Input: We demonstrate that precise higher order assemblies can be achieved by fine tuning the particular features of the individual building blocks.


Input: Nickel (II) Dithiocarbamate Complexes Containing Sulforhodamine B as Fluorescent Probes for Selective Detection of Nitrogen Dioxide.

Nickel (II) Dithiocarbamate

Sulforhodamine B

Nitrogen Dioxide


Input: We synthesized complexes of Ni (II) with dithiocarbamate ligands derived from the ortho and para isomers of sulforhodamine B fluorophores and demonstrated they are highly selective in reactions with nitrogen dioxide (NO2).

Ni (II)

dithiocarbamate

sulforhodamine B

nitrogen dioxide


Input: Compared with the para isomer, the ortho isomer showed a much greater fluorescence increase upon reaction with NO2, which led to oxidation and decomplexation of the dithiocarbamate ligand from Ni (II).

dithiocarbamate

Ni (II)


Input: We applied this probe for visual detection of 1 ppm NO2 in the gas phase and fluorescence imaging of NO2 in macrophage cells treated with a nitrogen dioxide donor.

nitrogen dioxide


Input: Cryptic genetic and wing pattern diversity in a mimetic Heliconius butterfly.


Input: Despite rampant colour pattern diversity in South America, Heliconius erato exhibits a' postman' wing pattern throughout most of Central America.


Input: We examined genetic variation across the range of H. erato, including dense sampling in Central America, and discovered a deep genetic break, centred on the mountain range that runs through Costa Rica.


Input: This break is characterized by a novel mitochondrial lineage, which is nearly fixed in northern Central America, that branches basal to all previously described mitochondrial diversity in the species.


Input: Strong genetic differentiation also appears in Z-linked and autosomal markers, and it is further associated with a distinct, but subtle, shift in wing pattern phenotype.


Input: Comparison of clines in wing phenotype, mtDNA and nuclear markers indicate they are all centred on the mountains dividing Costa Rica, but that cline width differs among data sets.


Input: Phylogeographical analyses, accounting for this new diversity, rewrite our understanding of mimicry evolution in this system.


Input: For instance, these results suggest that H. erato originated west of the Andes, perhaps in Central America, and as many as 1 million years before its co-mimic, H. melpomene.


Input: Overall our data indicate that neutral genetic markers and colour pattern loci are congruent and converge on the same hypothesis-H. erato originated in northwest South America or Central America with a' postman' phenotype and then radiated into the wealth of colour patterns present today.


Input: Magnetite Biomineralization in Magnetospirillum gryphiswaldense: Time-Resolved Magnetic and Structural Studies.

Magnetite


Input: Magnetotactic bacteria biosynthesize magnetite nanoparticles of high structural and chemical purity that allow them to orientate in the geomagnetic field.

magnetite


Input: In this work we have followed the process of biomineralization of these magnetite nanoparticles.

magnetite


Input: We have performed a time-resolved study on magnetotactic bacteria Magnetospirillum gryphiswaldense strain MSR-1.


Input: From the combination of magnetic and structural studies by means of Fe K-edge X-ray absorption near edge structure (XANES) and high-resolution transmission electron microscopy we have identified and quantified two phases of Fe (ferrihydrite and magnetite) involved in the biomineralization process, confirming the role of ferrihydrite as the source of Fe ions for magnetite biomineralization in M. gryphiswaldense.

Fe

ferrihydrite

magnetite

ferrihydrite

Fe

magnetite


Input: We have distinguished two steps in the biomineralization process: the first, in which Fe is accumulated in the form of ferrihydrite, and the second, in which the magnetite is rapidly biomineralized from ferrihydrite.

Fe

ferrihydrite

magnetite

ferrihydrite


Input: Finally, the XANES analysis suggests that the origin of the ferrihydrite could be at bacterial ferritin cores, characterized by a poorly crystalline structure and high phosphorus content.

ferrihydrite

phosphorus


Input: Exploiting the Unique ATP-Binding Pocket of Toxoplasma Calcium-Dependent Protein Kinase 1 To Identify Its Substrates.

ATP

Calcium


Input: Apicomplexan parasites rely on calcium as a second messenger to regulate a variety of essential cellular processes.

calcium


Input: Calcium-dependent protein kinases (CDPK), which transduce these signals, are conserved among apicomplexans but absent from mammalian hosts, making them attractive targets for therapeutic intervention.

Calcium


Input: Despite their importance, the signaling pathways CDPK regulate remain poorly characterized, and their protein substrates are completely unknown.


Input: In Toxoplasma gondii, CDPK1 is required for calcium-regulated secretion from micronemes, thereby controlling motility, invasion, and egress from host cells.

calcium


Input: CDPK1 is unique among parasite and mammalian kinases in containing glycine at the key " gatekeeper " residue, which results in an expanded ATP-binding pocket.

glycine

ATP


Input: In the present study, we use a synthetic ATP gamma S analogue that displays steric complementarity to the ATP-binding pocket and hence allows identification of protein substrates based on selective thiophosphorylation.

ATP


Input: The specificity of this approach was validated by the concordance between the identified phosphorylation sites and the in vitro substrate preference of CDPK1.


Input: We further demonstrate that the phosphorylation of predicted substrates is dependent on CDPK1 both in vivo and in vitro.


Input: This combined strategy for identifying the targets of specific protein kinases provides a platform for defining the roles of CDPKs in apicomplexans.


Input: In Vivo Degradation and Elimination of Injectable Ricinoleic Acid-Based Poly (ester-anhydride).

Ricinoleic Acid

Poly (ester-anhydride)


Input: The in vivo degradation and elimination after subcutaneous implantation of injectable p (SA-RA) 3: 7 copolymer in rats, followed by characterization of the polymer matrix composition during hydrolysis and erosion, is reported.

p (SA-RA) 3: 7


Input: Major chemical changes were observed during the first few days post implantation, the anhydride bonds hydrolyzed along with about 45% weight loss and a significant decrease in the molecular weight.


Input: (1) H NMR spectral analysis was used to determine the structures and content of ricinoleic acid containing oligomeric chains present in the degraded polymer.

(1) H

ricinoleic acid


Input: The polymer degrades into ester oligomers of 2-4 ricinoleic acid units which further degrade to ricinoleic acid, a natural fatty acid.

ricinoleic acid

ricinoleic acid

fatty acid


Input: The polymer hydrolytic degradation process fit the in vitro degradation process.


Input: Multipart Copolyelectrolyte Adhesive of the Sandcastle Worm, Phragmatopoma californica (Fewkes): Catechol Oxidase Catalyzed Curing through Peptidyl-DOPA.

Catechol

DOPA


Input: Tube-building sabellariid polychaetes have major impacts on the geology and ecology of shorelines worldwide.


Input: Sandcastle worms, Phragmatopoma californica (Fewkes), live along the western coast of North America.


Input: Individual sabellariid worms build tubular shells by gluing together mineral particles with a multipart polyelectrolytic adhesive.


Input: Distinct sets of oppositely charged components are packaged and stored in concentrated granules in separate cell types.


Input: Homogeneous granules contain sulfated macromolecules as counter-polyanion to polycationic Pc2 and Pc5 proteins, which become major components of the fully cured glue.


Input: Heterogeneous granules contain polyphosphoproteins, Pc3A/B, paired with divalent cations and polycationic Pc1 and Pc4 proteins.


Input: Both types of granules contain catechol oxidase that catalyzes oxidative cross-linking of L-DOPA.

catechol

L-DOPA


Input: Co-secretion of catechol oxidase guarantees rapid and spatially homogeneous curing with limited mixing of the preassembled adhesive packets.

catechol


Input: Catechol oxidase remains active long after the glue is fully cured, perhaps providing an active cue for conspecific larval settlement.

Catechol


Input: Progression to insulin for patients with diabetes mellitus on dual oral antidiabetic therapy using the US Department of Defense Database.


Input: AIM: To compare' progression to insulin' for three cohorts on oral antidiabetic medication combinations: metformin/sulphonylurea (Met/SU), metformin/thiazolidinedione (Met/TZD) and sulphonylurea/thiazolidinedione (SU/TZD).

metformin

sulphonylurea

Met

metformin

thiazolidinedione

Met

TZD

sulphonylurea

thiazolidinedione

TZD


Input: METHODS: Retrospective cohort analysis design was used.


Input: The subjects were US nationwide members of military and their families.


Input: A total of 5608 patients who were on antidiabetic monotherapy for at least 1 year before adding a second agent to their medication regimen between October 2001 and September 2008 participated in this study.


Input: Mean age ranged from 64 to 71 years among the cohorts.


Input: Cox regression compared the progression to insulin, adjusting for demographics, months of follow-up and co-morbidities [measured with Chronic Disease Score (CDS)].


Input: RESULTS: By the end of the 2-to 6-year follow-up period, 14. 3% of the Met/TZD cohort, 23. 6% of the Met/SU cohort and 28. 2% of the SU/TZD cohort had insulin added to their regimen.

Met

TZD

Met

TZD


Input: Those in the Met/SU cohort had a 1. 8 times higher probability of progression to insulin than those in the Met/TZD cohort [odds ratio (OR) = 1. 80, 95% confidence interval (CI) = 1. 51-2. 14), and those in the SU/TZD cohort had a 2. 5 times higher probability of progression to insulin than those in the Met/TZD cohort (OR = 2. 51, 95% CI = 2. 04-3. 08).

Met

Met

TZD

TZD

Met

TZD


Input: CONCLUSION: When sensitizers were paired (Met/TZD), a lower percentage of patients progressed to insulin during the study period, as opposed to patients who used a combination of a secretagogue with a sensitizer (SU/TZD or Met/SU).

Met

TZD

TZD

Met


Input: Murabutide revisited: a review of its pleiotropic biological effects.


Input: Despite the great efforts put into their development, the list of clinically approved immunological adjuvants is still very short.


Input: Evolution of the knowledge of the immune system has enabled for rational design of novel adjuvants and has led to the conclusion that more than one type of adjuvant will be required.


Input: Derivatives of muramyl dipeptide (MDP), the minimal immunomodulatory structure of bacterial cell wall peptidoglycan, have gained considerable attention in the past decades, because of their potent adjuvant effects.


Input: Murabutide is a safe derivative of MDP, which interacts with cells of the immune system, both innate and adaptive, and exerts its effect through activation of Nod2.


Input: The transcriptional response of murabutide-stimulated macrophages revealed enhanced expression of genes coding for various proteins such as immune mediators and their receptors, transcription factors and kinases, ion channels/transporters and proteins involved in cell metabolic activity, thus reflecting a broad spectrum of biological effects.


Input: In addition to its well recognized adjuvant effect, murabutide has also been shown to enhance the host' s resistance against microbial infections, nonspecific resistance against tumors and the induction of cytokines and chemokines implicated in enhancing the immune response and hematopoesis.


Input: This article provides an insight into the mechanism of action of murabutide and its interactions with the cells of the immune system in vitro and in vivo.


Input: On account of its numerous biological effects, murabutide has been the subject of several clinical studies.


Input: Many of these have confirmed its potential to synergize with cytokines of therapeutic interest in potentiating the tumoricidal activity of macrophages or targeting chronic viral diseases, as well as reducing the cytokine dosage needed to achieve a therapeutic effect.


Input: This review covers the findings of all relevant studies and focuses on the role of murabutide and its potential in the treatment of several microbial diseases.


Input: The Protective Effects of alpha-Lipoic Acid on Kidneys in Type 2 Diabetic Goto-Kakisaki Rats via Reducing Oxidative Stress.

alpha-Lipoic Acid


Input: To evaluate the protective effects of alpha-lipoic acid on the kidneys of Goto-Kakisaki (GK) diabetic rats, ten GK diabetic rats were randomly divided into a diabetic control group and a lipoic acid-treated diabetic group with alpha-lipoic acid 35 mg. Kg-1 intraperitoneal injections.

alpha-lipoic acid

lipoic acid

alpha-lipoic acid


Input: Four healthy Wistar rats served as normal controls.


Input: Malonaldehyde (MDA), ascorbic acid (vitamin C), vitamin E, glutathione (GSH) and superoxide dismutase (SOD) levels in renal homogenate, and urine protein excretion were measured.

Malonaldehyde

MDA

ascorbic acid

vitamin C

vitamin E

glutathione

GSH

superoxide


Input: The expression of mRNA for NF-kappa B, NADPH oxidase subunits p22phox and p47phox in renal tissue was examined by realtime PCR.

NADPH


Input: Pathological changes in renal tissue were evaluated by light and electron microscopy.


Input: There were significant increases in urine protein excretion, MDA levels and the expression of mRNA of NF-kappa B, p22phox and p47phox, and significant decreases in GSH, SOD, vitamin C and vitamin E levels in the diabetic control group compared with the normal control group.

MDA

GSH

vitamin C

vitamin E


Input: Pathological changes of renal tissue were more progressive in the diabetic control group than in the normal control group.


Input: All the parameters above were improved in the alpha-lipoic acid-treated diabetic group.

alpha-lipoic acid


Input: Oxidative stress is increased in the kidney of type 2 diabetic GK rats.


Input: It is associated with the progression of diabetic nephropathy.


Input: alpha-lipoic acid can protect renal function in diabetic rats via its antioxidant activity.

alpha-lipoic acid


Input: Effect of oxygen concentration and selected protocol factors on viability and gene expression of mouse liver slices.

oxygen


Input: Precision cut liver slices (PCLSs) are widely used as a model to study hepatotoxicity.


Input: For culturing of PCLS diverse protocols are used which could affect slices viability and results.


Input: We aimed to identify the most optimal culture protocol for mouse PCLS.


Input: Slices were cultured for 24h under different concentrations of serum, glucose, insulin, and oxygen.

glucose

oxygen


Input: Thereafter, slices viability was assessed by biochemical methods.


Input: Transcriptome analysis was performed to identify changes introduced by culture at different oxygen concentrations (20%, 40%, 60%, and 80% of oxygen).

oxygen

oxygen


Input: Medium composition did not affect the slices viability.


Input: Although metabolic competence was unaffected by oxygen concentrations, culturing at 80% of oxygen yielded slices with the best biochemical characteristics.

oxygen

oxygen


Input: The comparison of uncultured vs. cultured slices revealed 2524 genes to be differentially expressed.


Input: Genes involved in drug metabolism, peroxisomal and mitochondrial functions were down-regulated while several adaptive/stress response processes were up-regulated.


Input: Moreover, 80% of oxygen was the most favorable condition with respect to maintenance of expression of genes involved in drug and energy metabolism.

oxygen


Input: The outcome of this study indicates that mouse PCLS are a valuable tool in research on hepatic functions and toxicity, particularly if they are cultured under a controlled oxygen concentration of 80%.

oxygen


Input: The noncellular reduction of MTT tetrazolium salt by TiO2 nanoparticles and its implications for cytotoxicity assays.

MTT tetrazolium salt


Input: We report results of noncellular tests, revealing the occurrence of photocatalytic interactions between titanium dioxide (TiO2, titania) nanoparticles and the MTT [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium-bromide] cytotoxicity indicator.

titanium dioxide

titania

MTT

3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium-bromide


Input: These interactions induce the reduction of MTT and formation of purple formazan under biologically relevant conditions.

MTT


Input: Classical MTT assays have been performed to evaluate the production of formazan in DMEM-F12 and RPMI-1640 cell culture media (containing 10% fetal bovine serum-FBS) treated with Degussa-P25 TiO2 nanoparticles, in the absence of cells.

MTT

formazan

P25 TiO2


Input: The colorimetric determinations revealed the noncellular MTT to formazan transformation induced by TiO2 nanoparticles, under conditions commonly used for in vitro cytotoxicity testing of nanomaterials.

MTT

formazan


Input: The formazan precipitation was found to be proportional to the TiO2 concentration, being enhanced under laboratory daylight exposure.

formazan


Input: The photocatalytic nature of the studied effect was assessed under UV irradiation at 365nm.


Input: The biological significance of the reported reaction was established with respect to cellular reference experiments performed on V79-4, HeLa and B16 cell lines.


Input: The results show false viability increases with up to 14% (for TiO2 concentrations generally higher than 50 mu g/ml), induced by the TiO2-MTT reaction.

MTT


Input: This type of artifacts may lead to underestimated toxicity or false proliferation results.


Input: Streptococcal collagen-like protein A and general stress protein 24 are immunomodulating virulence factors of group A Streptococcus.


Input: In Western countries, invasive infections caused by M1T1 serotype group A Streptococcus (GAS) are epidemiologically linked to mutations in the control of virulence regulatory 2-component operon (covRS).


Input: In indigenous communities and developing countries, severe GAS disease is associated with genetically diverse non-M1T1 GAS serotypes.


Input: Hypervirulent M1T1 covRS mutant strains arise through selection by human polymorphonuclear cells for increased expression of GAS virulence factors such as the DNase Sda1, which promotes neutrophil resistance.


Input: The GAS bacteremia isolate NS88. 2 (emm 98. 1) is a covS mutant that exhibits a hypervirulent phenotype and neutrophil resistance yet lacks the phage-encoded Sda1.


Input: Here, we have employed a comprehensive systems biology (genomic, transcriptomic, and proteomic) approach to identify NS88. 2 virulence determinants that enhance neutrophil resistance in the non-M1T1 GAS genetic background.


Input: Using this approach, we have identified streptococcal collagen-like protein A and general stress protein 24 proteins as NS88. 2 determinants that contribute to survival in whole blood and neutrophil resistance in non-M1T1 GAS.


Input: This study has revealed new factors that contribute to GAS pathogenicity that may play important roles in resisting innate immune defenses and the development of human invasive infections-Tsatsaronis, J.


Input: A., Hollands, A., Cole, J.


Input: N., Maamary, P.


Input: G., Gillen, C.


Input: M., Ben Zakour, N.


Input: L., Kotb, M., Nizet, V., Beatson, S.


Input: A.


Input: Walker, M.


Input: J., Sanderson-Smith, M.


Input: L.


Input: Streptococcal collagen-like protein A and general stress protein 24 are immunomodulating virulence factors of group A Streptococcus.


Input: Systems approaches in risk assessment.


Input: Adverse drug events (ADEs) remain a universal problem in drug development, regulatory review, and clinical practice with a substantial financial burden on the global health-care system.


Input: Recent advances in molecular and " omics " technologies, along with online databases and bioinformatics, have enabled a more integrative approach to understanding drug-target (protein) interactions, both desirable and undesirable, within a biological system.


Input: This has led to the development of systems approaches to risk assessment in an attempt to complement and improve on contemporary observational and predictive strategies for assessing risk.


Input: Although still in an evolutionary phase, systems approaches have the potential to markedly advance our understanding of ADEs and ability to predict them.


Input: Systems approaches will also move personalized medicine forward by enabling better identification of individual and subgroup risk factors.


Input: Population structure, migration, and diversifying selection in the Netherlands.


Input: Genetic variation in a population can be summarized through principal component analysis (PCA) on genome-wide data.


Input: PCs derived from such analyses are valuable for genetic association studies, where they can correct for population stratification.


Input: We investigated how to capture the genetic population structure in a well-characterized sample from the Netherlands and in a worldwide data set and examined whether (1) removing long-range linkage disequilibrium (LD) regions and LD-based SNP pruning significantly improves correlations between PCs and geography and (2) whether genetic differentiation may have been influenced by migration and/or selection.


Input: In the Netherlands, three PCs showed significant correlations with geography, distinguishing between: (1) North and South; (2) East and West; and (3) the middle-band and the rest of the country.


Input: The third PC only emerged with minimized LD, which also significantly increased correlations with geography for the other two PCs.


Input: In addition to geography, the Dutch North-South PC showed correlations with genome-wide homozygosity (r = 0. 245), which may reflect a serial-founder effect due to northwards migration, and also with height (male: r = 0. 142, female: r = 0. 153).


Input: The divergence between subpopulations identified by PCs is partly driven by selection pressures.


Input: The first three PCs showed significant signals for diversifying selection (545 SNPs-the majority within 184 genes).


Input: The strongest signal was observed between North and South for the functional SNP in HERC2 that determines human blue/brown eye color.


Input: Thus, this study demonstrates how to increase ancestry signals in a relatively homogeneous population and how those signals can reveal evolutionary history. European Journal of Human Genetics advance online publication, 27 March 2013; doi: 10. 1038/ejhg. 2013. 48.


Input: Analysis of visible-light-active Sn (ii)-TiO2 photocatalysts.

Sn (ii)


Input: The influence of Sn (ii) species on TiO2 is investigated.

Sn (ii)


Input: The absorption spectra of these materials are red-shifted by 115 nm to the visible region of the solar spectrum compared with P25 TiO2.

P25 TiO2


Input: This prominent red-shift is attributed to the interaction of Sn (ii) 5s orbitals with the TiO2 decreasing the band gap of TiO2 by raising its valence band.

Sn (ii)


Input: The tin oxidation state and the materials electronic structure are evaluated using M o ssbauer spectroscopy and valence band X-ray photoelectron spectroscopy respectively.

tin


Input: These materials are active for sacrificial photo-generation of hydrogen in visible light.

hydrogen


Input: A pyrrolidinium nitrate protic ionic liquid-based electrolyte for very low-temperature electrical double-layer capacitors.

pyrrolidinium nitrate


Input: This study describes the use of the pyrrolidinium nitrate ([Pyrr] [NO3]) protic ionic liquid (PIL) in a mixture with gamma butyrolactone (gamma-BL) as an electrolyte for carbon-based supercapacitors with an operating voltage of 2. 0 V and at very low temperature.

pyrrolidinium nitrate

[Pyrr] [NO3]

gamma butyrolactone

gamma-BL

carbon


Input: Thermal and transport properties of this electrolyte were firstly evaluated from-40 degrees C to 80 degrees C.


Input: The evolution of conductivity with the addition of gamma-BL rendered it possible to determine the optimal composition for electrochemical application, with a molar fraction of gamma-BL of 0. 6.

gamma-BL

gamma-BL


Input: This mixture shows a Newtonian behavior with a low viscosity value of 5 mPa s at 25 degrees C, and exhibits high conductivity values of up to 65 mS cm (-1) at 80 degrees C.


Input: At the same time, exceptional residual conductivity was measured for this composition at-40 degrees C (9 mS cm (-1)), thanks to the superionic character of pyrrolidinium nitrate PIL.

pyrrolidinium nitrate


Input: Electrochemical characterization of this electrolyte demonstrated, at first, a passivation on the aluminum collector, secondly good cycling performances with an activated carbon electrode from 50 degrees C to-40 degrees C with capacitance up to 132 F g (-1) at room temperature and a wide voltage window (2. 0 V).

aluminum

carbon


Input: Finally at very low temperature (-40 degrees C), this system demonstrates an unprecedented combination of high specific capacitance (up to 117 F g (-1)), and rapid charging-discharging even at high current density, which is very promising for the progress of energy storage systems with environmentally friendly electrolytes at such very low temperatures.


Input: Effects of immunosuppression on alpha and beta cell renewal in transplanted mouse islets.


Input: AIMS/HYPOTHESIS: Immunosuppressive drugs used in human islet transplantation interfere with the balance between beta cell renewal and death, and thus may contribute to progressive graft dysfunction.


Input: We analysed the influence of immunosuppressants on the proliferation of transplanted alpha and beta cells after syngeneic islet transplantation in streptozotocin-induced diabetic mice.

streptozotocin


Input: METHODS: C57BL/6 diabetic mice were transplanted with syngeneic islets in the liver and simultaneously abdominally implanted with a mini-osmotic pump delivering BrdU alone or together with an immunosuppressant (tacrolimus, sirolimus, everolimus or mycophenolate mofetil [MMF]).

tacrolimus

sirolimus

everolimus

mycophenolate mofetil

MMF


Input: Glycaemic control was assessed for 4 weeks.


Input: The area and proliferation of transplanted alpha and beta cells were subsequently quantified.


Input: RESULTS: After 4 weeks, glycaemia was significantly higher in treated mice than in controls.


Input: Insulinaemia was significantly lower in mice treated with everolimus, tacrolimus and sirolimus.

everolimus

tacrolimus

sirolimus


Input: MMF was the only immunosuppressant that did not significantly reduce beta cell area or proliferation, albeit its levels were in a lower range than those used in clinical settings.

MMF


Input: CONCLUSIONS/INTERPRETATION: After transplantation in diabetic mice, syngeneic beta cells have a strong capacity for self-renewal.


Input: In contrast to other immunosuppressants, MMF neither impaired beta cell proliferation nor adversely affected the fractional beta cell area.

MMF


Input: Although human beta cells are less prone to proliferate compared with rodent beta cells, the use of MMF may improve the long-term outcome of islet transplantation.

MMF


Input: Adrenocortical reserves in hyperthyroidism.


Input: Explicit data regarding the changes in adrenocortical reserves during hyperthyroidism do not exist.


Input: We aimed to document the capability (response) of adrenal gland to secrete cortisol and DHEA-S during hyperthyroidism compared to euthyroidism, and to describe factors associated with these responses.

cortisol

DHEA


Input: A standard-dose (0. 25 mg/i. v.) ACTH stimulation test was performed to the same patients before hyperthyroidism treatment, and after attainment of euthyroidism.


Input: Baseline cortisol (Cor0), DHEA-S (DHEA-S0), cortisol binding globulin (CBG), ACTH, calculated free cortisol (by Coolen' s equation = CFC), free cortisol index (FCI), 60-min cortisol (Cor60), and DHEA-S (DHEA-S60), delta cortisol (Delta Cor), delta DHEA-S (Delta DHEA-S) responses were evaluated.

cortisol

DHEA

DHEA

cortisol

cortisol

cortisol

cortisol

DHEA

DHEA

delta cortisol

Delta Cor

delta DHEA

Delta DHEA


Input: Forty-one patients [22 females, 49. 5 +/- 15. 2 years old, 32 Graves disease, nine toxic nodular goiter] had similar Cor0, DHEA-S0, CFC, FCI, and DHEA-S60 in hyperthyroid and euthyroid states.

DHEA

DHEA


Input: Cor60, Delta Cor, and Delta DHEA-S were lower in hyperthyroidism.

Delta Cor

Delta DHEA


Input: In four (10%) patients the peak ACTH-stimulated cortisol values were lower than 18 mu g/dL.

cortisol


Input: When the test repeated after attainment of euthyroidism, all of the patients had normal cortisol response.

cortisol


Input: Regression analysis demonstrated an independent association of Cor60 with free T3 in hyperthyroidism.


Input: However, the predictors of CFC, FCI, and DHEA-S levels were serum creatinine levels in hyperthyroidism, and both creatinine and transaminase levels in euthyroidism.

DHEA

creatinine

creatinine


Input: ACTH-stimulated peak cortisol, delta cortisol, and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover.

cortisol

delta cortisol

delta DHEA


Input: Since about 10% of the subjects with hyperthyroidism are at risk for adrenal insufficiency, clinicians dealing with Graves' disease should be alert to the possibility of adrenal insufficiency during hyperthyroid stage.


Input: Tryptophan residue at active-site tunnel entrance of Trichoderma reesei cellobiohydrolase Cel7A is important to initiate degradation of crystalline cellulose.

Tryptophan


Input: Glycoside hydrolase family-7 cellobiohydrolase from Trichoderma reesei (TrCel7A) is one of the best-studied cellulases with the ability to degrade highly crystalline cellulose (HCC).


Input: The catalytic domain (cat) and cellulose-binding domain (CBD) are both necessary for full activity on crystalline substrates.


Input: Our previous high-speed AFM studies showed that mutation of tryptophan residue (Trp40; W40) at the entrance of the catalytic tunnel drastically decreases the ability to degrade crystalline cellulose.

tryptophan


Input: Here, we examined the activities of the wild-type (WT) enzyme and tryptophan to alanine mutant (W40A) enzyme, with and without the CBD, towards various substrates.

tryptophan

alanine


Input: Evaluation and comparison of the specific activities of the enzymes (WT, WTcat, W40A, and W40Acat) adsorbed on crystalline cellulose indicated that Trp40 is involved in recruiting individual substrate chains into the active site tunnel to initiate processive hydrolysis.


Input: This idea was supported by molecular dynamics simulation study, i. e., the reducing-end glucose unit was effectively loaded into the active site of WTcat, but not into that of W40Acat. when the simulation was started from subsite-7.

glucose


Input: However, when the similar simulations were carried out starting from subsite-5, both enzymes hold the substrate in 50 ns, indicating that the major difference between WTcat and W40Acat is the length of free chain-end of the substrate required to allow initiation of processive movements; this also reflects the difference between crystalline and amorphous celluloses.


Input: The CBD is important for enhancing the enzyme population on crystalline substrate, but it also decreases the specific activity of the adsorbed enzyme, possibly by attaching the enzyme to non-optimal places on cellulose surface and/or hindering processive hydrolysis.


Input: A Novel Automethylation Reaction in the Aspergillus nidulans LaeA Protein Generates S-Methylmethionine.

S-Methylmethionine


Input: The filamentous fungi in the genus Aspergillus are opportunistic plant and animal pathogens that can adapt to their environment by producing various secondary metabolites including lovastatin, penicillin, and aflatoxin.

lovastatin

penicillin

aflatoxin


Input: The synthesis of these small molecules is dependent on gene clusters that are globally regulated by the LaeA protein.


Input: Null mutants of LaeA in all pathogenic fungi examined to date show decreased virulence coupled with reduced secondary metabolism.


Input: Although the amino acid sequence of LaeA contains the motifs characteristic of seven-beta-strand methyltransferases, a methyl-accepting substrate of LaeA has not been identified.

amino acid

methyltransferases


Input: In this work, we did not find a methyl-accepting substrate in A. nidulans with various assays including in vivo S-adenosyl-[methyl-(3) H] methionine labeling, targeted in vitro methylation experiments using putative protein substrates, or in vitro methylation assays using whole cell extracts grown under different conditions.

methyl

S-adenosyl-[methyl-(3) H] methionine


Input: However, in each experiment LaeA was shown to self-methylate.


Input: Amino acid hydrolysis of radioactively-labeled LaeA followed by cation exchange and reverse phase chromatography identified methionine as the modified residue.

Amino acid

methionine


Input: Point mutations show that the major site of modification of LaeA is on methionine-207.

methionine


Input: However, in vivo complementation showed that methionine-207 is not required for the biological function of LaeA.

methionine


Input: LaeA is the first protein to exhibit automethylation at a methionine residue.

methionine


Input: These findings not only indicate LaeA may perform novel chemistry with S-adenosylmethionine, but also provide new insights into the physiological function of LaeA.

S-adenosylmethionine


Input: Synthesis and in Vitro Characterisation of Ifenprodil-Based Fluorescein Conjugates as GluN1/GluN2B N-Methyl-D-aspartate Receptor Antagonists.

Ifenprodil

Fluorescein

N-Methyl-D-aspartate


Input: GluN2B-containing NMDA receptors are involved in many important physiological functions and play a pivotal role in mediating pain as well as in several neurodegenerative disorders.

NMDA


Input: We aimed to develop fluorescent probes to target the GluN2B subunit selectively in order to allow better understanding of the relationships between receptor localisation and physiological importance.


Input: Ifenprodil, known as the GluNR2B antagonist of reference, was chosen as the template for the elaboration of probes.

Ifenprodil


Input: We had previously reported a fluorescein conjugate that was shown (by confocal microscopy imaging of DS-red-labelled cortical neurons) to bind specifically to GluN2B.

fluorescein


Input: To elaborate this probe, we explored the influence of both the nature and the attachment point of the spacer between the fluorophore and the parent compound, ifenprodil.

ifenprodil


Input: We performed chemical modifications of ifenprodil at the benzylic position and on the phenol ring by introducing secondary amine or amide functions and evaluated alkyl chains from two to 20 bonds either including or not including secondary amide functions as spacers.

ifenprodil

benzylic

phenol

secondary amine or amide

secondary amide


Input: The previously developed probe was found to display the greatest activity in the inhibition of NMDA-induced Ca (2 +) influx by calcium imaging experiments on HEK293 cells transfected with the cDNA encoding for GluN1-1A and GluN2B.

NMDA

Ca (2 +)

calcium


Input: Further investigations revealed that this probe had a neuroprotective effect equivalent to that of ifenprodil in a standard test for neurotoxicity.

ifenprodil


Input: Despite effects of lesser amplitude with these probes relative to ifenprodil, we demonstrated that they displaced [(3) H] ifenprodil in mouse brain slices in a similar manner.

ifenprodil

[(3) H] ifenprodil


Input: Highly efficient f o rster resonance energy transfer in a fast, serum-compatible immunoassay.


Input: Highly efficient FRET leads to important enhancements for homogeneous immunoassays.


Input: By using the novel phosphorescent dye EuLH and BHQ-10 as a donor-acceptor pair, the FRET efficiency increases to > 99. 5%, leading to significantly improved signal-to-background ratio, precision and linear range.


Input: The phosphorescence detection enabled full compatibility to serum samples for this fast-responding immunoassay.


Input: Extended h u ckel theory for carbon nanotubes: band structure and transport properties.

carbon


Input: Extended H u ckel theory (EHT) is a well established method for the description of the electronic structure of molecules and solids.


Input: In this article, we present a set of extended H u ckel parameters for carbon nanotubes (CNTs), obtained by fitting the ab initio band structure of the (6, 0) CNT.

carbon


Input: The new parameters are highly transferable to different types of CNTs.


Input: To demonstrate the versatility of the approach, we perform self-consistent EHT-based electron transport calculations for finite length CNTs with metal electrodes.


Input: Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal, and anti-HIV activities.

tricyclic guanidine

batzelladine K


Input: Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities.

batzelladine K


Input: Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC (50) 1. 25 and 0. 88 mu M and chloroquine-resistant W2 strain with IC (50) 1. 64 and 1. 07 mu M, respectively.

chloroquine

chloroquine


Input: Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC (50) 2. 39 and 2. 78 mu M and IC (90) 11. 27 and 12. 76 mu M, respectively.

nonyl


Input: Three analogues 12c, 14c, and 14i were the most active against various pathogenic bacteria and fungi with IC (50) < 3. 02 mu M and MIC/MBC/MFC < 6 mu M.


Input: Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens.

pentyl

methyl


Input: However, none was found active against HIV-1.


Input: Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity.

tricyclic guanidine


Input: Pickering-Emulsion-Polymerized Polystyrene/Fe2O3 Composite Particles and Their Magnetoresponsive Characteristics.

Polystyrene


Input: Core-shell-structured magnetic polystyrene (PS)/inorganic particles were fabricated by Pickering emulsion polymerization using nanosized Fe2O3 particles as a solid stabilizer.

polystyrene


Input: Scanning electron microscopy and transmission electron microscopy confirmed the synthesized PS/Fe2O3 particles to be comprised of a PS surface coated with Fe2O3 nanoparticles.


Input: The chemical structure of the composite nanospheres was characterized by Fourier transform infrared spectroscopy and X-ray diffraction.


Input: The thermal properties of composite nanospheres and corresponding pure polymer were examined by thermogravimetric analysis.


Input: The rheological properties of the core-shell-structured magnetic PS/inorganic particles dispersed in silicone oil were investigated under an external magnetic field strength using a rotational rheometer.


Input: The particles with extremely lower density than common magnetic particles exhibited solid-like magnetorheological phase characteristics, and the flow curves were fitted to the Cho-Choi-Jhon model of the rheological equation of state.


Input: Engineering the Microstructure of Electrospun Fibrous Scaffolds by Microtopography.


Input: Controlling the structure and organization of electrospun fibers is desirable for fabricating scaffolds and materials with defined microstructures.


Input: However, the effects of microtopography on the deposition and, in turn, the organization of the electrospun fibers are not well understood.


Input: In this study, conductive polydimethylsiloxane (PDMS) templates with different micropatterns were fabricated by combining photolithography, silicon wet etching, and PDMS molding techniques.

polydimethylsiloxane

PDMS

silicon

PDMS


Input: The fiber organization was varied by fine-tuning the microtopography of the electrospinning collector.


Input: Fiber conformity and alignment were influenced by the depth and the slope of microtopography features, resulting in scaffolds comprising either an array of microdomains with different porosity and fiber alignment or an array of microwells.


Input: Microtopography affected the fiber organization for hundreds of micrometers below the scaffold surface, resulting in scaffolds with distinct surface properties on each side.


Input: In addition, the fiber diameter was also affected by the fiber conformity.


Input: The effects of the fiber arrangement in the scaffolds on the morphology, migration, and infiltration of cells were examined by in vitro and in vivo experiments.


Input: Cell morphology and organization were guided by the fibers in the microdomains, and cell migration was enhanced by the aligned fibers and the three-dimensional scaffold structure.


Input: Cell infiltration was correlated with the microdomain porosity.


Input: Microscale control of the fiber organization and the porosity at the surface and through the thickness of the fibrous scaffolds, as demonstrated by the results of this study, provides a powerful means of engineering the three-dimensional structure of electrospun fibrous scaffolds for cell and tissue engineering.


Input: Directing Chondrogenesis of Stem Cells with Specific Blends of Cellulose and Silk.


Input: Biomaterials that can stimulate stem cell differentiation without growth factor supplementation provide potent and cost-effective scaffolds for regenerative medicine.


Input: We hypothesize that a scaffold prepared from cellulose and silk blends can direct stem cell chondrogenic fate.


Input: We systematically prepared cellulose blends with silk at different compositions using an environmentally benign processing method based on ionic liquids as a common solvent.


Input: We tested the effect of blend compositions on the physical properties of the materials as well as on their ability to support mesenchymal stem cell (MSC) growth and chondrogenic differentiation.


Input: The stiffness and tensile strength of cellulose was significantly reduced by blending with silk.


Input: The characterized materials were tested using MSCs derived from four different patients.


Input: Growing MSCs on a specific blend combination of cellulose and silk in a 75: 25 ratio significantly upregulated the chondrogenic marker genes SOX9, aggrecan, and type II collagen in the absence of specific growth factors.


Input: This chondrogenic effect was neither found with neat cellulose nor the cellulose/silk 50: 50 blend composition.


Input: No adipogenic or osteogenic differentiation was detected on the blends, suggesting that the cellulose/silk 75: 25 blend induced specific stem cell differentiation into the chondrogenic lineage without addition of the soluble growth factor TGF-beta.


Input: The cellulose/silk blend we identified can be used both for in vitro tissue engineering and as an implantable device for stimulating endogenous stem cells to initiate cartilage repair.


Input: Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA: cholesterol acyltransferase 2 (ACAT2) inhibitors: Part 2.

pyripyropene A

acyl-CoA

cholesterol


Input: Synthesis and structure-activity relationships of 7-O-p-cyanobenzoyl pyripyropene A derivatives with modification at C1 and 11 are described.

7-O-p-cyanobenzoyl pyripyropene A


Input: Regioselective mono-deprotection of di-tert-butylsilylene acetal was critical in their synthesis.

di-tert-butylsilylene acetal


Input: Disruption of AtWNK8 Enhances Tolerance of Arabidopsis to Salt and Osmotic Stresses via Modulating Proline Content and Activities of Catalase and Peroxidase.

Proline


Input: With no lysine kinases (WNKs) play important roles in plant growth and development.

lysine


Input: However, its role in salt and osmotic stress tolerance is unclear.


Input: Here, we report that AtWNK8 is mainly expressed in primary root, hypocotyl, stamen and pistil and is induced by NaCl and sorbitol treatment.

NaCl

sorbitol


Input: Compared to the wild-type, the T-DNA knock-out wnk8 mutant was more tolerant to severe salinity and osmotic stresses, as indicated by 27% and 198% more fresh weight in the NaCl and sorbitol treatment, respectively.

NaCl

sorbitol


Input: The wnk8 mutant also accumulated 1. 43-fold more proline than the wild-type in the sorbitol treatment.

proline

sorbitol


Input: Under NaCl and sorbitol stresses, catalase (CAT) activity in wnk8 mutant was 1. 92-and 3. 7-times of that in Col-0, respectively.

NaCl

sorbitol


Input: Similarly, under salt and osmotic stress conditions, peroxidase (POD) activities in wnk8 mutant were 1. 81-and 1. 58-times of that in Col-0, respectively.


Input: Taken together, we revealed that maintaining higher CAT and POD activities might be one of the reasons that the disruption of AtWNK8 enhances the tolerance to salt stress, and accumulating more proline and higher activities of CAT and POD might result in the higher tolerance of WNK8 to osmotic stress.

proline


Input: Lipid Status of the Two High Latitude Fish Species, Leptoclinus maculatus and Lumpenus fabricii.


Input: A comparative study of the lipid status (i. e., the total lipid and phospholipid concentrations and the percentage of fatty acids of the total lipids) of adult specimens of daubed shanny (Leptoclinus maculatus) from Svalbard waters (Isfjord) and slender eel blenny (Lumpenus fabricii) from the White Sea (Onega Bay and Tersky shore) was performed to study the metabolism and functions of lipids of these fishes in ontogeny and under various ecological conditions.

fatty acids


Input: Slender eel blenny from both areas of the White Sea were distinguished by a high level of sphingomyelin compared with the daubed shanny from Svalbard, and the amount of total phospholipids was higher in slender eel blenny from Onega Bay than in slender eel blenny from the Tersky shore.

sphingomyelin


Input: The extent of saturation and the signature of polyenic fatty acids varied according to the specific species of the Stichaeidae family under study.

polyenic fatty acids


Input: These results demonstrate the differences in the trophoecological and hydrobiological conditions of habitations of these species and highlighted the importance of considering certain trends in the lipid profiles of these fishes as specific features of the organization of the ecological and biochemical mechanisms of adaptation.


Input: Further evidence for involvement of the dorsal hippocampus serotonergic and gamma-aminobutyric acid (GABA) ergic pathways in the expression of contextual fear conditioning in rats.

gamma-aminobutyric acid

GABA


Input: Intra-dorsal hippocampus (DH) injections of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a serotonin-1A (5-hydroxytryptamine (5-HT)-1A) receptor agonist, were previously shown to inhibit the expression of contextual fear when administered six hours after conditioning.

8-hydroxy-2-(di-n-propylamino) tetralin

serotonin


Input: However, further understanding of the consolidation and expression of aversive memories requires investigations of these and other mechanisms at distinct time points and the regions of the brain to which they are transferred.


Input: Thus, the purpose of the present study was to investigate the role of DH serotonergic and gamma-aminobutyric acid (GABA) ergic mechanisms in the expression of contextual fear 24 h after conditioning, reflected by fear-potentiated startle (FPS) and freezing behavior.

gamma-aminobutyric acid

GABA


Input: The recruitment of the amygdala and medial prefrontal cortex (mPFC) in these processes was also evaluated by measuring Fos protein immunoreactivity.


Input: Although intra-DH injections of 8-OH-DPAT did not produce behavioral changes, muscimol reduced both FPS and the freezing response.


Input: Fos protein immunoreactivity revealed that contextual fear promoted wide activation of the mPFC, which was significantly reduced after intra-DH infusions of muscimol.

muscimol


Input: The present findings, together with previous data, indicate that in contrast to 5-HT, which appears to play a role during the early phases of contextual aversive memory consolidation, longer-lasting GABA-mediated mechanisms are recruited during the expression of contextual fear memories.

GABA


Input: Risk of ischemic stroke with the use of risperidone, quetiapine and olanzapine in elderly patients: a population-based, case-crossover study.

risperidone

quetiapine

olanzapine


Input: We conducted a case-crossover study to evaluate the comparative risk of ischemic stroke associated with the use of risperidone, quetiapine and olanzapine in geriatric patients using the Korean Health Insurance Review and Assessment Service database.

risperidone

quetiapine

olanzapine


Input: Cases included elderly patients > 64 years old who had experienced their first ischemic stroke (International Classification of Disease, Tenth Revision (ICD-10), I63) hospitalization from July 2005 to June 2006 and who had been without prior cerebrovascular diseases (ICD-10, I60-I69), or transient ischemic attack (ICD-10, G45).


Input: Exposures to risperidone, quetiapine and olanzapine were assessed during the 30 days prior to the stroke episode.

risperidone

quetiapine

olanzapine


Input: We set two control periods with lengths which were the same as the hazard periods.


Input: Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated by conditional logistic regression.


Input: A total of 1601 cases of ischemic stroke with a mean age of 75. 6 (+/- 6. 7) years were identified, among which 933 (58. 3%) were female.


Input: An increased risk of ischemic stroke was associated with the use of risperidone (aOR = 3. 5, 95% CI 3. 3-4. 6) and quetiapine (aOR = 2. 7, 95% CI 2. 0-3. 6) during the 30 days prior to stroke: however, no significant risk was observed with olanzapine (aOR = 1. 2, 95% CI 0. 7-2. 0).

risperidone

quetiapine

olanzapine


Input: The increased stroke risk in demented patients, assessed within 30 days after exposure, was also observed with olanzapine.

olanzapine


Input: However, the sample of olanzapine users was small and underpowered.

olanzapine


Input: Evaluation of Perturbations in Serum Thyroid Hormones During Human Pregnancy Due to Dietary Iodide and Perchlorate Exposure Using a Biologically Based Dose-Response Model.

Iodide

Perchlorate


Input: A biologically based dose-response model (BBDR) for the hypothalamic pituitary thyroid (HPT) axis was developed in the near-term pregnant mother and fetus.


Input: This model was calibrated to predict serum levels of iodide, total thyroxine (T4), free thyroxine (fT4), and total triiodothyronine (T3) in the mother and fetus for a range of dietary iodide intake.

iodide

thyroxine

thyroxine

triiodothyronine

iodide


Input: The model was extended to describe perchlorate, an environmental and food contaminant, that competes with the sodium iodide symporter protein for thyroidal uptake of iodide.

perchlorate

sodium iodide

iodide


Input: Using this mode-of-action framework, simulations were performed to determine the daily ingestion rates of perchlorate that would be associated with hypothyroxinemia or onset of hypothyroidism for varying iodide intake.

perchlorate

iodide


Input: Model simulations suggested that a maternal iodide intake of 75 to 250 micro g/day and an environmentally relevant exposure of perchlorate (~ 0. 1 micro g/kg/day) did not result in hypothyroxinemia or hypothyroidism.

iodide

perchlorate


Input: For a daily iodide-sufficient intake of 200 micro g/day, the dose of perchlorate required to reduce maternal fT4 levels to a hypothyroxinemic state was estimated at 32. 2 micro g/kg/day.

iodide

perchlorate


Input: As iodide intake was lowered to 75 micro g/day, the model simulated daily perchlorate dose required to cause hypothyroxinemia was reduced by eightfold.

iodide

perchlorate


Input: Similarly, the perchlorate intake rates associated with the onset of subclinical hypothyroidism ranged from 54. 8 to 21. 5 micro g/kg/day for daily iodide intake of 250-75 micro g/day.

perchlorate

iodide


Input: This BBDR-HPT axis model for pregnancy provides an example of a novel public health assessment tool that may be expanded to address other endocrine-active chemicals found in food and the environment.


Input: Interferon-gamma Promoter Is Hypermethylated in Blood DNA from Workers with Confirmed Diisocyanate Asthma.

Diisocyanate


Input: Risk factors have not been identified that determine susceptibility for development of diisocyanate-induced occupational asthma (DA).

diisocyanate


Input: We hypothesized that diisocyanate (DI) exposure could modify gene promoter regions regulating transcription of cytokine mediators and thereby influence expression of DA.

diisocyanate


Input: A cross-sectional study was designed to investigate the promoter methylation status of candidate genes in DI-exposed workers.


Input: Subjects consisted of 131 workers in three groups: 40 cases with DA confirmed by a positive specific inhalation challenge (SIC) (DA +), 41 exposed workers with lower respiratory symptoms and negative SIC (DA-), and 50 asymptomatic exposed workers (AWs).


Input: We studied four candidate genes (GSTM1, DUSP22, IFN-gamma, and IL-4) for which altered promoter methylation has been previously investigated for relationships with a variety of other environmental exposures.


Input: Methylation status was determined using methylation-specific quantitative PCR performed on genomic DNA extracted from whole blood.


Input: Results showed that relative methylation of IFN-gamma promoter was significantly increased in DA + in comparison with both comparator groups (DA-and AW), and it exhibited good sensitivity (77. 5%) and specificity (80%) for identifying DA workers in a multivariate predictive model after adjusting for type of DI exposure, smoking status, methacholine PC20, and gender.

methacholine


Input: IL-4 promoter was slightly less methylated only in DA + compared with AW among nonsmoking workers.


Input: Both GSTM1 and DUSP22 promoter methylations were found not associated with DA.


Input: Our finding suggests that exposure to occupational chemicals could play a heretofore undefined mechanistic role via epigenetic modification of specific genes in the promoter region.


Input: DNA Adduct Formation of 2-Amino-9H-pyrido [2, 3-b] indole and 2-Amino-3, 4-dimethylimidazo [4, 5-f] quinoline in Mouse Liver and Extrahepatic Tissues During a Subchronic Feeding Study.

2-Amino-9H-pyrido [2, 3-b] indole

2-Amino-3, 4-dimethylimidazo [4, 5-f] quinoline


Input: Tobacco smoking is a risk factor for cancers of the liver and gastrointestinal (GI) tract, but the causal agents responsible for these cancers are uncertain.


Input: 2-Amino-9H-pyrido [2, 3-b] indole (A alpha C) is an abundant heterocyclic aromatic amine present in tobacco smoke.

2-Amino-9H-pyrido [2, 3-b] indole

heterocyclic aromatic amine


Input: A alpha C is a liver carcinogen and both a transgene mutagen and inducer of aberrant crypt foci in the colon of mice.


Input: We hypothesize that A alpha C may contribute to DNA damage and tumorigenesis in these organs of smokers.


Input: The potential of A alpha C to induce DNA adduct formation in liver, organs of the GI tract, lung, and urinary bladder, which are target organs of cancer in smokers, was examined using the C57BL/6 mouse as an animal model.


Input: A alpha C (400 or 800 ppm) and 2-amino-3, 4-dimethylimidazo [4, 5-f] quinoline (MeIQ) (300 ppm), a liver and colon carcinogen in C57BL/6 mice, were given in the diet for up to 12 weeks.

2-amino-3, 4-dimethylimidazo [4, 5-f] quinoline

MeIQ


Input: Liquid chromatography/mass spectrometry was employed to measure DNA adducts.


Input: The major DNA adducts of both carcinogens were identified as deoxyguanosine-C8 adducts.

deoxyguanosine


Input: The levels of formation of A alpha C-and MeIQ-DNA adducts were similar in liver and extrahepatic tissues when adjusted for dose.

MeIQ


Input: The highest levels of adducts occurred in liver, followed by urinary bladder, and then in cecum and colon; lower DNA adduct levels were formed in the lung and pancreas following 12 weeks of feeding.


Input: The high levels of A alpha C adduct formed in liver, GI tract, and bladder of C57BL/6 mice reinforce the notion that A alpha C may contribute to DNA damage and cancer of these organs in smokers.


Input: Evidence of Anti-Proliferative Activities in Blue Mussel (Mytilus edulis) By-Products.


Input: Shellfish waste components contain significant levels of high quality protein and are therefore a potential source for biofunctional high-value peptides.


Input: The feasibility of applying a pilot scale enzymatic hydrolysis process to whole Mytilus edulis and, by fractionation, recover hydrolysates presenting a biological activity of interest, was evaluated.


Input: Fractions were tested on four immortalized cancerous cell lines: A549, BT549, HCT15 and PC3.


Input: The 50 kDa fraction, enriched in peptides, presented anti-proliferative activity with all cell lines and results suggest a bioactive molecule synergy within the fraction.


Input: At a protein concentration of 44 micro g/mL, the 50 kDa fraction induced a mortality of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines.


Input: At the low protein concentration of only 11 micro g/mL the 50 kDa fraction still entails a cell mortality of 76% for A549 and 87% for PC3 cell lines.


Input: The 50 kDa fraction contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis and the lowest levels detected of taurine and methionine and highest levels of threonine, proline and glycine amino acids.

taurine

methionine

threonine

proline

glycine amino acids


Input: The enzymatic hydrolysis process suggests that Mytilus edulis by-products should be viewed as high-valued products with strong potential as anti-proliferative agent and promising active ingredients in functional foods.


Input: Recent developments in design and synthesis of bicyclic azasugars, carbasugars and related molecules as glycosidase inhibitors.

bicyclic azasugars

carbasugars


Input: The importance of glycosidase inhibitors and especially the bicyclic molecules has led to design and assessment of many analogs of naturally occurring molecules.


Input: This review focuses on the synthesis and enzyme inhibitions of a few selected (synthetic or non-naturally occurring) molecules that have been reported in the last decade, which allow one to draw some connection between varying the structural features and their effect on glycosidase inhibitions.


Input: It is expected that further improvements based on these features could lead to improved inhibitors.


Input: Biomarkers of Lead Exposure Among a Population Under Environmental Stress.


Input: This study aimed to evaluate the relationship between blood lead and serum creatinine and blood lead and serum urea nitrogen levels as biomarkers of lead exposure from subjects living in a historic polymetallic mining area in China.

creatinine

urea nitrogen


Input: Elevated levels were found for blood lead, serum creatinine, and serum urea nitrogen in the mining area with mean values at 245. 65 mu g/l, 74. 16 mu mol/l, and 12. 79 mmol/l, which were significantly higher than those in the control area, respectively.

creatinine

urea nitrogen


Input: Moreover, the coefficients between paired results for blood lead and serum creatinine and blood lead and serum urea nitrogen were positively statistically significant (serum creatinine vs. blood lead, r = 0. 35, p < 0. 05; serum urea nitrogen vs. blood lead, r = 0. 48, p < 0. 05).

creatinine

urea nitrogen

creatinine

urea nitrogen


Input: With respect to the effects of sex and age on the blood lead, serum creatinine, and serum urea nitrogen levels, data analysis revealed there was a tendency for higher blood lead, serum creatinine, and serum urea nitrogen levels in females than in males, and the levels of blood lead, serum creatinine, and serum urea nitrogen increased among older residents.

creatinine

urea nitrogen

creatinine

urea nitrogen

creatinine

urea nitrogen


Input: We conclude that females and the older population in the mining area are more susceptible to lead exposure.


Input: Blood lead, serum creatinine, and serum urea nitrogen can be useful biomarkers of lead exposure among populations under environmental stress.

creatinine

urea nitrogen


Input: Neuroprotective Effects of Cilostazol on Retinal Ganglion Cell damage in Diabetic Rats.

Cilostazol


Input: Neurodegeneration is an important component of diabetic retinopathy with increasing evidence that retinal ganglion cell (RGC) death occurs early in diabetes.


Input: We investigated the effects of cilostazol, which has been widely used to manage diabetic complications, on retinal ganglion cell death in diabetic retina.

cilostazol


Input: Four-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats as matched nondiabetic controls were treated with daily oral cilostazol at 30mg/kg or 0. 9% saline solution.

cilostazol


Input: In OLETF rats at the age of 40 weeks, glial fibrillary acidic protein (GFAP) immunofluorescence staining was upregulated in vertical sections and showed a more ramified pattern in whole-mount retinas compared with that in LETO rats.


Input: Vascular endothelial growth factor (VEGF) expression was limited to the ganglion cell layer in LETO rats, but extended into the outer plexiform layer in OLETF rats.


Input: Immunofluorescence staining and western blotting demonstrated that cilostazol treatment reduced GFAP and VEGF expression in the retinas of OLETF rats.

cilostazol


Input: Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNLEL) staining revealed an increase in the RGC layer in OLETF compared with LETO rats (P < 0. 05), and cilostazol treatment reduced the number of TUNEL-positive cells in OLETF rats (P < 0. 05).

dUTP

cilostazol


Input: Relieving retinal ischemia by systemic cilostazol treatment had a noticeable protective effect on RGCs in diabetic rats.

cilostazol


Input: Cilostazol treatment may be useful for the management of diabetic retinal vascular dysfunction and neuronal degeneration.

Cilostazol


Input: Chrysin Ameliorates Chemically Induced Colitis in the Mouse Through Modulation of a PXR/NF-kappa B Signaling Pathway.

Chrysin


Input: Targeted activation of pregnane X receptor (PXR) in recent years has become a therapeutic strategy for inflammatory bowel disease (IBD).


Input: Chrysin is a naturally occurring flavonoid with anti-inflammation activity.

Chrysin

flavonoid


Input: The current study investigated the role of chrysin as a putative mouse PXR agonist in preventing experimental colitis.

chrysin


Input: Pre-administration of chrysin ameliorated inflammatory symptoms in mouse models of colitis (DSS-and TNBS-induced) and resulted in down-regulation of NF-kappa B target genes (iNOS, ICAM-1, MCP-1, Cox2, TNF-alpha and IL-6) in the colon mucosa.

chrysin


Input: Chrysin inhibited the phosphorylation/degradation of I kappa B alpha, which correlated with the decline in the activity of myeloperoxidase (MPO) and the levels of TNF-alpha and IL-6 in the colon.

Chrysin


Input: Consistent with the in vivo results, chrysin blocked LPS-stimulated nuclear translocation of NF-kappa B p65 in mouse macrophage RAW264. 7.

chrysin


Input: Furthermore, chrysin dose-dependently activated human/mouse PXR in reporter gene assays and up-regulated xenobiotic detoxification genes in the colon mucosa, but not in the liver.

chrysin


Input: Silencing of PXR by RNAi demonstrated necessity of PXR in mediating chrysin' s ability to induce xenobiotic detoxification genes and NF-kappa B inactivation.

chrysin


Input: The repression of NF-kappa B transcription activity by chrysin was confirmed by in vitro PXR transduction.

chrysin


Input: These findings suggest the effect of chrysin in preventing chemically induced colitis is mediated in large part by a PXR/NF-kappa B pathway.

chrysin


Input: The data also suggest that chrysin or chrysin-like flavonoids could be further developed as intestine-specific PXR activators.

chrysin

chrysin

flavonoids


Input: The protective effects of taurine on experimental acute pancreatitis in a rat model.

taurine


Input: The aim of this study was to investigate the protective effects of taurine (Tau) on experimental acute pancreatitis (AP) in a rat model by measuring cytokines and oxidant stress markers. Forty rats were randomly divided into four groups: sham, AP, Tau and AP + Tau.

taurine

Tau

Tau


Input: AP was induced with sodium taurocholate.

sodium taurocholate


Input: No treatment was given to the AP.


Input: All rats were killed 5 days later.


Input: Pancreatic tissues of rats and blood samples were obtained. Tau treatment significantly decreased serum amylase activity (p < 0. 001), total injury score (p < 0. 001), malondialdehyde levels (p < 0. 001) and myeloperoxidase (MPO) activity (p < 0. 001).

Tau

malondialdehyde


Input: There was no significant difference between the Tau and AP + Tau groups in serum and pancreatic tumor necrosis factor-alpha, interleukin (IL)-1 beta and IL-6 levels (p = 1. 000).

Tau

Tau


Input: Histopathologic scores in the AP + Tau and Tau groups were significantly lower compared with the AP group (both p < 0. 001). These results showed that Tau reduces lipid peroxidation, amylase and MPO activities and the concentrations of proinflammatory cytokines secondary to AP and also increases superoxide dismutase and glutathione peroxidase activities in rats with sodium taurocholate-induced AP.

Tau

Tau

Tau

superoxide

glutathione

sodium taurocholate


Input: It also has a marked ameliorative effect at histopathologic lesions.


Input: With these effects, Tau protects the cells from oxidative damage, reduces inflammation and promotes regression of pancreatic damage.


Input: Influence of oily vehicles on fetal testis and lipid profile of rats exposed to di-butyl phthalate.

di-butyl phthalate


Input: It has been hypothesized that oils containing high levels of omega-3 polyunsaturated fatty acids, such as canola and fish oil, could counteract some of the adverse effects induced by phthalates.

omega-3 polyunsaturated fatty acids

phthalates


Input: In the present study, the influence of different oily vehicles on di-butyl phthalate (DBP)-induced testicular toxicity and lipid profile was investigated.

di-butyl phthalate

DBP


Input: Pregnant Wistar rats were treated by oral gavage from gestation days 13 to 20 with DBP (500 mg/kg/day) diluted in three different vehicles: corn, canola or fish oil.

DBP


Input: Male fetuses were analyzed on gestation day 20.


Input: DBP exposure lowered intratesticular testosterone levels and anogenital distance, regardless of the vehicle used.

DBP

testosterone


Input: The percentage of seminiferous cords containing multinucleated gonocytes and cord diameter was increased in DBP-exposed groups, compared with vehicle controls, with no difference between the three DBP-exposed groups.

DBP

DBP


Input: Clustering of Leydig cells was seen in all DBP groups.

DBP


Input: Lipid profile indicated that administration of canola and fish oil can increase the content of omega-3 fatty acids in rat testis.

omega-3 fatty acids


Input: However, content of omega-3 was diminished in DBP-treated groups.

DBP


Input: Overall, our results indicate that different oily vehicles did not alter fetal rat testicular toxicity induced by a high DBP dose.

DBP


Input: Resveratrol inhibits proliferation, angiogenesis and induces apoptosis in colon cancer cells: Calorie restriction is the force to the cytotoxicity.

Resveratrol


Input: The aim of this study was to examine the antitumour activity of resveratrol in human colorectal cancer cell lines (HCT116 and Caco2) and to explore its mechanism of action assuming that it is by calorie-restriction effect.

resveratrol


Input: Resveratrol inhibited the proliferation of colon cancer cells with half maximal inhibitory concentration (IC50) equal to 50 and 130 mu M for HCT116 and Caco2, respectively.

Resveratrol


Input: Caco2 cells appeared with significant time-dependent increase in the glycolytic pathway, a behaviour that was absent in HCT116 cells.


Input: Resveratrol (100 mu M) significantly decreased the glycolytic enzymes (pyruvate kinase and lactate dehydrogenase) in Caco2 cells, while an increase in citrate synthase activity and a decrease in glucose consumption were observed in both cell lines.

Resveratrol

citrate

glucose


Input: Moreover, resveratrol downregulated the expressions of leptin and c-Myc, and decreased the content of vascular endothelial growth factor.

resveratrol


Input: The apoptotic markers, caspases 3 and 8, were activated and the Bax/BCl2 ratio was increased.


Input: The study suggested a promising anticancer activity of resveratrol, calorie-restriction pathway may be one of the driving forces for this activity.

resveratrol


Input: Differential effects of organic and inorganic selenium compounds on adenosine deaminase activity and scavenger capacity in cerebral cortex slices of young rats.

selenium

adenosine


Input: Selenium (Se) has anti-inflammatory and antioxidant properties and is necessary for the development and normal function of the central nervous system.

Selenium

Se


Input: This study was aimed to compare the in vitro effects of 3-methyl-1-phenyl-2-(phenylseleno) oct-2-en-1-one (C21H2HOSe; organoselenium) and sodium selenate (inorganic Se) on adenosine deaminase (ADA) activity, cell viability, lipid peroxidation, scavenger of nitric oxide (NO) and nonprotein thiols (NP-SH) content in the cerebral cortex slices of the young rats.

3-methyl-1-phenyl-2-(phenylseleno) oct-2-en-1-one

organoselenium

sodium selenate

Se

adenosine

nitric oxide

NO

thiols

SH


Input: A decrease in ADA activity was observed when the slices were exposed to organoselenium at the concentrations of 1, 10 and 30 micro M.

organoselenium


Input: The same compound showed higher scavenger capacity of NO than the inorganic compound.

NO


Input: Inorganic Se was able to protect against sodium nitroprusside-induced oxidative damage and increased the NP-SH content.

Se

sodium nitroprusside

SH


Input: Both the compounds displayed distinctive antioxidant capacities and were not cytotoxic for the cerebral cortex slices in the conditions tested.


Input: These findings are likely to be related to immunomodulatory and antioxidant properties of this compound.


Input: Comparison of the Relative Propensities of Isoamyl Nitrite and Sodium Nitrite to Ameliorate Acute Cyanide Poisoning in Mice and a Novel Antidotal Effect Arising from Anesthetics.

Isoamyl Nitrite

Sodium Nitrite

Cyanide


Input: Isoamyl nitrite has previously been considered acceptable as an inhaled cyanide antidote; therefore, the antidotal utility of this organic nitrite compared with sodium nitrite was investigated.

Isoamyl nitrite

cyanide

nitrite

sodium nitrite


Input: To facilitate a quantitative comparison, doses of both sodium nitrite and isoamyl nitrite were given intraperitoneally in equimolar amounts to sublethally cyanide-challenged mice.

sodium nitrite

isoamyl nitrite

cyanide


Input: Righting recovery from the knockdown state was clearly compromised in the isoamyl nitrite-treated animals, the effect being attributable to the toxicity of the isoamyl alchol produced during hydrolysis of the isoamyl nitrite to release nitrite anion.

isoamyl nitrite

isoamyl alchol

isoamyl nitrite

nitrite


Input: Subsequently, inhaled aqueous sodium nitrite aerosol was demonstrated to ameliorate sublethal cyanide toxicity, when provided to mice after the toxic dose, by the more rapid recovery of righting ability compared to that of the control animals given only the toxicant.

sodium nitrite

cyanide


Input: Aerosolized sodium nitrite has thus been shown by these experiments to have promise as a better alternative to organic nitrites for development as an inhaled cyanide antidote.

sodium nitrite

nitrites

cyanide


Input: The inhaled sodium nitrite led to the production of NO in the bloodstream as determined by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin.

sodium nitrite

NO


Input: The aerosol delivery was performed in an unmetered inhalation chamber, and in this study, no attempt was made to optimize the procedure.


Input: It is argued that administration of an effective inhaled aqueous sodium nitrite dose in humans is possible, though just beyond the capability of current individual metered-dose inhaler designs, such as those used for asthma.

sodium nitrite


Input: Finally, working at slightly greater than LD50 NaCN doses, it was fortuitously discovered that (i) anesthesia leads to significantly prolonged survival compared to that of unanesthetized animals and that (ii) the antidotal activity of nitrite anion was completely abolished under anesthesia.

NaCN

nitrite


Input: Plausible explanations for these effects in mice and their practical consequences in relation to testing putative cyanide antidotes are discussed.

cyanide


Input: Biotransformation of 2, 2', 4, 4'-Tetrabromodiphenyl Ether (BDE-47) by Human Liver Microsomes: Identification of Cytochrome P450 2B6 as the Major Enzyme Involved.

2, 2', 4, 4'-Tetrabromodiphenyl Ether


Input: Polybrominated diphenyl ethers (PBDEs) were widely used flame retardants that have become persistent environmental pollutants.

Polybrominated diphenyl ethers

PBDEs


Input: In the present study, we investigated the in vitro oxidative metabolism of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47), a major PBDE detected in human tissue and environmental samples.

2, 2', 4, 4'-tetrabromodiphenyl ether

PBDE


Input: Biotransformation of BDE-47 by pooled and individual human liver microsomes and by human recombinant cytochrome P450 (P450) enzymes was assessed using a liquid chromatography/tandem mass spectrometry-based method.


Input: Of the nine hydroxylated metabolites of BDE-47 produced by human liver microsomes, seven metabolites were identified using authentic standards.


Input: A monohydroxy-tetrabrominated and a dihydroxy-tetrabrominated metabolite remain unidentified.

monohydroxy

dihydroxy


Input: Kinetic analysis of the rates of metabolite formation revealed that the major metabolites were 5-hydroxy-2, 2', 4, 4'-tetrabromodiphenyl ether (5-OH-BDE-47), 6-hydroxy-2, 2', 4, 4'-tetrabromodiphenyl ether (6-OH-BDE-47), and possibly the unidentified monohydroxy-tetrabrominated metabolite.

5-hydroxy-2, 2', 4, 4'-tetrabromodiphenyl ether

6-hydroxy-2, 2', 4, 4'-tetrabromodiphenyl ether

monohydroxy


Input: Among the human recombinant P450 enzymes tested, P450 2B6 was the most active enzyme in the formation of the hydroxylated metabolites of BDE-47.


Input: Moreover, the formation of all metabolites of BDE-47 by pooled human liver microsomes was inhibited by a P450 2B6-specific antibody and was highly correlated with P450 2B6-mediated activity in single donor liver microsomes indicating that P450 2B6 was the major P450 responsible for the biotransformation of BDE-47.


Input: Additional experiments involving the incubation of liver microsomes with individual monohydroxy-tetrabrominated metabolites in place of BDE-47 demonstrated that 2, 4-dibromophenol was a product of BDE-47 and several primary metabolites, but the dihydroxy-tetrabrominated metabolite was not formed by sequential hydroxylation of any of the monohydroxy-tetrabrominated metabolites tested.

monohydroxy

2, 4-dibromophenol

dihydroxy

monohydroxy


Input: The present study provides a comprehensive characterization of the oxidative metabolism of BDE-47 by human liver microsomes and P450 2B6.


Input: Flavonoids of Dikamali: A phytochemical reinvestigation.

Flavonoids


Input: Eleven known flavonoids (1-11) were isolated from Dikamali, the gum resin of Gardenia lucida.

flavonoids


Input: Three of them, desmethylnobiletin, pectolinarigenin and xanthomicrol, are a new report from this source.

desmethylnobiletin

pectolinarigenin

xanthomicrol


Input: Nuclear magnetic resonance (NMR) data are being given for all the isolates.


Input: For two of them, viz., 3', 4'-dimethoxywogonin and 4'-hydroxywogonin, such data have not been reported in literature.

3', 4'-dimethoxywogonin


Input: Furthermore, correct NMR data are being provided for gardenin C as the data reported in literature were found to be incorrect.

gardenin C


Input: New triterpene glycoside and other chemical constituents from the leaves of Swartzia apetala Raddi var. glabra.

triterpene glycoside


Input: A new triterpene saponin (1) was isolated from a methanol extract of Swartzia apetala Raddi var. glabra, together with the flavonoids mauritianin (2), kaempferol (3) and the triterpene saponin beta-D-glucopyranosyl 3 beta-hydroxy-olean-12-en-28-oate (4).

triterpene saponin

methanol

flavonoids mauritianin

kaempferol

triterpene saponin beta-D-glucopyranosyl 3 beta-hydroxy-olean-12-en-28-oate


Input: These compounds were characterised on the basis of their spectral data, mainly one-dimension (1D; (1) H, (13) C, APT) and two-dimension (2D; (1) H-(1) H-COSY, HMQC and HMBC) nuclear magnetic resonance (NMR) and HR-ESI-MS, and comparison with values in the literature.

(1) H

(13) C

(1) H

(1) H


Input: The analysis by HR-ESI-MS showed a mass compatible with that of triterpene saponin 1.

triterpene saponin


Input: This proposal was supported by molecular modelling.


Input: LC-HR-ESI-MS experiment was also used to evaluate the purity of 1 and allowed to speculate about the possibility of the presence of 5 in very small quantity.


Input: The extract and four compounds were assayed for antifungal activity against nine strains of Candida spp.


Input: Measurements of Rate Constants for the OH Reactions with Bromoform (CHBr3), CHBr2Cl, CHBrCl2, and Epichlorohydrin (C3H5ClO).

OH

Bromoform

Epichlorohydrin


Input: Measurements of the rate constants for the gas phase reactions of OH radicals with bromoform (CHBr3) and epichlorohydrin (C3H5ClO) were performed using a flash photolysis resonance-fluorescence technique over the temperature range 230-370 K.

OH

bromoform

epichlorohydrin


Input: The temperature dependences of the rate constants can be represented by the following expressions: kBF (230-370 K) = (9. 94 +/- 0. 76) x 10 (-13) exp [-(387 +/- 22)/T] cm (3) molecule (-1) s (-1) and kECH (230-370 K) = 1. 05 x 10 (-14) (T/298) (5. 16) exp (+ 1082/T) cm (3) molecule (-1) s (-1).


Input: Rate constants for the reactions of OH with CHCl2Br and CHClBr2 were measured between 230 and 330 K.

OH


Input: They can be represented by the following expressions: kDCBM (230-330 K) = (9. 4 +/- 1. 3) x 10 (-13) exp [-(513 +/- 37)/T] cm (3) molecule (-1) s (-1) and kCDBM (230-330 K) = (9. 0 +/- 1. 9) x 10 (-13) exp [-(423 +/- 61)/T] cm (3) molecule (-1) s (-1).


Input: The atmospheric lifetimes due to reactions with tropospheric OH were estimated to be 57, 39, 72, and 96 days, respectively.

OH


Input: The total atmospheric lifetimes of the Br-containing methanes due to both reaction with OH and photolysis were calculated to be 22, 50, and 67 days for CHBr3, CHClBr2, and CHCl2Br, respectively.

Br

methanes

OH


Input: Integrated chemical and biological analysis to explain estrogenic potency in bile extracts of red mullet (Mullus barbatus).


Input: A biological screening was performed to establish the total exposure to estrogenic compounds of red mullet (Mullus barbatus) collected at several sites along the Spanish Mediterranean coast by testing male fish bile extracts using the in vitro ER-LUC reporter gene assay.


Input: In addition, major metabolites were identified and measurements of OH-PAHs (1-naphthol, 9-phenantrol, 9-fluorenol, 1-pyrenol, 1OH-BaP and 3OH-BaP) and alkylphenols (4-n-nonylphenol (4-n-NP) and 4-tertoctylphenol (4-tert-OP)) in the same fish bile extracts were taken by gas chromatography-mass spectrometry in electron ionization mode (GC-EI-MS).

OH-PAHs

alkylphenols


Input: Relative in vitro estrogenic potencies of the chemically quantified compounds were also tested.


Input: The highest biliary concentrations of 1-pyrenol, 9-fluorenol and 4-n-NP were found in fish from Barcelona and from the Mar Menor coastal lagoon.


Input: However, these concentrations can be considered relatively low compared to values reported in red mullet from other polluted waters in the Mediterranean Sea.


Input: The contribution of 1-pyrenol, 4-n-NP and 4-tert-OP to the total estrogenic potency measured in male fish bile was found to be negligible, indicating the presence of other estrogenic compounds in red mullet bile.


Input: Estrogenic potency in bile from male fish was markedly elevated in Mar Menor lagoon (234. 8 +/- 5. 7pgE2EQ/mu l), and further research will be necessary to explain whether the presence of natural and synthetic-hormones in the lagoon contributed to this finding.


Input: Values of approximately 15-16E2EQpg/mg bile can be regarded as preliminary baseline levels of bile estrogenicity in male red mullet from the western Mediterranean Sea.


Input: Antioxidant and anticancer activities of Chenopodium quinoa leaves extracts-In vitro study.


Input: The nutraceutical potential of Chenopodium quinoa Leaves (ChL) was assessed through analyses of their phenolic content, elucidation of the effect of ChL phenolic compounds on cancer cell properties and estimation of their antioxidative activity, bioaccessibility and bioavailability in vitro.

phenolic

phenolic


Input: Considerable amounts of ferulic, sinapinic and gallic acids, kaempferol, isorhamnetin and rutin were observed in the chemical ChL extract and were linked with its inhibitory effect on prostate cancer cell proliferation, motility and cellular competence for gap junctional communication.

ferulic, sinapinic and gallic acids

kaempferol

isorhamnetin

rutin


Input: Both extracts, chemical and obtained after simulated digestion, exerted an inhibitory effect on lipoxygenase activity, paralleled by their considerable chelating, antioxidative, antiradical and reducing power.


Input: These observations indicate that phenolic ChL compounds may exert a chemopreventive and anticarcinogenic effect on oxidative stress and ROS-dependent intracellular signaling via synergic effects.

phenolic


Input: The relatively high potential bioaccessibility and bioavailability of the compounds probably responsible for these effects demonstrates the suitability of ChL for dietary supplementation.


Input: An ultra-low dose of tetrahydrocannabinol provides cardioprotection.

tetrahydrocannabinol


Input: Tetrahydrocannabinol (THC), the major psychoactive component of marijuana, is a cannabinoid agonist that exerts its effects by activating at least two specific receptors (CB1 and CB2) that belong to the seven transmembrane G-protein coupled receptor (GPCR) family.

Tetrahydrocannabinol

THC


Input: Both CB1 and CB2 mRNA and proteins are present in the heart.


Input: THC treatment was beneficial against hypoxia in neonatal cardiomyocytes in vitro.

THC


Input: We also observed a neuroprotective effect of an ultra low dose of THC when applied to mice before brain insults.

THC


Input: The present study was aimed to test and characterize the cardioprotective effects of a very low dose (0. 002mg/kg) of THC which is 3-4 orders of magnitude lower than the conventional doses, administered before myocardial infarction in mice in vivo.

THC


Input: Three regimens of THC administration were tested: single THC application 2h or 48h before the induction of infarct, or 3 weeks continuous treatment before MI.

THC

THC


Input: All protocols of THC administration were found to be beneficial.

THC


Input: In the case of THC treatment 2h before MI, fractional shortening was elevated (37 +/- 4% vs. 42 +/- 1%, p < 0. 04), troponin T leakage to the blood was reduced (14 +/- 3ng/ml vs. 10 +/- 4ng/ml, p < 0. 008), infarct size decreased (29 +/- 4% vs. 23 +/- 4%, p < 0. 02), and the accumulation of neutrophils to the infarct area declined (36 +/- 10cells/field vs. 19 +/- 4cells/field, p < 0. 007) in THC-compared to vehicle-pretreated mice, 24h after MI.

THC

THC


Input: ERK1/2 phosphorylation following infarct was also inhibited by pre-treatment with THC (p < 0. 01).

THC


Input: CONCLUSION: A single ultra low dose of THC before ischemia is a safe and effective treatment that reduces myocardial ischemic damage.

THC


Input: Systematic evaluation of 640 FDA drugs for their effect on CD4 (+) Foxp3 (+) regulatory T cells using a novel cell-based high throughput screening assay.


Input: Regulatory T cells (Treg), which play a pivotal role in maintaining immune homeostasis by suppressing the proliferation of effector T cells, have great therapeutic potential for autoimmune diseases and transplantation.


Input: However, progress on their clinical application has been hampered by the lack of high throughput screening (HTS) strategies for the systematic and rapid evaluation of existing drugs and the identification of novel drug candidates.


Input: In this report, we present an innovative in vitro HTS assay using CD4 (+) T cells from Foxp3-GFP transgenic mice that specifically express the GFP signal in Foxp3 (+) Treg cells detectable by FACS analysis in a high throughput manner.


Input: Systematic evaluation of 640 FDA-approved drugs revealed that 70 drugs increased the number of Treg cells with suppression function only in the presence of TGF beta, 75 drugs increased Treg numbers even in the absence of TGF beta, and 32 drugs increased Treg numbers synergistically with TGF beta.


Input: The identified Treg-promoting drugs include those previously known to induce Treg (rapamycin and retinoic acid), statins, glucocorticoids and drugs in many other categories.

rapamycin

retinoic acid)


Input: Furthermore, Treg cells cultured with the identified drugs possess surface and intracellular markers characteristic of natural Treg cells and possess suppressive function.


Input: These results suggest that this Treg HTS assay can be used to screen compound libraries to identify novel chemical entities for Treg-based immune therapies.


Input: The effect of a Cimicifuga racemosa extracts Ze 450 in the treatment of climacteric complaints-an observational study.

Ze 450


Input: BACKGROUND: Root extracts of Cimicifuga racemosa (L.) Nutt. have been successfully used in the treatment of climacteric complaints.


Input: METHOD: In this observational study, Cimicifuga racemosa (CR) extract Ze 450 was studied in 442 unselected ambulatory female outpatients with menopausal complaints under daily practice conditions.

Ze 450


Input: Physicians were suggested to treat patients for the first 3 months with 13mg/d CR (high dose, HD) and to continue over additional 6 months either with this treatment or to switch to 6. 5mg/d CR (low dose, LD).


Input: The choice of treatment and its dose, however, was fully at the discretion of the physician.


Input: RESULTS: After 3-months treatment with HD, symptom severity (Kupperman Menopause Index, KMI) decreased significantly (p < 0. 001) from baseline values.


Input: Continuation of treatment with HD or LD decreased total KMI and its sub-item scores further (HD, LD: p < 0. 001).


Input: However, more patients (84. 9%) responded to HD than to LD (78. 4%) and showed an improvement of symptoms (p = 0. 011).


Input: CONCLUSION: This observational study demonstrated that treatment with CR in unselected patients with climacteric complaints under the conditions of daily practice resulted in a significant improvement of menopausal symptoms assessed by the total KMI score and its sub-item scores with an effect size similar to that in a previous randomized, controlled clinical trial.


Input: Combination of essential oils and antibiotics reduce antibiotic resistance in plasmid-conferred multidrug resistant bacteria.


Input: In this study we investigated the relationship between several selected commercially available essential oils and beta-lactam antibiotics on their antibacterial effect against multidrug resistant bacteria.

beta-lactam


Input: The antibacterial activity of essential oils and antibiotics was assessed using broth microdilution.


Input: The combined effects between essential oils of cinnamon bark, lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the checkerboard method against beta-lactamase-producing Escherichia coli.

ampicillin

piperacillin

cefazolin

cefuroxime

carbenicillin

ceftazidime

meropenem


Input: In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interaction between the combinations.


Input: Substantial susceptibility of the bacteria toward natural antibiotics and a considerable reduction in the minimum inhibitory concentrations (MIC) of the antibiotics were noted in some paired combinations of antibiotics and essential oils.


Input: Out of 35 antibiotic-essential oil pairs tested, four of them showed synergistic effect (FIC <= 0. 5) and 31 pairs showed no interaction (FIC > 0. 5-4. 0).


Input: The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against two of the three bacteria under study with a FIC index in the range 0. 26-0. 5.

piperacillin

piperacillin

piperacillin

meropenem


Input: The finding highlighted the potential of peppermint, cinnamon bark and lavender essential oils being as antibiotic resistance modifying agent.


Input: Reduced usage of antibiotics could be employed as a treatment strategy to decrease the adverse effects and possibly to reverse the beta-lactam antibiotic resistance.

beta-lactam


Input: Two new tryptophan derivatives from the seed kernels of Entada rheedei: Effects on cell viability and HIV infectivity.

tryptophan


Input: Two new tryptophan derivatives, N-sulfonyl-L-tryptophan (tryptorheedei A) (1) and 3-(N-sulfonylindolyl)-D-lactic acid (tryptorheedei B) (2) together with the known 5-O-beta-D-glucopyranosyl-2-hydroxyphenylacetic acid (3), 1-O-methylglucopyranoside, entadamide A, homogentisic acid and 3-O-beta-D-glucopyranosyl-beta-sitosterol, were isolated from the seed kernels of Entada rheedei (Mimosaceae).

tryptophan

N-sulfonyl-L-tryptophan

tryptorheedei A

3-(N-sulfonylindolyl)-D-lactic acid

tryptorheedei B

5-O-beta-D-glucopyranosyl-2-hydroxyphenylacetic acid

entadamide A

homogentisic acid

3-O-beta-D-glucopyranosyl-beta-sitosterol


Input: Their structures were established using 1D and 2D NMR spectroscopy, mass spectrometry and by comparison with spectroscopic data reported in the literature.


Input: Compounds 1 and 2 showed no toxicity to TZM and Human PBMC cells.


Input: Both compounds 1 and 2 were found to promote early infection events in HIV, likely by inhibiting the enzyme indolamine 2, 3-dioxygenase (IDO) and preventing tryptophan depletion.

indolamine

tryptophan


Input: Inhibition of IDO acutely in HIV infection inhibits viral replication, but chronic activation of IDO leads to immune impairment in AIDS.


Input: IDO is also the gatekeeper enzyme for kynurenine metabolism, a pathway involved in serotonin and melatonin biosynthesis and the regulation of glutamate and dopamine levels in the brain.

kynurenine

serotonin

glutamate

dopamine


Input: Therefore inhibition of IDO might explain both the reported medicinal and neuropsychiatric effects of E. rheedei.


Input: The conjugation of microcystin-RR by human recombinant GSTs and hepatic cytosol.

microcystin-RR


Input: Many cyanobacterial species can produce cyanotoxins, among which mycrocistins (MC) are a group of =~ 100 congeners of hepatotoxic cyclic heptapeptides.

mycrocistins

cyclic heptapeptides


Input: MC-RR differs from MC-LR, the most studied congener only for one residue (arginine vs leucine), resulting in a ten-fold difference in the acute toxicity in mice.

MC-RR

MC-LR

arginine

leucine


Input: Although humans may be exposed to MC through several routes and kinetics appeared to be the major factor affecting congener-specific toxicity, little is known on MC metabolism.


Input: The accepted pathway for MC detoxication is GSH conjugation: here the MC-RR conjugation with GSH catalyzed by 5 recombinant human GSTs and human liver cytosol (HLC) has been characterized and appeared to be more efficient than MC-LR conjugation.

GSH

MC-RR

GSH

MC-LR


Input: The catalytic efficiency score is T1-1 > A1-1 =~ P1-1 > M1-1 > A3-3 (0. 161-0. 056pmol GSMC-RR (mu gproteinmin mu M) (-1)).


Input: In HLC the spontaneous reaction is favored vs the enzymatic one (ratio 3: 1) at physiological GSH content.

GSH


Input: However, at low MC-RR concentrations, representative of repeated oral exposure, and low GSH content (down to 0. 05mM), possibly associated to exposure to drugs or in patients affected by several pathologies, the relevance of the enzymatic reaction progressively increases, providing the predominant contribution to MC-RR detoxication.

MC-RR

GSH

MC-RR


Input: Activating glucocorticoid receptor-ERK signaling pathway contributes to ginsenoside Rg1 protection against beta-amyloid peptide-induced human endothelial cells apoptosis.

ginsenoside Rg1


Input: The deposition of beta-amyloid (A beta) in neurons and vascular cells of the brain has been characterized in Alzheimer' s disease.


Input: Ginsenoside Rg1 (Rg1) is an active components in Panax ginseng, a famous traditional Chinese medicines recorded in Compendium of Materia Medica.

Ginsenoside Rg1


Input: Present study attempted to evaluate the potential mechanisms of A beta-mediated insult and the protective effects of Rg1 on human endothelial cells.


Input: Rg1 attenuated the A beta 25-35-associated mitochondrial apoptotic events, accompanied by inhibiting HIF-1 alpha expression followed by intracellular reactive nitrogen species generation, and protein nitrotyrosination.

nitrogen


Input: These protective effects were abolished by glucocorticoid receptor (GR) antagonist RU486 or p-ERK inhibitor U0126 rather than estrogen receptor alpha antagonist ICI 82, 780.

estrogen

ICI 82, 780


Input: Taken together, our results suggested that Rg1 protected against A beta 25-35-induced apoptosis at least in part by two complementary GR-dependent ERK phosphorylation pathways: (1) down-regulating HIF-1 alpha initiated protein nitrotyrosination, and (2) inhibiting mitochondrial apoptotic cascades.


Input: These data provided a novel insight to the mechanisms of Rg1protective effects on A beta 25-35-induced endothelial cells apoptosis, suggesting that GR-ERK signaling pathway might play an important role in it.


Input: Exposure to 2, 4-dichlorophenoxyacetic acid alters glucose metabolism in immature rat Sertoli cells.

2, 4-dichlorophenoxyacetic acid

glucose


Input: The purpose of this study was to determine the effects of 2, 4-D, an herbicide used worldwide also known as endocrine disruptor, in Sertoli cell (SC) metabolism.

2, 4-D


Input: Immature rat SCs were maintained 50h under basal conditions or exposed to 2, 4-D (100nM, 10 mu M and 1mM).

2, 4-D


Input: SCs exposed to 10 mu M and 1mM of 2, 4-D presented lower intracellular glucose and lactate content.

2, 4-D

glucose

lactate


Input: Exposure to 10 mu M of 2, 4-D induced a significant decrease in glucose transporter-3 mRNA levels and phosphofructokinase-1 mRNA levels decreased in cells exposed to 100nM and 10 mu M of 2, 4-D.

2, 4-D

glucose

2, 4-D


Input: Exposure to 100nM and 10 mu M also induced a decrease in lactate dehydrogenase (LDH) mRNA levels while the LDH protein levels were only decreased in cells exposed to 1mM of 2, 4-D.

lactate

2, 4-D


Input: Exposure to 2, 4-D altered glucose uptake and metabolization in SCs, as well as lactate metabolism and export that may result in impaired spermatogenesis.

2, 4-D

glucose

lactate


Input: Synthesis of some novel thieno [3, 2-d] pyrimidines as potential cytotoxic small molecules against breast cancer.

thieno [3, 2-d] pyrimidines


Input: A variety of novel thieno [3, 2-d] pyrimidines with different decorating functional groups were synthesized as a part of a study aiming to enrich the arsenal of chemotherapeutic agents for the treatment of cancer.

thieno [3, 2-d] pyrimidines


Input: The design of synthetic molecules based on DNA-interchelating properties by hydrogen bond formation.

hydrogen


Input: The reported compounds herein are: 4-aminothienopyrimidine derivatives 4a, b and their 4-substituted phenylamino analogues 8a, b; 4-thienopyrimidin-4-ones 5a, b; N-alkyl thienopyrimidin-4-ones 6a-g; 4-chlorothienopyrimidines 7a, b; and thienopyrimidoquinazolinones 9a, b which are the structural mimics of 8a, b.

4-substituted phenylamino

N-alkyl thienopyrimidin-4-ones

thienopyrimidoquinazolinones


Input: The synthesized molecules were evaluated for their in vitro cytotoxic activity against human breast cancer cell line (MCF-7).


Input: Biological screening revealed varying cytotoxic potencies of the tested molecules compared with Doxorubicin as a reference drug.

Doxorubicin


Input: The cytotoxicity results from the study suggested that the synthesized molecules are potential antitumor agents and compound 4a was the most potent with an IC 50 2. 04 nM.


Input: Cadmium Tolerance and Removal from Cunninghamella elegans Related to the Polyphosphate Metabolism.

Cadmium


Input: The aim of the present work was to study the cadmium effects on growth, ultrastructure and polyphosphate metabolism, as well as to evaluate the metal removal and accumulation by Cunninghamella elegans (IFM 46109) growing in culture medium.

cadmium


Input: The presence of cadmium reduced growth, and a longer lag phase was observed.

cadmium


Input: However, the phosphate uptake from the culture medium increased 15% when compared to the control.

phosphate


Input: Moreover, C. elegans removed 70%-81% of the cadmium added to the culture medium during its growth.

cadmium


Input: The C. elegans mycelia showed a removal efficiency of 280 mg/g at a cadmium concentration of 22. 10 mg/L, and the removal velocity of cadmium was 0. 107 mg/h.

cadmium

cadmium