adenosine receptor (ARs) and P2Y receptors (P2YRs) that respond to extracellular nucleosides/tides are associated with new directions for therapeutics.

Adenosine

nucleosides/tides


Input: The X-ray structures of the A2AAR complexes with agonists and antagonists are examined in relationship to the G protein-coupled receptor (GPCR) superfamily and applied to drug discovery.


Input: Much of the data on AR ligand structure from early SAR studies, now is explainable from the A2AAR X-ray crystallography.


Input: The ligand-receptor interactions in related GPCR complexes can be identified by means of modeling approaches, e. g. molecular docking.


Input: Thus, molecular recognition in binding and activation processes has been studied effectively using homology modeling and applied to ligand design.


Input: Virtual screening has yielded new nonnucleoside AR antagonists, and existing ligands have been improved with knowledge of the receptor interactions.


Input: New agonists are being explored for CNS and peripheral therapeutics based on in vivo activity, such as chronic neuropathic pain.


Input: Ligands for receptors more distantly related to the X-ray template, i. e. P2YRs, have been introduced and are mainly used as pharmacological tools for elucidating the physiological role of extracellular nucleotides.

nucleotides


Input: Other ligand tools for drug discovery include fluorescent probes, radioactive probes, multivalent probes, and functionalized nanoparticles.


Input: Fabrication of Quantum Dot Microarrays Using Electron Beam Lithography for Applications in Analyte Sensing and Cellular Dynamics.


Input: Quantum dot (QD) based micro-/nanopatterned arrays are of broad interest in applications ranging from electronics, photonics, to sensor devices for biomedical purposes.


Input: Here, we report on a rapid, physico-chemically mild approach to generate high fidelity micropattern arrays of prefunctionalized water-soluble quantum dots using electron beam lithography.


Input: We show that such patterns retain their fluorescence and bioaffinity upon electron beam lithography and, based on the streptavidin-biotin interaction, allow for detection of proteins, colloidal gold nanoparticles and magnetic microparticles.

biotin


Input: Furthermore, we demonstrate the applicability of QD based microarray patterns differing in their shape (circles, squares, grid-like), size (from 1 to 10 mu m) and pitch distance to study the adhesion, spreading and migration of human blood derived neutrophils.


Input: Using live cell confocal fluorescence microscopy, we show that pattern geometry and pitch distance influence the adhesion, spreading and migratory behavior of neutrophils.


Input: Research reported in this work paves the way for producing QD microarrays with multiplexed functionalities relevant for applications in analyte sensing and cellular dynamics.


Input: 2-Methoxyjuglone Induces Apoptosis in HepG2 Human Hepatocellular Carcinoma Cells and Exhibits in Vivo Antitumor Activity in a H22 Mouse Hepatocellular Carcinoma Model.


Input: In order to discover anticancer agents from natural sources, an ethanol-soluble extract of the root bark of Juglans cathayensis was investigated and showed cytotoxic effects against various human cancer cell lines.

ethanol


Input: A subsequent phytochemical study on the EtOAc-soluble fraction determined 2-methoxyjuglone (1) as one of the main active constituents.

EtOAc


Input: Compound 1 was shown to be cytotoxic against HepG2 cells.


Input: Morphological features of apoptosis were observed in 1-treated HepG2 cells, including cell shrinkage, membrane blebbing, nuclear condensation, and apoptotic body formation.


Input: Cell cycle analysis with propidium iodide staining showed that 1 induced cell cycle arrest at the S phase in HepG2 cells.

propidium iodide


Input: Flow cytometric analysis with annexin V and propidium iodide staining demonstrated that 1 induced HepG2 cell apoptotic events in a dose-dependent manner (0-8 mu g/mL).

propidium iodide


Input: Western blot analysis of apoptosis-related proteins revealed that 1 induces HepG2 cell apoptosis through mitochondrial cytochrome c-dependent activation of the caspase-9 and caspase-3 cascade pathway (intrinsic pathway).


Input: An in vivo experiment using tumor-bearing mice showed that treatment with 1 at 0. 5 and 1. 0 mg/kg per day decreased the tumor mass by 56% and 67%, respectively.


Input: Three-Dimensional Ab Initio Potential Energy Surface for H-CO (X (2) A').

H-CO (X (2) A')


Input: We present an ab initio potential for the H-CO (X (2) A') complex in which the CO bond length is varied and the long-range interactions between H and CO are accurately represented.

H-CO (X (2) A')

CO

H

CO


Input: It was computed using the spin-unrestricted open-shell single and double excitation coupled cluster method with perturbative triples [RHF-UCCSD (T)].


Input: Three doubly augmented correlation-consistent basis sets were utilized to extrapolate the correlation energy to the complete basis set limit.


Input: More than 4400 data points were calculated and used for an analytic fit of the potential: long-range terms with inverse power dependence on the H-CO distance R were fit to the data points for large R, the reproducing kernel Hilbert space (RKHS) method was applied to the data at smaller distances.

H

CO


Input: Our potential was compared with previous calculations and with some data extracted from spectroscopy.


Input: Furthermore, it was used in three-dimensional discrete variable representation (DVR) calculations of the vibrational frequencies and rotational constants of HCO, which agree very well with the most recently measured data.

HCO


Input: Also the dissociation energy D0 = 0. 623 eV of HCO into H + CO obtained from these calculations agrees well with experimental values.

HCO

H

CO


Input: Finally, we made preliminary two-dimensional (2D) calculations of the cross sections for rotationally inelastic H-CO collisions with the CO bond length fixed and obtained good agreement with recently published 2D results.

H

CO

CO


Input: Anti-inflammatory effect of prunetin via the suppression of NF-kappa B pathway.

prunetin


Input: Prunetin is an O-methylated isoflavone, which is found in Prunus yedoensis.

Prunetin

O-methylated isoflavone


Input: To date no report has been published on anti-inflammatory activities of prunetin.

prunetin


Input: In the present study, the anti-inflammatory effect of prunetin on LPS-stimulated RAW 264. 7 macrophage and LPS-induced septic shock model were investigated.

prunetin


Input: Inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) expressions were determined by western blot and or realtime-PCR (RT-PCR).

nitric oxide


Input: To elucidate its underlying mechanism, nuclear factor-kappa B (NF-kappa b) activation and its downstream pathways were investigated by NF-kappa B transcription factor assay, reporter gene expression, and western blot.


Input: In vivo anti-inflammatory effects of prunetin were evaluated in LPS-induced endotoxemia.

prunetin


Input: Promoter assay revealed that prunetin inhibits LPS-induced nitric oxide and prostaglandin E2 production through the suppression of iNOS and COX-2 at the transcriptional level.

prunetin

nitric oxide

prostaglandin E2


Input: In addition, prunetin inhibits NF-kappa B-dependent inflammatory responses by modulating I kappa B kinase (IKK)-inhibitor kappa B alpha (I kappa B alpha)-NF-kappa B signaling.

prunetin


Input: Consistent with these results, prunetin significantly reduced serum levels of inflammatory cytokines and mortality in mice challenged with lipopolysaccharide.

prunetin


Input: These findings offer a potential mechanism for the anti-inflammatory activity of prunetin.

prunetin


Input: Anti-diabetic activity of embelin: Involvement of cellular inflammatory mediators, oxidative stress and other biomarkers.

embelin


Input: Embelin (benzoquinone), an active constituent of methanolic extracts of the fruit of Embelia basal (Myrsinaceae), was studied in high fat diet (HFD) + streptozotocin (STZ) diabetic rats.

Embelin

benzoquinone

streptozotocin

STZ


Input: Treatment of embelin (25 and 50mg/kg/day, p. o.) for 3 weeks to HFD + STZ diabetic rats elicited insignificant increase in body weight, reduced the elevated plasma glucose, glycosylated haemoglobin and pro-inflammatory mediators (interleukin 6 and tumour necrosis factor alpha) significantly.

embelin

STZ

glucose


Input: Furthermore, embelin treatment at both the doses significantly decreased the elevated malondialdehyde, restored depleted glutathione, antioxidant enzymes, superoxide dismutase and catalase in liver.

malondialdehyde

glutathione

superoxide


Input: The increased lipid profiles in HFD + STZ diabetic rats were also reduced by embelin treatment significantly.

STZ

embelin


Input: Embelin treatment to HFD + STZ diabetic rats also improved the altered histoarchitecture of beta-islets of pancreas and hepatocytes.

Embelin

STZ


Input: The embelin effect on progression of type 2 diabetes mellitus in rats appears to be through the inhibition of intracellular pro-inflammatory mediators, lowering of lipid profile and amelioration of oxidative stress.

embelin


Input: Considering the pharmacological activity profile of embelin, it is suggested that embelin be a useful diabetic modulator or adjuvant along with clinically effective anti-diabetic drugs in the treatment of type 2 diabetes mellitus and needs to be clinically evaluated on human subjects.

embelin

embelin


Input: Ph alpha 1 beta toxin prevents capsaicin-induced nociceptive behavior and mechanical hypersensitivity without acting on TRPV1 channels.

capsaicin


Input: Ph alpha 1 beta toxin is a peptide purified from the venom of the armed spider Phoneutria nigriventer, with markedly antinociceptive action in models of acute and persistent pain in rats.


Input: Similarly to ziconotide, its analgesic action is related to inhibition of high voltage activated calcium channels with more selectivity for N-type.

calcium


Input: In this study we evaluated the effect of Ph alpha 1 beta when injected peripherally or intrathecally in a rat model of spontaneous pain induced by capsaicin.

capsaicin


Input: We also investigated the effect of Ph alpha 1 beta on Ca (2 +) transients in cultured dorsal root ganglia (DRG) neurons and HEK293 cells expressing the TRPV1 receptor.

Ca (2 +)


Input: Intraplantar or intrathecal administered Ph alpha 1 beta reduced both nocifensive behavior and mechanical hypersensitivity induced by capsaicin similarly to that observed with SB366791, a specific TRPV1 antagonist.

capsaicin


Input: Peripheral nifedipine and mibefradil did also decrease nociceptive behavior induced by intraplantar capsaicin.

nifedipine

mibefradil

capsaicin


Input: In contrast, omega-conotoxin MVIIA (a selective N-type Ca (2 +) channel blocker) was effective only when administered intrathecally.

Ca (2 +)


Input: Ph alpha 1 beta, MVIIA and SB366791 inhibited, with similar potency, the capsaicin-induced Ca (2 +) transients in DRG neurons.

capsaicin

Ca (2 +)


Input: The simultaneous administration of Ph alpha 1 beta and SB366791 inhibited the capsaicin-induced Ca (2 +) transients that were additive suggesting that they act through different targets.

capsaicin

Ca (2 +)


Input: Moreover, Ph alpha 1 beta did not inhibit capsaicin-activated currents in patch-clamp recordings of HEK293 cells that expressed TRPV1 receptors.

capsaicin


Input: Our results show that Ph alpha 1 beta may be effective as a therapeutic strategy for pain and this effect is not related to the inhibition of TRPV1 receptors.


Input: Nicotine primes the effect of cocaine on the induction of LTP in the amygdala.

Nicotine

cocaine


Input: In human populations, there is a well-defined sequence of involvement in drugs of abuse, in which the use of nicotine or alcohol precedes the use of marijuana, which in turn, precedes the use of cocaine.

nicotine

alcohol

cocaine


Input: The term " Gateway Hypothesis " describes this developmental sequence of drug involvement.


Input: In prior work, we have developed a mouse model to study the underlying metaplastic behavioral, cellular and molecular mechanisms by which exposure to one drug, namely nicotine, affects the response to another drug, namely cocaine.

nicotine

cocaine


Input: We found that nicotine enhances significantly the changes in synaptic plasticity in the striatum induced by cocaine (Levine et al., 2011).

nicotine

cocaine


Input: Here we ask: does the metaplastic effect of nicotine on cocaine also apply in the amygdala, a brain region that is involved in the orchestration of emotions and in drug addiction?

nicotine

cocaine


Input: We find that pretreatment with nicotine enhances long-term synaptic potentiation (LTP) in response to cocaine in the amygdala.

nicotine

cocaine


Input: Both short-term (1 day) and long-term (7 days) pre-exposure to nicotine facilitate the induction of LTP by cocaine.

nicotine

cocaine


Input: The effect of nicotine on LTP is unidirectional; exposure to nicotine following treatment with cocaine is ineffective.

nicotine

nicotine

cocaine


Input: This metaplastic effect of nicotine on cocaine is long lasting but reversible.

nicotine

cocaine


Input: The facilitation of LTP can be obtained for 24 but not 40 days after cessation of nicotine.

nicotine


Input: As is the case in the striatum, pretreatment with Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, simulates the priming effect of nicotine.

Suberoylanilide hydroxamic acid

SAHA

nicotine


Input: These results provide further evidence that the priming effect of nicotine may be achieved, at least partially, by the inhibition of histone acetylation and indicate that the amygdala appears to be an important brain structure for the processing of the metaplastic effect of nicotine on cocaine.

nicotine

nicotine

cocaine


Input: This article is part of a Special Issue entitled' GluR-dep synaptic plasticity'.


Input: Discovery, synthesis and in combo studies of a tetrazole analogue of clofibric acid as a potent hypoglycemic agent.

tetrazole

clofibric acid


Input: A tetrazole isosteric analogue of clofibric acid (1) was prepared using a short synthetic route and was characterized by elemental analysis, NMR ((1) H, (13) C) spectroscopy, and single-crystal X-ray diffraction.

tetrazole

clofibric acid

(1) H

(13) C


Input: The in vitro inhibitory activity of 1 against 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) was evaluated, showing a moderate inhibitory enzyme activity (51. 17% of inhibition at 10 mu M), being more active than clofibrate and clofibric acid.

11 beta-hydroxysteroid

clofibrate

clofibric acid


Input: The antidiabetic activity of compound 1 was determined at 50mg/Kg single dose using a non insulin dependent diabetes mellitus rat model.


Input: The results indicated a significant decrease of plasma glucose levels, during the 7h post-administration.

glucose


Input: Additionally, we performed a molecular docking of 1 into the ligand binding pocket of one subunit of human 11 beta-HSD1.


Input: In this model, compound 1 binds into the catalytic site of 11 beta-HSD1 in two different orientations.


Input: Both of them, show important short contacts with the catalytic residues Ser 170, Tyr 183, Asp 259 and also with the nicotinamide ring of NADP (+).

Ser

Tyr

Asp

nicotinamide

NADP (+)


Input: Sub-picometer structural information of graphene hidden in a 50 pm resolved image.

graphene


Input: In a 2D self-organized crystalline structure more than 1000 unit-cells can be observed in a single image.


Input: Here we exploit the benefits from having a large number of observations of the same unit cell utilizing an image processing methodology.


Input: We obtain sub-picometer resolution data from a 50 pm image of graphene, revealing a 1% axial elongation and a 3 fold symmetry, indicating a chair conformation.

graphene


Input: Suppression of ZIP8 expression is a common feature of cadmium-resistant and manganese-resistant RBL-2H3 cells.

cadmium

manganese


Input: Rat basophilic leukemia RBL-2H3 cells show markedly high sensitivity to both CdCl2 and MnCl2 compared with other rat cell lines, due to efficient accumulation of cadmium and manganese.

cadmium

manganese


Input: To clarify the roles of metal transporters in hyperaccumulation of cadmium and manganese in RBL-2H3 cells, Cd-resistant and Mn-resistant cells were developed from RBL-2H3 cells by continuous exposure to CdCl2 and MnCl2, respectively.

cadmium

manganese

Cd

Mn


Input: The established Cd-resistant (RBL-Cdr) and Mn-resistant (RBL-Mnr) cells exhibited about 20 times higher LC50 values of CdCl2 and MnCl2, respectively, than parental RBL-2H3 cells, and showed cross-resistance to each metal.

Cd

Mn


Input: The resistance to cadmium and manganese was primarily conferred by a marked decrease in the uptake of both metals.

cadmium

manganese


Input: RBL-Cdr cells also showed cross-resistance to HgCl2 and AgNO3 probably due to enhanced expression of metallothionein.


Input: Among the possible transporters involved in the uptake of Cd (2 +) and Mn (2 +), the expression of ZIP8 (Zrt-, Irt-related protein 8), encoded by Slc39a8, showed a marked suppression in both RBL-Cdr and RBL-Mnr cells.

Cd (2 +)

Mn (2 +)


Input: These results suggest that ZIP8 plays a pivotal role in the transport and toxicity of Cd (2 +) and Mn (2 +) in RBL-2H3 cells.

Cd (2 +)

Mn (2 +)


Input: Pharmacological and Chemical Study to Identify Wound-Healing Active Compounds in Ageratina pichinchensis.


Input: The aerial parts of Ageratina pichinchensis are used in Mexican traditional medicine for the treatment of skin wounds.


Input: Recently, it was demonstrated that the aqueous extract of this plant reduced the time required to cicatrize a wound induced in the rat.


Input: The same extract showed a capability to induce overgrowth in normal fetal lung cells (MRC-5).


Input: The objective of the present study was isolating and identifying the active compounds in A. pichinchensis that are capable of inducing cellular overgrowth, as well as performing a preliminary evaluation of their anti-inflammatory and toxic effects.


Input: By means of bioguided chemical separation of an aqueous extract of A. pichinchensis, the most active compound capable of inducing cellular overgrowth was identified as 7-O-(beta-D-glucopyranosyl)-galactin.


Input: In vivo inflammation induced with carrageenan in mice was significantly reduced by the aqueous extract of A. pichinchensis, reaching a decrease of up to 60. 6%.


Input: Acute (2 g/kg) and subchronic (1 g/kg for 28 days) oral administration of the aqueous extract of this plant did not affect hepatic function (through alanine aminotransferase and aspartate aminotransferase activity evaluation), while no alterations of the histologic samples of liver and kidney were evidenced.

alanine

aspartate


Input: Induction of C-X-C Chemokine Receptor Type 7 (CXCR7) Switches Stromal Cell-Derived Factor-1 (SDF-1) Signaling and Phagocytic Activity in Macrophages Linked to Atherosclerosis.


Input: The discovery of CXCR7 as a new receptor for SDF-1 places many previously described SDF-1 functions attributed to CXCR4 in question, though whether CXCR7 acts as a signaling or decoy receptor has been in debate.


Input: It is known that CXCR7 is not expressed in normal blood leukocytes; however, the potential role of leukocyte CXCR7 in disease states has not been addressed.


Input: The aim of this study was to determine the expression and function of macrophage CXCR7 linked to atherosclerosis.


Input: Here, we show that CXCR7 was detected in macrophage-positive area of aortic atheroma of ApoE-null mice, but not in healthy aorta.


Input: During monocytes differentiation to macrophages, CXCR7 was up-regulated at mRNA and protein levels, with more expression in M1 than in M2 phenotype.


Input: In addition, CXCR7 induction was associated with a SDF-1 signaling switch from the pro-survival ERK and AKT pathways in monocytes to the pro-inflammatory JNK and p38 pathways in macrophages.


Input: The latter effect was mimicked by a CXCR7-selective agonist TC14012 and abolished by siRNA knockdown of CXCR7.


Input: Furthermore, CXCR7 activation increased macrophage phagocytic activity, which was suppressed by CXCR7 siRNA silencing or by inhibiting either the JNK or p38 pathways, but was not affected by blocking CXCR4.


Input: Finally, activation of CXCR7 by I-TAC showed a similar signaling and phagocytic activity in macrophages with no detectable CXCR3.


Input: We conclude that CXCR7 is induced during monocyte-to-macrophage differentiation, which is required for SDF-1 and I-TAC signaling to JNK and p38 pathways, leading to enhanced macrophage phagocytosis, thus possibly contributing to atherogenesis.


Input: HSP90 functions to stabilize and activate the testis-specific serine/threonine kinases, a family of kinases essential for male fertility.

serine

threonine


Input: Spermiogenesis is characterized by a profound morphological differentiation of the haploid spermatid into spermatozoa.


Input: The testis-specific serine/threonine kinases (TSSKs) comprise a family of post-meiotic kinases expressed in spermatids, are critical to spermiogenesis and are required for male fertility in mammals.

serine

threonine


Input: To explore the role of HSP90 in regulation of TSSKs, the stability and catalytic activity of epitope-tagged murine TSSKs were assessed in 293T and COS-7 cells.


Input: TSSK1, 2, 4, and 6 (SSTK) were all found to associate with HSP90 and pharmacological inhibition of HSP90 function using the highly specific drugs 17-AAG, SNX-5422, or NVP-AUY922 reduced TSSK protein levels in cells.


Input: The attenuation of HSP90 function abolished the catalytic activities of TSSK4 and 6, but did not significantly alter the specific activities of TSSK1 and 2.


Input: Inhibition of HSP90 resulted in increased TSSK ubiquitination and proteasomal degradation indicating that HSP90 acts to control ubiquitin-mediated catabolism of the TSSKs.


Input: To study HSP90 and TSSKs in germ cells a mouse primary spermatid culture model was developed and characterized.


Input: Using specific antibodies against murine TSSK2 and 6, it was demonstrated that HSP90 inhibition resulted in a marked decrease of the endogenous kinases in spermatids.


Input: Together, our findings demonstrate that HSP90 plays a broad and critical role in stabilization and activation of the TSSK family of protein kinases.


Input: 5-Lipoxygenase inhibitors: a review of recent patents (2010-2012).


Input: Introduction: 5-Lipoxygenase (5-LO) is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) with the help of FLAP, the 5-LO-activating protein.

arachidonic acid


Input: LTs are inflammatory mediators playing a pathophysiological role in different diseases like asthma, allergic rhinitis as well as cardiovascular diseases and certain types of cancer.


Input: With the rising number of indications for anti-LT therapy, 5-LO inhibitor drug development becomes increasingly important.


Input: Areas covered: Here, both recent findings regarding the pathophysiological role of 5-LO and the patents claimed for 5-LO inhibitors are discussed.


Input: Focusing on direct inhibitors, several patents disclosing FLAP antagonists are also subject of this review.


Input: Novel compounds include 1, 5-diarylpyrazoles, indolizines and indoles and several natural product extracts.

1, 5-diarylpyrazoles

indolizines

indoles


Input: Expert opinion: Evaluation of the patent activities revealed only quite moderate action.


Input: Nevertheless, several auspicious drug-like molecules were disclosed.


Input: It seems that in the near future, FLAP inhibitors can be expected to enter the market for the treatment of asthma.


Input: With the resolved structure of 5-LO, structure-based drug design is now applicable.


Input: Together with the identification of downstream enzyme inhibitors and dual-targeting drugs within the AA cascade, several tools are at hand to cope with 5-LOs increasing pathophysiological roles.


Input: A Singlet Biradicaloid Zinc Compound and Its Nonradical Counterpart.

Zinc


Input: Metal ions with radical centers in their coordination sphere are key participants in biological and catalytic processes.


Input: In the present study, we describe the synthesis of the cAAC: ZnCl2 adduct (1) using a cyclic alkylaminocarbene (cAAC) as donor ligand.

cyclic alkylaminocarbene

cAAC


Input: Compound 1 was treated with 2 equiv of KC8 and LiB (sec-Bu) 3H to yield a deep blue-colored dicarbene zinc compound (cAAC) 2Zn (2) and the colorless hydrogenated zinc compound (cAACH) 2Zn (3), respectively.

LiB (sec-Bu) 3H

dicarbene zinc

(cAAC) 2Zn

zinc

(cAACH) 2Zn


Input: Compounds 2 and 3 were well characterized by spectroscopic methods and single-crystal X-ray structural analysis.


Input: Density functional theory calculations were performed for 2 which indicate that this molecule possesses a singlet biradicaloid character.


Input: Moreover, we show the application of 2 in CO2 activation, which yields a zwitterionic cAAC. CO2 adduct.

cAAC


Input: Chemical constituents from Solidago canadensis with hypolipidemic effects in HFD-fed hamsters.


Input: Two new compounds, 8-dehydroxymethylvisanol (1) and 9-O-[3-O-acetyl-beta-d-glucopyranosyl]-4-hydroxy-cinnamic acid (4), together with two known lignans, visanol (2) and 9-aldehydevibsanol (3), were isolated from the 80% EtOH extract of Solidago canadensis.

9-O-[3-O-acetyl-beta-d-glucopyranosyl]-4-hydroxy-cinnamic acid

lignans

visanol

EtOH


Input: The structures of the two new compounds were elucidated on the basis of 1D, 2D NMR, and mass spectral analysis.


Input: All the lignans exhibited moderate hypolipidemic activity in high-fat diet-fed hamsters.

lignans


Input: Layer-by-Layer Polyelectrolyte Deposition: A Mechanism for Forming Biocomposite Materials.


Input: Complex coacervates prepared from poly (aspartic acid) (polyAsp) and poly-l-histidine (polyHis) were investigated as models of the metastable protein phases used in the formation of biological structures such as squid beak.

poly (aspartic acid)

polyAsp

poly-l-histidine

polyHis


Input: When mixed, polyHis and polyAsp form coacervates whereas poly-l-glutamic acid (polyGlu) forms precipitates with polyHis.

polyHis

polyAsp

poly-l-glutamic acid

polyGlu

polyHis


Input: Layer-by-layer (LbL) structures of polyHis-polyAsp on gold substrates were compared with those of precipitate-forming polyHis-polyGlu by monitoring with iSPR and QCM-D.

polyHis

polyAsp

polyHis

polyGlu


Input: PolyHis-polyAsp LbL was found to be stiffer than polyHis-polyGlu LbL with most water evicted from the structure but with sufficient interfacial water remaining for molecular rearrangement to occur.

PolyHis

polyAsp

polyHis

polyGlu


Input: This thin layer is believed to be fluid and like preformed coacervate films, capable of spreading over both hydrophilic ethylene glycol as well as hydrophobic monolayers.

ethylene glycol


Input: These results suggest that coacervate-forming polyelectrolytes deserve consideration for potential LbL applications and point to LbL as an important process by which biological materials form.


Input: Cyclodextrin-Functionalized Fe3O4 @TiO2: Reusable, Magnetic Nanoparticles for Photocatalytic Degradation of Endocrine-Disrupting Chemicals in Water Supplies.


Input: Water-dispersible, photocatalytic Fe3O4 @TiO2 core-shell magnetic nanoparticles have been prepared by anchoring cyclodextrin cavities to the TiO2 shell, and their ability to capture and photocatalytically destroy endocrine-disrupting chemicals, bisphenol A and dibutyl phthalate, present in water, has been demonstrated.

bisphenol A

dibutyl phthalate


Input: The functionalized nanoparticles can be magnetically separated from the dispersion after photocatalysis and hence reused.


Input: Each component of the cyclodextrin-functionalized Fe3O4 @TiO2 core-shell nanoparticle has a crucial role in its functioning.


Input: The tethered cyclodextrins are responsible for the aqueous dispersibility of the nanoparticles and their hydrophobic cavities for the capture of the organic pollutants that may be present in water samples.


Input: The amorphous TiO2 shell is the photocatalyst for the degradation and mineralization of the organics, bisphenol A and dibutyl phthalate, under UV illumination, and the magnetism associated with the 9 nm crystalline Fe3O4 core allows for the magnetic separation from the dispersion once photocatalytic degradation is complete.

bisphenol A

dibutyl phthalate


Input: An attractive feature of these " capture and destroy " nanomaterials is that they may be completely removed from the dispersion and reused with little or no loss of catalytic activity.


Input: Two new glycosides from the florets of Carthamus tinctorius.


Input: Two new glycoside compounds, named saffloquinoside C (1) and (-)-4-hydroxybenzoic acid-4-O-[6'-O-(2''-methylbutyryl)-beta-D-glucopyranoside] (2), were isolated from the florets of Carthamus tinctorius.

saffloquinoside C

(-)-4-hydroxybenzoic acid-4-O-[6'-O-(2''-methylbutyryl)-beta-D-glucopyranoside]


Input: Their structures were elucidated by detailed spectroscopic means including UV, IR, HR-ESI-MS, 1D and 2D NMR, and CD data.


Input: Compound 1 was a rare quinochalcone glycoside with six five-membered dioxaspirocycle.

quinochalcone glycoside

dioxaspirocycle


Input: Brucine-loaded liposomes composed of HSPC and DPPC at different ratios: in vitro and in vivo evaluation.

Brucine


Input: Abstract Objective: The objective of this study is to test the hypothesis that the phase transition temperature (Tm), the main property of liposomes, can be easily controlled by changing the molar ratio of hydrogenated soy phosphatidylcholine (HSPC) and 1, 2-dipalmitoyl-sn-glycero-3-phosphacholine (DPPC) after drug encapsulation.

phosphatidylcholine

1, 2-dipalmitoyl-sn-glycero-3-phosphacholine

DPPC


Input: Materials and methods: Brucine, an antitumor alkaloid, was encapsulated into the liposomes with different HSPC/DPPC compositions.

Brucine

DPPC


Input: The Tms of the brucine-loaded liposomes (BLs) were determined by differential scanning calorimetry (DSC).

brucine


Input: Then the physicochemical properties and pharmacokinetics of the BLs with different HSPC/DPPC compositions were investigated and compared.

DPPC


Input: Results: The results of DSC revealed that HSPC and DPPC can combine into one phase.

DPPC


Input: The findings of molecular modeling study suggested that HSPC interacts with DPPC via electrostatic interaction.

DPPC


Input: The molar ratio of HSPC/DPPC influenced the sizes of BLs but had little effect on the entrapment efficiency (EE).

DPPC


Input: The stability of BLs was improved with the increase of the HSPC ratios, especially with the presence of plasma.


Input: Following i. v. administration, it was found that AUC values of BLs in vivo were directly related to the HSPC/DPPC ratios of BLs, namely the Tms of BLs.

DPPC


Input: Discussion: The behavior of liposomes, especially in vivo pharmacokinetic behavior, can be controlled by the modification of Tm.


Input: Conclusion: The characterization of BLs in vitro and in vivo had demonstrated that the Tm could be flexibly modified for liposomes composed of both HSPC and DPPC.

DPPC


Input: Using HSPC/DPPC composition may be an efficient strategy to control the Tm, thus control the in vivo pharmacokinetic behavio, of BLs.

DPPC


Input: Three new Lycopodium alkaloids from Lycopodium obscurum.


Input: Chemical investigation on the crude alkaloid portion of Lycopodium obscurum led to isolation of three new fawcettimine-type Lycopodium alkaloids, lycobscurines A-C (1-3), together with three known compounds.

fawcettimine

lycobscurines A-C


Input: Their structures were determined by spectroscopic methods including HR-ESI-MS and NMR techniques.


Input: All compounds were tested in an assay for acetylcholinesterase inhibitory activity.


Input: Chemical and preclinical studies on Hedyotis diffusa with anticancer potential.


Input: This paper presents the chemical and preclinical anticancer research on Hedyotis diffusa Willd. in detail, one of the most renowned herbs often prescribed in the polyherbal formulas for cancer treatment in traditional Chinese medicine.


Input: Anthraquinones, flavonoids, and terpenoids constitute the majority of the 69 compounds that have been isolated and identified from H. diffusa.

Anthraquinones

flavonoids

terpenoids


Input: The anticancer effects of the methanolic, ethanolic, and aqueous extracts in various preclinical cancer models have been described.


Input: This review also summarized the anticancer activity of constituents of the herb and the mechanisms of action.


Input: All the studies suggest that H. diffusa has enormous potential in the therapy of cancer and warrants further chemical and pharmacological investigation.


Input: Microbiological transformation of the triterpene nigranoic acid by the freshwater fungus Dictyosporium heptasporum.

nigranoic acid


Input: The microbiological transformation of the triterpene nigranoic acid (3, 4-secocycloarta-4 (28), 24 (Z)-diene-3, 26-dioic acid) (1) to 3, 4-secocycloarta-4 (28), 17 (20), 24 (Z)-triene-7 beta-hydroxy-16 beta, 26-lactone-3-oic acid (2) and 3, 4-secocycloarta-4 (28), 17 (20) (Z), 24 (Z)-triene-7 beta-hydroxy-16 beta-methoxy-3, 26-dioic acid (3) by the freshwater fungus Dictyosporium heptasporum YMF1. 01213 has been demonstrated.

nigranoic acid

3, 4-secocycloarta-4 (28), 24 (Z)-diene-3, 26-dioic acid

3, 4-secocycloarta-4 (28), 17 (20), 24 (Z)-triene-7 beta-hydroxy-16 beta, 26-lactone-3-oic acid

3, 4-secocycloarta-4 (28), 17 (20) (Z), 24 (Z)-triene-7 beta-hydroxy-16 beta-methoxy-3, 26-dioic acid


Input: The structures of the biotransformation products were determined by spectroscopic and MS analyses.


Input: Compound 2, characterized by the presence of a formed C-16/C-26 ester bridge, provided a novel nine-membered lactone ring structural skeleton for 3, 4-secocycloartane triterpenoid derivatives.

ester

lactone

3, 4-secocycloartane


Input: In addition, Compounds 1-3 exhibited weak anti-HIV activity in vitro.


Input: Compounds 2 and 3 were reported for the first time as natural product derivatives.


Input: CASK is a new intracellular modulator of P2X3 receptors.


Input: ATP-gated P2X3 receptors of sensory ganglion neurons are important transducers of painful stimuli and are modulated by extracellular algogenic substances, via changes in the receptor phosphorylation state.

ATP


Input: The present study investigated the role of calcium/calmodulin-dependent serine protein kinase CASK in interacting and controlling P2X3 receptor expression and function in mouse trigeminal ganglia.

calcium

serine


Input: Most ganglion neurons in situ or in culture co-expressed P2X3 and CASK.


Input: CASK was immunoprecipitated with P2X3 receptors from trigeminal ganglia and from P2X3/CASK-cotransfected HEK cells.


Input: Recombinant P2X3/CASK expression in HEK cells increased serine phosphorylation of P2X3 receptors, typically associated with receptor upregulation.

serine


Input: CASK deletion mutants also enhanced P2X3 subunit expression.


Input: After silencing CASK, cell surface P2X3 receptor expression was decreased, which is consistent with depressed P2X3 currents.


Input: The reduction of P2X3 expression levels was reversed by the proteasomal inhibitor MG-132.


Input: Moreover, neuronal CASK/P2X3 interaction was upregulated by NGF signaling and downregulated by P2X3 agonist-induced desensitization.


Input: These data suggest a novel interaction between CASK and P2X3 receptors with positive outcome for receptor stability and function.


Input: As CASK-mediated control of P2X3 receptors was dependent on the receptor activation state, CASK represents an intracellular gateway to regulate purinergic nociceptive signaling.


Input: This article is protected by copyright.


Input: All rights reserved.


Input: Secondary metabolites from the endophytic fungi Penicillium polonicum and Aspergillus fumigatus.


Input: Two new compounds, rhodostegone (1) from endophytic fungus Penicillium polonicum and cyclo-(l-Val-l-Leu) (2) from Aspergillus fumigatus, together with six known diketopiperazines (3-8), were isolated.

rhodostegone

cyclo-(l-Val-l-Leu)

diketopiperazines


Input: The structures of these compounds were characterized through a combination of extensive IR, MS, NMR, and CD analysis.


Input: Hydrodynamic Interactions between Two Equally Sized Spheres in Viscoelastic Fluids in Shear Flow.


Input: The effect of using a viscoelastic suspending medium on the in-plane hydrodynamic interaction between two equally sized spheres in shear flow is studied experimentally to understand flow-induced assembly behavior (i. e., string formation).


Input: A counterrotating device equipped with a Couette geometry is used together with quantitative videomicroscopy.


Input: To evaluate the effects of differences in rheological properties of the suspending media, fluids have been selected that highlight specific constitutive features.


Input: These include a reference Newtonian fluid (N), a constant-viscosity, high-elasticity Boger fluid (BF), a wormlike micellar surfactant solution with a single dominant relaxation time (WMS), and a broad spectrum shear-thinning elastic polymer solution (ST).


Input: As expected, the trajectories are symmetric in the Newtonian fluid.


Input: In the BF, the midpoints of the spheres are observed to remain in the same plane before and after the interaction, as in the Newtonian fluid, although the path lines are in this case no longer symmetric.


Input: Interactions in the ST and WMS are highly asymmetric.


Input: Two fundamentally different kinds of path lines are observed in the WMS and ST: reversing and open trajectories.


Input: The type of trajectory depends on the initial configuration of the spheres with respect to each other and on the shear rate.


Input: On the basis of the obtained results, shear-thinning of the viscosity seems to be the key rheological parameter that determines the overall nature of the interactions, rather than the relative magnitude of the normal stress differences.


Input: Two novel furostanol saponins from the tubers of Ophiopogon japonicus.

furostanol saponins


Input: Phytochemical investigation of the fresh tubers of Ophiopogon japonicus led to the isolation of two new furostanol saponins (1 and 2) together with two known steroidal saponins (3 and 4).

furostanol saponins

steroidal saponins


Input: Comprehensive spectroscopic analysis allowed the chemical structures of two new compounds to be elucidated as (25R)-26-O-[beta-d-glucopyranosyl-(1 --> 2)-beta-d-glucopyranosyl]-5-ene-furost-1 beta, 3 beta, 22 alpha, 26-tetraol-3-O-alpha-l-rhamnopyranosyl-(1 --> 2)-[beta-d-xylopyranosyl-(1 --> 4)]-beta-d-glucopyranoside (1, ophiopogonin P) and (25R)-26-O-[beta-d-glucopyranosyl-(1 --> 6)-beta-d-glucopyranosyl]-5-ene-furost-1 beta, 3 beta, 22 alpha, 26-tetraol-3-O-alpha-l-rhamnopyranosyl-(1 --> 2)-[beta-d-xylopyranosyl-(1 --> 4)]-beta-d-glucopyranoside (2, ophiopogonin Q).

(25R)-26-O-[beta-d-glucopyranosyl-(1 --> 2)-beta-d-glucopyranosyl]-5-ene-furost-1 beta, 3 beta, 22 alpha, 26-tetraol-3-O-alpha-l-rhamnopyranosyl-(1 --> 2)-[beta-d-xylopyranosyl-(1 --> 4)]-beta-d-glucopyranoside

ophiopogonin P

(25R)-26-O-[beta-d-glucopyranosyl-(1 --> 6)-beta-d-glucopyranosyl]-5-ene-furost-1 beta, 3 beta, 22 alpha, 26-tetraol-3-O-alpha-l-rhamnopyranosyl-(1 --> 2)-[beta-d-xylopyranosyl-(1 --> 4)]-beta-d-glucopyranoside

ophiopogonin Q


Input: Furostanol saponins with the disaccharide chain linked at C-26 hydroxy group of the aglycone have been rarely reported from natural sources.

Furostanol saponins

disaccharide

C-26 hydroxy


Input: 24 (S)-hydroxycholesterol is actively eliminated from neuronal cells by ABCA1.

24 (S)-hydroxycholesterol


Input: High cholesterol turnover catalyzed by cholesterol 24-hydroxylase is essential for neural functions, especially learning.

cholesterol

cholesterol


Input: Because 24 (S)-hydroxycholesterol (24-OHC), produced by 24-hydroxylase, induces apoptosis of neuronal cells, it is vital to eliminate it rapidly from cells.

24 (S)-hydroxycholesterol


Input: Here, using differentiated SH-SY5Y neuron-like cells as a model, we examined whether 24-OHC is actively eliminated via transporters induced by its accumulation.


Input: The expression of ABCA1 and ABCG1 was induced by 24-OHC, as well as TO901317 and retinoic acid, which are ligands of the nuclear receptors LXR/RXR.

retinoic acid


Input: When the expression of ABCA1 and ABCG1 was induced, 24-OHC efflux was stimulated in the presence of high density lipoprotein (HDL), whereas apolipoprotein A-I was not an efficient acceptor.


Input: The efflux was suppressed by the addition of siRNA against ABCA1, but not by ABCG1 siRNA.


Input: To confirm the role of each transporter, we analyzed HEK293 cells stably expressing human ABCA1 or ABCG1; we clearly observed 24-OHC efflux in the presence of HDL, whereas efflux in the presence of apolipoprotein A-I was marginal.


Input: Furthermore, the treatment of primary cerebral neurons with LXR/RXR ligands suppressed the toxicity of 24-OHC.


Input: These results suggest that ABCA1 actively eliminates 24-OHC in the presence of HDL as a lipid acceptor and protects neuronal cells.


Input: This article is protected by copyright.


Input: All rights reserved.


Input: Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases.

Diaminothiazole


Input: Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression.

serine

threonine


Input: We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0. 0009-0. 0015 mu M) from a single hit compound with weak inhibitory activity (IC50 = 15 mu M), discovered by high-throughput screening.

diaminothiazole


Input: Structure-based design was performed using 35 cocrystal structures of CDK2 liganded with distinct analogues of the parent compound.


Input: The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6.


Input: Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0. 27 and 6. 9 mu M, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis.


Input: Combined, the results demonstrate the potential of this new inhibitors series for further development into CDK-specific chemical probes or therapeutics.


Input: Physicochemical and biological characterization of Pep-1/elastin complexes.


Input: Transdermal drug delivery of proteins is challenging because the skin acts as a natural and protective barrier.


Input: Several techniques including using the cell penetrating peptides (CPPs) have been studied to increase the penetration of therapeutic proteins into and through the skin.


Input: CPPs facilitate and improve the transduction of large and hydrophilic cargo molecules through plasma membrane.


Input: We have recently reported an efficient skin delivery of elastin protein in complex with a CPP called Pep-1.


Input: Since the biophysical characteristics of CPP/protein complexes have been linked with their biological responses, in the present study, we investigated biophysical properties of Pep-1/elastin complexes (ratio 10: 1) stored in three temperatures (-20 degrees C, 4 degrees C and 25 degrees C) by Photon Correlation Spectroscopy (PCS), Circular Dichroism (CD) and isothermal denaturation.


Input: We also evaluated the ability of transduction of this complex into cells and skin tissue using both fluorescence microscopy and Kodak In-Vivo FX Pro Imaging System.


Input: This article is protected by copyright.


Input: All rights reserved.


Input: The influence of latitude on the concentration of vitamin D3 and 25-hydroxy-vitamin D3 in Australian red meat.

vitamin D3

25-hydroxy-vitamin D3


Input: There is little information on the vitamin D content of Australian red meat or on the possible influence of latitude on this content.

vitamin D


Input: To determine the content of vitamin D3 and 25-hydroxy-vitamin D3 (25OHD3), lamb and beef were analysed from 34 degrees S with LC-IT-MS.

vitamin D3

25-hydroxy-vitamin D3


Input: To investigate the possible influence of latitude on vitamin D in meat, the lean meat and fat from five cuts of beef were analysed from 17 degrees S and 41 degrees S.

vitamin D


Input: Lamb contained 0. 10 mu g vitamin D3/100g and 0. 20 mu g 25OHD3/100g lean meat, while beef contained 0. 12 mu g vitamin D3 and 0. 27 mu g 25OHD3/100g (lean meat).

vitamin D3

vitamin D3


Input: Latitude had no effect on the vitamin D3 (P = 0. 21) or 25OHD3 (P = 0. 29) content of lean beef, but fat from cattle in the 17 degrees S latitude group contained significantly higher (P < 0. 01) concentrations of vitamin D3 than fat from the 41 degrees S group of cattle.

vitamin D3

vitamin D3


Input: Development of a regional food composition table for West Africa.


Input: Knowledge of the nutrient content of foods is fundamental for virtually all nutrition-related projects, programmes and policies.


Input: Low quality compositional data may lead to inappropriate policies and funds spent unnecessarily.


Input: Existing food composition tables (FCT) for most West African countries date back to 1960 and 1970 and contain in general few foods and components without documentation.


Input: As a result of the recommendations by the Economic Community of West African States (ECOWAS) Nutrition forum and other high level meetings, FAO/INFOODS, WAHO/ECOWAS and Bioversity International developed the West African FCT.


Input: It contains 472 foods and 28 components.


Input: Emphasis was given to include data on food biodiversity by incorporating cultivars/varieties and underutilized foods.


Input: The West African FCT enables users to address diet-related health problems, strengthen local development, enhance trade and promote biodiversity.


Input: In addition it contributes to poverty alleviation in both rural and urban areas.


Input: The FCT needs to be updated regularly and it is the most recent example of INFOODS for regional food composition activities.


Input: Progress with a global branded food composition database.


Input: Excess energy, saturated fat, sugar and salt from processed and fast foods are a major cause of chronic disease worldwide.

sugar


Input: In 2010 The Food Monitoring Group established a global branded food composition database to track the nutritional content of foods and make comparisons between countries, food companies and over time.


Input: A protocol for the project was agreed and published in 2011 with 24 collaborating countries.


Input: Standardised tools and a website have been developed to facilitate data collection and entry.


Input: In 2010 data were obtained from nine countries, in 2011 from 12 and in 2012 data are anticipated from 10 additional countries.


Input: This collaborative approach to the collation of food composition data offers potential for cross-border collaboration and support in developed and developing countries.


Input: The project should contribute significantly to tracking progress of the food industry and governments towards commitments made at the recent UN high level meeting on chronic disease.


Input: Nutritional composition of minor indigenous fruits: Cheapest nutritional source for the rural people of Bangladesh.


Input: In line of the development of a food composition database for Bangladesh, 10 minor indigenous fruits were analysed for their nutrient composition comprising ascorbic acid, carotenoids and mineral values.

ascorbic acid


Input: Nutrient data obtained have been compared with published data reported in different literatures, book and United States Department of Agriculture-National Nutrient Database for Standard Reference.


Input: Ascorbic acid was highest in Wood apple and lowest in Roselle.

Ascorbic acid


Input: Monkey jack contained the highest amount of carotenoids, zinc and copper.

zinc

copper


Input: Content of calcium, magnesium and phosphorous were found highest in Antidesma velutinum.

calcium

magnesium

phosphorous


Input: Potassium was the highest in Wood apple followed by in Moneky jack.

Potassium


Input: It was noted that most of the minor fruits have much higher amount of ascorbic acid than the national fruit-Jack fruit ripe, the king fruit-Mango ripe of Bangladesh and exotic fruits-Apple and Grapes.

ascorbic acid


Input: The nutrient values of these minor fruits would make awareness among the people for their mass consumption for healthy life and to grow more minor fruit trees from extinction in order to maintain biodiversity.


Input: A review of composition studies of Cameroon traditional dishes: Macronutrients and minerals.


Input: This paper reviews published data that contributes to the knowledge of the ingredients and nutrients of Cameroon traditional dishes.


Input: Macronutrient (energy, carbohydrates, protein, total fat, fibre and ash) and mineral (iron, zinc, magnesium, calcium, phosphorus, copper, manganese, potassium, sodium and selenium) data are presented for 117 commonly consumed dishes from three eco-regions.

carbohydrates

iron

zinc

magnesium

calcium

phosphorus

copper

manganese

potassium

sodium

selenium


Input: Tables providing an overview of the main ingredients and nutrient values (range of means per 100g edible portion) are presented.


Input: Considerable variability in nutrient values has been reported among dishes.


Input: Water contents range from 29. 8 to 95. 9g/100g edible portion while energy values range from 12 to 403kcal/100g.


Input: Energy yielding-constituents are the major nutrients recorded in published data, followed by iron, zinc and magnesium.

iron

zinc

magnesium


Input: The Slovenian food composition database.


Input: The preliminary Slovenian food composition database was created in 2003, through the application of the Data management and Alimenta nutritional software.


Input: In the subsequent projects, data on the composition of meat and meat products of Slovenian origin were gathered from analyses, and low-quality data of the preliminary database were discarded.


Input: The first volume of the Slovenian food composition database was published in 2006, in both electronic and paper versions.


Input: When Slovenia joined the EuroFIR NoE, the LanguaL indexing system was adopted.


Input: The Optijed nutritional software was developed, and later upgraded to the OPEN platform.


Input: This platform serves as an electronic database that currently comprises 620 foods, and as the Slovenian node in the EuroFIR virtual information platform.


Input: With the assimilation of the data on the compositions of foods of plant origin obtained within the latest project, the Slovenian database provides a good source for food compositional values of consistent and compatible quality.


Input: Improvement of the AOAC 2009. 01 total dietary fibre method for bread and other high starch containing matrices.


Input: The dietary fibre (DF) content in wheat grain based food products have been established with both the classical AOAC 985. 29 dietary fibre and the new AOAC 2009. 01 total dietary fibre protocol.


Input: There is a good agreement between the high molecular weight dietary fibre (HMWDF) contents measured with the AOAC 2009. 01 method and (DF) content measured with the classical AOAC 985. 29 method in wheat grain based food products.


Input: With the AOAC 2009. 01 method also a significant amount of low molar weight dietary fibre (LMWDF), ranging from 1% to 3% w/w, was measured which is not quantified with the AOAC 985. 29 method.


Input: With semi-preparative GPC the LMWDF (DP <= 3) fractions in the wheat grain based food products were isolated.


Input: The monosaccharide composition of the dissolved LMWDF constituents was determined.

monosaccharide


Input: Glucose was by far the most abundant monosaccharide present with arabinose, galactose, xylose and mannose as minor constituents.

Glucose

monosaccharide

arabinose

galactose

xylose

mannose


Input: It appeared that the LMWDF contains still not fully converted digestible starch/malto-oligosaccharide fragments with DP <= 3, which are erroneously quantified as LMWDF.


Input: By introducing an extra AMG hydrolysis step in the AOAC 2009. 01 protocol after evaporation of the ethanol and dissolving the residue in deionised water, these malto-oligosaccharides are fully hydrolysed resulting in that way in a correct and lower LMWDF content.

ethanol


Input: Empirical evidence does not support an association between less ambitious pre-treatment goals and better treatment outcomes: a meta-analysis.


Input: Setting realistic weight loss goals may play a role in weight loss.


Input: We abstracted data from randomized controlled trials and observational studies conducted between 1998 and 2012 concerning the association of weight loss goals with weight loss.


Input: Studies included those that (i) were conducted in humans; (ii) delivered a weight loss intervention; (iii) lasted >= 6 weeks; (iv) assessed baseline weight loss goals; (vi) assessed pre-and post-weight either in the form of body mass index or some other measure that could be converted to weight loss based on information included in the original study or later provided by the author (s); and (vii) assessed the correlation between weight loss goals and final weight loss or provided data to calculate the correlation.


Input: Studies that included interventions to modify weight loss goals were excluded.


Input: Eleven studies met inclusion criteria.


Input: The overall correlation between goal weight and weight at intervention completion was small and statistically insignificant (rho = 0. 0 5; P = 0. 20).


Input: The current evidence does not demonstrate that setting realistic goals leads to more favourable weight loss outcomes.


Input: Thus, our field may wish to reconsider the value of setting realistic goals in successful weight loss.


Input: Radiosynthesis and evaluation of [(11) C] EMPA as a potential PET tracer for orexin 2 receptors.

[(11) C] EMPA


Input: EMPA is a selective antagonist of orexin 2 (OX2) receptors.

EMPA


Input: Previous literature with [(3) H]-EMPA suggest that it may be used as an imaging agent for OX2 receptors; however, brain penetration is known to be modest.

[(3) H]-EMPA


Input: To evaluate the potential of EMPA as a PET radiotracer in non-human primate (as a step to imaging in man), we radiolabeled EMPA with carbon-11.

EMPA

carbon


Input: Radiosynthesis of [(11) C] N-ethyl-2-(N-(6-methoxypyridin-3-yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl) acetamide ([(11) C] EMPA), and evaluation as a potential PET tracer for OX2 receptors is described.

[(11) C] N-ethyl-2-(N-(6-methoxypyridin-3-yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl) acetamide

[(11) C] EMPA


Input: Synthesis of an appropriate non-radioactive O-desmethyl precursor was achieved from EMPA with sodium iodide and chlorotrimethylsilane.

O

EMPA

sodium iodide

chlorotrimethylsilane


Input: Selective O-methylation using [(11) C] CH3I in the presence of cesium carbonate in DMSO at room temp afforded [(11) C] EMPA in 1. 5-2. 5% yield (non-decay corrected relative to trapped [(11) C] CH3I at EOS) with <= 95% chemical and radiochemical purities.

O

[(11) C] CH3I

cesium carbonate

DMSO

[(11) C] EMPA

[(11) C] CH3I


Input: The total synthesis time was 34-36min from EOB.


Input: Studies in rodent suggested that uptake in tissue was dominated by nonspecific binding.


Input: However, [(11) C] EMPA also showed poor uptake in both rats and baboon as measured with PET imaging.

[(11) C] EMPA


Input: Optimization of a 1, 5-dihydrobenzo [b] [1, 4] diazepine-2, 4-dione series of HIV capsid assembly inhibitors 2: Structure-activity relationships (SAR) of the C3-phenyl moiety.

1, 5-dihydrobenzo [b] [1, 4] diazepine-2, 4-dione

phenyl


Input: Detailed structure-activity relationships of the C3-phenyl moiety that allow for the optimization of antiviral potency of a series of 1, 5-dihydrobenzo [b] [1, 4] diazepine-2, 4-dione inhibitors of HIV capsid (CA) assembly are described.

phenyl

1, 5-dihydrobenzo [b] [1, 4] diazepine-2, 4-dione


Input: Combination of favorable substitutions gave additive SAR and allowed for the identification of the most potent compound in the series, analog 27.


Input: Productive SAR also transferred to the benzotriazepine and spirobenzodiazepine scaffolds, providing a solution to the labile stereocenter at the C3 position.

benzotriazepine

spirobenzodiazepine


Input: The molecular basis of how compound 27 inhibits mature CA assembly is rationalized using high-resolution structural information.


Input: Our understanding of how compound 27 may inhibit immature Gag assembly is also discussed.


Input: Preparation of S14161 and its analogues and the discovery of 6-bromo-8-ethoxy-3-nitro-2H-chromene as a more potent antitumor agent in vitro.


Input: The small chemical compound 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene (S14161) was recently identified as an inhibitor of the phosphoinositide 3-kinase (PI3K).

8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene


Input: In the present study, we designed a novel synthesis of S14161 and prepared a series of its analogues via the oxa-Michael-Henry reaction in the presence of catalytic amounts of l-proline and triethylamine.

l-proline

triethylamine


Input: Further structural simplification led to the identification of 6-bromo-8-ethoxy-3-nitro-2H-chromene (BENC-511) that exhibited potent antiproliferative activities against a panel of 12 tumor cell lines.


Input: Compared with S14161, BENC-511 was more potent in blocking the AKT phosphorylation and inducing cancer cell apoptosis.


Input: BENC-511 also displayed more potent effects on human umbilical vein epithelial cells (HUVEC) migration, suggesting its anti-angiogenesis activity.


Input: Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors.


Input: 2-Phenyl-4-piperidinyl-6, 7-dihydrothieno [3, 4-d] pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50 = 150nM).

2-Phenyl-4-piperidinyl-6, 7-dihydrothieno [3, 4-d] pyrimidine


Input: A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized.

pyrimidines


Input: Among these, 5, 5-dioxo-7, 8-dihydro-6H-thiopyrano [3, 2-d] pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50 = 25 nM).

5, 5-dioxo-7, 8-dihydro-6H-thiopyrano [3, 2-d] pyrimidine


Input: Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50 = 7. 5nM) and TNF-alpha production in mouse splenocytes (IC50 = 9. 8nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50 = 18mg/kg).

N-propylacetamide


Input: The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex.


Input: Discovery of diarylurea P2Y1 antagonists with improved aqueous solubility.

diarylurea


Input: Preclinical data suggests that P2Y1 antagonists, such as diarylurea compound 1, may provide antithrombotic efficacy similar to P2Y12 antagonists and may have the potential of providing reduced bleeding liabilities.

diarylurea


Input: This manuscript describes a series of diarylureas bearing solublizing amine side chains as potent P2Y1 antagonists.

diarylureas

amine


Input: Among them, compounds 2l and 3h had improved aqueous solubility and maintained antiplatelet activity compared with compound 1.


Input: Compound 2l was moderately efficacious in both rat and rabbit thrombosis models and had a moderate prolongation of bleeding time in rats similar to that of compound 1.


Input: Cisplatin-induced cell death in Saccharomyces cerevisiae is programmed and rescued by proteasome inhibition.

Cisplatin


Input: Cisplatin is a highly effective chemotherapeutic drug used in the treatment of several tumors.

Cisplatin


Input: It is a DNA-damaging agent that induces apoptosis of rapidly proliferating cells, an important factor underlying its therapeutic efficacy.


Input: Unfortunately, cellular resistance occurs often.


Input: A large fraction of tumor cells harbor mutations in p53, contributing to defects in apoptotic pathways and drug resistance.


Input: However, cisplatin-induced apoptosis can also occur in p53 deficient cells; thus, elucidation of the molecular mechanism involved will potentially yield new strategies to eliminate tumors that have defects in the p53 pathway.

cisplatin


Input: Most of the studies in this field have been conducted in cultured mammalian cells, not amenable to systematic genetic manipulation.


Input: Therefore, we aimed to establish a simplified model devoid of a p53 ortholog to study cisplatin-induced programmed cell death (PCD), using the yeast Saccharomyces cerevisiae.

cisplatin


Input: Our results indicate cisplatin induces an active form of cell death in yeast, as this process was partially dependent on de novo protein synthesis and did not lead to loss of membrane integrity.

cisplatin


Input: Cisplatin also increased DNA condensation and fragmentation/degradation, but no significant mitochondrial dysfunction other than partial fragmentation.

Cisplatin


Input: Co-incubation with the proteasome inhibitor MG132 increased resistance to cisplatin and, accordingly, yeast strains deficient in proteasome activity were more resistant to cisplatin than wild-type strains.

cisplatin

cisplatin


Input: Proteasome inhibitors can sensitize tumor cells to cisplatin, but protect others from cisplatin-induced cell death.

cisplatin

cisplatin


Input: Our results indicate inhibition of the proteasome protects budding yeast from cisplatin-induced cell death and validate yeast as a model to study the role of the proteasome in cisplatin-induced PCD.

cisplatin

cisplatin


Input: Elucidation of this mechanism will aid in the development of new strategies to increase the efficacy of chemotherapy.


Input: In vitro and in vivo safety evaluation of Acer tegmentosum.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Acer tegmentosum, which contains salidroside and tyrosol, has been used for the treatment of hepatic disorders in eastern Asia.

salidroside

tyrosol


Input: However, little is known about its safety.


Input: AIM OF THE STUDY: To determine the safety of Acer tegmentosum, we evaluated its acute oral toxicity and genotoxicity profiles.


Input: MATERIALS AND METHODS: Salidroside and tyrosol present in Acer tegmentosum were quantified using high-performance liquid chromatography.

Salidroside

tyrosol


Input: Acute oral toxicity testing of Acer tegmentosum was performed in rats.


Input: Genotoxicity of Acer tegmentosum was assessed by bacterial reverse mutation, chromosomal aberration, and bone marrow micronucleus tests.


Input: All the tests were conducted in accordance with the good laboratory practices.


Input: RESULTS: The amounts of salidroside and tyrosol in Acer tegmentosum were found to be 85. 01 +/- 1. 21mg/g and 3. 12 +/- 0. 04mg/g, respectively.

salidroside

tyrosol


Input: In the bacterial reverse mutation test, Acer tegmentosum increased the number of revertant Salmonella typhimurium TA98 colonies, regardless of metabolic activation by S9 mixture.


Input: In contrast, Acer tegmentosum application did not significantly increase the number of chromosomal aberrations in Chinese hamster ovary (CHO)-K1 cells and micronucleated polychromatic erythrocytes in mice.


Input: In the acute oral toxicity test, the median lethal dose (LD50) of Acer tegmentosum was found to be > 2000mg/kg in rats.


Input: CONCLUSION: Take together, Acer tegmentosum exhibits mutagenicity, which was evident from the bacterial reverse mutation test.


Input: Further studies are needed to identify the components responsible for such an effect and the underlying mechanisms.


Input: Evaluation of reproductive and developmental toxicities of Pu-erh black tea (Camellia sinensis var. assamica) extract in Sprague Dawley rats.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Pu-erh black tea, which is obtained by first parching crude green tea leaves and followed by secondary fermentation with microorganisms, has been believed to be beneficial beverages for health in PR China.


Input: But its potential toxicity when administered at a high dose as concentrated extract has not been completely investigated.


Input: AIM OF THE STUDY: The present study was aimed at evaluating potential reproductive and developmental toxicities of Pu-erh black tea extract (BTE) in Sprague Dawley rats.


Input: MATERIALS AND METHODS: Growing rats were given BTE by gavage at levels of 0, 200, 700 and 2500mg/kg/day as the F0 generation in reproductive toxicity study.


Input: Additionally, BTE was administered to mate female rats from gestation day 0. 5 through 19. 5 at the doses of 0, 200, 700 and 2500mg/kg/day to evaluate the developmental toxicity.


Input: RESULTS: In the reproductive toxicity study, only 2500mg/kg/day BTE reduced the body weight gain and altered the relative organ weights including testes, prostata and ovary both for F0 parents and F1 offspring compared to the controls.


Input: High dose of BTE (2500mg/kg/day) administration caused developmental disturbances in embryo-to-foetus period including resorbed embryos, decreased embryo size and skeletal anomalies.


Input: CONCLUSION: In conclusion, the no-observed-adverse-effect level of BTE is 700mg/kg/day both for reproductive toxicity and developmental toxicities.


Input: Pregnancy Outcome following in utero Exposure to Hydroxychloroquine: A prospective comparative observational study.

Hydroxychloroquine


Input: OBJECTIVE: To evaluate pregnancy safety of hydroxychloroquine (HCQ) for rheumatologic diseases.

hydroxychloroquine

HCQ


Input: DESIGN: Prospective comparative observational study done at the Israeli teratology information service between 1998 and 2006.


Input: RESULTS: 114 HCQ-exposed pregnancies (98. 2% in the first trimester, T1) were followed-up and compared with 455 pregnancies of women counseled for non-teratogenic exposure.

HCQ


Input: The difference in the rate of congenital anomalies was not statistically significant [7/97 (7. 2%) vs. 15/440 (3. 4%), p = 0. 094].


Input: The analysis was repeated among those exposed in T1 excluding genetic or cytogenetic anomalies or congenital infections [5/95 (5. 3%) vs. 14/440 (3. 2%), p = 0. 355].


Input: There were no cases of neonatal lupus erythematosus.


Input: The gestational age at delivery was earlier, rate of preterm delivery higher, and birth weight lower, in the HCQ group.

HCQ


Input: CONCLUSION: The present study suggests that HCQ treatment in pregnancy is not a major human teratogen.

HCQ


Input: The earlier gestational age and lower birth weight might be associated with maternal disease.


Input: Monoterpene pyridine alkaloids and phenolics from Scrophularia ningpoensis and their cardioprotective effect.

Monoterpene pyridine alkaloids

phenolics


Input: Scrophularianines A-C (1-3), three new unusual monoterpene pyridine alkaloids with cyclopenta [c] pyridine skeleton reported from the genus Scrophularia for the first time, together with 15 known compounds (4-18), were isolated from the extract of Scrophularia ningpoensis.

Scrophularianines A-C

monoterpene pyridine alkaloids

cyclopenta [c] pyridine


Input: Their structures were elucidated on the basis of extensive analyses of spectroscopic evidences.


Input: The biogenetic relationship between monoterpene pyridine alkaloids and iridoids was proposed preliminarily.

monoterpene pyridine

iridoids


Input: The myocardial protective bioassay indicated that compounds 13 and 14 with a concentration of 10 (-4) M exhibited significantly protective effect against H2O2-induced apoptosis in cardiomyocytes.


Input: Neuroactive effects of cotinine on the hippocampus: Behavioral and biochemical parameters.

cotinine


Input: The present work evaluated the effects of nicotine (NIC), cotinine (COT), mecamylamine (MEC), methyllycaconitine (MLA) and dihydro-beta-eritroidine (DH beta E) on memory extinction and the following biochemical parameters of the hippocampus: lipid peroxidation (LPO), antioxidant capacity (AC) and the phosphorylation of Extracellular-Signal-Regulated Kinase (ERK 1/2).

nicotine

NIC

cotinine

COT

mecamylamine

MEC

methyllycaconitine

MLA

dihydro-beta-eritroidine

DH beta E


Input: Young male rats that were implanted bilaterally with cannulae were submitted to memory extinction tests sessions, and their hippocampi were dissected for biochemical assays.


Input: The extinction of fear memory was significantly improved by both nicotine and its metabolite.

nicotine


Input: Cotinine significantly increased LPO, while nicotine significantly decreased it.

Cotinine

nicotine


Input: Antioxidant capacity was increased by all treatments.


Input: Our results showed that cotinine, unlike nicotine, may increase oxidative stress in the hippocampus, but this increase depends upon the dose used and happens without causing corresponding impairments in cognitive function.

cotinine

nicotine


Input: Cotinine also increased the phosphorylation of ERK 1/2 in a similar fashion as nicotine.

Cotinine

nicotine


Input: Considering these results, it is plausible to wonder to what extent nicotine-attributed effects are really due to the actions of this alkaloid and whether they could be due instead to cotinine or to cotinine-nicotine interactions within the brain.

nicotine

cotinine

cotinine

nicotine


Input: Presynaptic CaMKII alpha modulates dopamine D3 receptor activation in striatonigral terminals of the rat brain in a Ca (2 +) dependent manner.

dopamine

Ca (2 +)


Input: CaMKII alpha is expressed at high density in the nucleus accumbens where it binds to postsynaptic D3 receptors inhibiting their effects.


Input: In striatonigral projections, activation of presynaptic D3 receptors potentiates D1 receptor-induced stimulation of cAMP production and GABA release.


Input: In this study we examined whether the presynaptic effects of D3 receptor stimulation in the substantia nigra reticulata (SNr) are modulated by Ca (2 +) activation of CaMKII alpha.

Ca (2 +)


Input: In SNr synaptosomes two procedures that increase cytoplasmic Ca (2 +), ionomycin and K (+)-depolarization, blocked the additional stimulation of cAMP accumulation produced by coactivating D3 and D1 dopamine receptors.

Ca (2 +)

ionomycin

K (+)

cAMP

dopamine


Input: The selective CaMKII alpha inhibitor KN-62 reversed the blockade produced by ionomycin and K (+)-depolarization.

ionomycin

K (+)


Input: Incubation in either Ca (2)-free solutions or with the selective Ca (2 +) blocker nifedipine, also reversed the blocking effects of K (+)-depolarization.

Ca (2)

Ca (2 +)

nifedipine

K (+)


Input: Immunoblot studies showed that K (+)-depolarization increased CaMKII alpha phosphorylation in a KN-62 sensitive manner and promoted CaMKII alpha binding to D3 receptors.

K (+)


Input: In K (+)-depolarized tissues, D3 receptors potentiated D1 receptor-induced stimulation of [(3) H] GABA release only when CaMKII alpha was blocked with KN-62.

K (+)

[(3) H] GABA


Input: In the presence of this inhibitor, the selective D3 agonist PD 128, 907 reduced the ED50 for the D1 agonist SKF 38393 from 56 to 4 nM.

PD 128, 907

SKF 38393


Input: KN-62 also enhanced the effects of dopamine on depolarization induced [(3) H] GABA release.

dopamine

[(3) H] GABA


Input: KN-62 changed ED50 for dopamine from 584 to 56 nM.

dopamine


Input: KN-62 did not affect D1 and D4 receptor responses.


Input: These experiments show that in striatonigral projections, CaMKII alpha inhibits the action of D3 receptors in a Ca (2 +) dependent manner blocking their modulatory effects on GABA release.

Ca (2 +)

GABA


Input: These findings suggest a mechanism through which the frequency of action potential discharge in presynaptic terminals regulates dopamine effects.

dopamine


Input: Structure-dependent activities of hydroxylated polybrominated diphenyl ethers on human estrogen receptor.

hydroxylated polybrominated diphenyl ethers

estrogen


Input: Polybrominated diphenyl ethers (PBDEs) have been shown to affect the estrogen receptor (ER) signaling pathway, and one of the proposed disruption mechanisms is direct binding of hydroxylated PBDE (OH-PBDE) to ER.

Polybrominated diphenyl ethers

PBDEs

estrogen

PBDE

OH-PBDE


Input: In this paper, the binding affinity of 22 OH-PBDEs with different degrees of bromination to ER was assessed quantitatively using a surface plasmon resonance biosensor technique.

OH-PBDEs


Input: Seven OH-PBDEs were found to bind directly with ER with KD ranging from 1. 46 x 10 (-7) M to 7. 90 x 10 (-6) M, and the affinity is in the order of 6-OH-BDE-047 >= 4'-OH-BDE-049 > 4'-OH-BDE-017 > 6'-OH-BDE-099 >= 5'-OH-BDE-099 > 2'-OH-BDE-007 > 3'-OH-BDE-028.

OH-PBDEs


Input: In MVLN luciferase gene reporter assays, 10 low-brominated OH-PBDEs induced luciferase activity alone, but are 10 (5) to 10 (7) fold less potent than E2.

OH-PBDEs


Input: Their estrogenic activity is in the order of 4'-OH-BDE-049 > 4'-OH-BDE-017 > 2'-OH-BDE-007 > 3'-OH-BDE-028 > 3-OH-BDE-047 >= 3'-OH-BDE-007.


Input: The good correlation between estrogenic activity and ER binding affinity of the low-brominated OH-PBDEs strongly suggest that these compounds induce ER transcriptional activity by binding directly with ER.

OH-PBDEs


Input: The other 12 high-brominated OH-PBDEs inhibited luciferase activity of E2 to various degrees, demonstrating their antagonistic activity.

OH-PBDEs


Input: Molecular docking analysis of the ER/OH-PBDE complexes revealed two distinctive binding modes between low-and high-brominated OH-PBDEs which provided rationale for the difference in their ER activity.

OH-PBDE

OH-PBDEs


Input: Arsenic upregulates the expression of angiotensin II Type I receptor in mouse aortic endothelial cells.

Arsenic


Input: Although chronic arsenic exposure is a well-known risk for cardiovascular disease and has a strong correlation with hypertension, the molecular pathogenesis underlying arsenic exposure-induced hypertension remains poorly understood.

arsenic

arsenic


Input: To delineate the pathogenesis, we examined changes in the mRNA levels of 2 angiotensin II Type I receptor (AT1R) subtypes, AT1AR and AT1BR, in a mouse aortic endothelial cell line, END-D.


Input: Quantitative real-time PCR analysis revealed significant increases in the mRNA levels of 2 AT1R subtypes, AT1AR and AT1BR following sodium arsenite (SA) treatment.

sodium arsenite


Input: Flow cytometry analysis revealed that SA increases the generation of reactive oxygen species (ROS) in a dose-dependent manner.

oxygen


Input: In addition, western blot analysis revealed that SA enhances the phosphorylations of c-Jun N-terminal kinases (JNK) and activated protein 1 (AP-1).

N


Input: These phosphorylations were inhibited by N-acetylcysteine (NAC), an anti-oxidant.

N-acetylcysteine

NAC


Input: Finally, SA-induced AT1R expression was found to be prevented both by NAC and specific JNK inhibitor, SP6001325, strongly indicating that AT1R upregulation is a result of the ROS-mediated activation of the JNK signaling pathway.


Input: Taken together, our results indicate that arsenic indeed upregulates the AT1R expression, thus highlighting a role of arsenic-induced aberrant AT1R signaling in the pathogenesis of hypertension.

arsenic

arsenic


Input: Binding of new cationic porphyrin-tetrapeptide conjugates to nucleoprotein complexes.

porphyrin

tetrapeptide


Input: Ongoing research on DNA binding of cationic porphyrin derivatives and their conjugates is a subject of growing interest because of their possible DNA binding and demonstrated biological properties.

porphyrin


Input: In this study nucleoprotein binding of tri-cationic meso-tri (4-N-methylpyridyl)-mono-(4-carboxyphenyl) porphyrin (TMPCP) and tetrapeptides conjugated TMPCP (TMPCP-4P) and bi-cationic meso-5, 10-bis (4-N-methylpyridyl)-15, 20-di-(4-carboxyphenyl) porphyrin (BMPCP-4P2) was investigated with comprehensive spectroscopic methods.

tri-cationic meso-tri (4-N-methylpyridyl)-mono-(4-carboxyphenyl) porphyrin

TMPCP

tetrapeptides

TMPCP

bi-cationic meso-5, 10-bis (4-N-methylpyridyl)-15, 20-di-(4-carboxyphenyl) porphyrin


Input: The key observation is that tetrapeptide-conjugates of cationic porphyrins with two or three positive charges bind to encapsidated DNA in T7 phage nucleoprotein complex.

tetrapeptide

porphyrins


Input: The binding modes were analyzed by fluorescent energy transfer, fluorescent life time and CD measurements.


Input: Intercalative binding is most feasible when tricationic ligands complex with DNA, especially when it is in close connection with protein capsid.


Input: It was found that larger ligand BMPCP-4P2 binds externally to encapsidated T7 DNA, and complex externally as well as by intercalation when the DNA accommodate to relaxed B-conformation.


Input: In the case of TMPCP and TMPCP-4P the intercalation is the predominant binding form both in nucleoprotein (NP) and preheated complexes.

TMPCP


Input: Further, melting experiments revealed that bound porphyrins do not influence the capsid stability or protein-DNA interactions, but efficiently stabilize the double helical structure of DNA without respect to binding form.

porphyrins


Input: A good correlation was found between porphyrin/base pair ration and DNA strand separation temperature.

porphyrin


Input: Reproductive toxicity of Campomanesia xanthocarpa (Berg.) in female Wistar rats.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: There is no evidence in the literature that substantiates the safety of Campomanesia xanthocarpa (Berg.) use during pregnancy.


Input: MATERIALS AND METHODS: Thirty three female rats were randomly assigned to three groups.


Input: One group of animals received the Campomanesia xanthocarpa extract via gavage at a dose of 26. 3mg/kg/day from 6 to 15 days of pregnancy (organogenic period, T1) and another group received the same extract throughout the gestational period (from the 1st to the 20th day of pregnancy, T2).


Input: Control groups received distilled water.


Input: Euthanasia was done on 20th day, when the liver, kidney, spleen ovaries, fetuses and their respective placentas were removed.


Input: Implantations, reabsorptions, live and dead fetuses were recorded.


Input: RESULTS AND CONCLUSIONS: Campomanesia xanthocarpa, in these experimental conditions, did not disturb the reproductive function of female rats and did not interrupt the progress of the embryofetal development.


Input: Moreover, our results provide further evidence that the Campomanesia xanthocarpa treatment reduces reabsorption sites, increases placenta weight and the number of live fetuses and may therefore have therapeutic applications.


Input: Anti-epileptogenic and antioxidant effect of Lavandula officinalis aerial part extract against pentylenetetrazol-induced kindling in male mice.

pentylenetetrazol


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Repeated application of Lavandula officinalis (L. officinalis) has been recommended for a long time in Iranian traditional medicine for some of nervous disorders like epilepsy and dementia.


Input: However, there is no available report for the effect of chronic administration of Lavandula extract in development (acquisition) of epilepsy.


Input: Therefore, this study was designed to investigate the anti-epileptogenic and antioxidant activity of repeated administration of Lavandula officinalis extract on pentylenetetrazol (PTZ) kindling seizures in mice model.

pentylenetetrazol

PTZ


Input: MATERIALS AND METHODS: Lavandula officinalis was tested for its ability (i) to suppress the seizure intensity and lethal effects of PTZ in kindled mice (anti-epileptogenic effect), (ii) to attenuate the PTZ-induced oxidative injury in the brain tissue (antioxidant effect) when given as a pretreatment prior to each PTZ injection during kindling development.

PTZ

PTZ

PTZ


Input: Valproate (Val), a major antiepileptic drug, was also tested for comparison.

Valproate

Val


Input: RESULTS: Val and Lavandula officinalis extract showed anti-epileptogenic properties as they reduced seizure score of kindled mice and PTZ-induced mortality.

Val

PTZ


Input: In this regard, Lavandula officinalis was more effective than Val.

Val


Input: Both Lavandula officinalis and Val suppressed brain nitric oxide (NO) level of kindled mice in comparison with the control and PTZ group.

Val

nitric oxide

NO

PTZ


Input: Meanwhile, Lavandula officinalis suppressed NO level more than Val and Lavandula officinalis also decreased brain MDA level relative to PTZ group.

NO

Val

MDA

PTZ


Input: CONCLUSION: This is the first report to demonstrate NO suppressing and anti-epileptogenic effect of chronic administration of Lavandula officinalis extract on acquisition of epilepsy in PTZ kindling mice model.

NO

PTZ


Input: In this regard, Lavandula officinalis extract was more effective than Val, possibly and in part via brain NO suppression.

Val

NO


Input: Toluquinol, a marine fungus metabolite, is a new angiosuppresor that interferes the Akt pathway.

Toluquinol


Input: Toluquinol, a methylhydroquinone produced by a marine fungus, was selected in the course of a blind screening for new potential inhibitors of angiogenesis.

Toluquinol

methylhydroquinone


Input: In the present study we provide the first evidence that toluquinol is a new anti-angiogenic-compound.

toluquinol


Input: In a variety of experimental systems, representing the sequential events of the angiogenic process, toluquinol treatment of activated endothelial cells resulted in strong inhibitory effect.

toluquinol


Input: Toluquinol inhibited the growth of endothelial and tumor cells in culture in the micromolar range.

Toluquinol


Input: Our results indicate that the observed growth inhibitory effect could be due, at least in part, to an induction of apoptosis.


Input: Toluquinol induced endothelial cell death is mediated via apoptosis after a cell cycle block and caspase activation.

Toluquinol


Input: Capillary tube formation on Matrigel and migratory, invasive and proteolytic capabilities of endothelial cells were inhibited by addition of toluquinol at subtoxic concentrations.

toluquinol


Input: Inhibition of the mentioned essential steps of in vitro angiogenesis agrees with the observed inhibition of the in vivo angiogenesis, substantiated by using the chick chorioallatoic membrane assay and confirmed by the murine Matrigel plug, the zebrafish embryo neovascularization and the zebrafish caudal fin regeneration assays.


Input: Data here shown altogether indicate that toluquinol has antiangiogenic effects both in vitro and in vivo that are exerted partly by suppression of the VEGF and FGF-induced Akt activation of endothelial cells.

toluquinol


Input: These effects are carried out at lower concentrations to those required for other inhibitors of angiogenesis, what makes toluquinol a promising drug candidate for further evaluation in the treatment of cancer and other angiogenesis-related pathologies.

toluquinol


Input: Dehydroepiandrosterone post-transcriptionally modifies CYP1A2 induction involving androgen receptor.

Dehydroepiandrosterone

androgen


Input: The pharmacological dosage of dehydroepiandrosterone (DHEA) protects against chemically induced carcinogenesis.

dehydroepiandrosterone

DHEA


Input: The chemoprotective activity of DHEA is attributed to its inhibitory potential for the expression of CYP1A enzymes, which are highly responsible for metabolic activation of several mutagenic and carcinogenic chemicals.

DHEA


Input: The present work investigated whether the chemoprevention by DHEA was due to diminished transcriptional activation of CYP1A genes or to the post-transcriptional modulation of CYP1A expression.

DHEA


Input: In primary human hepatocytes, DHEA diminished the increase in CYP1A activities (7-ethoxyresorufin O-dealkylation and phenacetin O-dealkylation) and in CYP1A2 mRNA level induced by 3-methylcholanthrene, but did not alter the amount of CYP1A1 and CYP1B1 mRNA.

DHEA

7-ethoxyresorufin O

phenacetin O


Input: The androgen receptor seemed to be involved in DHEA-mediated diminishment of CYP1A2 induction, which was attenuated in the presence of bicalutamide, the androgen receptor antagonist.

androgen

DHEA

bicalutamide

androgen


Input: The potential role of the glucocorticoid receptor and estrogen receptor in DHEA-mediated decrease in CYP1A2 induction was excluded.

estrogen

DHEA


Input: The developed computational model of CYP1A2 induction kinetics and CYP1A2 mRNA degradation proposed that a post-transcriptional mechanism was likely to be the primary mechanism of the DHEA-mediated diminishment of CYP1A2 induction.

DHEA


Input: The hypothesis was confirmed by the results of actinomycin D-chase experiments in MCF-7 and LNCaP cells, displaying that the degradation rates of CYP1A2 mRNA were significantly higher in the cells exposed to DHEA.

actinomycin D

DHEA


Input: The novel findings on DHEA-mediated modulation of CYP1A2 mRNA stability may account for the beneficial effects of DHEA by decreasing the metabolic activation of pro-carcinogenic compounds.

DHEA

DHEA


Input: Piperidine, pyridine alkaloid inhibition of fetal movement in a day 40 pregnant goat model.

Piperidine

pyridine alkaloid


Input: Inhibition of fetal movement is one mechanism behind the development of multiple congenital contracture-type defects in developing fetuses of humans and animals.


Input: We tested the alkaloids anabasine, lobeline, and myosmine for agonist actions, and sensitivity to alpha conotoxins EI and GI blockade at fetal muscle-type nicotinic acetylcholine receptors (nAChR) expressed by TE-671 cells.

anabasine

lobeline

myosmine

acetylcholine


Input: We also determined if the alkaloids decreased fetal movement in an IV dosed, day 40 pregnant goat model.


Input: In TE-671 cells, all three alkaloids elicited concentration-dependent changes in membrane potential sensing dye fluorescence.


Input: 1. 0 mu M alpha conotoxin GI shifted the concentration-effect curves of anabasine and myosmine to the right, and decreased maximal responses.

alpha conotoxin GI

anabasine

myosmine


Input: Neither of the conotoxins blocked the actions of lobeline in TE-671 cells.

lobeline


Input: In the day 40 pregnant goats, 0. 8mg/kg anabasine abolished fetal movement at 30 and 60min after dosing and fetal movement was reduced by lobeline and myosmine.

anabasine

lobeline

myosmine


Input: The blockade of anabasine and myosmine actions in TE-671 cells by alpha conotoxin GI indicates that they are agonists at fetal muscle-type nAChR.

anabasine

myosmine

alpha conotoxin GI


Input: All three alkaloids did significantly decrease fetal movement in the day 40 pregnant goat model suggesting a potential for these alkaloids to cause multiple congenital contracture-type defects in developing fetuses.


Input: Ellagic acid attenuates bleomycin and cyclophosphamide-induced pulmonary toxicity in Wistar rats.

Ellagic acid

bleomycin

cyclophosphamide


Input: Use of bleomycin (BLM) and cyclophosphamide (CP) as chemotherapeutic drugs is associated with side effects including toxicity to respiratory system.

bleomycin

BLM

cyclophosphamide


Input: Their co-administration may enhance lung toxicity which may subsequently progress to the lung fibrosis.


Input: Natural compounds have shown mitigating effects against toxicity of anticancer drugs.


Input: Ellagic acid (EA), a polyphenolic compound present in many fruits and nuts in addition to walnut has shown promising protective effect against toxicity of drugs and chemicals.

Ellagic acid


Input: We studied the ameliorative effect of EA on lung toxicity in rats exposed to CP (150mg/kgb. w., i. p.) and BLM (10U/kgb. w., i. t.).

BLM


Input: EA (15mg/kgb. w., p. o. x 14days) treatment modulated enhanced hydroxyproline level, lipid peroxidation, myeloperoxidase activity, nitric oxide production and protein carbonyl formation in lungs of rats exposed to toxic anticancer drugs.

hydroxyproline

nitric oxide

carbonyl


Input: There was a marked decrease in GSH content and activities of antioxidant enzymes as a result of BLM and CP treatment.

GSH

BLM


Input: Bronchoalveolar lavage fluid showed increased level of cytotoxicity markers in drug treated animals.


Input: Treatment with EA attenuated these changes.


Input: Histopathological findings also showed protective effects of EA.


Input: In conclusion, EA emerged as a natural protectant with an ability to protect lungs from onslaught of pulmonary toxicity of anticancer drugs.


Input: How to measure hazards/risks following exposures to nanoscale or pigment-grade titanium dioxide particles.

titanium dioxide


Input: Due to its multifunctional applications, titanium dioxide particles have widespread use in commerce.

titanium dioxide


Input: The particle-types function as sources of pigment color, in food products, anti-bacterial components, ultraviolet radiation scavengers, catalysts, as well as in cosmetics.


Input: Because of its inherent properties in a diverse number of products, exposures may occur via any of the major point-of-entry routes, i. e., inhalation, oral or dermal.


Input: Although the majority of TiO2 applications are known to exist in the pigment-grade form, nanoscale forms of TiO2 are also common components in several products.


Input: This brief review is designed to identify relevant toxicology and risk-related issues which inform health effects assessments on the various forms of titanium dioxide particles.

titanium dioxide


Input: While there has been an abundance of hazard data generated on titanium dioxide particulates, many of the published reports have limited informational value for assessing health effects due, in large part, to shortcomings in experimental design issues, such as: (1) inadequate material characterization of test samples; (2) questionable relevance of experimental systems employed to simulate human exposures; (3) applications of generally high doses, exclusive focus on acute toxicity endpoints, and a lack of reference benchmark control materials, to afford interpretation of measured results; and/or (4) failure to recognize fundamental differences between hazard and risk concepts.

titanium dioxide


Input: Accordingly, a number of important toxicology issues are identified and integrated herein to provide a more comprehensive assessment of the health risks of different forms of pigment-grade and nanoscale titanium dioxide particles.

titanium dioxide


Input: It is important to note that particle-types of different TiO2 compositions may have variable toxicity potencies, depending upon crystal structure, particle size, particle surface characteristics and surface coatings.


Input: In order to develop a more robust health risk evaluation of TiO2 particle exposures, this review focuses on the following issues: A comprehensive evaluation of the existing animal and human health data is a necessary prerequisite for facilitating accurate assessments of human health risks to TiO2 exposures.


Input: Non-peptidyl insulin mimetics as a potential antidiabetic agent.


Input: Insulin has an important role in the maintenance of blood sugar.


Input: It is the only available therapeutic agent for the treatment of type 1 diabetes mellitus and there is a dire need for an oral substitute.


Input: Different categories of compounds including mono and di substituted benzoquinones, vanadium based compounds and natural products have been reported to cause insulin-like effects either by increasing phosphorylation of insulin receptor (IR) or inhibiting the protein tyrosine phosphatases.

benzoquinones

vanadium

tyrosine


Input: This review summarizes the development of various insulin mimetics with special emphasis on their structure-activity relationships and various biological actions they produce.


Input: Is autologous chondrocyte implantation (ACI) an adequate treatment option for repair of cartilage defects in paediatric patients?


Input: Cartilage lesions in the knee of juvenile patients require an effective repair to regain life-long functional activity of the joint.


Input: Autologous chondrocyte implantation (ACI) is discussed to be advantageous over other methods for cartilage repair regarding long-term outcome.


Input: ACI has successfully been applied in juvenile patients, although currently recommended for patients >= 18 years of age.


Input: Only few controlled clinical trials present evidence of efficacy and safety of ACI in adolescent patients.


Input: ACI products have to undergo the process of a marketing authorisation application, including the submission of a paediatric investigation plan (PIP).


Input: Data from prospective clinical studies or retrospective collection of long-term data in paediatric patients should be submitted for risk-benefit evaluation by the Paediatric Committee (PDCO).


Input: FOXO3 growth inhibition of colonic cells is dependent on intraepithelial lipid droplet density.


Input: Forkhead transcription factor FOXO3 plays a critical role in suppressing tumor growth, in part, by increasing cell cycle inhibitor p27kip1, and Foxo3 deficiency in mice results in marked colonic epithelial proliferation.


Input: Here, we show in Foxo3 deficient colonic epithelial cells a striking increase in intracytoplasmic lipid droplets (LDs), a dynamic organelle recently observed in human tumor tissue.


Input: While the regulation and function of LDs in non-adipocytes is unclear, we hypothesize that the anti-proliferative effect of FOXO3 was dependent on lowering LD density, thus decreasing fuel energy in both normal and colon cancer cells.


Input: In mouse colonic tumors, we found an increased expression of LD coat protein PLIN2 compared to normal colonic epithelial cells.


Input: Stimulation of LD density in human colon cancer cells led to PI3K dependent loss of FOXO3 and a decrease in the negative regulator of lipid metabolism Sirtuin6 (SIRT6).


Input: Foxo3 deficiency also led to a decrease in SIRT6, revealing the existence of the LD and FOXO3 feedback regulation in colonic cells.


Input: In parallel, LD dependent loss of FOXO3 led to its dissociation from the promoter and decreased expression of the cell cycle inhibitor p27kip1.


Input: Stimulation of LD density promoted proliferation in colon cancer cells, while silencing PLIN2 or overexpression of FOXO3 inhibited proliferation.


Input: Taken together, FOXO3 and LDs might serve as new targets for therapeutic intervention of colon cancer.


Input: Exploration of the Orthosteric/Allosteric Interface in Human M1 Muscarinic Receptors by Bitopic Fluorescent Ligands.


Input: Bitopic binding properties apply to a variety of muscarinic compounds that span and simultaneously bind to both the orthosteric and allosteric receptor sites.