Input: CONCLUSION: Our findings demonstrate that (R)-omeprazole HI correlated better with CYP2C19 genotype groups than racemic-omeprazole HI, and these results may be useful for classification among patients in CYP2C19 genotype groups prior to omeprazole treatment.

(R)-omeprazole

racemic-omeprazole


Input: Marine ecosystem health status assessment through integrative biomarker indices: a comparative study after the Prestige oil spill " Mussel Watch ".


Input: Five integrative biomarker indices are compared: Bioeffects Assessment Index (BAI), Health Status Index (HSI), integrated biological response (IBR), ecosystem health condition chart (EHCC) and Integrative Biomarker Index (IBI).


Input: They were calculated on the basis of selected biomarker data collected in the framework of the Prestige oil spill (POS) Mussel Watch monitoring (2003-2006) carried out in Galicia and the Bay of Biscay.


Input: According to the BAI, the health status of mussels was severely affected by POS and signals of recovery were evidenced in Galicia after April-04 and in Biscay Bay after April-05.


Input: The HSI (computed by an expert system) revealed high levels of environmental stress in 2003 and a recovery trend from April-04 to April-05.


Input: In July-05, the health status of mussels worsened but in October-05 and April-06 healthy condition was again recorded in almost all localities.


Input: IBR/n and IBI indicated that mussel health was severely affected in 2003 and improved from 2004 onwards.


Input: EHCC reflected a deleterious environmental condition in 2003 and a recovery trend after April-04, although a healthy ecosystem condition was not achieved in April-06 yet.


Input: Whereas BAI and HSI provide a basic indication of the ecosystem health status, star plots accompanying IBR/n and IBI provide complementary information concerning the mechanisms of biological response to environmental insult.


Input: Overall, although the integrative indices based on biomarkers show different sensitivity, resolution and informative output, all of them provide coherent information, useful to simplify the interpretation of biological effects of pollution in marine pollution monitoring.


Input: Each others' advantages, disadvantages and applicability for ecosystem health assessment are discussed.


Input: Effect of sinapic acid against dimethylnitrosamine-induced hepatic fibrosis in rats.

sinapic acid

dimethylnitrosamine


Input: Sinapic acid is a member of the phenylpropanoid family and is abundant in cereals, nuts, oil seeds, and berries.

Sinapic acid

phenylpropanoid


Input: It exhibits a wide range of pharmacological properties.


Input: In this study, we investigated the hepatoprotective and antifibrotic effects of sinapic acid on dimethylnitrosamine (DMN)-induced chronic liver injury in rats.

sinapic acid

dimethylnitrosamine

DMN


Input: Sinapic acid remarkably prevented DMN-induced loss of body weight.

Sinapic acid

DMN


Input: This was accompanied by a significant increase in levels of serum alanine transaminase, aspartate transaminase, and liver malondialdehyde content.

alanine

aspartate

malondialdehyde


Input: Furthermore, sinapic acid reduced hepatic hydroxyproline content, which correlated with a reduction in the expression of type I collagen mRNA and histological analysis of collagen in liver tissue.

sinapic acid

hydroxyproline


Input: Additionally, the expression of hepatic fibrosis-related factors such as alpha-smooth muscle actin and transforming growth factor-beta 1 (TGF-beta 1), were reduced in rats treated with sinapic acid.

sinapic acid


Input: Sinapic acid exhibited strong scavenging activity.

Sinapic acid


Input: In conclusion, we find that sinapic acid exhibits hepatoprotective and antifibrotic effects against DMN-induced liver injury, most likely due to its antioxidant activities of scavenging radicals, its capacity to suppress TGF-beta 1 and its ability to attenuate activation of hepatic stellate cells.

sinapic acid

DMN


Input: This suggests that sinapic acid is a potentially useful agent for the protection against liver fibrosis and cirrhosis.

sinapic acid


Input: Simple and sensitive liquid chromatography-tandem mass spectrometry methods for quantification of tadalafil in rat plasma: application to pharmacokinetic study in rats.

tadalafil


Input: A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated in rat plasma for quantification of tadalafil, a novel therapeutic agent for erectile dysfunction.

tadalafil


Input: Tadalafil and acebutolol (internal standard) were extracted by liquid-liquid extraction with tert-butyl methyl ether.

Tadalafil

acebutolol

tert-butyl methyl ether


Input: The chromatographic separation was performed on a reverse phase C18 column with a mobile phase consisting of 0. 1% formic acid and acetonitrile (45: 55, v/v) at a flow rate of 0. 3 mL/min.

formic acid

acetonitrile


Input: The protonated analyte was quantitated by multiple reaction monitoring with a Waters Quattro micro (TM) API mass spectrometer.


Input: The calibration curve was linear over a concentration range of 2-2000 ng/mL, and the lower limit of quantification was 2 ng/mL with a precision (CV%) of 10. 9%.


Input: Acceptable intra-day and inter-day precision and accuracy were obtained at 3 concentration levels (3, 200, and 1500 ng/mL).


Input: Tadalafil was found to be stable in a battery of studies, including bench top, freeze-thaw, and autosampler conditions.

Tadalafil


Input: The validated method was successfully used to determine tadalafil concentration in rat plasma samples after oral administration at a dose of 1 mg/kg.

tadalafil


Input: Anti-inflammatory effect of pristimerin on lipopolysaccharide-induced inflammatory responses in murine macrophages.

pristimerin


Input: Pristimerin, a quinonemethide triterpenoid derived from Celastraceae and Hippocrateaceae, has recently been found to suppress tumor promotion, metastasis and angiogenesis.

Pristimerin

quinonemethide triterpenoid


Input: In the present study, we evaluated the anti-inflammatory potentials of pristimerin in a cell culture system.

pristimerin


Input: Pristimerin suppressed not only the generation of nitric oxide (NO) and prostaglandin E2, but also the expression of inducible NO synthase and cyclooxygenase-2 induced by lipopolysacharide (LPS) in murine macrophage RAW264. 7 cells.

Pristimerin

nitric oxide

NO

prostaglandin E2

NO


Input: Similarly, pristimerin inhibited the release of pro-inflammatory cytokines, namely, tumor necrosis factor-alpha and interleukin-6, induced by LPS.

pristimerin


Input: The underlying mechanism of the anti-inflammatory action of pristimerin was correlated with down-regulation of nuclear factor-kappa B and the mitogen-activated protein kinase signal pathway.

pristimerin


Input: A review on cholinesterase inhibitors for Alzheimer' s disease.


Input: Alzheimer' s disease (AD), a progressive neurodegenerative disorder, is characterized by the deficits in the cholinergic system and deposition of beta amyloid (A beta) in the form of neurofibrillary tangles and amyloid plaques.


Input: Since the cholinergic system plays an important role in the regulation of learning and memory processes, it has been targetted for the design of anti-Alzheimer' s drugs.


Input: Cholinesterase inhibitors enhance cholinergic transmission directly by inhibiting the enzyme acetylcholinesterase (AChE) which hydrolyses acetylcholine.

acetylcholinesterase


Input: Furthermore, it has been also demonstrated that both acetylcholinesterase and butrylcholinesterase (BuChE) play an important role in A beta-aggregation during the early stages of senile plaque formation.


Input: Therefore, AChE and BuChE inhibition have been documented as critical targets for the effective management of AD by an increase in the availability of acetylcholine in the brain regions and decrease in the A beta deposition.

acetylcholine


Input: This review discusses the different classes of cholinesterase inhibitors including tacrine, donepezil, rivastigmine, galantamine, xanthostigmine, para-aminobenzoic acid, coumarin, flavonoid, and pyrrolo-isoxazole analogues developed for the treatment of AD.

tacrine

donepezil

rivastigmine

galantamine

xanthostigmine

para-aminobenzoic acid

coumarin

flavonoid

pyrrolo-isoxazole


Input: Potent alpha-glucosidase and protein tyrosine phosphatase 1B inhibitors from Artemisia capillaris.

tyrosine


Input: As a part of our ongoing effort to identify anti-diabetic constituents from natural sources, we examined the inhibitory activity of the methanol extracts of 12 species of the genus Artemisia, against alpha-glucosidase and protein tyrosine phosphatase 1B (PTP1B).

methanol

tyrosine


Input: The methanol extracts of different species exhibited promising alpha-glucosidase and PTP1B inhibitory activities.

methanol


Input: Since the methanol extract of Artemisia capillaris exhibited the highest alpha-glucosidase inhibitory activity together with significant PTP1B inhibitory activity, it was selected for further investigation.

methanol


Input: Repeated column chromatography based on bioactivity guided fractionation yielded 10 coumarins (esculetin, esculin, scopolin, isoscopolin, daphnetin, umbelliferone, 7-methoxy coumarin, scoparone, scopoletin, 6-methoxy artemicapin C), 8 flavonoids (hyperoside, quercetin, isorhamnetin, cirsilineol, arcapillin, isorhamnetin 3-robinobioside, linarin, isorhamnetin 3-glucoiside), 6 phenolic compounds (1, 5-dicaffeoylquinic acid, 3, 4-dicaffeoylquinic acid, 3, 5-dicaffeoylquinic acid, 3, 5-dicaffeoylquinic acid methyl ester, 4, 5-dicaffeoylquinic acid, 3-caffeoylquinic acid), and one chromone (capillarisin).

coumarins

esculetin

esculin

scopolin

isoscopolin

daphnetin

umbelliferone

7-methoxy coumarin

scoparone

scopoletin

6-methoxy artemicapin C

flavonoids

hyperoside

quercetin

isorhamnetin

cirsilineol

arcapillin

isorhamnetin 3-robinobioside

linarin

isorhamnetin 3-glucoiside

phenolic

1, 5-dicaffeoylquinic acid

3, 4-dicaffeoylquinic acid

3, 5-dicaffeoylquinic acid

3, 5-dicaffeoylquinic acid methyl ester

4, 5-dicaffeoylquinic acid

3-caffeoylquinic acid

chromone

capillarisin


Input: Among these compounds, esculetin, scopoletin, quercetin, hyperoside, isorhamnetin, 3, 5-dicaffeoylquinic acid methyl ester, 3, 4-dicaffeoylquinic acid, and 1, 5-dicaffeoylquinic acid exhibited potent alpha-glucosidase inhibitory activity when compared to the positive control acarbose.

esculetin

scopoletin

quercetin

hyperoside

isorhamnetin

3, 5-dicaffeoylquinic acid methyl ester

3, 4-dicaffeoylquinic acid

1, 5-dicaffeoylquinic acid

acarbose


Input: In addition, esculetin and 6-methoxy artemicapin C displayed PTP1B inhibitory activity.

esculetin

6-methoxy artemicapin C


Input: Interestingly, all isolated dicaffeoylquinic acids showed significant PTP1B inhibitory activity.

dicaffeoylquinic acids


Input: Therefore, the results of the present study clearly demonstrate the potential of the A. capillaris extract to inhibit alpha-glucosidase and PTP1B.


Input: These inhibitory properties can be largely attributed to a combination of different chemical structures, including coumarins, flavonoids, and dicaffeoylquinic acids, which could be further explored to develop therapeutic or preventive agents for the treatment of diabetes.

coumarins

flavonoids

dicaffeoylquinic acids


Input: Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome.

acamprosate


Input: RATIONALE: Fragile X syndrome (FXS) is an inherited form of developmental disability and a single gene cause of autism.


Input: As a disorder with increasingly understood pathophysiology, FXS is a model form of developmental disability for targeted drug development efforts.


Input: Preclinical animal model findings have focused targeted drug treatment development in FXS on an imbalance between excessive glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission.

glutamate

gamma-aminobutyric acid

GABA


Input: METHODS: We conducted a prospective open-label 10-week trial of acamprosate in 12 youth aged 6-17 years (mean age: 11. 9 years) with FXS.

acamprosate


Input: RESULTS: Acamprosate use (mean dose: 1, 054 +/- 422 mg/day) was associated with treatment response (defined by a Clinical Global Impressions Improvement (CGI-I) scale score of " very much improved " or " much improved ") in nine of 12 (75%) subjects.

Acamprosate


Input: Improvement was noted in social behavior and inattention/hyperactivity using multiple standard behavioral outcome measures.


Input: No significant adverse effects or changes in vital signs, including weight or laboratory measures, occurred during treatment with acamprosate.

acamprosate


Input: Additionally, pre-and post-treatment blood biomarker analyses looking at brain-derived neurotrophic factor (BDNF) levels found a significant increase in BDNF with treatment.


Input: In our pilot sample, treatment response did not correlate with change in BDNF with treatment.


Input: CONCLUSIONS: Acamprosate was generally safe and well tolerated and was associated with a significant improvement in social behavior and a reduction in inattention/hyperactivity.

Acamprosate


Input: The increase in BDNF that occurred with treatment may be a useful pharmacodynamic marker in future acamprosate studies.

acamprosate


Input: Given these findings, a double-blind, placebo-controlled study of acamprosate in youth with FXS is warranted.

acamprosate


Input: Clinical risk factors for adverse events in allopurinol users.

allopurinol


Input: Allopurinol, one of the most commonly used uric acid-lowering agents, can cause serious adverse events.

Allopurinol

uric acid


Input: To investigate the risk factors for allopurinol-induced adverse events, the authors enrolled 94 patients who developed allopurinol-induced adverse events and 378 controls who were randomly chosen from 1934 patients who used allopurinol but did not develop any adverse events in this retrospective case control study.

allopurinol

allopurinol

allopurinol


Input: Univariate analysis showed that patients who developed allopurinol-induced adverse events had more chronic kidney disease (46% vs 30%, P =. 005), more hypertension (42% vs 30%, P =. 036), less tumor lysis syndrome (P =. 030), higher cholesterol (P =. 013), and lower aspartate aminotransferase (P =. 002) and alanine aminotransferase levels (P =. 033) and more commonly used angiotensin receptor blockers (27% vs 15%, P =. 007), colchicines (16% vs 5%, P =. 010), or statins (19% vs 8%, P =. 002) than those who did not.

allopurinol

cholesterol

aspartate

alanine

colchicines

statins


Input: In multiple logistic regression analysis, the use of colchicines (odds ratio, 3. 11; 95% confidence interval, 1. 28-7. 58; P =. 012) and statins (2. 10; 1. 03-4. 25; P =. 041) was an independent risk factor predicting adverse events in allopurinol users.

colchicines

statins

allopurinol


Input: In conclusion, patients who use colchicine or statins are at significant risk for developing allopurinol-induced adverse events.

colchicine

statins

allopurinol


Input: Vemurafenib-associated pancreatitis: case report.

Vemurafenib


Input: Vemurafenib is a novel BRAF kinase inhibitor indicated in metastatic melanoma patients with V600E mutation.

Vemurafenib


Input: We report the first case of vemurafenib-associated pancreatitis.

vemurafenib


Input: Two weeks after initiation of vemurafenib, a patient presented to the emergency department with severe epigastric pain and a serum lipase of 1544 units/L.

vemurafenib


Input: Drug-induced pancreatitis was diagnosed on exclusion of all other potential causes.


Input: Vemurafenib was rechallenged at half the daily dose and the patient subsequently developed exacerbated symptoms of pancreatitis after two doses.

Vemurafenib


Input: The strong temporal relationship between drug exposure and toxicity, along with the positive results from a rechallenge study, strongly support a conclusion of causality.


Input: To our knowledge, this is the first report of vemurafenib-induced pancreatitis.

vemurafenib


Input: Weak-field, multiple-cycle carrier envelope phase effects in laser excitation.


Input: Although the absolute or carrier envelope phase (CEP) of a laser pulse is usually assumed to be effective for ultrashort and/or ultrastrong pulses only, it is demonstrated that these limitations can eventually be removed.


Input: Therefore, the excitation of a model positively charged homonuclear diatomic molecule, in which four electronic states are coupled by the laser field, is studied.


Input: In an initial step, nuclear wave packets in two dissociative states are prepared.


Input: Upon reaching the fragment channel, a weak pulse interacts with the system and prepares CEP-dependent asymmetries associated with electron density localized on one or the other fragmentation product.


Input: Thermal and Electrical Conduction in Ultrathin Metallic Films: 7 nm down to Sub-Nanometer Thickness.


Input: For ultrathin metallic films (e. g., less than 5 nm), no knowledge is yet available on how electron scattering at surface and grain boundaries reduces the electrical and thermal transport.


Input: The thermal and electrical conduction of metallic films is characterized down to 0. 6 nm average thickness.


Input: The electrical and thermal conductivities of 0. 6 nm Ir film are reduced by 82% and 50% from the respective bulk values.


Input: The Lorenz number is measured as 7. 08 x 10 (-8) W Omega K (-2), almost a twofold increase of the bulk value.


Input: The Mayadas-Shatzkes model is used to interpret the experimental results and reveals very strong electron reflection (> 90%) at grain boundaries.


Input: A combination strategy to inhibit Pim-1: synergism between noncompetitive and ATP-competitive inhibitors.

ATP


Input: Pim-1 is a serine/threonine kinase critically involved in the initiation and progression of various types of cancer, especially leukemia, lymphomas and solid tumors such as prostate, pancreas and colon, and is considered a potential drug target against these malignancies.

serine

threonine


Input: In an effort to discover new potent Pim-1 inhibitors, a previously identified ATP-competitive indolyl-pyrrolone scaffold was expanded to derive structure-activity relationship data.

ATP

indolyl-pyrrolone


Input: A virtual screening campaign was also performed, which led to the discovery of additional ATP-competitive inhibitors as well as a series of 2-aminothiazole derivatives, which are noncompetitive with respect to both ATP and peptide substrate.

ATP

ATP


Input: This mechanism of action, which resembles allosteric inhibition, has not previously been characterized for Pim-1.


Input: Notably, further evaluation of the 2-aminothiazoles indicated a synergistic inhibitory effect in enzymatic assays when tested in combination with ATP-competitive inhibitors.

ATP


Input: A synergistic effect in the inhibition of cell proliferation by ATP-competitive and ATP-noncompetitive compounds was also observed in prostate cancer cell lines (PC3), where all Pim-1 inhibitors tested in showed synergism with the known anticancer agent, paclitaxel.

ATP

ATP

paclitaxel


Input: These results further establish Pim-1 as a target in cancer therapy, and highlight the potential of these agents for use as adjuvant agents in the treatment of cancer diseases in which Pim-1 is associated with chemotherapeutic resistance.


Input: Discovery of Novel Dual Inhibitors of the Wild-Type and the Most Prevalent Drug-Resistant Mutant, S31N, of the M2 Proton Channel from Influenza A Virus.


Input: Anti-influenza drugs, amantadine and rimantadine, targeting the M2 channel from influenza A virus are no longer effective because of widespread drug resistance.

amantadine

rimantadine


Input: S31N is the predominant and amantadine-resistant M2 mutant, present in almost all of the circulating influenza A strains as well as in the pandemic 2009 H1N1 and the highly pathogenic H5N1 flu strains.

amantadine


Input: Thus, there is an urgent need to develop second-generation M2 inhibitors targeting the S31N mutant.


Input: However, the S31N mutant presents a huge challenge to drug discovery, and it has been considered undruggable for several decades.


Input: Using structural information, classical medicinal chemistry approaches, and M2-specific biological testing, we discovered benzyl-substituted amantadine derivatives with activity against both S31N and WT, among which 4-(adamantan-1-ylaminomethyl)-benzene-1, 3-diol (44) is the most potent dual inhibitor.

benzyl

amantadine

4-(adamantan-1-ylaminomethyl)-benzene-1, 3-diol


Input: These inhibitors demonstrate that S31N is a druggable target and provide a new starting point to design novel M2 inhibitors that address the problem of drug-resistant influenza A infections.


Input: Evidence for the Involvement of Descending Pain-Inhibitory Mechanisms in the Antinociceptive Effect of Hecogenin Acetate.

Hecogenin Acetate


Input: Hecogenin is a sapogenin present in the leaves of species from the Agave genus, with a wide spectrum of reported pharmacological activities.

Hecogenin


Input: The present study was undertaken to evaluate whether hecogenin acetate (1) has antinociceptive properties and to determine its mechanism of action.

hecogenin acetate


Input: The nociceptive threshold was evaluated using the tail flick test in mice.


Input: Mice motor performance was evaluated in a Rotarod test.


Input: By using Fos expression as a marker of neural activation, the involvement of the periaqueductal gray in 1-induced antinociception was evaluated.


Input: Intraperitoneal administration of 1 (5-40 mg/kg) produced a dose-dependent increase in the tail flick latency time compared to vehicle-treated group (p < 0. 01).


Input: Mice treated with 1 (40 mg/kg) did not show motor performance alterations.


Input: The antinociception of 1 (40 mg/kg) was prevented by naloxone (nonselective opioid receptor antagonist; 5 mg/kg), CTOP (mu-opioid receptor antagonist; 1 mg/kg), nor-BNI (kappa-opioid receptor antagonist; 0. 5 mg/kg), naltrindole (delta-opioid receptor antagonist; 3 mg/kg), or glibenclamide (ATP-sensitive K (+) channel blocker; 2 mg/kg).

naloxone

CTOP

nor-BNI

naltrindole

glibenclamide

ATP

K (+)


Input: Systemic administration of 1 (5-40 mg/kg) increased the number of Fos positive cells in the periaqueductal gray.


Input: The present study has demonstrated for the first time that 1 produces consistent antinociception mediated by opioid receptors and endogenous analgesic mechanisms.


Input: Consequences of Membrane Topography.


Input: The surface of mammalian cells is neither smooth nor flat and cells have several times more plasma membrane than the minimum area required to accommodate their shape.


Input: We discuss the biological function of this apparent excess membrane that allows the cells to migrate, undergo shape changes and probably plays a role in signal transduction.


Input: Methods for studying membrane folding and topography; atomic force microscopy, scanning ion conductance microscopy, fluorescence polarisation microscopy and linear dichroism, are described and evaluated.


Input: Membrane folding and topography is frequently ignored when interpreting microscopy data.


Input: This has resulted in several misconceptions for instance regarding colocalisation, membrane organisation and molecular clustering.


Input: We suggest simple ways to avoid these pitfalls and invoke Occam' s razor-that simple explanations are preferable to complex ones.


Input: Topography, i. e. deviations from a smooth surface, should always be ruled out as the cause of anomalous data before other explanations are presented.


Input: (c) 2013 The Authors Journal compilation (c) 2013 FEBS.


Input: Quantitative analysis of the coverage density of Br-ions on Pd {100} facets and its role in controlling the shape of Pd nanocrystals.

Br-

Pd

Pd


Input: We report an approach based on a combination of inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy for quantitative analysis of the role played by Br (-) ions in the synthesis of Pd nanocrystals.

Br (-)

Pd


Input: The Br (-) ions were found to adsorb onto Pd {100} facets selectively with a coverage density of ca.

Br (-)

Pd


Input: 0. 8 ion per surface Pd atom.

Pd


Input: The chemisorbed Br (-) ions could be removed via desorption at an elevated temperature under reductive conditions.

Br (-)


Input: They could also be gradually released from the surface when Pd cubic seeds grew into cuboctahedrons and then octahedrons.

Pd


Input: On the basis of the coverage density information, we were able to estimate the minimum concentration of Br (-) ions needed for the formation of Pd nanocubes with a specific size.

Br (-)

Pd


Input: If the concentration of Br (-) ions was below this minimum value, not all of the {100} facets could be stabilized by the capping agent, leading to the formation of nanocubes with truncated corners.

Br (-)


Input: The quantitative analysis developed in this study is potentially extendable to other systems involving chemisorbed capping agents.


Input: Systematic review of atomoxetine data in childhood and adolescent attention-deficit hyperactivity disorder 2009-2011: Focus on clinical efficacy and safety.

atomoxetine


Input: Background: Clinicians obtain critical prescribing knowledge from clinical papers and review articles.


Input: This is the first published systematic review of clinical atomoxetine data covering 2009-2011. Objective: We aim to update clinicians on current clinical atomoxetine data with specific reference to time of onset of efficacy and maximal efficacy.

atomoxetine

atomoxetine


Input: These data may allow critical analysis of comparative efficacy between atomoxetine and stimulant medications. Methods: A formal systematic review of atomoxetine data from January 2009-June 2011 was conducted.

atomoxetine

atomoxetine


Input: The search term used was " atomoxetine " in the English language.

atomoxetine


Input: The search yielded 747 citations from which 106 are clinical data.


Input: This paper includes clinical efficacy and safety data and excludes quality-of-life and review papers. Results: Atomoxetine has an onset of action within 4 weeks (possibly within 1 week in subsequent responders) but requires at least 12 weeks for full response to be demonstrated.

Atomoxetine


Input: Treatment-na i ve cohorts (6-12 weeks) report effect sizes of 0. 6-1. 3.


Input: Using minimum 6-week clinical trial criteria, atomoxetine may demonstrate similar efficacy to methylphenidate comparing reduction in core ADHD symptoms in meta-analysis, although the diversity of the data makes interpretation complex.

atomoxetine

methylphenidate


Input: From epidemiological databases, cardiovascular and suicide-related events were similar to those seen in patients taking methylphenidate. Conclusions: Incremental response time to atomoxetine should be considered in the design of future comparative efficacy trials.

methylphenidate

atomoxetine


Input: A network model of the molecular organization of chromatin in Drosophila.


Input: Chromatin governs gene regulation and genome maintenance, yet a substantial fraction of the chromatin proteome is still unexplored.


Input: Moreover, a global model of the chromatin protein network is lacking.


Input: By screening > 100 candidates we identify 42 Drosophila proteins that were not previously associated with chromatin, which all display specific genomic binding patterns.


Input: Bayesian network modeling of the binding profiles of these and 70 known chromatin components yields a detailed blueprint of the in vivo chromatin protein network.


Input: We demonstrate functional compartmentalization of this network, and predict functions for most of the previously unknown chromatin proteins, including roles in DNA replication and repair, and gene activation and repression.


Input: Orthogonal patterning of multiple biomolecules using an organic fluorinated resist and imprint lithography.


Input: The ability to spatially deposit multiple biomolecules onto a single surface with high-resolution while retaining biomolecule stability and integrity is critical to the development of micro-and nanoscale biodevices.


Input: While conventional lithographic patterning methods are attractive for this application, they typically require the use of UV exposure and/or harsh solvents and imaging materials, which may be damaging to fragile biomolecules.


Input: Here, we report the development of a new patterning process based on a fluorinated patterning material that is soluble in hydrofluoroether solvents, which we show to be benign to biomolecules, including proteins and DNA.

hydrofluoroether


Input: We demonstrate the implementation of these materials into an orthogonal processing system for patterning multibiomolecule arrays by imprint lithography at room temperature.


Input: We further showcase this method' s capacity for fabricating patterns of receptor-specific ligands for fundamental cell studies.


Input: Microfluidic synthesis of cell-type-specific artificial extracellular matrix hydrogels.


Input: Droplet microfluidic technology is applied for the high-throughput synthesis via Michael-type addition of reactive, micrometer-sized poly (ethylene glycol) (PEG) hydrogels (" microgels ") with precisely controlled dimension and physicochemical properties.

poly (ethylene glycol)

PEG


Input: A versatile chemical scheme is used to modify the reactive PEG microgels with tethered biomolecules to tune their bioactive properties for the bioreactor culture and manipulation of various (stem) cell types.

PEG


Input: Post-partum variation in the expression of paternal care is unrelated to urinary steroid metabolites in marmoset fathers.

steroid


Input: The organization and activation of maternal care are known to be highly regulated by hormones and there is growing evidence that expression of paternal care is also related to endocrine substrates.


Input: We examined the relationship between paternal behavior and steroid hormones in marmoset fathers (Callithrix geoffroyi) and evaluated whether hormone-paternal behavior relationships were altered by previous offspring-care experience in males.

steroid


Input: Based on previous findings, we predicted that testosterone, estradiol, and cortisol would decrease following the birth of offspring and would be lowest during the period of maximal infant carrying.

testosterone

estradiol

cortisol


Input: Furthermore, we predicted that post-partum changes in carrying effort and hormone levels would be influenced by the level of offspring-care experience.


Input: Carrying effort and other paternal care behaviors underwent temporal changes over the post-partum period, but these patterns were not related to variation in hormone concentrations over the same period.


Input: There was a limited effect of offspring-care experience on hormone concentrations, but experience was found to play a role in the expression of paternal care, with experienced fathers engaging in significantly more infant allogrooming than inexperienced fathers.


Input: Furthermore, inexperienced fathers increased the frequency of food sharing in response to infant begging across the post-partum period, while experienced fathers displayed consistently low levels.


Input: We posit that a combination of experiential factors and an increased role for alloparents in offspring-care led to these changes.


Input: However, it appears that hormonal changes may not influence paternal responsiveness in white-faced marmoset fathers and that hormone-paternal behavior relationships are not critically dependent on a male' s previous offspring-care experience.


Input: pH-gradient PAMPA-based in vitro model assay for drug-induced phospholipidosis in early stage of drug discovery.


Input: In the present study we validated a widely used, high-throughput in vitro permeability model (PAMPA) to be used at the early stage of drug discovery for the phospholipidosis (PLD) prediction of drug-like compounds.


Input: Regarding the mechanism of action of PLD, our pH-gradient PAMPA system is the first noncell based model to mimic one-way transport of cationic amphiphilic drugs (CADs) from cytosol to the lysosome.


Input: Moreover, due to the fact that PLD can mainly occur in lung, liver, brain, kidney and heart, we have used similar commercially available original tissue-derived lipid fractions (heart, liver, brain), and in the case mimicking membrane of kidney and lung tissue we prepared tissue-mimetic artificial lipid mixtures in house.


Input: Metabolism of a drug can change the degree of PLD depending on the physicochemical properties of metabolites and the rate of metabolism.


Input: Our data from 57 drugs and 4 metabolites of earlier and 2 metabolites of newly recognized outliers (phenacetin and bupropion) using our pH-gradient PAMPA system show a good correlation with in vivo PLD data.

phenacetin

bupropion


Input: Moreover, predictive ability of our best system, the lung specific pH-gradient PAMPA model was significantly better than widely used in silico models and it was also slightly better than that of the known noncell based models on our selection of compounds.


Input: Our pH-gradient PAMPA systems therefore offer mechanistically alternative, accurate and cost-effective screening tools for the early prediction of PLD potential of drug-like compounds.


Input: NADPH Oxidase NOX5-S and Nuclear Factor kappa B1 Mediate Acid-Induced Microsomal Prostaglandin E Synthase-1 Expression in Barrett' s Esophageal Adenocarcinoma Cells.

NADPH

Prostaglandin E


Input: The mechanisms of progression from Barrett' s esophagus (BE) to esophageal adenocarcinoma (EA) are not known.


Input: Cycloxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) has been shown to be important in esophageal tumorigenesis.

prostaglandin E2


Input: We have shown that COX-2 mediates acid-induced PGE2 production.


Input: The prostaglandin E synthase (PGES) responsible for acid-induced PGE2 production in BE, however, is not known.

prostaglandin E


Input: We found that microsomal PGES1 (mPGES1), mPGES2, and cytosolic PGES (cPGES) were present in FLO EA cells.


Input: Pulsed acid treatment significantly increased mPGES1 mRNA and protein levels but had little or no effect on mPGES2 or cPGES mRNA.


Input: Knockdown of mPGES1 by mPGES1 small interfering RNA (siRNA) blocked acid-induced increase in PGE2 production and thymidine incorporation.

thymidine


Input: Knockdown of NADPH oxidase, NOX5-S, a variant lacking calcium-binding domains, by NOX5 siRNA significantly inhibited acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production.

NADPH

calcium

thymidine


Input: Overexpression of NOX5-S significantly increased the luciferase activity in FLO cells transfected with a nuclear factor kappa B (NF-kappa B) in vivo activation reporter plasmid pNF-kappa B-Luc.


Input: Knockdown of NF-kappa B1 p50 by p50 siRNA significantly decreased acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production.

thymidine


Input: Two novel NF-kappa B binding elements, GGAGTCTCCC and CGGGACACCC, were identified in the mPGES1 gene promoter.


Input: We conclude that mPGES1 mediates acid-induced increase in PGE2 production and cell proliferation.


Input: Acid-induced mPGES1 expression depends on activation of NOX5-S and NF-kappa B1 p50.


Input: Microsomal PGES1 may be a potential target to prevent or treat EA.


Input: E6AP/UBE3A Ubiquitin Ligase Harbors Two E2 ~ ubiquitin Binding Sites.


Input: By exploiting (125) I-polyubiquitin chain formation as a functional readout of enzyme activity, we have quantitatively examined the mechanism of human E6AP/UBE3A for the first time.

(125) I


Input: Initial rate studies identify UbcH7 as the cognate E2 carrier protein for E6AP, although related Ubc5 isoforms and the ISG15-specific UbcH8 paralog also support E6AP with reduced efficacy due to impaired binding and catalytic competence.


Input: Initial rates of polyubiquitin chain formation displayed hyperbolic kinetics with respect to UbcH7 concentration (Km = 57. 6 +/- 5. 7 nm and kcat = 0. 032 +/- 0. 001 s (-1)) and substrate inhibition above 2 mu m.


Input: Competitive inhibition by an isosteric UbcH7C86S-ubiquitin oxyester substrate analog (Ki = 64 +/- 18 nm) demonstrates that Km reflects intrinsic substrate affinity.

oxyester


Input: In contrast, noncompetitive inhibition by a UbcH7C86A product analog (Ki = 7 +/- 0. 7 mu m) and substrate inhibition at high concentrations require two functionally distinct E2 ~ ubiquitin substrate binding sites.


Input: The kinetics of polyubiquitin chain formation reflect binding at a cryptic Site 1 not previously recognized that catalyzes E6AP ~ ubiquitin thioester formation.

thioester


Input: Subsequent binding of E2 ~ ubiquitin at the canonical Site 2 present in the extant crystal structure is responsible for polyubiquitin chain elongation.


Input: Other rate studies show that the conserved-4 Phe (849) residue is required for polyubiquitin chain formation rather than target protein conjugation as originally suggested.

Phe


Input: The present studies unambiguously preclude earlier models for the mechanism of Hect domain-catalyzed conjugation through the canonical binding site suggested by the crystal structure and define a novel two-step mechanism for formation of the polyubiquitin degradation signal.


Input: Induction of xenobiotic receptors, transporters, and drug metabolizing enzymes by oxycodone.

oxycodone


Input: Perturbations of the expression of transporters and drug-metabolizing enzymes (DMEs) by opioids can be the locus of deleterious drug-drug interactions (DDIs).


Input: Many transporters and DMEs are regulated by xenobiotic receptors [XRs; e. g., pregnane X receptor (PXR), constitutive androstane receptor (CAR), and Aryl hydrocarbon receptor (AhR)]; however, there is a paucity of information regarding the influence of opioids on XRs.

androstane

Aryl hydrocarbon


Input: The objective of this study was to determine the influence of oxycodone administration (15 mg/kg intraperitoneally twice daily for 8 days) on liver expression of XRs, transporters, and DMEs in rats.

oxycodone


Input: Microarray, quantitative real-time polymerase chain reaction and immunoblotting analyses were used to identify significantly regulated genes.


Input: Three XRs (e. g., PXR, CAR, and AhR), 27 transporters (e. g., ABCB1 and SLC22A8), and 19 DMEs (e. g., CYP2B2 and CYP3A1) were regulated (P < 0. 05) with fold changes ranging from-46. 3 to 17. 1.


Input: Using MetaCore (computational platform), we identified a unique gene-network of transporters and DMEs assembled around PXR, CAR, and AhR.


Input: Therefore, a series of transactivation/translocation assays were conducted to determine whether the observed changes of transporters/DMEs are mediated by direct activation of PXR, CAR, or AhR by oxycodone or its major metabolites (noroxycodone and oxymorphone).

oxycodone

noroxycodone

oxymorphone


Input: Neither oxycodone nor its metabolites activated PXR, CAR, or AhR.

oxycodone


Input: Taken together, these findings identify a signature hepatic gene-network associated with repeated oxycodone administration in rats and demonstrate that oxycodone alters the expression of many transporters and DMEs (without direct activation of PXR, CAR, and AhR), which could lead to undesirable DDIs after coadministration of substrates of these transporters/DMEs with oxycodone.

oxycodone

oxycodone

oxycodone


Input: Conformation-dependent conductance through a molecular break junction.


Input: Ab initio molecular dynamics simulations have been performed of a gold-1, 4-benzenedithiol (BDT)-gold nanojunction under mechanical stress.

gold-1, 4-benzenedithiol

BDT


Input: For three different pulling rates between 10 and 40 m s (-1), it is found that the nanowire always ruptures between the second and third Au atom from the thiol sulfur.

Au

thiol sulfur


Input: Larger rupture forces and longer extensions are required at higher pulling rates and vice versa.


Input: The electrical conductance was calculated along a pulling trajectory using the DFT-NEGF method to study the effect of thermal and stress-induced structural changes on the electrical transport properties.


Input: While the mechanically induced stretching of the junction is seen to lower the time-averaged conductance, thermal conformational changes are capable of altering the conductance by one order of magnitude.


Input: No single geometric quantity could be identified as the main contributor to the conductance fluctuations.


Input: Small modulations, however, can be explained in terms of C = C double bond vibrations in the BDT molecule.

C = C

BDT


Input: The dependence of the conductance on different geometric variables has further been investigated systematically by performing constrained geometry optimizations along a number of angle and dihedral coordinates.


Input: The largest changes in the conductance are observed when the Au-S-C angle and the Au-S-C-C dihedral are simultaneously constrained.

Au-S-C

Au-S-C-C


Input: A practical and scalable manufacturing process for an anti-fungal agent, Nikkomycin Z.

Nikkomycin Z


Input: A scalable and reliable manufacturing process for Nikkomycin Z HCl on a 170 g scale has been developed and optimized.

Nikkomycin Z HCl


Input: The process is characterized by a 2. 3 g/L fermentation yield, 79% purification yield, and > 98% relative purity of the final product.


Input: This method is suitable for further scale up and cGMP production.

cGMP


Input: The Streptomyces tendae Delta NikQ strain developed during the course of this study is superior to any previously reported strain in terms of higher yield and purity of Nikkomycin Z.

Nikkomycin Z


Input: Graphene-Bonded and-Encapsulated Si Nanoparticles for Lithium Ion Battery Anodes.

Graphene

Si

Lithium


Input: Silicon (Si) has been considered a very promising anode material for lithium ion batteries due to its high theoretical capacity.

Silicon

Si

lithium


Input: However, high-capacity Si nanoparticles usually suffer from low electronic conductivity, large volume change, and severe aggregation problems during lithiation and delithiation.

Si


Input: In this paper, a unique nanostructured anode with Si nanoparticles bonded and wrapped by graphene is synthesized by a one-step aerosol spraying of surface-modified Si nanoparticles and graphene oxide suspension.

Si

graphene

Si

graphene oxide


Input: The functional groups on the surface of Si nanoparticles (50-100 nm) not only react with graphene oxide and bind Si nanoparticles to the graphene oxide shell, but also prevent Si nanoparticles from aggregation, thus contributing to a uniform Si suspension.

Si

graphene oxide

Si

graphene oxide

Si

Si


Input: A homogeneous graphene-encapsulated Si nanoparticle morphology forms during the aerosol spraying process.

graphene

Si


Input: The open-ended graphene shell with defects allows fast electrochemical lithiation/delithiation, and the void space inside the graphene shell accompanied by its strong mechanical strength can effectively accommodate the volume expansion of Si upon lithiation.

graphene

graphene

Si


Input: The graphene shell provides good electronic conductivity for Si nanoparticles and prevents them from aggregating during charge/discharge cycles.

graphene

Si


Input: The functionalized Si encapsulated by graphene sample exhibits a capacity of 2250 mAh g (-1) (based on the total mass of graphene and Si) at 0. 1C and 1000 mAh g (-1) at 10C, and retains 85% of its initial capacity even after 120 charge/discharge cycles.

Si

graphene

graphene

Si


Input: The exceptional performance of graphene-encapsulated Si anodes combined with the scalable and one-step aerosol synthesis technique makes this material very promising for lithium ion batteries.

graphene

Si

lithium


Input: Associations of gender and age with the reporting of drug-induced hepatic failure: data from the VigiBase (TM).


Input: Patient gender and age are considered to be the risk factors for developing drug-induced liver injury (DILI).


Input: The aim of this study was to analyze gender and age differences in reporting of drug-induced hepatic failure (HF) to the VigiBase (TM).


Input: VigiBase (TM) was screened for the HF reports submitted from 2000 to 2009.


Input: The information retrieved referred to the suspected drug, age, gender, and a reporting country.


Input: Variables were examined by using descriptive statistics and the binomial test.


Input: During the 10-year period there were in total 6, 370 HF reports from 38 countries.


Input: After the exclusion of cases with missing gender data (379 cases), females counted for 54. 03%.


Input: The largest portion of HF cases referred to age < 55 (42. 57%) with female predominance (56. 81%), whereas age >= 55 (32. 57%) showed almost even gender distribution.


Input: Overall, there were 941 different drugs or their combinations reported.


Input: Females significantly predominated in HF cases associated with analgesics, antiepileptics, antiinflamatory and antirheumatic drugs, psychoanaleptics, antibacterials for systemic use, and antidiabetic drugs.


Input: Males were significantly overrepresented in HF cases associated with antivirals for systemic use.


Input: Differences between genders and/or age groups in the reporting of drug-induced HF depend on drug and/or drug class but may be influenced by multiple factors.


Input: Loading and distribution of a model small molecule drug in poly (N-isopropylacrylamide) brushes: a neutron reflectometry and AFM study.

poly (N-isopropylacrylamide)


Input: The structure of a hydrated poly (N-isopropylacrylamide) brush loaded with 5 vol% Isoniazid is studied as a function of temperature using neutron reflectometry (NR) and atomic force microscopy (AFM).

hydrated poly (N-isopropylacrylamide)

Isoniazid


Input: NR measurements show that Isoniazid increases the thickness of the brush before, during and after the polymer collapse, and it is retained inside the brush at all measured temperatures.

Isoniazid


Input: The Isoniazid concentration in the expanded brush is ~ 14% higher than in the bulk solution, and the concentration nearly doubles in the collapsed polymer, suggesting stronger binding between Isoniazid and the polymer compared to water, even at temperatures below the lower critical solution temperature (LCST) where the polymer is hydrophilic.

Isoniazid

Isoniazid


Input: Typically, additives that bind strongly to the polymer backbone and increase the hydrophilicity of the polymer will delay the onset of the LCST, which is suggested by AFM and NR measurements.


Input: The extent of small-molecule loading and distribution throughout a thermo-responsive polymer brush, such as pNIPAAm, will have important consequences for applications such as drug delivery and gating.

pNIPAAm


Input: Ca (2 +)-calmodulin interacts with DdCAD-1 and promotes DdCAD-1 transport by contractile vacuoles in Dictyostelium cells.

Ca (2 +)


Input: The Ca (2 +)-dependent cell-cell adhesion molecule DdCAD-1, encoded by the cadA gene of Dictyostelium discoideum, is synthesized at the onset of development as a soluble protein and then transported to the plasma membrane by contractile vacuoles.

Ca (2 +)


Input: Calmodulin associates with contractile vacuoles in a Ca (2 +)-dependent manner, and co-localizes with DdCAD-1 on the surface of contractile vacuoles.

Ca (2 +)


Input: Bioinformatics analysis revealed multiple calmodulin-binding motifs in DdCAD-1.


Input: Co-immunoprecipitation and pull-down studies showed that only Ca (2 +)-bound calmodulin was able to bind DdCAD-1.

Ca (2 +)


Input: Structural integrity of DdCAD-1, but not the native conformation, was required for its interaction with calmodulin.


Input: To investigate the role of calmodulin in the import of DdCAD-1 into contractile vacuoles, an in vitro import assay consisting of contractile vacuoles derived from cadA (-) cells and recombinant proteins was employed.


Input: Prior stripping of the bound calmodulin from contractile vacuoles by EGTA impaired import of DdCAD-1, which was restored by addition of exogenous calmodulin.


Input: The calmodulin antagonists W-7 and compound 48/80 blocked the binding of calmodulin onto stripped contractile vacuoles, and inhibited the import of DdCAD-1.


Input: Together, the data show that calmodulin forms a complex with DdCAD-1 and promotes the docking and import of DdCAD-1 into contractile vacuoles.


Input: STRUCTURED DIGITAL ABSTRACT: CaM physically interacts with DdCAD-1 by pull down (View Interaction: 1, 2) DdCAD-1 binds to CaM by far western blotting (View interaction) DdCAD-1 physically interacts with CaM by anti bait coimmunoprecipitation (View interaction).


Input: Double C-H bond activation of hydrocarbons by a gas phase neutral oxide cluster: the importance of spin state.

C-H

hydrocarbons

oxide


Input: The neutral cluster V2O5 is generated and detected in the gas phase.


Input: Its reactivity toward butane is studied both experimentally and theoretically.


Input: Experimental results show clearly that neutral V2O5 can react with n-butane (C4H10) to generate V2O5H2, indicating double hydrogen atom transfer from C4H10 to V2O5 to produce C4H8.

n-butane

hydrogen


Input: Further experimental evidence indicates that V2O5 is only partially reacted even at very high concentrations of C4H10.


Input: Density functional theory (DFT) studies show that the lowest energy triplet state of V2O5 is reactive toward C4H10, whereas the ground state singlet V2O5 is inert.


Input: Calculated results are in agreement with experimental findings, and a detailed reaction mechanism is provided.


Input: Reactions of V2O5H2 with several oxidants are also studied theoretically to find a path to regenerate V2O5.


Input: Neutral (3) V2O5 can also react with C2H6 to form V2O5H2 and C2H4, but only as a minor reaction channel; the major product is the adsorption product V2O5 (C2H6).


Input: Epigenetic reactivation of Nrf2 in murine prostate cancer TRAMP C1 cells by natural phytochemicals Z-ligustilide and Radix angelica sinensis via promoter CpG demethylation.

Z-ligustilide


Input: Cancer development has been linked to epigenetic modifications of cancer oncogenes and tumor suppressor genes; in advanced metastatic cancers, severe epigenetic modifications are present.


Input: We previously demonstrated that the progression of prostate tumors in TRAMP mice is associated with methylation silencing of the Nrf2 promoter and a reduced level of transcription of Nrf2 and Nrf2 target genes.


Input: Radix Angelicae Sinensis (RAS; Danggui) is a medicinal herb and health food supplement that has been widely used in Asia for centuries.


Input: Z-Ligustilide (Lig) is one of the bioactive components of RAS.

Z-Ligustilide

Lig


Input: We investigated the potential of Lig and RAS to restore Nrf2 gene expression through epigenetic modification in TRAMP C1 cells.

Lig


Input: Lig and RAS induced the mRNA and protein expression of endogenous Nrf2 and Nrf2 downstream target genes, such as HO-1, NQO1, and UGT1A1.

Lig


Input: Bisulfite genomic sequencing revealed that Lig and RAS treatment decreased the level of methylation of the first five CpGs of the Nrf2 promoter.

Bisulfite

Lig


Input: A methylation DNA immunoprecipitation assay demonstrated that Lig and RAS significantly decreased the relative amount of methylated DNA in the Nrf2 gene promoter region.

Lig


Input: Lig and RAS also inhibited DNA methyltransferase activity in vitro.

Lig


Input: Collectively, these results suggest that Lig and RAS are able to demethylate the Nrf2 promoter CpGs, resulting in the re-expression of Nrf2 and Nrf2 target genes.

Lig


Input: Epigenetic modifications of genes, including Nrf2, may therefore contribute to the overall health benefits of RAS, including the anticancer effect of RAS and its bioactive component, Lig.

Lig


Input: Probing the Photoisomerization of CHBr3 and CHI3 in Solution with Transient Vibrational and Electronic Spectroscopy.


Input: Transient infrared absorption spectroscopy monitors condensed-phase photodissociation dynamics of 30 mM CHBr3 and 50 mM CHI3 in liquid CCl4.


Input: The experiments have picosecond time resolution and monitor the C-H stretch region of both the parent polyhalomethanes and their photolytically generated isomers.

C

H

polyhalomethanes


Input: The C-H stretching transitions of these isomers, in which the emergent halogen atom returns to form a C-X-X bonding motif, appear about 9 ps after photolysis for iso-CHBr2-Br and in about 46 ps for iso-CHI2-I.

C

H

halogen

C

Br

I


Input: These time scales are consistent with, but differ from, the time evolution of the transient electronic absorption spectra of the same samples, highlighting the subtle differences between monitoring the vibrational and electronic chromophores.


Input: The specificity of using vibrational transitions to track condensed-phase reaction dynamics permits reassessment of the transient electronic spectrum of photolysis in neat CHBr3, which has an additional prompt feature near 400 nm.


Input: Calculations show that this feature, which arises from a precursor to the isomer, is a charge-transfer transition of a contact pair between the nascent Br fragment and a nearby CHBr3 molecule.

Br


Input: Dilution and solvent studies show that transition is independent of the solvent.


Input: The iso-CHBr2-Br transition wavelength, however, shifts over the range of 400 to 510 nm depending on the solvent.

Br


Input: Time-dependent density functional calculations faithfully reproduce these trends.


Input: Density Functional Study of Organocatalytic Cross-Aldol Reactions between Two Aliphatic Aldehydes: Insight into Their Functional Differentiation and Origins of Chemo-and Stereoselectivities.

Aliphatic Aldehydes


Input: The chemo-, diastereo-, and enantioselectivities in proline and axially chiral amino sulfonamide-catalyzed direct aldol reactions between two enolizable aldehydes with different electronic nature have been studied with the aid of density functional theory (DFT) method.

proline

amino sulfonamide

aldehydes


Input: The potential energy profiles for the enamine formation between each aliphatic aldehyde and the catalyst confirm that two subject catalysts can successfully differentiate between 3-methylbutanal as an enamine component and alpha-chloroaldehydes as a carbonyl component.

enamine

aliphatic aldehyde

enamine

alpha-chloroaldehydes

carbonyl


Input: Transition states associated with the stereochemistry-determining C-C bond-forming step with the enamine intermediate addition to the aldehyde acceptor for proline and chiral amino sulfonamide-promoted aldol reactions are reported.

C

C

enamine

aldehyde

proline

amino sulfonamide


Input: DFT calculations not only provide a good explanation for the formation of the sole cross-aldol product between two aliphatic aldehydes both bearing alpha-methylene protons but also well reproduce the opposite syn vs anti diastereoselectivities in the chiral amino sulfonamide and proline-catalyzed aldol reactions.

aliphatic aldehydes

alpha-methylene

amino sulfonamide

proline


Input: On the generation of the hydrated electron during the sonolysis of aqueous solutions.


Input: The formation of the hydrated electron through the secondary reaction, H + OH (-) --> H (2) O + e (aq), has been examined in the sonolysis of argon-saturated aqueous solutions at an ultrasound frequency of 355 kHz.

H

OH (-)

H (2) O

argon


Input: The detection of the hydrated electron was achieved by measuring its reaction with the one-electron acceptors Fe (CN) (6) (3-) and methyl viologen.

Fe (CN) (6) (3-)

methyl


Input: The results obtained indicate that hydrated electrons are produced predominately at the bubble/aqueous solution interface at comparatively high local concentrations, estimated to be > 1. 5 x 10 (-3) M.


Input: The half life of the hydrated electron under such conditions is estimated to be < 60 ns.


Input: Phenol formation in gamma radiolysis of aqueous benzene solution with sodium hypochlorite.

Phenol

benzene

sodium hypochlorite


Input: Phenol formation by gamma radiolysis of an aqueous benzene solution containing sodium hypochlorite is reported.

Phenol

benzene

sodium hypochlorite


Input: The phenol formation in a benzene solution containing sodium hypochlorite irradiated with (60) Co gamma-rays is about six times higher than that without sodium hypochlorite.

benzene

sodium hypochlorite

sodium hypochlorite


Input: Ten micromolar sodium hypochlorite enhanced the formation of phenol up to a total dose of 6 Gy.

sodium hypochlorite

phenol


Input: Above 6 Gy in solutions containing sodium hypochlorite, the rate of phenol yield sharply decreased and was essentially the same as that without sodium hypochlorite.

sodium hypochlorite

phenol

sodium hypochlorite


Input: The yield of phenol with sodium hypochlorite is 0. 89 mu mol J (-1) and is larger than the sum of yield for the radicals and reactive oxygen species by water radiolysis such as * OH, e (-), H, H2, and H2O2.

phenol

sodium hypochlorite

oxygen

* OH

H


Input: The formation of phenol with sodium hypochlorite was reduced by NaCl.

phenol

sodium hypochlorite

NaCl


Input: Results suggest that the radiolytic formation of phenol in a benzene solution with sodium hypochlorite relates to the reaction process involving chlorine atoms.

phenol

benzene

sodium hypochlorite

chlorine


Input: Sodium hypochlorite can be applied as a sensitizer for a benzene chemical dosimetry system.

Sodium hypochlorite

benzene


Input: The lower limit of dose detection calculated from the detection limit of phenol and the G value of phenol was estimated to be 1 x 10 (-3) Gy.

phenol

phenol


Input: Analysis and refactoring of the A-74528 biosynthetic pathway.


Input: A-74528 is a C30 polyketide natural product that functions as an inhibitor of 2', 5'-oligoadenylate phosphodiesterase (2'-PDE), a key regulatory enzyme of the interferon pathway.

C30 polyketide


Input: Modulation of 2'-PDE represents a unique therapeutic approach for regulating viral infections.


Input: The gene cluster responsible for biosynthesis of A-74528 yields minute amounts of this natural product together with considerably larger quantities of a structurally dissimilar C30 cytotoxic agent, fredericamycin.

fredericamycin


Input: Through construction and analysis of a series of knockout mutants, we identified the genes necessary for A-74528 biosynthesis.


Input: Remarkably, the formation of six stereocenters and the regiospecific formation of six rings in A-74528 appear to be catalyzed by only two tailoring enzymes, a cyclase and an oxygenase, in addition to the core polyketide synthase.


Input: The inferred pathway was genetically refactored in a heterologous host, Streptomyces coelicolor CH999, to produce 3 mg/L A-74528 in the absence of fredericamycin.

fredericamycin


Input: Osteogenesis of mesenchymal stem cells by nanoscale mechanotransduction.


Input: It is likely that mesenchymal stem cells will find use in many autologous regenerative therapies.


Input: However, our ability to control cell stem growth and differentiation is presently limited, and this is a major hurdle to the clinical use of these multipotent cells especially when considering the desire not to use soluble factors or complex media formulations in culture.


Input: Also, the large number of cells required to be clinically useful is currently a hurdle to using materials-based (stiffness, chemistry, nanotopography, etc.) culture substrates.


Input: Here we give a first demonstration of using nanoscale sinusoidal mechanotransductive protocols (10-14 nm displacements at 1 kHz frequency), " nanokicking ", to promote osteoblastogenesis in human mesenchymal stem cell cultures.


Input: On the basis of application of the reverse piezo effect, we use interferometry to develop the optimal stem cell stimulation conditions, allowing delivery of nanoscale cues across the entire surface of the Petri dishes used.


Input: A combination of immunofluorescence, PCR, and microarray has then been used to demonstrate osteoblastogenesis, and the arrays implicate RhoA as central to osteoblastic differentiation in agreement with materials-based strategies.


Input: We validate this with pharmacological inhibition of RhoA kinase.


Input: It is easy to envisage such stimulation protocols being up-scaled to form large-scale osteoblast bioreactors as standard cell culture plates and incubators are used in the protocol.


Input: The influence of clan structure on the genetic variation in a single Ghanaian village.


Input: Socioeconomic and cultural factors are thought to have an important role in influencing human population genetic structure.


Input: To explain such population structure differences, most studies analyse genetic differences among widely dispersed human populations.


Input: In contrast, we have studied the genetic structure of an ethnic group occupying a single village in north-eastern Ghana.


Input: We found a markedly skewed male population substructure because of an almost complete lack of male gene flow among Bimoba clans in this village.


Input: We also observed a deep male substructure within one of the clans in this village.


Input: Among all males, we observed only three Y-single-nucleotide polymorphism (SNP) haplogroups: E1b1a *-M2, E1b1a7a *-U174 and E1b1a8a *-U209, P277, P278.


Input: In contrast to the marked Y-chromosomal substructure, mitochondrial DNA HVS-1 sequence variation and autosomal short-tandem repeats variation patterns indicate high genetic diversities and a virtually random female-mediated gene flow among clans.


Input: On the extreme micro-geographical scale of this single Bimoba village, correspondence between the Y-chromosome lineages and clan membership could be due to the combined effects of the strict patrilocal and patrilineal structure.


Input: If translated to larger geographic scales, our results would imply that the extent of variation in uniparentally inherited genetic markers, which are typically associated with historical migration on a continental scale, could equally likely be the result of many small and different cumulative effects of social factors such as clan membership that act at a local scale.


Input: Such local scale effects should therefore be considered in genetic studies, especially those that use uniparental markers, before making inferences about human history at large. European Journal of Human Genetics advance online publication, 27 February 2013; doi: 10. 1038/ejhg. 2013. 12.


Input: Regulation of Translation Initiation under Biotic and Abiotic Stresses.


Input: Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to.


Input: Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations.


Input: Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response.


Input: In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery.


Input: Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation.


Input: In others, the mechanisms leading to the control of translation are viral-or stress-specific.


Input: In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants.


Input: In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations.


Input: Low temperature solution-processed high performance photodiode based on Si-ZnO core-shell structure.

Si

ZnO


Input: Radial heterojunction photodiodes based on a silicon nanowire arrays (SiNWs)-zinc oxide (ZnO) core-shell structure is demonstrated in this report.

silicon

zinc oxide

ZnO


Input: The heterojunction can be constructed by spin-coating ZnO nanoparticles onto SiNWs and a low temperature post-annealing process (< 270 degrees C).

ZnO


Input: The photodiode displays typical diode rectifying characteristics with an ideality factor of as low as 1. 28, and shows an excellent photoresponse in both visible and near infrared regions in which a peak value of 0. 54 A/W at zero bias was attained.


Input: The sensitivity is superior to that of previously reported devices fabricated with vacuum-deposition methods.


Input: In contrast, the planar silicon-ZnO junction only displays the peak photoresponsivity of 0. 34 A/W.

silicon

ZnO


Input: The superior performance of radial junction is ascribed to the highlight-harvesting capability, large interfacial area and efficient charge carrier collection arising from the core (SiNWs)-shell (ZnO) structure.

ZnO


Input: Here, high temperature processes are dispensable by using facile solution-processed techniques, which avoid thermal minority lifetime degradation of silicon and simplify the fabrication process of the photodiodes.

silicon


Input: In vivo evaluation of the interaction between titanium dioxide nanoparticle and rat liver DNA.

titanium dioxide


Input: Titanium dioxide nanoparticles (TiO2 NPs) are massively produced and widely used in daily life, which may pose potential risk to human health via uncharacterized interaction between DNAs.

Titanium dioxide


Input: This research aims to examine the interaction between DNA and three types of TiO2 NPs of different sizes and crystallines.


Input: The interaction between TiO2 NPs and liver DNA molecules obtained from Sprague-Dawley rats was systematically evaluated in vivo using atomic force microscopy, transmission electron microscopy, various spectroscopic techniques and gel electrophoresis.


Input: We found that TiO2 NPs (diameter < 25 nm and < 100 nm) in anatase crystalline can covalently interact with liver DNA by either inserting itself in between DNA base pairs or binding to DNA nucleotide via P-O-Ti-O bond.

nucleotide

O-Ti-O


Input: Such interaction may not be NP size-dependent but may be crystalline phase-dependent, because such interaction did not occur in rutile crystal phase, in which the DNA damage was potentially caused by reactive oxygen species.

oxygen


Input: A population-based study of dosing and persistence with anti-dementia medications.


Input: PURPOSE: Cholinesterase inhibitors and memantine are the mainstay of pharmacological intervention for the cognitive symptoms of Alzheimer' s disease (AD).

memantine


Input: This study assessed the adequacy of dosing and persistence with AD medications and the predictors of these variables in the' real world' (outside the clinical trial setting).


Input: METHODS: The Health Service Executive-Primary Care Reimbursement Services prescription claims database in the Republic of Ireland contains prescription information for 1. 6 million people.


Input: Patients aged > 70 years who received at least two prescriptions for donepezil, rivastigmine, galantamine and memantine between January 2006 and December 2010 were included in the study.

donepezil

rivastigmine

galantamine

memantine


Input: Rates of dose-maximisation were recorded by examining the initiation dose of each AD drug commenced during the study period and any subsequent dose titrations.


Input: Non-persistence was defined by a gap in prescribing of more than 63 consecutive days.


Input: Predictors of dose-maximisation and non-persistence were also analysed.


Input: RESULTS: Between January 2006 and December 2010, 20, 729 patients aged > 70 years received a prescription for an AD medication.


Input: Despite most patients on donepezil and memantine receiving a prescription for the maximum drug dose, this dose was maintained for 2 consecutive months in only two-thirds of patients.

donepezil

memantine


Input: Patients were significantly more likely to have their doses of donepezil and memantine maximised if prescribed in more recent years (2010 vs. 2007).

donepezil

memantine


Input: Rates of non-persistence were 30. 1% at 6 months and 43. 8% at 12 months.


Input: Older age [75 + vs. < 75 years; hazards ratio (HR) 1. 16, 95% confidence interval (CI) 1. 06-1. 27] and drug type (rivastigmine vs. donepezil; HR 1. 15, 95% CI 1. 03-1. 27) increased the risk of non-persistence.

rivastigmine

donepezil


Input: Non-persistence was lower for those commencing therapy in more recent years (2010 vs. 2007; HR 0. 81, 95% CI 0. 73-0. 89, p < 0. 001) and for those on multiple anti-dementia medications (HR 0. 59, 95% CI 0. 54-0. 65, p < 0. 001).


Input: Persistence was significantly higher when memantine was co-prescribed with donepezil (p < 0. 0001).

memantine

donepezil


Input: CONCLUSION: Future studies should explore the reasons underlying non-persistence and failure to maintain dose-maximisation in patients on AD medications.


Input: There may be scope to improve the dosing and persistence with these medications in the community.


Input: Microfluidic oxygen imaging using integrated optical sensor layers and a color camera.

oxygen


Input: In this work we present a high resolution oxygen imaging approach, which can be used to study 2D oxygen distribution inside microfluidic environments.

oxygen

oxygen


Input: The presented setup comprises a fabrication process of microfluidic chips with integrated luminescent sensing films combined with referenced oxygen imaging applying a color CCD-camera.

oxygen


Input: Enhancement of the sensor performance was achieved by applying the principle of light harvesting.


Input: This principle enabled ratiometric imaging employing the red and the green channel of a color CCD-camera.


Input: The oxygen sensitive emission of platinum (ii)-5, 10, 15, 20-tetrakis-(2, 3, 4, 5, 6-pentafluorphenyl)-porphyrin (PtTFPP) was detected by the red channel, while the emission of a reference dye was detected by the green channel.

oxygen

platinum (ii)-5, 10, 15, 20-tetrakis-(2, 3, 4, 5, 6-pentafluorphenyl)-porphyrin

PtTFPP


Input: This measurement setup allowed for accurate real-time 2D oxygen imaging with superior quality compared to intensity imaging.

oxygen


Input: The sensor films were subsequently used to measure the respiratory activity of human cell cultures (HeLa carcinoma cells and normal human dermal fibroblasts) in a microfluidic system.


Input: The sensor setup is well suited for different applications from spatially and temporally resolving oxygen concentration inside microfluidic channels to parallelization of oxygen measurements and paves the way to novel cell based assays, e. g. in tissue engineering, tumor biology and hypoxia reperfusion phenomena.

oxygen

oxygen


Input: Emtricitabine/tenofovir disoproxil fumarate: a review of its use in HIV-1 pre-exposure prophylaxis.

Emtricitabine

tenofovir disoproxil fumarate


Input: The fixed-dose combination of emtricitabine (FTC) 200 mg and tenofovir disoproxil fumarate (TDF) 300 mg (Truvada ((R))), administered orally once daily, is widely used as part of first-line regimens for the treatment of HIV-1 infection.

emtricitabine

FTC

tenofovir disoproxil fumarate

TDF

Truvada


Input: Recently, once-daily administration of FTC/TDF was approved in the USA for pre-exposure prophylaxis in conjunction with safer sex practices to reduce the risk of sexually acquired HIV-1 in high-risk adults who are not infected.

FTC

TDF


Input: To date, results of four large, randomized, double-blind, placebo-controlled, multicentre trials with FTC/TDF as pre-exposure prophylaxis have been published.

FTC

TDF


Input: Three studies showed statistically significant reductions in the number of individuals with emergent HIV-1 infection when FTC/TDF was compared with placebo over the =~ 1-to 2-year study periods.

FTC

TDF


Input: Efficacy (i. e. risk reduction relative to placebo) was 44% in the iPrEx trial in men who have sex with men, 75% in the Partners PrEP study in heterosexual HIV-1-serodiscordant couples and 62% in the TDF2 trial in heterosexual men and women.


Input: The fourth study (FEM-PrEP) in heterosexual women did not show a statistically significant difference between FTC/TDF and placebo, although low adherence rates reported in this trial may have been a factor.

FTC

TDF


Input: No unexpected adverse events were reported in the trials.


Input: However, since pre-exposure prophylaxis involves long-term administration of drugs to healthy individuals, it is important to monitor the long-term safety of FTC/TDF (e. g. renal function, bone mineral density) in this setting.

FTC

TDF


Input: Other notable considerations include adherence, cost and the potential for development of drug resistance.


Input: Interim guidelines are available for prescribing FTC/TDF as pre-exposure prophylaxis.

FTC

TDF


Input: If used appropriately in selected high-risk individuals, pre-exposure prophylaxis with FTC/TDF represents an important additional strategy to reduce the spread of HIV-1 infection, which continues to be a significant global concern.

FTC

TDF


Input: Population pharmacokinetic analysis of a nevirapine-based HIV-1 prevention of mother-to-child transmission program in Uganda to assess the impact of different dosing regimens for newborns.

nevirapine


Input: Single-dose nevirapine for mothers and newborns at delivery is the simplest prevention strategy for vertical HIV-1 transmission and hence widely used in resource-constrained settings.

nevirapine


Input: HIV-1-positive mothers and newborns received single-dose nevirapine in a prevention of mother-to-child HIV-1 transmission (PMTCT) program in Uganda.

nevirapine


Input: In a pharmacokinetic investigation, breast milk and plasma samples of mothers and newborns were collected.


Input: The nonlinear mixed-effects modeling approach was suitable for analysis (average: 1. 8 samples/matrix/individual).


Input: For describing the nevirapine pharmacokinetics in mothers and newborns, a 1-compartment model was demonstrated to be sufficient.

nevirapine


Input: The plasma-placenta transfer could be quantified, revealing a transfer fraction of 11% to 25% (with a significant influence of time span between maternal nevirapine intake and birth) and a high transfer rate constant from maternal drug administration.

nevirapine


Input: Interindividual variability was moderate between mothers and high between newborns.


Input: Simulations revealed that newborns born early (< 1 hour) after maternal nevirapine intake would benefit from a 3-fold higher nevirapine dosage (6 mg/kg) after birth for analogous protective plasma concentrations over the first 2 weeks.

nevirapine

nevirapine


Input: In contrast, postnatal nevirapine dosage seemed to be dispensable for newborns born late (> 24 hours) after maternal nevirapine intake.

nevirapine

nevirapine


Input: These dosing recommendations should be evaluated in prospective studies, including additional antiretroviral drugs in accordance with current PMTCT guidelines.


Input: A study on the effects of pica and iron-deficiency anemia on oxidative stress, antioxidant capacity and trace elements.

iron


Input: Pica is defined as developmentally inappropriate consumption of nonnutritive substances for at least 1 month.


Input: There are a few studies on serum trace element levels of patients with pica.


Input: The literature contains contracting data on the levels of oxidative stress and antioxidant levels in patients with iron-deficiency anemia (IDA).

iron


Input: The effect of pica on oxidative stress and antioxidant capacity has not been investigated yet.


Input: The present study evaluated the effects of pica and IDA on oxidative stress and antioxidant capacity as well as on the levels of trace elements including serum zinc and selenium in 47 children with IDA plus pica, 22 children with IDA only and 21 nonanemic children as controls.

zinc

selenium


Input: The results demonstrated significantly lower levels of serum selenium and zinc in pica and IDA groups compared to the control group.

selenium

zinc


Input: Total oxidant levels were highest in the pica group and consistently, the lowest total antioxidant capacity was observed again in the pica group.


Input: Comparison of pica and IDA groups yielded significantly lower levels of total antioxidant levels and significantly higher oxidative stress index in the pica group.


Input: Consequently, it is thought that the detrimental effects of pica within the organism were mediated by adverse impacts on antioxidant capacity and oxidative stress.


Input: These effects should be kept in mind while managing patients with pica.


Input: Significance of reductive metabolism in human intestine and quantitative prediction of intestinal first-pass metabolism by cytosolic reductive enzymes.


Input: The number of new drug candidates that are cleared via non-cytochrome P450 (P450) enzymes has increased.


Input: However, unlike oxidation by P450, the roles of reductive enzymes are less understood.


Input: The metabolism in intestine is especially not well known.


Input: The purposes of this study were to investigate the significance of reductive metabolism in human intestine, and to establish a quantitative prediction method of intestinal first-pass metabolism by cytosolic reductive enzymes, using haloperidol, mebendazole, and ziprasidone.

haloperidol

mebendazole

ziprasidone


Input: First, we estimated the metabolic activities for these compounds in intestine and liver using subcellular fractions.


Input: Metabolic activities were detected in human intestinal cytosol (HIC) for all three compounds, and the intrinsic clearance values were higher than those in human liver cytosol for haloperidol and mebendazole.

haloperidol

mebendazole


Input: These metabolic activities in HIC were NADPH-and/or NADH-dependent.

NADPH

NADH


Input: Furthermore, the metabolic activities for all three compounds in HIC were largely inhibited by menadione, which has been used as a carbonyl reductase (CBR)-selective chemical inhibitor.

menadione

carbonyl


Input: Therefore, considering subcellular location, cofactor requirement, and chemical inhibition, these compounds might be metabolized by CBRs in human intestine.


Input: Subsequently, we tried to quantitatively predict intestinal availability (Fg) for these compounds using human intestinal S9 (HIS9).


Input: Our prediction model using apparent permeability of parallel artificial membrane permeability assay and metabolic activities in HIS9 could predict Fg in humans for the three compounds well.


Input: In conclusion, CBRs might have higher metabolic activities in human intestine than in human liver.


Input: Furthermore, our prediction method of human Fg using HIS9 is applicable to substrates of cytosolic reductive enzymes.


Input: Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides.

ginsenosides


Input: Panax ginseng is one of the most popular herbal remedies.


Input: Ginsenosides, major bioactive constituents in P. ginseng, have shown good antidiabetic action, but the precise mechanism was not fully understood.

Ginsenosides


Input: Glucagon-like peptide-1 (GLP1) is considered to be an important incretin that can regulate glucose homeostasis in the gastrointestinal tract after meals.

glucose


Input: The aim of this study was to investigate whether ginseng total saponins (GTS) exerts its antidiabetic effects via modulating GLP1 release.

saponins


Input: Ginsenoside Rb1 (Rb1), the most abundant constituent in GTS, was selected to further explore the underlying mechanisms in cultured NCI-H716 cells.

Ginsenoside Rb1


Input: Diabetic rats were developed by a combination of high-fat diet and low-dose streptozotocin injection.

streptozotocin


Input: The diabetic rats orally received GTS (150 or 300 mg/kg) daily for 4 weeks.


Input: It was found that GTS treatment significantly ameliorated hyperglycemia and dyslipidemia, accompanied by a significant increase in glucose-induced GLP1 secretion and upregulation of proglucagon gene expression.

glucose


Input: Data from NCI-H716 cells showed that both GTS and Rb1 promoted GLP1 secretion.


Input: It was observed that Rb1 increased the ratio of intracellular ATP to ADP concentration and intracellular Ca (2) (+) concentration.

ATP

ADP

Ca (2) (+)


Input: The metabolic inhibitor azide (3 mM), the KATP channel opener diazoxide (340 mu M), and the Ca (2) (+) channel blocker nifedipine (20 mu M) significantly reversed Rb1-mediated GLP1 secretion.

azide

diazoxide

Ca (2) (+)

nifedipine


Input: All these results drew a conclusion that ginsenosides stimulated GLP1 secretion both in vivo and in vitro.

ginsenosides


Input: The antidiabetic effects of ginsenosides may be a result of enhanced GLP1 secretion.

ginsenosides


Input: Defective DNA damage response and repair in liver cells expressing hepatitis B virus surface antigen.


Input: Hepatitis B virus (HBV) is implicated in liver cancer.


Input: The aim of this study was to find out whether HBV or its components [HBV surface antigen (HBsAg), HBV core protein (HBc), and HBV X protein (HBx)] could interfere with the host DNA damage response and repair pathway.


Input: The full HBV genome or individual HBV open-reading frame (ORF) was introduced into HepG2 cells to examine the effect on host genomic stability, DNA repair efficacy in response to double-strand DNA damage, and DNA damage-induced cell death.


Input: Responses to apoptosis induction in the HBV ORF-transfected HepG2 cells were also compared with those in HBV-positive and HBV-negative human hepatocellular carcinoma (HCC) cells.


Input: In the absence of HBV replication, accumulation of HBsAg in liver cells without other HBV proteins enhanced DNA repair protein and tumor suppressor promyelocytic leukemia (PML) degradation, which resulted in resistance to apoptosis induction and deficient double-strand DNA repair.


Input: However, HBsAg-positive cells exhibited increased cell death with exposure to the poly (ADP-ribose) polymerase inhibitor that blocks single-strand DNA repair.

poly (ADP-ribose)


Input: These results indicate that suppression of PML by HBsAg disrupts cellular mechanisms that respond to double-strand DNA damage for DNA repair or apoptosis induction, which may facilitate hepatocarcinogenesis and open up a synthetic lethality strategy for HBsAg-positive HCC treatment.-Chung, Y.-L.


Input: Defective DNA damage response and repair in liver cells expressing hepatitis B virus surface antigen.


Input: Fanconi anemia pathway--the way of DNA interstrand cross-link repair.


Input: The study of rare genetic diseases usually inspires the research of cancer biology.


Input: Fanconi anemia (FA), is a rare cancer susceptibility syndrome with an incidence of only 1 per 350, 000 births.


Input: FA is an autosomal recessive disease with three main features: chromosome instability, hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC), cisplatin and so on, and susceptible to a number of cancer types, mainly leukemia and squamous cell carcinomas of the head and neck or gynecologic system.

mitomycin C

MMC

cisplatin


Input: DNA crosslinking agents may led to DNA cross-linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross-linking.


Input: However, FA pathway is closely linked with carcinogenesis and tumor drug resistance.


Input: This paper mainly focuses on the FA pathway and its progress in cancer research.


Input: Effects of a new sustained-release microsphere formulation of exenatide, DA-3091, on obese and non-alcoholic fatty liver disease mice.


Input: The aim of this study was to examine the effects of a new sustained-release (SR) microsphere formulation of exenatide, DA-3091, on body weight gain and hepatic injury in high fat diet (HFD)-induced obese mice and high sucrose diet (HSD)-induced non-alcoholic fatty liver disease (NAFLD) mice.


Input: Then, we determined whether DA-3091 has the potency as a drug for the treatment of metabolic disease.


Input: In obese mice, after 8-week treatment, the body weight gain was significantly more suppressed by both 1 mg/kg and 2 mg/kg of DA-3091, monthly subcutaneous administered, than by 10 mg/kg/day of sibutramin, a drug against obesity.

sibutramin


Input: In NAFLD mice, a significant reduction in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, representative markers of hepatic injury, was observed after biweekly subcutaneous administration of 1 mg/kg and 2 mg/kg of DA-3091 for 8 weeks.

alanine

aspartate


Input: A significant reduction in hepatic lipid accumulation was observed in DA-3091 treated groups as well.


Input: Based on these results, it is demonstrated that DA-3091 has the potency as a drug for the treatment of metabolic disease.


Input: Effects of insulin-like growth factor-1 on neurochemical phenotypes of cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate.

glutamate


Input: Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons.


Input: The neuropeptide-and neurofilament (NF)-immunoreactive (IR) neurons are two major phenotypical classes in DRG.


Input: Whether IGF-1 affects neurochemical phenotypes of DRG neurons remains unknown.


Input: In the present study, primary cultured DRG neurons were used to determine the effects of IGF-1 on neurochemical phenotypes of the neurons with excitotoxicity induced by glutamate (Glu).

glutamate

Glu


Input: DRG neurons were dissociated and cultured for 48 hours and then exposed to IGF-1 (20 nmol/L), Glu (0. 2 mmol/L), Glu (0. 2 mmol/L) plus IGF-1 (20 nmol/L) for additional 24 hours.

Glu

Glu


Input: The DRG neurons were continuously exposed to culture media as control.


Input: After that, all above cultured DRG neurons were processed for detecting mRNA levels of calcitonin gene-related peptide (CGRP) and neurofilament-200 (NF-200) by real time-PCR analysis.


Input: CGRP and NF-200 expression in situ was determined by fluorescent labeling technique.


Input: The results showed that CGRP mRNA, but not NF-200 mRNA, increased after IGF-1 administration in the absence or presence of Glu.

Glu


Input: IGF-1 could increase the percentage of CGRP-expressing neurons, but not NF-200-expressing neurons, in the absence or presence of Glu.

Glu


Input: The ability of IGF-1 on CGRP expression may play a role in neurogenic inflammation or nociception.


Input: Incision wound healing activity of pine bark extract containing topical formulations: a study with histopathological and biochemical analyses in albino rats.


Input: The present study was designed to identify and compare the in vivo wound healing capacity of a bark extract from Pinus brutia and Pycnogenol in an incision wound model in rats.


Input: O/W cream formulations were prepared incorporating 2% Pycnogenol and P. brutia bark extract.


Input: The rats were divided into three groups (n = 8).


Input: Subsequently placebo and test formulations were applied to animals once a day from day " 0 " until the 9th day.


Input: Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) were studied in addition to histopathological examinations.

Malondialdehyde

MDA

superoxide


Input: Treatment with F. brutia extract containing cream inhibited lipid peroxidation by a 35% decrease in MDA and 46. 8% increase in SOD activity, whereas 19. 3% decrease in MDA and 34. 7% increase in SOD activity were attained with Pynogenol compared to control.

MDA

MDA


Input: The histological data revealed a better performance of P. brutia extract enriched formulation in terms of degeneration of hair roots, increased vascularization and a decrease in necrotic area.


Input: Consequently, a high wound healing activity was observed in animals treated with P. brutia extract significantly accelerating the wound healing process.


Input: Isolation, Structure Elucidation, and Iron-Binding Properties of Lystabactins, Siderophores Isolated from a Marine Pseudoalteromonas sp.

Iron

Lystabactins


Input: The marine bacterium Pseudoalteromonas sp.


Input: S2B, isolated from the Gulf of Mexico after the Deepwater Horizon oil spill, was found to produce lystabactins A, B, and C (1-3), three new siderophores.

lystabactins A, B, and C


Input: The structures were elucidated through mass spectrometry, amino acid analysis, and NMR.

amino acid


Input: The lystabactins are composed of serine (Ser), asparagine (Asn), two formylated/hydroxylated ornithines (FOHOrn), dihydroxy benzoic acid (Dhb), and a very unusual nonproteinogenic amino acid, 4, 8-diamino-3-hydroxyoctanoic acid (LySta).

lystabactins

serine

Ser

asparagine

Asn

formylated/hydroxylated ornithines

FOHOrn

dihydroxy benzoic acid

Dhb

nonproteinogenic amino acid

4, 8-diamino-3-hydroxyoctanoic acid

LySta


Input: The iron-binding properties of the compounds were investigated through a spectrophotometric competition.


Input: Vectorization efforts to increase gram-negative intracellular drug concentration: a case study on HldE-K inhibitors.


Input: In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their gram-negative intracellular concentration.


Input: Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed.


Input: While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin.

erythromycin


Input: Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies.

amines

erythromycin


Input: Arylazanylpyrazolone derivatives as inhibitors of mutant superoxide dismutase 1 dependent protein aggregation for the treatment of amyotrophic lateral sclerosis.

Arylazanylpyrazolone

superoxide


Input: The arylsulfanylpyrazolone and aryloxanylpyrazolone scaffolds previously were reported to inhibit Cu/Zn superoxide dismutase 1 dependent protein aggregation and to extend survival in the ALS mouse model.

arylsulfanylpyrazolone

aryloxanylpyrazolone

Cu

Zn superoxide


Input: However, further evaluation of these compounds indicated weak pharmacokinetic properties and a relatively low maximum tolerated dose.


Input: On the basis of an ADME analysis, a new series of compounds, the arylazanylpyrazolones, has been synthesized, and structure-activity relationships were determined.

arylazanylpyrazolones


Input: The SAR results showed that the pyrazolone ring is critical to cellular protection.

pyrazolone


Input: The NMR, IR, and computational analyses suggest that phenol-type tautomers of the pyrazolone ring are the active pharmacophore with the arylazanylpyrazolone analogues.

phenol

pyrazolone

arylazanylpyrazolone


Input: A comparison of experimental and calculated IR spectra is shown to be a valuable method to identify the predominant tautomer.


Input: Drug-initiated ring-opening polymerization of O-carboxyanhydrides for the preparation of anticancer drug-poly (O-carboxyanhydride) nanoconjugates.

O-carboxyanhydrides

poly (O-carboxyanhydride)


Input: We report a novel synthetic strategy of polymer-drug conjugates for nanoparticulate drug delivery: hydroxyl-containing drug (e. g., camptothecin, paclitaxel, doxorubicin and docetaxel) can initiate controlled polymerization of phenyl O-carboxyanhydride (Phe-OCA) to afford drug-poly (Phe-OCA) conjugated nanoparticles, termed drug-PheLA nanoconjugates (NCs).

hydroxyl

camptothecin

paclitaxel

doxorubicin

docetaxel

phenyl O-carboxyanhydride

Phe-OCA

Phe-OCA

PheLA


Input: Our new NCs have well-controlled physicochemical properties, including high drug loading, quantitative drug loading efficiency, controlled particle size with narrow particle size distribution, and sustained drug release profile over days without " burst " release effect as observed in conventional polymer/drug encapsulates.


Input: Compared with polylactide NCs, the PheLA NCs have increased noncovalent hydrophobic interchain interactions and thereby result in remarkable stability in human serum with negligible particle aggregation.

polylactide

PheLA


Input: Such distinctive properties can reduce the premature disassembly of NCs upon dilution in the bloodstream and prolong NCs' in vivo circulation with the enhancement of intratumoral accumulation of NCs, which has a bearing on therapeutic effectiveness.


Input: CYP2J2 overexpression increases EETs and protects against angiotensin II-induced abdominal aortic aneurysm in mice.

EETs


Input: Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acids to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on the cardiovascular system.

arachidonic acids

epoxyeicosatrienoic acids

EETs


Input: However, whether increasing EETs production by CYP2J2 overexpression in vivo could prevent abdominal aortic aneurysm (AAA) remains unknown.

EETs


Input: Here we investigated the effects of recombinant adeno-associated virus (rAAV)-mediated CYP2J2 overexpression on angiotensin (Ang) II-induced AAA in apoE-deficient mice.


Input: rAAV-CYP2J2 delivery led to an abundant aortic CYP2J2 expression and increased EETs generation.

EETs


Input: It was shown that CYP2J2 overexpression attenuated matrix metalloproteinase expression and activity, elastin degradation, and AAA formation, which was associated with reduced aortic inflammation and macrophage infiltration.


Input: In cultured vascular smooth muscle cells (VSMCs), rAAV-mediated CYP2J2 overexpression and EETs markedly suppressed Ang II-induced inflammatory cytokine expression.

EETs


Input: Moreover, overexpressed CYP2J2 and EETs inhibited Ang II-induced macrophage migration in a VSMC-macrophage coculture system.

EETs


Input: We further indicated that these protective effects were mediated by peroxisome proliferator-activated receptor (PPAR) gamma activation.


Input: Taken together, these results provide evidence that rAAV-mediated CYP2J2 overexpression prevents AAA development which is likely via PPAR gamma activation and anti-inflammatory action, suggesting that increasing EETs levels could be considered as a potential strategy to prevent and treat AAA.

EETs


Input: Single-molecule chemical denaturation of riboswitches.


Input: To date, single-molecule RNA science has been developed almost exclusively around the effect of metal ions as folding promoters and stabilizers of the RNA structure.


Input: Here, we introduce a novel strategy that combines single-molecule F o rster resonance energy transfer (FRET) and chemical denaturation to observe and manipulate RNA dynamics.


Input: We demonstrate that the competing interplay between metal ions and denaturant agents provides a platform to extract information that otherwise will remain hidden with current methods.


Input: Using the adenine-sensing riboswitch aptamer as a model, we provide strong evidence for a rate-limiting folding step of the aptamer domain being modulated through ligand binding, a feature that is important for regulation of the controlled gene.

adenine


Input: In the absence of ligand, the rate-determining step is dominated by the formation of long-range key tertiary contacts between peripheral stem-loop elements.


Input: In contrast, when the adenine ligand interacts with partially folded messenger RNAs, the aptamer requires specifically bound Mg (2 +) ions, as those observed in the crystal structure, to progress further towards the native form.

adenine

Mg (2 +)


Input: Moreover, despite that the ligand-free and ligand-bound states are indistinguishable by FRET, their different stability against urea-induced denaturation allowed us to discriminate them, even when they coexist within a single FRET trajectory; a feature not accessible by existing methods.

urea


Input: Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions.

cAMP

cAMP


Input: Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers.

cAMP


Input: The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and gene transcription, is reflected by the award of five Nobel prizes.

cAMP

calcium


Input: The discovery of Epac (exchange protein directly activated by cAMP) has ignited a new surge of cAMP-related research and has depicted novel cAMP properties independent of protein kinase A and cyclic nucleotide-gated channels.

cAMP

cAMP

cAMP

nucleotide


Input: The multidomain architecture of Epac determines its activity state and allows cell-type specific protein-protein and protein-lipid interactions that control fine-tuning of pivotal biologic responses through the " old " second messenger cAMP.

cAMP


Input: Compartmentalization of cAMP in space and time, maintained by A-kinase anchoring proteins, phosphodiesterases, and beta-arrestins, contributes to the Epac signalosome of small GTPases, phospholipases, mitogen-and lipid-activated kinases, and transcription factors.

cAMP


Input: These novel cAMP sensors seem to implement certain unexpected signaling properties of cAMP and thereby to permit delicate adaptations of biologic responses.

cAMP

cAMP


Input: Agonists and antagonists selective for Epac are developed and will support further studies on the biologic net outcome of the activation of Epac.


Input: This will increase our current knowledge on the pathophysiology of devastating diseases, such as diabetes, cognitive impairment, renal and heart failure, (pulmonary) hypertension, asthma, and chronic obstructive pulmonary disease.


Input: Further insights into the cAMP dynamics executed by the Epac signalosome will help to optimize the pharmacological treatment of these diseases.

cAMP


Input: Ion-induced synthesis of uniform single-crystalline sulphide-based quaternary-alloy hexagonal nanorings for highly efficient photocatalytic hydrogen evolution.

sulphide

hydrogen