Input: Multiphase chemistry of atmospheric amines.

amines


Input: Heterogeneous reactions of amines have been recently shown to play an important role in the formation and transformation of atmospheric aerosols.

amines


Input: This perspective summarizes the latest laboratory progress in the multiphase chemistry of amines.

amines


Input: Particular emphasis is given to the contributions of amines to new particle formation, growth of submicron particles, and alteration in the physiochemical properties of pre-existing particles, including hygroscopicity, thermostability, density, phase, and optical properties, from exposure to gaseous amines.

amines

amines


Input: The atmospheric implications of the multiphase reactions of amines, including the potential impact on direct and indirect climate forcing of aerosols, and future research directions are discussed.

amines


Input: When direct health-care professional communications have an impact on inappropriate and unsafe use of medicines.


Input: Serious safety issues relating to drugs are communicated to health-care professionals via Direct Health-Care Professional Communications (DHPCs).


Input: We explored which characteristics determined the impact of DHPCs issued in the Netherlands for ambulatory-care drugs (2001-2008).


Input: With multiple linear regression, we examined the impact on the relative change in new drug use post-DHPC of the following: time to DHPC, trend in use, degree of innovation, specialist drug, first/repeated DHPC, DHPC template, and type of safety issue.


Input: DHPCs have less impact on use of specialist drugs than nonspecialist drugs (P < 0. 05).


Input: The DHPCs' impact increased after availability of a template emphasizing the main problem (P < 0. 05), and for safety issues with a risk of death and/or disability (both P < 0. 05) (adjusted R (2) = 0. 392).


Input: Risk communication can be effective, specifically in case of well-structured information, and very serious safety issues.


Input: Effectiveness may improve by tailoring DHPCs and adding other communication channels, for example for drugs that are increasingly being used.


Input: Estimation of renal cell carcinoma treatment effects from disease progression modeling.


Input: To improve future drug development efficiency in renal cell carcinoma (RCC), a disease-progression model was developed with longitudinal tumor size data from a phase III trial of sorafenib in RCC.

sorafenib


Input: The best-fit model was externally evaluated on 145 placebo-treated patients in a phase III trial of pazopanib; the model incorporated baseline tumor size, a linear disease-progression component, and an exponential drug effect (DE) parameter.

pazopanib


Input: With the model-estimated effect of sorafenib on RCC growth, we calculated the power of randomized phase II trials between sorafenib and hypothetical comparators over a range of effects.

sorafenib

sorafenib


Input: A hypothetical comparator with 80% greater DE than sorafenib would have 82% power (one-sided alpha = 0. 1) with 50 patients per arm.

sorafenib


Input: Model-based quantitation of treatment effect with computed tomography (CT) imaging offers a scaffold on which to develop new, more efficient, phase II trial end points and analytic strategies for RCC.


Input: Effect of miR-21 on Renal Fibrosis by Regulating MMP-9 and TIMP1 in kk-ay Diabetic Nephropathy Mice.


Input: MicroRNAs (miRs) play important roles in initiation and progression of many pathologic processes.


Input: However, the roles of miRs in diabetic nephropathy remain unclear.


Input: This study was to determine whether miR-21 was involved in diabetic nephropathy and to explore the relationship between miR-21 and MMP9/TIMP1 expression in diabetic nephropathy.


Input: In situ hybridization studies showed that miR-21 was primarily localized and distributed in cortical glomerular and renal tubular cells in diabetic kk-ay kidney.


Input: Real-time quantitative RT-PCR demonstrated that the expression of miR-21 was significantly increased in kk-ay mice, compared with control C57BL mice.


Input: Interestingly, miR-21 expression positively correlated with urine albumin creatine ratio (ACR), TIMP1, collagen IV (ColIV), and fibronectin (FN); while negatively correlated with creatine clearance ratio (Ccr) and MMP-9 protein.

creatine

creatine


Input: Importantly, antagomir-21 not only ameliorated Ccr and ACR but also decreased TIMP1, ColIV, and FN proteins.


Input: In conclusion, our data demonstrate that miR-21 contributes to renal fibrosis by mediating MMP9/TIMP1 and that inhibition of miR-21 may be a novel target for diabetic nephropathy.


Input: Probing the Metabotropic Glutamate Receptor 5 (mGlu5) Positive Allosteric Modulator (PAM) Binding Pocket: Discovery of Point Mutations That Engender a " Molecular Switch " in PAM Pharmacology.

Glutamate


Input: Positive allosteric modulation of metabotropic glutamate receptor subtype 5 (mGlu5) is a promising novel approach for the treatment of schizophrenia and cognitive disorders.

glutamate


Input: Allosteric binding sites are topographically distinct from the endogenous ligand (orthosteric) binding site, allowing for co-occupation of a single receptor with the endogenous ligand and an allosteric modulator.


Input: Negative allosteric modulators (NAMs) inhibit and positive allosteric modulators (PAMs) enhance the affinity and/or efficacy of the orthosteric agonist.


Input: The molecular determinants that govern mGlu5 modulator affinity versus cooperativity are not well understood.


Input: Focusing on the modulators based on the acetylene scaffold, we sought to determine the molecular interactions that contribute to PAM versus NAM pharmacology.

acetylene


Input: Generation of a comparative model of the transmembrane-spanning region of mGlu5 served as a tool to predict and interpret the impact of mutations in this region.


Input: Application of an operational model of allosterism allowed for determination of PAM and NAM affinity estimates at receptor constructs that possessed no detectable radioligand binding as well as delineation of effects on affinity versus cooperativity.


Input: Novel mutations within the transmembrane domain (TM) regions were identified that had differential effects on acetylene PAMs versus 2-methyl-6-(phenylethynyl)-pyridine, a prototypical NAM.

acetylene


Input: Three conserved amino acids (Y658, T780, and S808) and two nonconserved residues (P654 and A809) were identified as key determinants of PAM activity.

amino acids


Input: Interestingly, we identified two point mutations in TMs 6 and 7 that, when mutated, engender a mode switch in the pharmacology of certain PAMs.


Input: Coactivators enable glucocorticoid receptor recruitment to fine-tune estrogen receptor transcriptional responses.

estrogen


Input: Nuclear receptors (NRs) are central regulators of pathophysiological processes; however, how their responses intertwine is still not fully understood.


Input: The aim of this study was to determine whether and how steroid NRs can influence each other' s activity under co-agonist treatment.

steroid


Input: We used a unique system consisting of a multicopy integration of an estrogen receptor responsive unit that allows direct visualization and quantification of estrogen receptor alpha (ER alpha) DNA binding, co-regulator recruitment and transcriptional readout.

estrogen

estrogen


Input: We find that ER alpha DNA loading is required for other type I nuclear receptors to be co-recruited after dual agonist treatment.


Input: We focused on ER alpha/glucocorticoid receptor interplay and demonstrated that it requires steroid receptor coactivators (SRC-2, SRC-3) and the mediator component MED14.

steroid


Input: We then validated this cooperative interplay on endogenous target genes in breast cancer cells.


Input: Taken together, this work highlights another layer of mechanistic complexity through which NRs cross-talk with each other on chromatin under multiple hormonal stimuli.


Input: Variation in prescribing patterns and therapeutic drug monitoring of intravenous busulfan in pediatric hematopoietic cell transplant recipients.

busulfan


Input: Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant.

busulfan


Input: The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008.

busulfan

busulfan

busulfan


Input: The initial IV busulfan dose in children weighing <= 12 kg ranged 4. 8-fold, with only 19% prescribed the package insert dose of 1. 1 mg/kg.

busulfan


Input: In those children weighing > 12 kg, the initial dose ranged 5. 4-fold, and 79% were prescribed the package insert dose.


Input: The initial busulfan dose achieved the target exposure in only 24. 3% of children.

busulfan


Input: A wide range of busulfan exposures were targeted for children with the same disease (eg, 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia).

busulfan

busulfan


Input: Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained.


Input: Busulfan clearance varied by age and dosing frequency but not by underlying disease.

Busulfan


Input: The authors-group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children.

busulfan


Input: Comparing the pharmacokinetics of doxylamine/pyridoxine delayed-release combination in nonpregnant women of reproductive age and women in the first trimester of pregnancy.

doxylamine

pyridoxine


Input: Although Diclectin (doxylamine/pyridoxine delayed-released combination) is widely used in Canada, its pharmacokinetics (PK) during pregnancy has never been described.

Diclectin

doxylamine

pyridoxine


Input: The objective of this study was to compare the PK of doxylamine/pyridoxine delayed-released combination in pregnant versus nonpregnant women.

doxylamine

pyridoxine


Input: The apparent clearances (CL) of doxylamine and pyridoxal 5'-phosphate (PLP; the active metabolite of vitamin B (6)) during the first-trimester pregnancy in women who participated in a Diclectin randomized trial were compared with those of healthy, adult, nonpregnant women who participated in a voluntary PK trial.

doxylamine

pyridoxal 5'-phosphate

PLP

vitamin B (6)

Diclectin


Input: Eighteen nonpregnant women were compared with 50 pregnant women who were treated with Diclectin.

Diclectin


Input: There was no difference in the apparent CL of doxylamine in women in their first trimester of pregnancy when compared with nonpregnant women on day 4 (median = 196. 7 vs 249. 5 mL/h/kg, respectively, P =. 065), day 8 (median = 248. 4 vs 249. 5 mL/h/kg, respectively, P =. 82), and day 15 (median = 200. 9 vs 249. 5 mL/h/kg, respectively, P =. 55).

doxylamine


Input: No difference was found in the apparent CL of PLP on day 15 (median = 342. 3 vs 314. 7 mL/h/kg, respectively, P =. 92).


Input: There was no pregnancy-induced effect in the apparent CL of either doxylamine or PLP in women during the first trimester of pregnancy despite the existence of morning sickness.

doxylamine

PLP


Input: Light energy collection in a porphyrin-imide-corrole ensemble.

porphyrin-imide-corrole


Input: An assembly consisting of three units, that is, a meso-substituted corrole (), 1, 8 naphthaleneimide (), and a Zn porphyrin (), has been synthesized.

meso-substituted corrole

1, 8 naphthaleneimide

Zn porphyrin


Input: NIE is connected to C3 through a 1, 3-phenylene bridge and to the ZnP unit through a direct C <F8FF> C bond.

NIE

1, 3-phenylene

ZnP

C <F8FF> C


Input: The convergent synthetic strategy includes the preparation of a trans-A2 B-corrole possessing the imide unit, followed by Sonogashira coupling with a meso-substituted A3 B-porphyrin.

trans-A2 B-corrole

imide

meso-substituted A3 B-porphyrin


Input: The photophysical processes in the resulting triad are examined and compared with those of the corresponding dyad and the constituent reference models,, and.


Input: Excitation of the NIE unit in leads to a fast energy transfer of 98% efficiency to C3 with a rate ken = 7. 5 x 10 (10) s (-1), whereas excitation of the corrole unit leads to a reactivity of the excited state identical to that of the model, with a deactivation rate to the ground state k = 2. 5 x 10 (8) s (-1).

NIE

corrole


Input: Energy transfer to C3 and to ZnP moieties follows excitation of NIE in the triad.

ZnP

NIE


Input: The rates are ken = 7. 5 x 10 (10) s (-1) and ken = 2. 5 x 10 (10) s (-1) for the sensitization of the C3 and ZnP unit, respectively.

ZnP


Input: The light energy transferred from NIE to Zn porphyrin unit is ultimately funneled to the corrole component, which is the final recipient of the excitation energy absorbed by the different components of the array.

NIE

Zn porphyrin

corrole


Input: The latter process occurs with a rate ken = 3. 4 x 10 (9) s (-1) and 89% efficiency.


Input: Energy transfer processes take place in all cases by a F o rster (dipole-dipole) mechanism.


Input: The theory predicts quite satisfactorily the rate for the ZnP/C3 couple, where components are separated by about 23 A, but results in calculated rates that are one to two orders of magnitude higher for the couples NIE/ZnP (D/A) and NIE/C3, which are separated by distances of about 14 and 10 A, respectively.

ZnP

NIE

ZnP

NIE


Input: Protective effect of butylated hydroxytoluene on ferric nitrilotriacetate induced hepatotoxicity and oxidative stress in mice.

butylated hydroxytoluene

ferric nitrilotriacetate


Input: The present study was undertaken to evaluate the possible ameliorating effect of butylated hydroxyl toluene (BHT), associated with ferric nitrilotriacetate (Fe-NTA)-induced oxidative stress and liver injury in mice.

butylated hydroxyl toluene

BHT

ferric nitrilotriacetate

Fe-NTA


Input: The treatment of mice with Fe-NTA alone enhances ornithine decarboxylase activity to 4. 6 folds, protein carbonyl formation increased up to 2. 9 folds and DNA synthesis expressed in terms of [(3) H] thymidine incorporation increased to 3. 2 folds, and antioxidants and antioxidant enzymes decreased to 1. 8-2. 5 folds, compared with the corresponding saline-treated controls.

Fe-NTA

ornithine

carbonyl

[(3) H] thymidine


Input: These changes were reversed significantly (p < 0. 001) in animals receiving a pretreatment of BHT.

BHT


Input: Our data show that BHT can reciprocate the toxic effects of Fe-NTA and can serve as a potent chemopreventive agent.

BHT

Fe-NTA


Input: Cytotoxicity and uptake of archaeosomes prepared from Aeropyrum pernix lipids.


Input: Archaeon Aeropyrum pernix K1 is an obligate aerobic hyperthermophilic organism with C (25, 25)-archeol membrane lipids with head groups containing inositol.

inositol


Input: Interactions of archaeosomes, liposomes prepared from lipids of A. pernix, with mammalian cells in vitro were studied.


Input: In vitro cytotoxicity was tested on five different cell lines: rodent mouse melanoma cells (B16-F1) and Chinese hamster ovary (CHO) cells, and three human cell lines-epithelial colorectal adenocarcinoma cells (CACO-2), liver hepatocellular carcinoma cell line (Hep G2) and endothelial umbilical vein cell line (EA. hy926).


Input: Archaeosomes were nontoxic to human Hep G2, CACO-2 and mildly toxic to rodent CHO and B16-F1 cells but showed strong cytotoxic effect on EA. hy926 cells.


Input: Confocal microscopy revealed that archaeosomes are taken up by endocytosis.


Input: The uptake of archaeosomes and the release of loaded calcein are more prominent in EA. hy926 cells, which is in line with high toxicity toward these cells.

calcein


Input: The mechanisms of uptake, release and action in these cells as well as in vivo functioning have to be further studied for possible targeted drug delivery.


Input: A 90-day subchronic toxicity study of neem oil, a Azadirachta indica oil, in mice.


Input: To determine the no-observed-adverse-effect level (NOAEL) of exposure and target organs of neem oil for establishing safety criteria for human exposure, the subchronic toxicity study with neem oil in mice was evaluated.


Input: The mice (10 per sex for each dose) was orally administered with neem oil with the doses of 0 (to serve as a control), 177, 533 and 1600 mg/kg/day for 90 days.


Input: After the treatment period, observation of reversibility or persistence of any toxic effects, mice were continuously fed without treatment for the following 30 days.


Input: During the two test periods, the serum biochemistry, organ weight and histopathology were examined.


Input: The results showed that the serum biochemistry and organ coefficient in experimental groups had no statistical difference compared with those of the control group.


Input: At the 90th day, the histopathological examinations showed that the 1600 mg/kg/day dose of neem oil had varying degrees of damage on each organ except heart, uterus and ovarian.


Input: After 30-day recovery, the degree of lesions to the tissues was lessened or even restored.


Input: The NOAEL of neem oil was 177 mg/kg/day for mice and the target organs of neem oil were determined to be testicle, liver and kidneys.


Input: Simultaneous high-performance liquid chromatographic determination of a rhein-diclofenac prodrug and its active compounds.

rhein

diclofenac


Input: In order to study the hydrolytic characterization of an anti-inflammatory prodrug (RD-1) in vitro, a simple, specific, precise and accurate method for the simultaneous determination of prodrug and its two hydrolytic active compounds was development using reverse phase high-performance liquid chromatography (RP-HPLC).


Input: The chromatographic separation was performed on an ODS-2 C18 column (250 mm x 4. 6 mm, 5. 0 microm particle size) with a simple elution programme.


Input: The mobile phase was methanol-0. 1% phosphoric acid solution (adjusted pH to 2. 3) (80: 20, v/v); wavelength of 257nm and mobile phase flow rate of 1. 0 mL/min was utilized for the quantitative analysis.

methanol

phosphoric acid


Input: Excellent linear behaviors over the investigated concentration ranges were observed with the values of R2 higher than 0. 999 for all the analytes.


Input: The validated method was successfully applied to the simultaneous determination of prodrug and its active components.


Input: Rapid identification of sibutramine in dietary supplements using a stepwise approach.

sibutramine


Input: Adulteration of botanical food supplements with undeclared synthetic drugs is a common problem.


Input: One of the most affected product groups are the slimming agents.


Input: There are no analytical protocols for the detection of synthetic adulterants from these products.


Input: The present study aimed at the development of a multistep analytical method for the quick and reliable determination of sibutramine, one of the most common adulterants among botanical food supplements.

sibutramine


Input: The extract of a sibutramine-containing slimming formula was analysed by colour tests, TLC, HPLC-DAD, MS and NMR.

sibutramine


Input: The multistep method proposed by the authors allows the quick identification of sibutramine in counterfeit samples in laboratories with different instrumentation.

sibutramine


Input: Development and validation of a simple LC method for the determination of phenacetin, coumarin, tolbutamide, chlorzoxazone, testosterone and their metabolites as markers of cytochromes 1A2, 2A6, 2C11, 2E1 and 3A2 in rat microsomal medium.

phenacetin

coumarin

tolbutamide

chlorzoxazone

testosterone


Input: Cytochrome P450 enzymes are responsible for the oxidative metabolism of most pharmaceutical compounds.


Input: A " cocktail " approach which employs simultaneous administration of a mixture of substrates of CYP enzymes was often used to assess the metabolic activity of multiple P450 forms in one experiment.


Input: Phenacetin, coumarin, tolbutamide, chlorzoxazone and testosterone are commonly used as probe substrates to evaluate cytochrome P450 function.

Phenacetin

coumarin

tolbutamide

chlorzoxazone

testosterone


Input: An analytical strategy to simultaneously extract and analyze the five probe substrates and their major metabolites by HPLC-DAD was developed.


Input: The incubation was done with all the substrates in one step.


Input: The ten analytes were extracted simultaneously by solid-phase extraction (SPE) from rat liver microsomes.


Input: A C18 analytical column and mobile phase composed of acetonitrile and 0. 02% aqueous phosphoric acid were used for the chromatographic separation with DAD detection.

acetonitrile

phosphoric acid


Input: Limits of quantification varied between 0. 02378 and 0. 2361 microg/mL which contributed to quantify all these drugs and metabolites with UV detection.


Input: The method is applicable for the modeling and description of pharmacological interactions on rat cytochromes P450 or can be used for in vitro evaluation of cytochromes 1A2, 2A6, 2C11, 2E1 and 3A2.


Input: Synergistic antitumor activity from two-stage delivery of targeted toxins and endosome-disrupting nanoparticles.


Input: Plant-derived Type I toxins are candidate anticancer therapeutics requiring cytosolic delivery into tumor cells.


Input: We tested a concept for two-stage delivery, whereby tumor cells precoated with an antibody-targeted gelonin toxin were killed by exposure to endosome-disrupting polymer nanoparticles.


Input: Co-internalization of particles and tumor cell-bound gelonin led to cytosolic delivery and > 50-fold enhancement of toxin efficacy.


Input: This approach allows the extreme potency of gelonin to be focused on tumors with significantly reduced potential for off-target toxicity.


Input: Temperature dependence of transport properties of spiro-MeOTAD as a hole transport material in solid-state dye-sensitized solar cells.

spiro-MeOTAD


Input: The internal transport and recombination parameters of solid-state dye-sensitized solar cells (ssDSCs) using the amorphous organic semiconductor 2, 2', 7, 7'-tetrakis (N, N-di-p-methoxyphenylamine)-9, 9'-spirobifluorene (spiro-MeOTAD) as a hole transport material (HTM) are investigated using electrical impedance spectroscopy.

2, 2', 7, 7'-tetrakis (N, N-di-p-methoxyphenylamine)-9, 9'-spirobifluorene

spiro-MeOTAD


Input: Devices were fabricated using flat and nanostructured TiO2 and compared to systems using nanostructured ZrO2 to differentiate between the transport processes within the different components of the ssDSC.


Input: The effect of chemically p-doping the HTM on its transport was investigated, and its temperature dependence was examined and analyzed using the Arrhenius equation.


Input: Using this approach the activation energy of the hole hopping transport within the undoped spiro-MeOTAD film was determined to be 0. 34 +/- 0. 02 and 0. 40 +/- 0. 02 eV for the mesoporous TiO2 and ZrO2 systems, respectively.

spiro-MeOTAD


Input: In vivo genotoxicity and oxidative stress evaluation of an ethanolic extract from piqui a (Caryocar villosum) pulp.


Input: In this study, the ethanolic extract obtained from piqui a pulp was assessed for genotoxicity and oxidative stress by employing the micronucleus test in bone marrow and peripheral blood cells in addition to comet, thiobarbituric-acid-reactive substances (TBARS), and reduced glutathione assays in the liver, kidney, and heart.

thiobarbituric-acid

reduced glutathione


Input: Additionally, phytochemical analyses were performed to identify and quantify the chemical constituents of the piqui a extract.


Input: Wistar rats were treated by gavage with an ethanolic extract from piqui a pulp (75 mg/kg body weight) for 14 days, and 24 h prior to euthanasia, they received an injection of saline or doxorubicin (15 mg/kg body weight, intraperoneally).

doxorubicin


Input: The results demonstrated that piqui a extract at the tested dose was genotoxic but not mutagenic, and it increased the TBARS levels in the heart.


Input: Further studies are required to fully elucidate how the properties of ethanolic extract of piqui a pulp can affect human health.


Input: Kimchi, a fermented vegetable, improves serum lipid profiles in healthy young adults: randomized clinical trial.


Input: Abstract Vegetable-based diets have generally focused on their health benefits including negative associations with the serum cholesterol concentrations.

cholesterol


Input: The aim of this study was to investigate whether serum lipid concentrations are influenced by the amount of kimchi intake.


Input: For the study, 100 volunteers were assigned to 2 dietary groups, low (15 g/day, n = 50) and high (210 g/day, n = 50) kimchi intake, and were housed together in a dormitory for 7 days.


Input: Identical meals except with different amount of kimchi were provided and subjects were instructed to maintain their normal physical activity.


Input: Concentrations of fasting blood glucose (FBG), total glucose, total cholesterol and low density lipoprotein (LDL)-C significantly decreased in both groups after 7 days of kimchi intake, but the effects were dose dependent.

glucose

glucose

cholesterol


Input: Lipid lowering effects of kimchi were more profound in the subjects with total cholesterol and LDL-C level over 190 and 130 mg/dL, respectively, in both groups.

cholesterol


Input: FBG was significantly decreased in the high kimchi intake as compared to the low intake group (P =. 003).


Input: In conclusion, greater consumption of kimchi improved FBG and serum total cholesterol in young healthy adults.

cholesterol


Input: Chronic food administration of Salvia sclarea oil reduces animals' anxious and dominant behavior.


Input: Recent studies indicate that an oil extract from Salvia sclarea may provide clinical benefits in various pathological conditions.


Input: In comparison to extracts from other Salvia species, S. sclarea oil contains twice as much omega-3 fatty acids, which are involved in eicosanoid synthesis pathways, and has been found to contain significant levels of the psychoactive monoterpane linalool.

omega-3 fatty acids

eicosanoid

linalool


Input: In the present study, we examined the mood stabilizing and anxiolytic-like effects of chronic food administration of S. sclarea oil extract on behavioral and physiological parameters of mice with prominent dominant and submissive features in behavioral assays used to test mood stabilizing and antidepressant drugs.


Input: Experimental animals received oil supplemented food from the age of 4 weeks or from conception via their pregnant dams.


Input: Each age group received either S. sclarea oil-or sunflower oil-enriched feed.


Input: Dominant animals, whose pregnant mothers received S. sclarea oil-enriched feed from the date of conception, showed a significant reduction of dominant and anxiety-like behavior, in comparison to their sunflower oil-treated counterparts.


Input: S. sclarea oil-treated submissive animals exhibited a similar tendency, and showed a significant reduction in blood corticosterone levels.

corticosterone


Input: These findings enforce the hypothesis that S. sclarea oil possesses anxiolytic properties.


Input: Development of an in vitro dendritic cell-based test for skin sensitizer identification.


Input: The sensitizing potential of chemicals is currently assessed using animal models.


Input: However, ethical and economic concerns and the recent European legislative framework triggered intensive research efforts in the development and validation of alternative methods.


Input: Therefore, the aim of this study was to develop an in vitro predictive test based on the analysis and integration of gene expression and intracellular signaling profiles of chemical-exposed skin-derived dendritic cells.


Input: Cells were treated with four known sensitizers and two nonsensitizers, and the effects on the expression of 20 candidate genes and the activation of MAPK, PI3K/Akt, and NF-kappa B signaling pathways were analyzed by real-time reverse transcription polymerase chain reaction and Western blotting, respectively.


Input: Genes Trxr1, Hmox1, Nqo1, and Cxcl10 and the p38 MAPK and JNK signaling pathways were identified as good predictor variables and used to construct a dichotomous classifier.


Input: For validation of the model, 12 new chemicals were then analyzed in a blind assay, and from these, 11 were correctly classified.


Input: Considering the total of 18 compounds tested here, 17 were correctly classified, representing a concordance of 94%, with a sensitivity of 92% (12 of 13 sensitizers identified) and a specificity of 100% (5 of 5 nonsensitizers identified).


Input: Additionally, we tested the ability of our model to discriminate sensitizers from nonallergenic but immunogenic compounds such as lipopolysaccharide (LPS).


Input: LPS was correctly classified as a nonsensitizer.


Input: Overall, our results indicate that the analysis of proposed gene and signaling pathway signatures in a mouse fetal skin-derived dendritic cell line represents a valuable model to be integrated in a future in vitro test platform.


Input: Single-molecule spectroscopy on RC-LH1 complexes of Rhodopseudomonas acidophila strain 10050.


Input: We have revisited the RC-LH1 complex from Rhodopseudomonas (Rps.) acidophila for single-molecule spectroscopy.


Input: For the current study the pigment-protein complexes were stabilized in the detergent buffer solution using a relatively mild detergent (dodecyl-beta-D-maltoside (DDM) instead of lauryldimethylamine N-oxide (LDAO)).

dodecyl-beta-D-maltoside

DDM

lauryldimethylamine N-oxide

LDAO


Input: This leads to a significant reduction of the fraction of broken/dissociated RC-LH1 complexes with respect to previous studies and has allowed us to investigate a sufficiently large sample of individual RC-LH1 complexes.


Input: For most of the complexes the fluorescence-excitation spectra exhibit a narrow spectral feature at the red end of the spectrum.


Input: Analysis of the statistics of the spectral properties yields a close resemblance with the results obtained on RC-LH1 complexes from Rps. palustris for which a low-resolution X-ray structure is available.


Input: Based on this comparison we come to the conclusion that for both species the RC-LH1 complex can be described by the same structural model, that is, an overall elliptical assembly of pigments that features a gap.


Input: Examination of the Mode of Action of the Almiramide Family of Natural Products against the Kinetoplastid Parasite Trypanosoma brucei.

Almiramide


Input: Almiramide C is a marine natural product with low micromolar activity against Leishmania donovani, the causative agent of leishmaniasis.

Almiramide C


Input: We have now shown that almiramide C is also active against the related parasite Trypanosoma brucei, the causative agent of human African trypanosomiasis.

almiramide C


Input: A series of activity-based probes have been synthesized to explore both the molecular target of this compound series in T. brucei lysates and site localization through epifluorescence microscopy.


Input: These target identification studies indicate that the almiramides likely perturb glycosomal function through disruption of membrane assembly machinery.

almiramides


Input: Glycosomes, which are organelles specific to kinetoplastid parasites, house the first seven steps of glycolysis and have been shown to be essential for parasite survival in the bloodstream stage.


Input: There are currently no reported small-molecule disruptors of glycosome function, making the almiramides unique molecular probes for this understudied parasite-specific organelle.

almiramides


Input: Additionally, examination of toxicity in an in vivo zebrafish model has shown that these compounds have little effect on organism development, even at high concentrations, and has uncovered a potential side effect through localization of fluorescent derivatives to zebrafish neuromast cells.


Input: Combined, these results further our understanding of the potential value of this lead series as development candidates against T. brucei.


Input: Achievement of pregnancies in women with primary ovarian insufficiency using close monitoring of follicle development: case reports.


Input: Women with primary ovarian insufficiency (POI)/premature ovarian failure exhibit hypergonadotropic hypogonadism due to follicle dysfunction and depletion before the age of 40 years.


Input: Because ovulation is extremely rare and thought to be unpredictable in women with POI and because no ovulation induction regimens have been shown to be efficacious, oocyte donation is the only evidence-based treatment for women with POI with desired fertility.


Input: Oocyte donation is, however, extremely limited in several countries including Japan.


Input: Here, we report four women with POI who achieved pregnancies resulting from timed intercourse or intrauterine insemination in combination with cyclic estrogen/progesterone therapy and close monitoring of follicle development.

estrogen

progesterone


Input: These four patients were diagnosed with POI at the mean age of 27. 5 +/- 8. 5 (mean +/- SD; range, 19-35), subjected to follicle monitoring at the mean age of 29. 8 +/- 5. 7 (23-35), and conceived at the mean age of 34. 5 +/- 3. 9 (29-38).


Input: The interval between the initiation of follicle monitoring and pregnancy was 4. 8 +/- 2. 8 (2-8) years.


Input: In one of the patients, her most recent ovulation occurred after a three-year interval.


Input: All four patients had uncomplicated pregnancies with term deliveries.


Input: In the event that oocyte donation and adoption are not available and/or various treatments with intensive ovulation induction have been unsuccessful, close and continuous monitoring of follicle growth to identify very rare ovulatory events might be considered for patients with POI and desired fertility.


Input: Artificial leaf structures as a UV detector formed by the self-assembly of ZnO nanoparticles.

ZnO


Input: Artificial leaf structures have been fabricated by the self-assembly of ZnO nanoparticles.

ZnO


Input: A hydrothermal method was used to synthesize the nanoparticles.


Input: The self-assembly patterns showed asymmetric dendritic morphologies, larger surface-to-volume ratios, a broad absorption band and high resistance.


Input: A non-equilibrium two-stage-formation process included diffusion limited aggregation, and the phase-field model was introduced to explain the formation mechanism of the pattern.


Input: A high-performance ultraviolet detector was fabricated on the artificial leaf structures, which showed that the current under the irradiation of a UV lamp (1. 21 mW cm (-2)) was about 10 (4) times greater than in the dark.


Input: The various and functional properties of the pattern show us the vast prospects of potential applications for light harvesting systems and other optical-electric devices.


Input: Synthesis of pyrido [2, 3-d] [1, 2, 4] triazolo [4, 3-a] pyrimidin-5-ones as potential antimicrobial agents.

pyrido [2, 3-d] [1, 2, 4] triazolo [4, 3-a] pyrimidin-5-ones


Input: Synthesis of new derivatives of pyrido [2, 3-d] [1, 2, 4] triazolo [4, 3-a] pyrimidin-5-one via reaction of 7-(4-bromophenyl)-1, 2-dihydro-5-(4-fluorophenyl)-2-thioxopyrido [2, 3-d] pyrimidin-4 (3H)-one with hydrazonoyl chlorides or reaction of 2-hydrazino-pyrido [2, 3-d] pyrimidin-4 (3H)-one with different aldehydes followed by cyclization of the products.

pyrido [2, 3-d] [1, 2, 4] triazolo [4, 3-a] pyrimidin-5-one

7-(4-bromophenyl)-1, 2-dihydro-5-(4-fluorophenyl)-2-thioxopyrido [2, 3-d] pyrimidin-4 (3H)-one

hydrazonoyl chlorides

2-hydrazino-pyrido [2, 3-d] pyrimidin-4 (3H)-one

aldehydes


Input: All the newly synthesized compounds were evaluated for their antimicrobial activities and also their minimum inhibitory concentration against most of test organisms was performed.


Input: Amongst the tested compounds displayed excellent activity against all the tested microorganisms except SR and PA.


Input: Glutathione dimerization-based plasmonic nanoswitch for biodetection of reactive oxygen and nitrogen species.

Glutathione

oxygen

nitrogen


Input: Reactive oxygen and nitrogen species (ROS and RNS) are continuously produced in the cellular systems and are controlled by several antioxidant mechanisms.

oxygen

nitrogen


Input: Here, we developed a straightforward, sensitive, and quantitative assay for the colorimetric and spectroscopic detection of various ROS and RNS such as H2O2,. OH, (-) OCl, NO., and O2 (-) using glutathione-modified gold nanoparticles (GSH-AuNPs).

. OH

(-) OCl

NO.

O2 (-)

glutathione

GSH


Input: A basic principle here is that the GSHs on the AuNP surface can be readily detached via the formation of glutathione disulfides upon the addition of ROS and RNS, and destabilized particles can aggregate to generate the plasmonic couplings between plasmonic AuNPs that trigger the red shift in UV-vis spectrum and solution color change.

GSHs

glutathione disulfides


Input: For nonradical species such as H2O2, this process can be more efficiently achieved by converting them into radical species via the Fenton reaction.


Input: Using this strategy, we were able to rapidly and quantitatively distinguish among cancerous and normal cells based on ROS and RNS production.


Input: Twisting bilayer graphene superlattices.

graphene


Input: Bilayer graphene is an intriguing material in that its electronic structure can be altered by changing the stacking order or the relative twist angle, yielding a new class of low-dimensional carbon system.

graphene

carbon


Input: Twisted bilayer graphene can be obtained by (i) thermal decomposition of SiC; (ii) chemical vapor deposition (CVD) on metal catalysts; (iii) folding graphene; or (iv) stacking graphene layers one atop the other, the latter of which suffers from interlayer contamination.

graphene

SiC

graphene

graphene


Input: Existing synthesis protocols, however, usually result in graphene with polycrystalline structures.

graphene


Input: The present study investigates bilayer graphene grown by ambient pressure CVD on polycrystalline Cu.

graphene

Cu


Input: Controlling the nucleation in early stage growth allows the constituent layers to form single hexagonal crystals.


Input: New Raman active modes are shown to result from the twist, with the angle determined by transmission electron microscopy.


Input: The successful growth of single-crystal bilayer graphene provides an attractive jumping-off point for systematic studies of interlayer coupling in misoriented few-layer graphene systems with well-defined geometry.

graphene

graphene


Input: Acyclic nucleoside phosphonates containing a second phosphonate group are potent inhibitors of 6-oxopurine phosphoribosyltransferases and have antimalarial activity.

Acyclic nucleoside phosphonates

phosphonate


Input: Acyclic nucleoside phosphonates (ANPs) that contain a 6-oxopurine base are good inhibitors of the Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) 6-oxopurine phosphoribosyltransferases (PRTs).

Acyclic nucleoside phosphonates

ANPs


Input: Chemical modifications based on the crystal structure of 2-(phosphonoethoxy) ethylguanine (PEEG) in complex with human HGPRT have led to the design of new ANPs.

2-(phosphonoethoxy) ethylguanine

PEEG

ANPs


Input: These novel compounds contain a second phosphonate group attached to the ANP scaffold.

phosphonate

ANP


Input: {[(2-[(Guanine-9H-yl) methyl] propane-1, 3-diyl) bis (oxy)] bis (methylene)} diphosphonic acid (compound 17) exhibited a Ki value of 30 nM for human HGPRT and 70 nM for Pf HGXPRT.

{[(2-[(Guanine-9H-yl) methyl] propane-1, 3-diyl) bis (oxy)] bis (methylene)} diphosphonic acid


Input: The crystal structure of this compound in complex with human HGPRT shows that it fills or partially fills three critical locations in the active site: the binding sites of the purine base, the 5'-phosphate group, and pyrophosphate.

purine

pyrophosphate


Input: This is the first HG (X) PRT inhibitor that has been able to achieve this result.


Input: Prodrugs have been synthesized resulting in IC50 values as low as 3. 8 mu M for Pf grown in cell culture, up to 25-fold lower compared to the parent compounds.


Input: Synthesis of novel estrogen receptor antagonists using metal-catalyzed coupling reactions and characterization of their biological activity.

estrogen


Input: Estrogen receptor (ER) antagonists are valuable in the treatment of ER-positive human breast cancer.

Estrogen


Input: In this study, we designed and synthesized nine new derivatives of 17 beta-estradiol (E2) with a bulky side chain attached to its C-7 alpha position, and determined their ER antagonistic activity using in vitro bioassays.

17 beta-estradiol


Input: Four of the derivatives showed a strong inhibition of ER alpha transactivation activity in a luciferase reporter assay and blocked ER alpha interactions with coactivators.


Input: Similarly, these derivatives also strongly inhibited the growth of the ER alpha-positive human breast cancer cells.


Input: Computational docking analysis was conducted to model the interaction of these antagonists with the human ER alpha and showed that they could tightly bind to the ER alpha in a manner similar to that of ICI-182, 780, a pure ER antagonist.

ICI-182, 780


Input: These results provide an example that attachment of a bulky side chain to the C-7 alpha position of E2 can produce ER antagonists with ER affinity comparable to that of ICI-182, 780.

ICI-182, 780


Input: Device physics and operation of lateral bulk heterojunction devices.


Input: Measurements of lateral bulk heterojunction (BHJ) devices have recently been reported as a means to characterize charge transport and recombination properties within organic photovoltaic (OPV) materials.


Input: These structures allow for the direct measurement of the lateral extents of the space charge regions, potential and electric field profiles, current versus voltage characteristics, and other physical and chemical properties.


Input: This article describes numerical simulations that show three different transport regimes present within lateral BHJ devices and two different experimental methods, which verify those findings.


Input: These measurement techniques utilize typical confocal microscopy tools as well as steady-state current versus voltage measurements on high aspect ratio nanofabricated structures in order to probe the material properties between the electrodes.


Input: Experimental results show that the lateral extents of space charge regions within these devices are approximately 1-5 mu m, which are related to the drift lengths of the charge carriers, and that the mechanism of bimolecular recombination is shown to be a bulk material property.


Input: The results within this article describe a series of methods to evaluate charge transport and recombination along the in-plane direction in BHJ films and provide complementary insights to those obtained from vertical-device-based measurements.


Input: Practical approach for measuring heat capacity of pharmaceutical crystals/glasses by modulated-temperature differential scanning calorimetry.


Input: A practical protocol to obtain accurate heat capacity values of pharmaceutical compounds using modulated-temperature differential scanning calorimetry was established.


Input: Three pharmaceutical compounds, acetaminophen, indomethacin, and tri-O-methyl-beta-cyclodextrin were used as model compounds.

acetaminophen

indomethacin

tri-O-methyl-beta-cyclodextrin


Input: Powder samples did not produce reproducible results, presumably due to inclusion of gas in gap of powders that influenced the measured heat capacity and thermal homogeneity in the sample.


Input: Thus, the amorphous characteristics were evaluated using quench-cooled samples.


Input: Crystalline samples were obtained by partially melting the sample to allow recrystallization using the residual crystal as a template.


Input: Optimum sample mass was about 10 mg.


Input: Use of too small sample size resulted in poor reproducibility due to localization of the sample in the pan, while too large size resulted in low heat capacity values probably because of heterogeneity of the sample temperature.


Input: The optimum modulation period was in the range of 60 s and 90 s, to which the ramp rates of 2 degrees C/min and 1 degrees C/min, respectively, were applied.


Input: The ramp amplitude was less significant in the evaluation.


Input: This information should help in comprehending basic characteristics of pharmaceutical compounds.


Input: Particle condition change in emulsion admixture evaluated by in situ flow particle imaging analysis.


Input: We evaluated the particle state change in emulsion admixtures using in situ flow particle imaging analysis (FPIA).


Input: Ropion (R) intravenous (flurbiprofen axetil: Ropion (R)) served as the model emulsion formulation.

Ropion

flurbiprofen axetil

Ropion


Input: A binary mixture of Ropion (R) and normal saline (NS), and a ternary admixture of Ropion (R), NS, and Gaster (R) injection (famotidine: Gaster (R)) or Primperan (R) injection (metoclopramide hydrochloride: Primperan (R)) were prepared and the change in emulsion particle state was analyzed using FPIA under in situ condition.

Ropion

Ropion

Gaster

famotidine

Gaster

Primperan

metoclopramide hydrochloride

Primperan


Input: The effect of storage on pH change and the chemical stability of flurbiprofen axetil were also investigated.

flurbiprofen axetil


Input: In Ropion (R), various particle images (mean diameter: 2. 4 micro m) were obtained.

Ropion


Input: From our analysis of changes in scattergrams and particle images, changing behaviors of emulsion particles as a function of storage time depended on the systems of admixture samples.


Input: In Ropion (R)/NS and Ropion (R)/Gaster (R)/NS systems, mean particle size and particle number increased with lengthening storage time; however, these values were dramatically increased beyond 6 h in the Ropion (R)/Primperan (R)/NS system, corresponding to a decrease in measured pH.

Ropion

Ropion

Gaster

Ropion

Primperan


Input: The decomposition of flurbiprofen axetil due to incompatibility was not observed in all systems.

flurbiprofen axetil


Input: Detailed information on the change in emulsion particle state was obtained using FPIA, indicating that this method is useful to evaluate state changes in emulsion admixtures under in situ condition.


Input: Ca2 +-dependent protein kinase11 and 24 modulate the activity of the inward rectifying K + channels in Arabidopsis pollen tubes.

Ca2 +

K +


Input: Potassium (K (+)) influx into pollen tubes via K (+) transporters is essential for pollen tube growth; however, the mechanism by which K (+) transporters are regulated in pollen tubes remains unknown.

Potassium

K (+)

K (+)

K (+)


Input: Here, we report that Arabidopsis thaliana Ca (2 +)-dependent protein kinase11 (CPK11) and CPK24 are involved in Ca (2 +)-dependent regulation of the inward K (+) (K (+) in) channels in pollen tubes.

Ca (2 +)

Ca (2 +)

K (+)

K (+)


Input: Using patch-clamp analysis, we demonstrated that K (+) in currents of pollen tube protoplasts were inhibited by elevated [Ca (2 +)] cyt.

K (+)

Ca (2 +)


Input: However, disruption of CPK11 or CPK24 completely impaired the Ca (2 +)-dependent inhibition of K (+) in currents and enhanced pollen tube growth.

Ca (2 +)

K (+)


Input: Moreover, the cpk11 cpk24 double mutant exhibited similar phenotypes as the corresponding single mutants, suggesting that these two CDPKs function in the same signaling pathway.


Input: Bimolecular fluorescence complementation and coimmunoprecipitation experiments showed that CPK11 could interact with CPK24 in vivo.


Input: Furthermore, CPK11 phosphorylated the N terminus of CPK24 in vitro, suggesting that these two CDPKs work together as part of a kinase cascade.

N


Input: Electrophysiological assays demonstrated that the Shaker pollen K (+) in channel is the main contributor to pollen tube K (+) in currents and acts as the downstream target of the CPK11-CPK24 pathway.

K (+)

K (+)


Input: We conclude that CPK11 and CPK24 together mediate the Ca (2 +)-dependent inhibition of K (+) in channels and participate in the regulation of pollen tube growth in Arabidopsis.

Ca (2 +)

K (+)


Input: Overdosage of Hand2 causes limb and heart defects in the human chromosomal disorder partial trisomy distal 4q.


Input: Partial trisomy distal 4q (denoted 4q +) is a human chromosomal disorder caused by duplication of the distal end of the long arm of chromosome 4 (Chr4).


Input: This disorder manifests typical phenotypes, including craniofacial, renal, heart and thumb developmental defects.


Input: Although these clinical features are likely caused by a dosage imbalance in the gene network involving the trisomic region, the causative gene or genes and the molecular bases are largely unknown.


Input: Here, we report mouse Recombination-induced mutation 4 (Rim4) as a model animal of 4q +.


Input: The Rim4 genome contains an insertion of a 6. 5 Mb fragment from mouse chromosome 8 into chromosome 6.


Input: This insertion fragment contains 17 genes, including Hand2, that encode the basic helix-loop-helix transcription factor and is syntenic to the distal end of human Chr4, 4q32. 3 to 4q34. 1, which is responsible for 4q +.


Input: A comparison of phenotypes between patients with Rim4 and 4q + revealed that Rim4 shows direct parallels with many phenotypes of 4q + such as craniofacial, heart, cervical vertebra and limb deformities.


Input: Rebalancing the gene dosage by a genetic cross with Hand2 knockout mice ameliorated symptoms of the heart and limb deformities of Rim4.


Input: Conversely, an increase in copy number of Hand2 in wild-type mice recaptures the heart and limb deformities of Rim4.


Input: Our results collectively demonstrate that overdosage of Hand2 is a major cause for at least the limb and heart phenotypes of 4q + and that mouse Rim4 provides a unique animal model for understanding the molecular bases underlying the complex phenotypes of 4q +.


Input: Ultrasensitive non-resonant detection of ultrasound with plasmonic metamaterials.


Input: Optical sensors for ultrasound detection provide high sensitivity and bandwidth, essential for photoacoustic imaging in clinical diagnostics and biomedical research.


Input: Implementing plasmonic metamaterials in a non-resonant regime facilitates sub-nanosecond, highly sensitive detectors while eliminating cumbersome optical alignment necessary for resonant sensors.


Input: Luminescent conjugated oligothiophenes for sensitive fluorescent assignment of protein inclusion bodies.

oligothiophenes


Input: Small hydrophobic ligands identifying intracellular protein deposits are of great interest, as protein inclusion bodies are the pathological hallmark of several degenerative diseases.


Input: Here we report that fluorescent amyloid ligands, termed luminescent conjugated oligothiophenes (LCOs), rapidly and with high sensitivity detect protein inclusion bodies in skeletal muscle tissue from patients with sporadic inclusion body myositis (s-IBM).

oligothiophenes


Input: LCOs having a conjugated backbone of at least five thiophene units emitted strong fluorescence upon binding, and showed co-localization with proteins reported to accumulate in s-IBM protein inclusion bodies.

thiophene


Input: Compared with conventional amyloid ligands, LCOs identified a larger fraction of immunopositive inclusion bodies.


Input: When the conjugated thiophene backbone was extended with terminal carboxyl groups, the LCO revealed striking spectral differences between distinct protein inclusion bodies.

thiophene

carboxyl


Input: We conclude that 1) LCOs are sensitive, rapid and powerful tools for identifying protein inclusion bodies and 2) LCOs identify a wider range of protein inclusion bodies than conventional amyloid ligands.


Input: Comparative Binding Energy (COMBINE) Analysis for Understanding the Binding Determinants of Type II Dehydroquinase Inhibitors.


Input: Herein we report comparative binding energy (COMBINE) analyses to derive quantitative structure-activity relationship (QSAR) models that help rationalize the determinants of binding affinity for inhibitors of type II dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway.

shikimic acid


Input: Independent COMBINE models were derived for Helicobacter pylori and Mycobacterium tuberculosis DHQ2, which is an essential enzyme in both these pathogenic bacteria that has no counterpart in human cells.


Input: These studies quantify the importance of the hydrogen bonding interactions between the ligands and the water molecule involved in the DHQ2 reaction mechanism.

hydrogen


Input: They also highlight important differences in the ligand interactions with the interface pocket close to the active site that could provide guides for future inhibitor design.


Input: Over-the-Counter Access to Emergency Contraception without Age Restriction: An Opinion of the Women' s Health Practice and Research Network of the American College of Clinical Pharmacy.


Input: Family planning remains a high priority area for the United States, with goals to increase the proportion of pregnancies that are intended, reduce pregnancy rates among adolescents, and increase contraceptive use prioritized in the Healthy People 2020 objectives.


Input: Contraception intended for use after unprotected intercourse, known as emergency contraception, remains underutilized.


Input: Levonorgestrel is one method of oral emergency contraception, which prevents fertilization and does not disrupt an already established pregnancy; thus, timing of administration is critical.

Levonorgestrel


Input: Despite data demonstrating safety and efficacy, evidence-based decision making has been overshadowed by politically charged actions involving levonorgestrel emergency contraception for over a decade.

levonorgestrel


Input: The Women' s Health Practice and Research Network of the American College of Clinical Pharmacy supports expanded access to levonorgestrel emergency contraception and removal of barriers such as age restrictions on the nonprescription drug product.

levonorgestrel


Input: Pharmacists remain a key provider of emergency contraceptive services and can help ensure timely access.


Input: In states where direct pharmacy access to emergency contraception is available, pharmacists are encouraged to participate.


Input: Education, research, and advocacy are other important responsibilities for pharmacists in this arena.


Input: Selective functionalization of the internal and the external surfaces of mesoporous silicon by liquid masking.

silicon


Input: A general approach for selective, differential functionalization of the interior and exterior surfaces of mesoporous Si is reported.

Si


Input: The method employs two immiscible liquids, one inert and the other chemically reactive with the porous Si nanostructure.

Si


Input: First, a porous Si sample is prepared by electrochemical etch and then it is mildly oxidized, which places a thin layer of silicon oxide at the surface.

Si

silicon oxide


Input: The inner pore walls of the partially oxidized porous Si film are then infiltrated with an inert liquid (octane).

Si

octane


Input: The sample is then immersed in aqueous solution containing hydrogen fluoride (HF), which serves as the reactive liquid.

hydrogen fluoride

HF


Input: The hydrophobic phase is retained in the interior of the porous nanostructure, and HF (aq) attacks only the exposed surfaces of the oxidized porous Si sample, generating a hydrophobic, hydrogen-terminated (Si-H) outer layer.

HF

Si

hydrogen

Si-H


Input: The reaction is self-limiting due to the immiscibility of octane and water, and the extent of penetration of the Si-H surface into the porous layer is dependent on the time of exposure to HF (aq).

octane

Si-H

HF


Input: The Si-H surface can then be modified by thermal hydrosilylation (1-dodecene or 10-bromo-1-decene) in a subsequent step, resulting in a bifunctional porous Si film containing hydrophobic pore entrances to hydrophilic inner pores.

Si-H

Si


Input: The hydrophobic dodecyl species at the mouths of the pores is found to form a barrier for molecular transport; it decreases the rate of leaching (into water) of a rhodamine test molecule that is preloaded into the sample by > 8 fold.

dodecyl

rhodamine


Input: What Can We Learn about Dispersion from the Conformer Surface of n-Pentane?

n-Pentane


Input: In earlier work [Gruzman, D.; Karton, A.; Martin, J. M. L. J. Phys. Chem. A 2009, 113, 11974], we showed that conformer energies in alkanes (and other systems) are highly dispersion-driven and that uncorrected DFT functionals fail badly at reproducing them, while simple empirical dispersion corrections tend to overcorrect.

alkanes


Input: To gain greater insight into the nature of the phenomenon, we have mapped the torsional surface of n-pentane to 10-degree resolution at the CCSD (T)-F12 level near the basis set limit.

n-pentane


Input: The data obtained have been decomposed by order of perturbation theory, excitation level, and same-spin vs opposite-spin character.


Input: A large number of approximate electronic structure methods have been considered, as well as several empirical dispersion corrections.


Input: Our chief conclusions are as follows: (a) the effect of dispersion is dominated by same-spin correlation (or triplet-pair correlation, from a different perspective); (b) singlet-pair correlation is important for the surface, but qualitatively very dissimilar to the dispersion component; (c) single and double excitations beyond third order are essentially unimportant for this surface; (d) connected triple excitations do play a role but are statistically very similar to the MP2 singlet-pair correlation; (e) the form of the damping function is crucial for good performance of empirical dispersion corrections; (f) at least in the lower-energy regions, SCS-MP2 and especially MP2. 5 perform very well; (g) novel spin-component scaled double hybrid functionals such as DSD-PBEP86-D2 acquit themselves very well for this problem.


Input: Adhesion of Mussel Foot Protein-3 to TiO2 Surfaces: the Effect of pH.


Input: The underwater adhesion of marine mussels relies on mussel foot proteins (mfps) rich in the catecholic amino acid 3, 4-dihydroxyphenylalanine (Dopa).

3, 4-dihydroxyphenylalanine

Dopa


Input: As a side chain, Dopa is capable of strong bidentate interactions with a variety of surfaces, including many minerals and metal oxides.

Dopa

metal oxides


Input: Titanium is among the most widely used medical implant material and quickly forms a TiO2 passivation layer under physiological conditions.

Titanium


Input: Understanding the binding mechanism of Dopa to TiO2 surfaces is therefore of considerable theoretical and practical interest.

Dopa


Input: Using a surface forces apparatus, we explored the force-distance profiles and adhesion energies of mussel foot protein 3 (mfp-3) to TiO2 surfaces at three different pHs (pH 3, 5. 5 and 7. 5).


Input: At pH 3, mfp-3 showed the strongest adhesion force on TiO2, with an adhesion energy of ~-7. 0 mJ/m (2).


Input: Increasing the pH gives rise to two opposing effects: (1) increased oxidation of Dopa, thus, decreasing availability for the Dopa-mediated adhesion, and (2) increased bidentate Dopa-Ti coordination, leading to the further stabilization of the Dopa group and, thus, an increase in adhesion force.

Dopa

Dopa

Dopa

Ti

Dopa


Input: Both effects were reflected in the resonance-enhanced Raman spectra obtained at the three deposition pHs.


Input: The two competing effects give rise to a higher adhesion force of mfp-3 on the TiO2 surface at pH 7. 5 than at pH 5. 5.


Input: Our results suggest that Dopa-containing proteins and synthetic polymers have great potential as coating materials for medical implant materials, particularly if redox activity can be controlled.

Dopa


Input: Synthetic Approaches to RBC Mimicry and Oxygen Carrier Systems.

Oxygen


Input: Whole blood or red blood cell (RBC) transfusions are highly significant, clinically, for blood replacement therapies in traumatic injuries, presurgical conditions, and anemias.


Input: However, natural RBC-based products suffer from limited shelf life due to pathological contamination and also present risks of refractoriness, graft-versus-host disease, immunosuppression, and acute lung injury.


Input: These issues can be only partially resolved by pathogen reduction technologies, serological blood testing, leukoreduction, and specialized storage; hence, they severely affect the efficacy and safety of the blood products.


Input: Consequently, there is a significant interest in synthetic RBC analogues that can mimic its oxygen-transport properties while allowing convenient manufacture, reproducibility, long shelf life, and reduced biological risks.

oxygen


Input: To this end, the current Review provides a comprehensive description and discussion of the various research approaches and current state-of-the-art in synthetically mimicking RBC' s oxygen-carrying biochemical properties, as well as the biophysical parameters (shape, size and mechanical modulus) that influence RBCs' hemodynamic transport properties in blood flow.

oxygen


Input: Diabetes, perioperative ischaemia and volatile anaesthetics: consequences of derangements in myocardial substrate metabolism.


Input: Volatile anaesthetics exert protective effects on the heart against perioperative ischaemic injury.


Input: However, there is growing evidence that these cardioprotective properties are reduced in case of type 2 diabetes mellitus.


Input: A strong predictor of postoperative cardiac function is myocardial substrate metabolism.


Input: In the type 2 diabetic heart, substrate metabolism is shifted from glucose utilisation to fatty acid oxidation, resulting in metabolic inflexibility and cardiac dysfunction.

glucose

fatty acid


Input: The ischaemic heart also loses its metabolic flexibility and can switch to glucose or fatty acid oxidation as its preferential state, which may deteriorate cardiac function even further in case of type 2 diabetes mellitus. Recent experimental studies suggest that the cardioprotective properties of volatile anaesthetics partly rely on changing myocardial substrate metabolism.

glucose

fatty acid


Input: Interventions that target at restoration of metabolic derangements, like lifestyle and pharmacological interventions, may therefore be an interesting candidate to reduce perioperative complications.


Input: This review will focus on the current knowledge regarding myocardial substrate metabolism during volatile anaesthesia in the obese and type 2 diabetic heart during perioperative ischaemia.


Input: Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression.


Input: Targeted gene regulation on a genome-wide scale is a powerful strategy for interrogating, perturbing, and engineering cellular systems.


Input: Here, we develop a method for controlling gene expression based on Cas9, an RNA-guided DNA endonuclease from a type II CRISPR system.


Input: We show that a catalytically dead Cas9 lacking endonuclease activity, when coexpressed with a guide RNA, generates a DNA recognition complex that can specifically interfere with transcriptional elongation, RNA polymerase binding, or transcription factor binding.


Input: This system, which we call CRISPR interference (CRISPRi), can efficiently repress expression of targeted genes in Escherichia coli, with no detectable off-target effects.


Input: CRISPRi can be used to repress multiple target genes simultaneously, and its effects are reversible.


Input: We also show evidence that the system can be adapted for gene repression in mammalian cells.


Input: This RNA-guided DNA recognition platform provides a simple approach for selectively perturbing gene expression on a genome-wide scale.


Input: Novel effects of ectoine, a bacteria-derived natural tetrahydropyrimidine, in experimental colitis.

ectoine

tetrahydropyrimidine


Input: Evidence suggests an important role of intestinal barrier dysfunction in the etiology of inflammatory bowel disease (IBD).


Input: Therefore stabilizing mucosal barrier function constitutes a new therapeutic approach in its management.


Input: Ectoine is a compatible solute produced by aerobic chemoheterotrophic and halophilic/halotolerant bacteria, where it acts as osmoprotectant and effective biomembrane stabilizer, protecting the producing cells from extreme environmental stress.

Ectoine


Input: Since this natural compound was also shown to prevent inflammatory responses associated with IBD, its potential usefulness was studied in a model of colitis.


Input: Groups of rats were treated orally with different doses of ectoine (30-300mg/kg) or sulfasalazine (reference drug) daily for 11 days.

ectoine

sulfasalazine


Input: On day 8 colitis was induced by intracolonic instillation of 2, 4, 6-trinitrobenzenesulfonic acid, when overt signs of lesions develop within the next 3 days.

2, 4, 6-trinitrobenzenesulfonic acid


Input: On day 12, blood was withdrawn from the retro-orbital plexus of the rats and the animals were sacrificed.


Input: The colon was excised and examined macroscopically and microscopically.


Input: Relevant parameters of oxidative stress and inflammation were measured in serum and colon homogenates.


Input: Induction of colitis led to marked weight loss, significant histopathological changes of the colon, and variable changes in levels of myeloperoxidase, reduced glutathione, malondialdehyde, and all inflammatory markers tested.

glutathione

malondialdehyde


Input: Treatment with ectoine ameliorated the inflammatory changes in TNBS-induced colitis.

ectoine


Input: This effect was associated with reduction in the levels of TNF-alpha, IL-1 beta, ICAM-1, PGE2 and LTB4.


Input: The findings suggest that intestinal barrier stabilizers from natural sources could offer new therapeutic measures for the management of IBD.


Input: Cytotoxic effect of leaf essential oil of Lippia gracilis Schauer (Verbenaceae).


Input: Medicinal plants are one of the most important sources of drugs used in the pharmaceutical industry.


Input: Among traditional medicinal plants, Lippia gracilis Schauer (Verbenaceae) had been used for several medicinal purposes in Brazilian northeastern.


Input: In this study, leaf essential oil (EO) of L. gracilis was prepared using hydrodistillation.


Input: Followed by GC-MS analysis, its composition was characterized by the presence of thymol (55. 50%), as major constituent.

thymol


Input: The effects of EO on cell proliferation and apoptosis induction were investigated in HepG2 cells.


Input: Furthermore, mice bearing Sarcoma 180 tumor cells were used to confirm its in vivo effectiveness.


Input: EO and its constituents (thymol, p-cymene, gamma-terpinene and myrcene) displayed cytotoxicity to different tumor cell lines.

thymol

p-cymene

gamma-terpinene

myrcene


Input: EO treatment caused G1 arrest in HepG2 cells accompanied by the induction of DNA fragmentation without affecting cell membrane integrity.


Input: Cell morphology consistent with apoptosis and a remarkable activation of caspase-3 were also observed, suggesting induction of caspase-dependent apoptotic cell death.


Input: In vivo antitumor study showed tumor growth inhibition rates of 38. 5-41. 9%.


Input: In conclusion, the tested essential oil of L. gracilis leaves, which has thymol as its major constituent, possesses significant in vitro and in vivo antitumor activity.

thymol


Input: These data suggest that leaf essential oil of L. gracilis is a potential medicinal resource.


Input: A mitochondrial ribosomal and RNA decay pathway blocks cell proliferation.


Input: Proliferating cells require coordinated gene expression between the nucleus and mitochondria in order to divide, ensuring sufficient organelle number in daughter cells [1].


Input: However, the machinery and mechanisms whereby proliferating cells monitor mitochondria and coordinate organelle biosynthesis remain poorly understood.


Input: Antibiotics inhibiting mitochondrial translation have emerged as therapeutics for human cancers because they block cell proliferation [2, 3].


Input: These proliferative defects were attributable to modest decreases in mitochondrial respiration [3, 4], even though tumors are mainly glycolytic [5] and mitochondrial respiratory chain function appears to play a minor role in cell proliferation in vivo [6].


Input: Here we challenge this interpretation by demonstrating that one class of antiproliferative antibiotic induces stalled mitochondrial ribosomes, which triggers a mitochondrial ribosome and RNA decay pathway.


Input: Rescue of the stalled mitochondrial ribosomes initiates a retrograde signaling response to block cell proliferation and occurs prior to any loss of mitochondrial respiration.


Input: The loss of respiratory chain function is simply a downstream effect of impaired mitochondrial translation and not the antiproliferative signal.


Input: This mitochondrial ribosome quality-control pathway is actively monitored in cells and constitutes an important organelle checkpoint for cell division.


Input: High rates of pregnancy loss by subordinates leads to high reproductive skew in wild golden lion tamarins (Leontopithecus rosalia).


Input: Across taxa, cooperative breeding has been associated with high reproductive skew.


Input: Cooperatively breeding golden lion tamarins (Leontopithecus rosalia) were long thought to have a monogynous mating system in which reproduction was limited to a single dominant female.


Input: Subordinates with few reproductive opportunities delayed dispersal and remained in the natal group to provide alloparental care to siblings, thus allowing dominant reproductive females to meet the energetic needs associated with high rates of reproduction and successful infant rearing.


Input: The goal of this study was to re-assess monogyny in wild golden lion tamarin groups based upon pregnancy diagnoses that used non-invasive enzyme immunoassay for progesterone and cortisol, combined with weekly data on individual weight gain, bi-annual physical examinations noting pregnancy and lactation status and daily behavioral observations.

progesterone

cortisol


Input: We established quantitative and qualitative criteria to detect and determine the timing of pregnancies that did not result in the birth of infants.


Input: Pregnancy polygyny occurred in 83% of golden lion tamarin groups studied.


Input: The loss of 64% of subordinate pregnancies compared to only 15% by dominant females limited reproductive success mainly to dominant females, thus maintaining high reproductive skew in female golden lion tamarins.


Input: Pregnancy loss by subordinate adults did not appear to result from dominant interference in subordinate hormonal mechanisms, but more likely resulted from subordinate abandonment of newborn infants to mitigate dominant aggression.


Input: Synthesis of novel 2-amino-4-(5'-substituted 2'-phenyl-1H-indol-3'-yl)-6-aryl-4H-pyran-3-carbonitrile derivatives as antimicrobial and antioxidant agents.

2-amino-4-(5'-substituted 2'-phenyl-1H-indol-3'-yl)-6-aryl-4H-pyran-3-carbonitrile


Input: As a part of systematic investigation of synthesis and biological activities of indole analogues linked to various heterocyclic systems, we have synthesized new compounds viz., 2-amino-4-(5'-substituted 2'-phenyl-1H-indol-3'-yl)-6-aryl-4H-pyran-3-carbonitriles (2a-i), 4, 5-diamino-6-(5'-substituted 2'-phenyl-1H-indol-3'-yl)-8-aryl-2-oxo-2, 6-dihydrodipyrano [2, 3-b: 3, 2-e] pyridine-3-carbonitriles (3a-i), 4-amino-5-(5'-substituted 2'-phenyl-1H-indol-3-yl)-7-aryl-1H-pyrano [2, 3-d] pyrimidin-2 (5H)-ones (4a-i), 4-amino-5-(5'-substituted 2'-phenyl-1H-indol-3'-yl)-7-aryl-1H-pyrano [2, 3-d] pyrimidin-2 (5H)-thiones (5a-i), 4-(5'-subtituted 2'-phenyl-1H-indol-3'-yl)-6-aryl-1, 4-dihydropyrano [2, 3-c] pyrazol-3-amines (6a-i) and 5-(5'-substituted 2'-phenyl-1H-indol-3'-yl)-7-aryl-3H-pyrano [2, 3-d] pyrimidin-4 (5H)-ones (7a-i).

indole

2-amino-4-(5'-substituted 2'-phenyl-1H-indol-3'-yl)-6-aryl-4H-pyran-3-carbonitriles

4, 5-diamino-6-(5'-substituted 2'-phenyl-1H-indol-3'-yl)-8-aryl-2-oxo-2, 6-dihydrodipyrano [2, 3-b: 3, 2-e] pyridine-3-carbonitriles

4-amino-5-(5'-substituted 2'-phenyl-1H-indol-3-yl)-7-aryl-1H-pyrano [2, 3-d] pyrimidin-2 (5H)-ones

4-amino-5-(5'-substituted 2'-phenyl-1H-indol-3'-yl)-7-aryl-1H-pyrano [2, 3-d] pyrimidin-2 (5H)-thiones

4-(5'-subtituted 2'-phenyl-1H-indol-3'-yl)-6-aryl-1, 4-dihydropyrano [2, 3-c] pyrazol-3-amines

5-(5'-substituted 2'-phenyl-1H-indol-3'-yl)-7-aryl-3H-pyrano [2, 3-d] pyrimidin-4 (5H)-ones


Input: Antibacterial activity results revealed that, compound 6a showed promising activity versus Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae.


Input: Compound 6d exhibited good activity against S. aureus, K. pneumoniae and Pseudomonas aeruginosa.


Input: Antifungal activity results indicated that, compound 4d exhibited maximum zone of inhibition against Aspergillus oryzae and Aspergillus flavus.


Input: In case of antioxidant activity, compound 4a showed promising radical scavenging activity, ferric ions (Fe (3 +)) reducing antioxidant power (FRAP) and metal chelating activity.

ferric

Fe (3 +)


Input: Antiproliferative effect of two novel COX-2 inhibitors on human keratinocytes.


Input: Selective COX-2 inhibitors (COXib) belonging to the class of diaryl heterocycles (e. g., celecoxib, rofecoxib, etc.), are devoid of the undesirable effects due to their capacity to inhibit selectively inducible (COX-2), responsible for inflammatory effects but not constitutive cyclooxygenase-1 (COX-1) (COX); responsible for cytoprotective effects on gastric mucosa.

diaryl heterocycles

celecoxib

rofecoxib


Input: In addition, several reports have identified an increased risk of cardiovascular events associated with the use of COXib.


Input: We have developed a new series of anti-inflammatory agents (1, 5-diarylpyrrole-3-alkoxyethyl esters and ethers).

1, 5-diarylpyrrole-3-alkoxyethyl esters and ethers


Input: To evaluate the effect of two 1, 5-diarylpyrrole-3-alkoxyethyl ethers, VA441 and VA428 (up to 100 mu M), respectively, in comparison with two well known COXib, celecoxib and rofecoxib, on HaCaT cell (keratinocytes) proliferation and toxicity.

1, 5-diarylpyrrole-3-alkoxyethyl ethers

celecoxib

rofecoxib


Input: Crucial molecules in cell cycle progression, i. e. NF kappa B and ERK as targets/mediators and cyclin D1 and p21 Cip1/Kip as final effectors were evaluated by Western blot, immunohystochemistry and q-PCR analysis.


Input: Both compounds, VA441 and VA428, showed a strong inhibition of cell proliferation, and did not exhibit cytotoxicity.


Input: The anti-proliferative effect was accompanied by a strong activation of ERK and induction of the cell cycle inhibitor p21.


Input: In addition, there was a clear inhibition of the transcription factor NF-kappa B and downregulation of cyclin D1, with enforced inhibition of the HaCaT cell cycle progression.


Input: These data suggest that compounds VA441 and VA428, along with their role in inhibiting COX-2 and inflammation, could have a possible therapeutic (topical and systemic) use against skin proliferative disorders, such as psoriasis.


Input: Role of oxidative stress in chemical allergens induced skin cells activation.


Input: Allergic contact dermatitis (ACD) is an important occupational and environmental disease caused by topical exposure to chemical allergens.


Input: It describes the adverse effects that may results when exposure to a chemical elicits a T cell-mediated inflammatory skin disease.


Input: The ability of contact sensitizers to induce the oxidative stress pathway in keratinocytes and dendritic cells has been confirmed by several authors.


Input: Reactive oxygen species (ROS) can serve as essential second messengers mediating cellular responses resulting in immune cells activation.

oxygen


Input: Oxidative stress may be the starter point, as it leads to the activation of transcription factors and signaling pathways, including NF-kB and p38 MAPK, which leads to the release of cytokines and chemokines.


Input: ROS are also involved in the activation of the NLRP3/NALP3 inflammasome, which is required to direct the proteolytic maturation of inflammatory cytokines such as IL-1 beta and IL-18, which are all integral to the process of dendritic cells mobilization, migration and functional maturation.


Input: Moreover, emerging evidence correlates ROS to changes in the constitution of the extracellular microenvironment found to facilitate ACD.


Input: The purpose of this review is to provide both conceptual and technical frameworks on the role of oxidative stress in chemical allergy.


Input: Relative expression of cholesterol transport-related proteins and inflammation markers through the induction of 7-ketosterol-mediated stress in Caco-2 cells.

cholesterol


Input: Human diets contain sterol oxidation products that can induce cytotoxic effects, mainly caused by cholesterol oxides.

sterol

cholesterol oxides


Input: However, phytosterol oxides effects have been less extensively investigated.

phytosterol oxides


Input: This study evaluates the production of inflammatory biomarkers (IL-1 beta, IL-8, IL-10, TNF alpha) and the influence of gene expression transporters and enzymes related to cholesterol absorption and metabolism (NPC1L1, ABCG5/8, HMGCoA, ACAT) produced by 7-ketosterols (stigmasterol/cholesterol) in Caco-2 cells.

cholesterol

HMGCoA

stigmasterol

cholesterol


Input: These effects were linked to intracellular signaling pathways by using several inhibitors.


Input: Results showed 7-ketostigmasterol to have a greater proinflammatory potential than 7-ketocholesterol.


Input: In non-pre-treated cells, only efflux transporters were down-regulated by 7-ketosterols, showing a greater influence upon ABCG5 expression.


Input: Cell-pre-incubation with bradykinin induced changes in ABCG expression levels after 7-ketostigmasterol-incubation; however, the energetic metabolism inhibition reduced NPC1L1 expression only in 7-ketocholesterol-incubated cells.

bradykinin


Input: In non-pre-treated cells, HMG-CoA was up-regulated by both 7-ketosterols.

HMG-CoA


Input: However, exposure to inhibitors down-regulated the expression levels, mainly in 7-ketocholesterol-incubated cells.


Input: While ACAT expression values in non-pre-treated cells were unchanged, exposure to inhibitors caused down-regulation of mRNA levels.


Input: These results suggest that internalization and excretion of 7-ketostigmasterol is probably influenced by [Ca] i, which also could mediate HMGCoA activity in POPs metabolism.

Ca

HMGCoA


Input: However, energetic metabolism and reducing equivalents exert different influences upon the 7-ketosterol internalization.


Input: Neuroprotective effects of neolignans isolated from Magnoliae Cortex against glutamate-induced apoptotic stimuli in HT22 cells.

neolignans

glutamate


Input: In the course of screening for neuroprotective natural products, Magnoliae Cortex showed potent inhibition of hippocampal neuronal HT22 cell death.


Input: Obovatol, honokiol, and magnolol were isolated from the ethanolic extract of Magnoliae Cortex.

Obovatol

honokiol

magnolol


Input: Isolated compounds obovatol, honokiol, and magnolol were protective against 5mM glutamate-induced cell death.

obovatol

honokiol

magnolol

glutamate


Input: When cells were stressed using glutamate, cell viability decreased to 16. 98 +/- 4. 58% over the control (100. 00 +/- 10. 15%).

glutamate


Input: In contrast, 10 mu M obovatol, 10 mu M honokiol, and 50 mu M magnolol increased cell viability to 91. 80 +/- 1. 70%, 93. 59 +/- 1. 93%, and 85. 36 +/- 7. 40%, respectively.

obovatol

honokiol

magnolol


Input: The neuroprotective effects of obovatol and honokiol were attributable to the inhibition of intracellular reactive oxygen species production, followed by protection of the mitochondrial membrane potential (Delta Psi m), recovery of Bcl-2 and Bid levels, inhibition of apoptosis-inducing factor expression, and phosphorylation of mitogen-activated protein kinases such as p38 kinases, extracellular signal-regulated kinases, and c-Jun N-terminal kinases.

obovatol

honokiol

oxygen

N


Input: On the contrary, magnolol did not show any significant effect on the Delta Psi m and apoptotic factors.

magnolol


Input: Among three compounds, obovatol most strongly scavenged 2, 2-diphenyl-1-picrylhydrazyl radicals and inhibited the elevation of intracellular reactive oxygen species levels in glutamate-stressed HT22 cells.

obovatol

2, 2-diphenyl-1-picrylhydrazyl

oxygen

glutamate


Input: These data suggest that obovatol and honokiol may have clinical applications for preventing neurodegenerative disorders.

obovatol

honokiol


Input: Inhibition of angiogenesis and invasion by DMBT is mediated by downregulation of VEGF and MMP-9 through Akt pathway in MDA-MB-231 breast cancer cells.

DMBT


Input: Invasion, either directly or via metastasis formation, is the main cause of death in cancer patients, development of efficient anti-invasive agents is an important research challenge.


Input: In order to obtain more potent inhibitors, a series of brartemicin analogs were synthesized and evaluated for their inhibitory activity against invasion.

brartemicin


Input: Among the synthetic analogs tested, DMBT, 6, 6'-bis (2, 3-dimethoxybenzoyl)-a, a-d-trehalose, was found to be the most potent anti-invasive agent.

DMBT

6, 6'-bis (2, 3-dimethoxybenzoyl)-a, a-d-trehalose


Input: But the effects of DMBT on breast cancer cells were not known.

DMBT


Input: In this study, the effects of DMBT on invasion and metastasis in MDA-MB-231 cells were investigated.

DMBT


Input: MTT assay showed that no obvious inhibitory or cytotoxic effect of DMBT was found.

MTT

DMBT


Input: DMBT could inhibit invasion, migration and tube formation of HUVECs.

DMBT


Input: Gelatin zymography showed that DMBT inhibited secretion and activity of MMP-9.

DMBT


Input: Western blotting demonstrated that DMBT effectively suppressed the expression of VEGF, p-VEGFR-2, p-EGFR, and p-Akt.

DMBT


Input: These results suggested that DMBT could inhibit invasion and angiogenesis by downregulation of VEGFand MMP-9, resulting from the inhibition of Akt pathway.

DMBT


Input: DMBT might be a promising lead molecule for the anti-metastasis and serve as a therapeutic agent to inhibit breast cancer cell invasion and metastasis.

DMBT


Input: Curcumin loaded solid lipid nanoparticles: An efficient formulation approach for cerebral ischemic reperfusion injury in rats.

Curcumin


Input: SCOPE: To evaluate curcumin loaded solid lipid nanoparticles (C-SLNs) in the experimental paradigm of cerebral ischemia (BCCAO model) in rats.

curcumin


Input: METHODS AND RESULTS: Oral administration of free curcumin and C-SLNs (25 and 50mg/kg) was started 5days prior and continued for 3days after BCCAO.

curcumin


Input: Alleviation in behavioral, oxidative and nitrosative stress, acetylcholinesterase, mitochondrial enzyme complexes, and physiological parameters were assessed.


Input: Confirmation of effective brain delivery of C-SLNs (p. o) was done using biodistribution studies in mice and confocal microscopy of rat brain section.


Input: There was an improvement of 90% in cognition and 52% inhibition of acetylcholinesterase versus cerebral ischemic group (I/R).


Input: Neurological scoring improved by 79%.


Input: Levels of superoxide dismutase, catalase, glutathione, and mitochondrial complex enzyme activities were significantly increased, while lipid peroxidation, nitrite, and acetylcholinesterase levels decreased (p < 0. 05) after C-SLNs administration.

superoxide

glutathione

nitrite


Input: It is noteworthy to report the restoration of SOD, GSH, catalase, and mitochondrial complex enzyme levels equivalent to sham control values.

GSH


Input: Gamma-scintigraphic studies show 16. 4 and 30 times improvement in brain bioavailability (AUC) upon oral and i. v administration of C-SLNs versus solubilized curcumin (C-S).

curcumin


Input: CONCLUSIONS: Study indicates protective role of curcumin against cerebral ischemic insult; provided it is packaged suitably for improved brain delivery.

curcumin


Input: Steroids excreted in urine by neonates with 21-hydroxylase deficiency.

Steroids


Input: Characterization, using GC-MS and GC-MS/MS, of 11oxo-pregnanes and 11oxo-pregnenes.


Input: In 21-hydroxylase deficiency, urinary metabolites of 21-deoxycortisol, mainly derived from its 11oxo form 21-deoxycortisone, are indicators of intra-adrenal overproduction of 17-hydroxyprogesterone.


Input: In affected neonates these metabolites are numerous and most have not been previously described.


Input: This work forms the concluding part of a comprehensive study of urinary steroids, aiming to enhance the diagnosis of this disorder and to further elucidate steroid metabolism in neonates.

steroids

steroid


Input: Cortisol metabolites found in untreated patients, similarly almost exclusively present in their 11oxo form in neonates, have been included for completeness.

Cortisol


Input: Steroids were analyzed, after extraction and enzymatic conjugate hydrolysis, as methyloxime-trimethylsilyl ether derivatives on gas-chromatographs coupled to quadrupole and ion-trap mass-spectrometers.

Steroids

methyloxime-trimethylsilyl ether


Input: GC-MS and GC-MS/MS spectra were used together to determine the structure of hitherto undescribed 11oxo-pregnane (enes).

11oxo-pregnane (enes)


Input: Few GC-MS features were associated with the presence of the non-derivatizeable 11oxo group in pregnane (ene) s.

pregnane (ene) s


Input: GC-MS/MS contributed only to the characterization of structures outside the C-ring, as described in the preceding parts of this study.


Input: Parallels were found between the metabolism of 21-deoxycortisone and cortisone.

cortisone


Input: The major metabolic pathway was that of classical 3 alpha, 5 beta-reduction with a prominent further hydroxylation, predominantly at C6.


Input: Oxidation of the 6-hydroxyl was also common.


Input: We conclude that further oxygenated metabolites of 21-deoxycortisone have potential as more reliable markers of 21-hydroxylase deficiency in the early neonatal period, because their levels are higher during that period of life than for the classical marker 11oxo-pregnanetriol.


Input: In vivo assessment of specific cytotoxic T lymphocyte killing.


Input: The direct killing of target cells by cytotoxic T lymphocytes (CTLs) plays a fundamental role in protective immunity to viral, bacterial, protozoan and fungi infections, as well as to tumor cells.


Input: In vivo cytotoxic assays take into account the interaction of target and effector cells in the context of the proper microenvironment making the analysis biologically more relevant than in vitro cytotoxic assays.


Input: Thus, the development, improvement and validation of in vivo methods are necessary in view of the importance of the results they may provide.


Input: We describe and discuss in this manuscript a method to evaluate in vivo specific cytotoxic T lymphocyte killing.


Input: We used as model system mice immunized with human recombinant replication-deficient adenovirus 5 (HAd5) containing different transgenes as the trigger of a CTL-mediated immune response.


Input: To these mice, we adoptively transferred syngeneic cells labeled with different vital fluorescent dyes.


Input: Donor cells were pulsed (target) or not (control non-target) with distinct CD8 T-cell epitopes, mixed in a 1: 1 ratio and injected i. v. into immunized or non-immunized recipient mice.


Input: After 18-24h, spleen cells are collected and analysed by flow cytometry.


Input: A deviation from the 1: 1 ratio of control and target cell populations indicates antigen specific lysis of target cells.


Input: Protein nitration promotes inducible nitric oxide synthase transcription mediated by NF-kappa B in high glucose-stimulated human lens epithelial cells.

nitric oxide

glucose


Input: Although an important event in hyperglycaemia-induced oxidative stress is the nuclear factor-kappa b (NF-kappa B)-activated inducible nitric oxide synthase (iNOS) expression, the underlying mechanism is not fully characterized.

nitric oxide


Input: Peroxynitrite, formed from NO and superoxide, can induce multiple proteins nitration, even including NF-kappa B and iNOS, to alter their functions.

Peroxynitrite

NO

superoxide


Input: In this study, we found high glucose caused conspicuous nitration of nuclear NF-kappa B p65 and its co-activator p300 in human lens epithelial cells.

glucose


Input: The nitration of NF-kappa B and p300 promoted their co-localization and binding to ensure the activation of the iNOS gene transcription.


Input: Moreover, nearly all predicted NF-kappa B binding sites in the human iNOS gene promoter were responsive to high glucose stimulation, might for a synergistic role.

glucose


Input: While, only the NF-kappa B binding site-5212 showed significant alterations by high glucose and peroxynitrite stimulations, indicating it a more important role in the protein nitration promoted iNOS gene transcription.

glucose

peroxynitrite


Input: Our results demonstrated that protein nitration can promote the NF-kappa B-activated iNOS gene transcription in human lens epithelial cells by high glucose stimulation.

glucose


Input: Effect of serum on diesel exhaust particles (DEP)-induced apoptosis of airway epithelial cells in vitro.


Input: Patients with chronic airway diseases may be more susceptible to adverse effects of air pollutants including diesel exhaust particles (DEP).


Input: We investigated effects of foetal calf serum (FCS) on DEP-induced changes in airway epithelial cell apoptosis and inflammation.


Input: DEP (50-200 mu g/ml) increased A549 cell viability in the absence of FCS.


Input: In the presence of 3. 3% FCS, DEP (50-400 mu g/ml) decreased A549 cell viability.


Input: N-acetylcysteine (NAC, 33 mM) and the c-jun N-terminal kinase (JNK) inhibitor (SP600125, 33 mu M) further decreased the viability in the presence of DEP (200 mu g/ml) and 3. 3% FCS.

N-acetylcysteine

NAC

N


Input: Under serum-free (SF) condition, DEP (50 mu g/ml) reduced apoptotic cells; however, when 3. 3% FCS added to the culture medium, this effect was abolished.


Input: DEP (200 mu g/ml) induced mRNA expression of p21 (CIP1/WAF1) both in absence or presence of 3. 3% FCS and enhanced JNK2 mRNA expression only in the presence of 3. 3% FCS.


Input: Under SF condition, DEP (50 mu g/ml) induced mRNA expression for p27 and p53, whereas cyclin E mRNA expression was inhibited by DEP (50 and 200 mu g/ml).


Input: Furthermore, DEP (200 mu g/ml) decreased the release of interleukin (IL)-8 in the absence of FCS.


Input: In conclusion, FCS modulates effects of DEP on cell death, cell cycle and apoptosis regulating proteins, and IL-8 release by activating oxidant stress pathways, JNK and NF-kappa B.


Input: Extravasation of serum, as occurs in the inflamed airways of patients with chronic airway diseases such as asthma and COPD, may render airway epithelial cells more susceptible to the deleterious effects of DEP.


Input: Neuropeptide S enhances memory and mitigates memory impairment induced by MK801, scopolamine or A beta 1-42 in mice novel object and object location recognition tasks.

scopolamine


Input: Neuropeptide S (NPS), the endogenous ligand of NPSR, has been shown to promote arousal and anxiolytic-like effects.


Input: According to the predominant distribution of NPSR in brain tissues associated with learning and memory, NPS has been reported to modulate cognitive function in rodents.


Input: Here, we investigated the role of NPS in memory formation, and determined whether NPS could mitigate memory impairment induced by selective N-methyl-d-aspartate receptor antagonist MK801, muscarinic cholinergic receptor antagonist scopolamine or A beta 1-42 in mice, using novel object and object location recognition tasks.

N-methyl-d-aspartate

scopolamine


Input: Intracerebroventricular (i. c. v.) injection of 1 nmol NPS 5 min after training not only facilitated object recognition memory formation, but also prolonged memory retention in both tasks.


Input: The improvement of object recognition memory induced by NPS could be blocked by the selective NPSR antagonist SHA 68, indicating pharmacological specificity.

SHA 68


Input: Then, we found that i. c. v. injection of NPS reversed memory disruption induced by MK801, scopolamine or A beta 1-42 in both tasks.

scopolamine


Input: In summary, our results indicate that NPS facilitates memory formation and prolongs the retention of memory through activation of the NPSR, and mitigates amnesia induced by blockage of glutamatergic or cholinergic system or by A beta 1-42, suggesting that NPS/NPSR system may be a new target for enhancing memory and treating amnesia.


Input: Antivenom for snakebite envenoming in Sri Lanka: The need for geographically specific antivenom and improved efficacy.


Input: Sri Lanka is a tropical developing island nation that endures significant economic and medical burden as a result of snakebite envenomation, having not only a high prevalence of envenomations, but also one of the highest incidence rates (200 snakebites/100, 000 people/year) of venomous snakebite in the world (Kasturiratne et al., 2005).


Input: Ironically, the very snakes responsible for this human morbidity and mortality are a valuable a biomedical and ecological national resource, despite the medical and economic consequences of envenomation.


Input: Currently, no snake antivenom is produced using venoms from native Sri Lankan snakes as immunogens, and there is a true need for an efficacious Sri Lanka, poly-specific snake antivenom.


Input: An approach to fulfilling this need via combining the scientific, technological and economical resources from Costa Rica and the United States with the knowledge and talent of Sri Lankan official governmental agencies, legal counsels, environmental, medical and veterinary academic institutions, and religious and cultural leaders has been initiated, coordinated and funded by Animal Venom Research International (AVRI), a nonprofit charity.


Input: This bridging of nations and the cooperative pooling of their resources represents a potential avenue for antivenom development in a developing country that suffers the consequences of few specific resources for the medical management of venomous snakebite.


Input: The desired final outcome of such an endeavor for Sri Lanka is, most importantly, improved medical outcomes for snakebite patients, with enhanced and expanded science and technology relating to snake venoms and antivenoms, and the collateral benefits of reduced economic cost for the country.


Input: In chemico evaluation of prohapten skin sensitizers: behavior of 2-methoxy-4-((1) (3) C) methylphenol in the peroxidase peptide reactivity assay (PPRA) as an alternative to animal testing.

2-methoxy-4-((1) (3) C) methylphenol


Input: In chemico methods, based on the assessment of a hapten' s reactivity toward peptides, have been proposed as alternative methods for the assessment of the skin sensitizing potential of chemicals.


Input: However, even with these approaches showing promise, a major drawback is the activation of prohaptens, i. e. molecules needing a metabolic activation to become reactive and therefore sensitizing.


Input: Recently, it has been proposed to couple an enzymatic activation step based on horseradish peroxidase (HRP)/hydrogen peroxide to such peptide reactivity assays.

hydrogen peroxide


Input: To evaluate this approach, the behavior of 2-methoxy-4-methylphenol (2M4MP), reported as a moderate sensitizer according to the Local Lymph Node Assay (LLNA), has been investigated in this assay.


Input: To follow the reaction with the peptides and characterize more easily intermediates and adducts, the molecule was first (13) C isotopically substituted at the most probable reactive position.

(13) C


Input: When 2M4MP was incubated with HRP/H2O2 in a mixture PBS (pH 7. 4, 0. 1M)/acetonitrile 2: 1, two main products were formed deriving from the formation of a quinone methide 2M4MQ subsequently trapped by either H2O2 or H2O to form a benzylic hydroperoxide or alcohol, respectively.

acetonitrile

benzylic hydroperoxide

alcohol


Input: When nucleophiles such as GSH or a peptide containing a cysteine residue (Pep-Cys) were present in the reaction medium, the quinone methide 2M4MQ was trapped by the more nucleophilic thiol function to form thio-adducts.

GSH

cysteine

Cys

thiol

thio


Input: No modifications of 2M4MP were observed when the same reactions were carried out without HRP confirming that the activation of the molecule was enzyme related.


Input: Amino nucleophiles were shown to be far less reactive towards the quinone methide 2M4MQ with only tiny formation of adducts with lysine or arginine side chains.

Amino

lysine

arginine


Input: In addition we demonstrated that the same enzymatic activation could also take place in a microemulsion based on sodium dodecyl sulfate/tert-butanol/chloroform/buffer.

sodium dodecyl sulfate

tert-butanol

chloroform


Input: Which metabolites circulate?


Input: Characterization of the circulating metabolites for a new chemical entity in humans is essential for safety assessment, an understanding of their contributions to pharmacologic activities, and their potential involvement in drug-drug interactions.


Input: This review examines the abundance of metabolites relative to the total parent drug [metabolite-to-parent (M/P) ratio] from 125 drugs in relation to their structural and physicochemical characteristics, lipoidal permeability, protein binding, and fractional formation from parent (fm).


Input: Our analysis suggests that fm is the major determinant of total drug M/P ratio for amine, alcohol, N-and S-oxide, and carboxylic acid metabolites.

amine

alcohol

N-and S-oxide

carboxylic acid


Input: Passage from the hepatocyte to systemic circulation does not appear to be limiting owing to the vast majority of metabolites formed being relatively lipid permeable.


Input: In some cases, active transport plays an important role in this process (e. g., carboxylic acid metabolites).

carboxylic acid