Input: Rescue of both impaired extinction acquisition and deficient extinction consolidation/retrieval was achieved with prior extinction training administration of valproic acid (a GABAergic enhancer and HDAC inhibitor) or AMN082 [metabotropic glutamate receptor 7 (mGlu7) agonist], while MS-275 or PEPA (AMPA receptor potentiator) failed to affect extinction acquisition in S1 mice.

valproic acid

glutamate

PEPA

AMPA


Input: Collectively, these data identify potential beneficial effects of DBS and various drug treatments, including those with HDAC inhibiting or mGlu7 agonism properties, as adjuncts to overcome treatment resistance in exposure-based therapies.


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Alleviation of high salt toxicity-induced oxidative damage by salicylic acid pretreatment in two wheat cultivars.

salicylic acid


Input: Role of exogenous salicylic acid (SA) in the antioxidative response to salt toxicity of two wheat (Triticum aestivum) cultivars (Gerek-79 and Bezostaya) was investigated.

salicylic acid


Input: Hydroponic growth environment of 10-day wheat seedlings grown under normal conditions (22/20 degrees C) was adjusted to 0. 0, 0. 25, 0. 50 and 0. 75 M of salt (NaCl), and then freshly prepared SA solutions (0. 0, 0. 01 and 0. 1 mM) were once sprayed on leaves of the same seedlings.

NaCl


Input: Activities of superoxide dismutase (SOD), peroxidase (POX) and catalase (CAT) were determined in fresh leaves obtained from 15-day seedlings.

superoxide


Input: Treatment with SA alone increased all the antioxidant activities in Gerek-79.


Input: However, the same treatments with SA decreased the activities of CAT and SOD in Bezostaya, while increased that of POX.


Input: Salt applications alone increased the activities of POX and SOD, while decreased that of CAT in Bezostaya.


Input: The same salt applications increased the POX activity, while decreased the activities of CAT and SOD in Gerek-79.


Input: In plants under saline conditions, except 0. 75 M NaCl, treatments with SA increased the activities of CAT, POX and SOD in both the varieties compared with plants applied salt alone.

NaCl


Input: In plants applied with 0. 75 M NaCl, however, treatments with SA decreased CAT activity.

NaCl


Input: Results showed that salt toxicity caused a derangement in the regulation of antioxidant enzyme activities by decreasing CAT activity especially in both the varieties, but treatments with SA could turn back the derangement in the antioxidative enzymes caused by salt toxicity.


Input: SA can involve in increasing salt tolerance by regulating the activities of antioxidant enzymes in wheat cultivars exposed to salt toxicity.


Input: Possibility for the development of cosmetics with PLGA nanospheres.

PLGA


Input: The optimized preparation of Poly-(lactide-co-glycolic acid) (PLGA) nanospheres containing ubiquinone (UQ) for cosmetic products was pursued.

Poly-(lactide-co-glycolic acid)

PLGA


Input: By investigating various conditions for the preparation of UQ/PLGA nanospheres such as the molecular weight of PLGA, PLGA concentration, and UQ concentration, UQ/PLGA nanospheres with increased stability and slower drug release at a higher drug loading efficiency were prepared.

PLGA

PLGA

PLGA

PLGA


Input: Permeation tests on the prepared nanospheres using iontophoresis via electric dermal administration on membrane filters (200 nm pore size) and hairless mouse skin samples were also carried out.


Input: After iontophoresis, the nanospheres choked the membrane filter and remained on the horny layer of the hairless mouse skin, even after washing.


Input: Therefore, the prepared UQ/PLGA nanospheres and the established iontophoresis technique with the PLGA nanospheres in the present study can be applied to the future development of cosmetics.

PLGA

PLGA


Input: Melamine in prenatal and postnatal organs in rats.

Melamine


Input: Melamine can be transferred to fetus in utero through placenta and to infant ex utero by breast feeding.

Melamine


Input: In this study, we characterized the pharmacokinetics of melamine in prenatal and postnatal organs in rats.

melamine


Input: Single bolus of melamine was administered to pregnant rats at different gestational stages and to infants at different postnatal stages.

melamine


Input: Distribution of melamine in maternal serum was about 30% higher in late pregnancy than that in early pregnancy; and it was 2 folds higher in postnatal serum in early infants in young adulthood.

melamine


Input: Distribution of melamine in all postnatal organs was higher than that in prenatal organs.

melamine


Input: Postnatal kidneys in early infants had the highest maximum concentration and the lowest clearance of melamine than the other postnatal organs.

melamine


Input: It may relate to the high vulnerability to the toxicity of melamine in this population.

melamine


Input: Selective GABA (A) alpha 5 positive allosteric modulators improve cognitive function in aged rats with memory impairment.

GABA


Input: A condition of excess activity in the hippocampal formation is observed in the aging brain and in conditions that confer additional risk during aging for Alzheimer' s disease.


Input: Compounds that act as positive allosteric modulators at GABA (A) alpha 5 receptors might be useful in targeting this condition because GABA (A) alpha 5 receptors mediate tonic inhibition of principal neurons in the affected network.

GABA

GABA


Input: While agents to improve cognitive function in the past focused on inverse agonists, which are negative allosteric modulators at GABA (A) alpha 5 receptors, research supporting that approach used only young animals and predated current evidence for excessive hippocampal activity in age-related conditions of cognitive impairment.

GABA


Input: Here, we used two compounds, Compound 44 [6, 6-dimethyl-3-(3-hydroxypropyl) thio-1-(thiazol-2-yl)-6, 7-dihydro-2-benzothiophen-4 (5H)-one] and Compound 6 [methyl 3, 5-diphenylpyridazine-4-carboxylate], with functional activity as potentiators of gamma-aminobutyric acid at GABA (A) alpha 5 receptors, to test their ability to improve hippocampal-dependent memory in aged rats with identified cognitive impairment.

6, 6-dimethyl-3-(3-hydroxypropyl) thio-1-(thiazol-2-yl)-6, 7-dihydro-2-benzothiophen-4 (5H)-one

methyl 3, 5-diphenylpyridazine-4-carboxylate

gamma-aminobutyric acid

GABA


Input: Improvement was obtained in aged rats across protocols differing in motivational and performance demands and across varying retention intervals.


Input: Significant memory improvement occurred after either intracereboventricular infusion with Compound 44 (100 mu g) in a water maze task or systemic administration with Compound 6 (3 mg/kg) in a radial arm maze task.


Input: Furthermore, systemic administration improved behavioral performance at dosing shown to provide drug exposure in the brain and in vivo receptor occupancy in the hippocampus.


Input: These data suggest a novel approach to improve neural network function in clinical conditions of excess hippocampal activity.


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: A Safety Assessment of the Antimalarial Herb Artemisia annua During Pregnancy in Wistar Rats.


Input: Artemisia annua is a Chinese antimalarial herb that has been used for more than 2000 years.


Input: The maternal and foetal safety of the ethanolic leaf extract of therapeutically active Artemisia annua (EAA), with previously determined artemisinin yield of 1. 098% was evaluated in Wistar rats.


Input: Twenty pregnant rats, divided into four study groups of saline treated (control), and test groups administered orally with 100, 200 and 300 mg/kg body weights of EAA, respectively, from gestation days (GD) 8 to 19.


Input: Following overnight fast, animals were sacrificed on GD 20, and maternal blood was collected to evaluate biochemical and haematological markers.


Input: Foetuses were carefully removed, weighed, and observed for any possible malformation.


Input: Biochemical and haematological studies revealed that EAA did not result in maternal hepatotoxicity, haematotoxicity, and hyperlipidemia.


Input: While litter size significantly decreased (p < 0. 05) at 100 mg/kg EAA, maternal estrogen levels decreased in all the EAA-treated groups.

estrogen


Input: Non-viable (21%) and malformed (31%) foetuses were observed at the 300 mg/kg dose of EAA, which implies that although consumption of the leaf extract may not predispose users to hepatotoxicity, haematotoxicity, and hyperlipidemia, it should be taken with caution during pregnancy due to possible risk of embryotoxicity at concentrations higher than the therapeutic dose.


Input: Copyright (c) 2012 John Wiley & Sons, Ltd.


Input: Up-regulation of cytochrome P450 and phase II enzymes by xenobiotics in precision-cut tissue slices.


Input: 1. Induction of the drug-metabolising enzyme systems is a major cause of clinically relevant drug interactions.


Input: The potential of a drug to engage in such interactions may be assessed in in vitro systems such as precision-cut tissue slices.


Input: 2. Precision-cut tissue slices have a number of important advantages compared with the use of cells in culture, especially when tissues with a heterogeneous cellular population are concerned.


Input: 3. Extensive studies concerned with the induction of cytochrome P450 and Phase II enzymes in precision-cut tissue slices from various animal and human tissues, such as liver, lung and intestine, using established inducing agents have revealed that slices mimic the in vivo situation.


Input: 4. Precision-cut tissue slices is a reliable, informative and cost-effective technique for assessing the potential of chemicals to up-regulate drug-metabolising enzyme systems.


Input: The pathways of mitophagy for quality control and clearance of mitochondria.


Input: Selective autophagy of mitochondria, known as mitophagy, is an important mitochondrial quality control mechanism that eliminates damaged mitochondria.


Input: Mitophagy also mediates removal of mitochondria from developing erythrocytes, and contributes to maternal inheritance of mitochondrial DNA through the elimination of sperm-derived mitochondria.


Input: Recent studies have identified specific regulators of mitophagy that ensure selective sequestration of mitochondria as cargo.


Input: In yeast, the mitochondrial outer membrane protein autophagy-related gene 32 (ATG32) recruits the autophagic machinery to mitochondria, while mammalian Nix is required for degradation of erythrocyte mitochondria.


Input: The elimination of damaged mitochondria in mammals is mediated by a pathway comprised of PTEN-induced putative protein kinase 1 (PINK1) and the E3 ubiquitin ligase Parkin.


Input: PINK1 and Parkin accumulate on damaged mitochondria, promote their segregation from the mitochondrial network, and target these organelles for autophagic degradation in a process that requires Parkin-dependent ubiquitination of mitochondrial proteins.


Input: Here we will review recent advances in our understanding of the different pathways of mitophagy.


Input: In addition, we will discuss the relevance of these pathways in neurons where defects in mitophagy have been implicated in neurodegeneration.


Input: Nicotine facilitates memory consolidation in perceptual learning.

Nicotine


Input: Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices.


Input: The cholinergic system is known to modulate declarative learning.


Input: In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation.

acetylcholine


Input: However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning.


Input: Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT).


Input: One group received chewing tobacco containing nicotine for 1 h directly following the TDT training.

nicotine


Input: The other group received a similar tasting control substance without nicotine.

nicotine


Input: Electroencephalographic recordings during substance consumption showed reduced alpha activity and P300 latencies in the nicotine group compared to the control group.

nicotine


Input: When re-tested on the TDT the following day, both groups responded more accurately and more rapidly than during training.


Input: These improvements were specific to the retinal location and orientation of the texture elements of the TDT suggesting that learning involved early visual cortex.


Input: A group comparison showed that learning effects were more pronounced in the nicotine group than in the control group.

nicotine


Input: These findings suggest that oral consumption of nicotine enhances the efficacy of nicotinic acetylcholine receptors.

nicotine

acetylcholine


Input: Our findings further suggest that enhanced efficacy of the cholinergic system facilitates memory consolidation in perceptual learning (and possibly other types of non-declarative learning).


Input: In that regard acetylcholine seems to affect consolidation processes in perceptual learning in a different manner than in declarative learning.

acetylcholine


Input: Alternatively, our findings might reflect dose-dependent cholinergic modulation of memory consolidation.


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Gene therapy and neurodevelopmental disorders.


Input: With a number of recent clinical successes, gene therapy is quickly becoming a realistic treatment option for neurological disorders.


Input: Advancements in global central nervous system (CNS) gene delivery, in particular, have accelerated to the point that treatments for neurological disorders such as lysosomal storage diseases seem within reach.


Input: Other neurodevelopmental disorders, such as Rett Syndrome, Fragile X, and autism still face significant obstacles to overcome before a viable human gene therapy can be considered.


Input: This review focuses on the most common CNS gene delivery vehicle, adeno-associated virus (AAV), and the current state of AAV vector design and delivery for CNS gene therapy.


Input: Relevant examples of gene therapy studies for neurodevelopmental disorders, as well as outstanding challenges, are discussed.


Input: This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.


Input: Phytochemical analysis of the essential oils of 10 endemic Cephalaria species from Turkey.


Input: The volatile composition of 10 endemic Cephalaria (Dipsacaceae) species (Cephalaria gazipashensis, Cephalaria lycica, Cephalaria paphlagonica, Cephalaria elmaliensis, Cephalaria stellipilis, Cephalaria scoparia, Cephalaria isaurica, Cephalaria cilicica, Cephalaria elazigensis var. purpurea and Cephalaria davisiana) was investigated.


Input: The essential oil mixtures were obtained by steam distillation in a Clevenger-type apparatus.


Input: Twenty-eight components were identified by GC-FID and GC-MS techniques.


Input: While total volatile percentages ranged from 68. 99% to 84. 57%, the total essential oil yields ranged between 38. 15% and 64. 05%.


Input: Geraniol, alpha-cedrene and p-cymene were determined as the main components.

Geraniol

alpha-cedrene

p-cymene


Input: Geraniol was detected as a major component in C. cilicica (14. 64%), and alpha-cedrene was detected as a major component with 26. 03% for C. lycica, 16. 93% for C. scoparia, 13. 01% for C. davisiana and 10. 94% for C. paphlagonica.

Geraniol

alpha-cedrene


Input: Cephalaria scoparia, C. davisiana and C. gazipashensis have considerable amount of p-cymene as 12. 86%, 12. 70% and 11. 16%, respectively.

p-cymene


Input: This was the first essential oil report concerning the Cephalaria genus.


Input: Auraptene and its Effects on the Re-emergence of Colon Cancer Stem Cells.

Auraptene


Input: Recent studies indicate that auraptene (7-geranyloxycoumarin, AUR), a geranyloxycoumarin extracted from fruits of edible plants belonging to the Rutaceae family, may represent a novel lead compound for dietary colon cancer chemoprevention in rodents.

auraptene

AUR

geranyloxycoumarin


Input: As a continuation of studies aimed to better depict the pharmacological effects and mechanism of action of the title natural compound, the current investigation was undertaken to determine whether AUR would be able to prevent the growth and sphere (surrogate tumors) formation of FOLFOX-resistant colon cancer cells that are highly enriched in cancer stem cells (CSCs).

AUR


Input: Our results demonstrate that AUR at a concentration of 10 mu M was able to inhibit the growth and formation of colonospheres of FOLFOX-resistant colon cancer HT-29 cells in vitro.

AUR


Input: The corresponding parental cells were also similarly affected by AUR at the same concentration level.

AUR


Input: The reduction in the growth and colonospheres formation in FOLFOX-resistant HT-29 was also associated with a concomitant decrease in phospho-epidermal growth factor receptor.

phospho


Input: These findings suggest that AUR could prevent the re-emergence of CSCs.

AUR


Input: Copyright (c) 2012 John Wiley & Sons, Ltd.


Input: Zanthoxylum usambarense (Engl.) Kokwaro (Rutaceae) Extracts Inhibit the Growth of the Breast Cancer Cell Lines MDA-MB-231 and MCF-7, But Not the Brain Tumour Cell Line U251 In Vitro.


Input: Zanthoxylum usambarense (Engl.) Kokwaro has traditionally been used for the treatment of malaria, upper respiratory tract infections, cough, rheumatism, tooth decay and sore gums in Kenya and other African countries.


Input: Dried ground parts of Z. usambarense were extracted by maceration using methanol (MeOH) at room temperature, extract was dried and reconstituted in 70% aq.

methanol

MeOH


Input: MeOH and partitioned against n-hexane and chloroform (CHCl3) to obtain MeOH, n-hexane and CHCl3 extracts.

MeOH

n-hexane

chloroform

MeOH

n-hexane


Input: All extracts were assessed for cytotoxicity against two breast cancer cell lines, MDA-MB-231 and MCF-7, and the brain tumour cell line U251 by the MTT assay.

MTT


Input: The free-radical scavenging activity of the extracts was also determined by the 2, 2-diphenyl-1-picryhydrazyl (DPPH) assay.

2, 2-diphenyl-1-picryhydrazyl

DPPH


Input: In the DPPH assay, the MeOH extract was found to be the most active free-radical scavenger with a RC50 value of 41. 1 x 10 (-3) mg/mL.

DPPH

MeOH


Input: It also displayed significant cytotoxicity against the MCF-7 cell line (IC50 42. 9 micro g/mL) and appeared to have induced cell death through apoptosis.


Input: None of the test extracts showed any activity against the U251 cell line at test concentrations.


Input: The present findings demonstrated that Z. usambarense could be a potential source for new cytotoxic compounds for possible anticancer drug development.


Input: Copyright (c) 2012 John Wiley & Sons, Ltd.


Input: Perturbing peptide cation-radical electronic states by thioxoamide groups: formation, dissociations, and energetics of thioxopeptide cation-radicals.

thioxoamide


Input: Thioxodipeptides Gly-thio-Lys (GtK), Ala-thio-Lys (AtK), and Ala-thio-Arg (AtR) in which the amide group has been modified to a thioxoamide were made into dications by electrospray ionization and converted to cation-radicals, (GtK + 2H) (+ *), (AtK + 2H) (+ *), and (AtR + 2H) (+ *), by electron transfer dissociation (ETD) tandem mass spectrometry using fluoranthene anion-radical as an electron donor.

Thioxodipeptides Gly-thio-Lys

GtK

Ala-thio-Lys

AtK

Ala-thio-Arg

AtR

amide

thioxoamide

GtK

AtK

AtR

fluoranthene anion-radical


Input: The common and dominant dissociation of these cation-radicals was the loss of a hydrogen atom.

hydrogen


Input: The dissociation products were characterized by collision-induced dissociation (CID) multistage tandem mass spectrometry up to CID-MS (5).


Input: The ground electronic states of several (GtK + 2H) (+ *), (AtK + 2H) (+ *), and (AtR + 2H) (+ *) conformers were explored by extensive ab initio and density functional theory calculations of the potential energy surface.

GtK

AtK

AtR


Input: In silico electron transfer to the precursor dications, (GtK + 2H) (2 +), (AtK + 2H) (2 +), and (AtR + 2H) (2 +), formed zwitterionic intermediates containing thioenol anion-radical and ammonium cation groups that were local energy minima on the potential energy surface of the ground electronic state.

GtK

AtK

AtR

thioenol anion-radical

ammonium cation


Input: The zwitterions underwent facile isomerization by N-terminal ammonium proton migration to the thioenol anion-radical group forming aminothioketyl intermediates.

N

ammonium

thioenol anion-radical

aminothioketyl


Input: Combined potential energy mapping and RRKM calculations of dissociation rate constants identified N-C (alpha) bond cleavages as the most favorable dissociation pathways, in a stark contrast to the experimental results.

N-C (alpha)


Input: This discrepancy is interpreted as being due to the population upon electron transfer of low-lying excited electronic states that promote loss of hydrogen atoms.

hydrogen


Input: For (GtK + 2H) (+ *), these excited states were characterized by time-dependent density functional theory as A-C states that had large components of Rydberg-like 3s molecular orbitals at the N-terminal and lysine ammonium groups that are conducive to hydrogen atom loss.

GtK

N

lysine ammonium

hydrogen


Input: Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study.


Input: In this multicenter, double-blind, placebo-controlled, randomized, four way cross-over proof-of-mechanism study, we tested the effect of the positive allosteric alpha 7 nicotinic acetylcholine receptor (nAChR) modulator JNJ-39393406 in a key translational assay (sensory P50 gating) in 39 regularly smoking male patients with schizophrenia.

acetylcholine


Input: All patients were clinically stable and JNJ-39393406 was administered as an adjunct treatment to antipsychotics.


Input: No indication was found that JNJ-39393406 has the potential to reverse basic deficits of information processing in schizophrenia (sensory P50 gating) or has a significant effect on other tested electrophysiological markers (MMN, P300 and quantitative resting EEG).


Input: Sensitivity analyses including severity of disease, baseline P50 gating, medication and gene variants of the CHRNA7 gene did not reveal any subgroups with consistent significant effects.


Input: It is discussed that potential positive effects in subgroups not present or not large enough in the current study or upon chronic dosing are possible, but unlikely to be developed.


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Terminal differentiation and loss of tumorigenicity of human cancers via pluripotency-based reprogramming.


Input: Pluripotent cells can be derived from various types of somatic cells by nuclear reprogramming using defined transcription factors.


Input: It is, however, unclear whether human cancer cells can be similarly reprogrammed and subsequently terminally differentiated with abrogation of tumorigenicity.


Input: Here, using sarcomas we show that human-derived complex karyotype solid tumors: (1) can be reprogrammed into a pluripotent-like state as defined by all in vitro criteria used to define pluripotent stem cells generated from somatic cells; (2) can be terminally differentiated into mature connective tissue and red blood cells; and (3) terminal differentiation is accompanied with loss of both proliferation and tumorigenicity.


Input: We go on to perform the first global DNA promoter methylation and gene expression analyses comparing human cancers to their reprogrammed counterparts and report that reprogramming/differentiation results in significant epigenetic remodeling of oncogenes and tumor suppressors, while not significantly altering the differentiation status of the reprogrammed cancer cells, in essence dedifferentiating them to a state slightly before the mesenchymal stem cell differentiation stage.


Input: Our data demonstrate that direct nuclear reprogramming can restore terminal differentiation potential to human-derived cancer cells, with simultaneous loss of tumorigenicity, without the need to revert to an embryonic state.


Input: We anticipate that our models would serve as a starting point to more fully assess how nuclear reprogramming overcomes the multitude of genetic and epigenetic aberrancies inherent in human cancers to restore normal terminal differentiation pathways.


Input: Finally, these findings suggest that nuclear reprogramming may be a broadly applicable therapeutic strategy for the treatment of cancer.


Input: Effects of collisional and vibrational velocity on proton and deuteron transfer in the reaction of HOD + with CO.

deuteron

HOD +

CO


Input: Reaction of HOD (+) with CO was studied over the collision energy (E (col)) range between 0. 18 and 2. 87 eV, for HOD (+) in its ground state and with one quantum in each of its vibrational modes: (001)--predominantly OH stretch; (010)--bend, and (100)--predominately OD stretch.

HOD (+)

CO

HOD (+)

OH

OD


Input: In addition to integral cross sections, product recoil velocity distributions were also measured for each initial condition.


Input: The dominant reactions are near-thermoneutral proton and deuteron transfer, generating HCO (+) and DCO (+) product ions by a predominantly direct mechanism.

deuteron

HCO (+)

DCO (+)


Input: The HCO (+) and DCO (+) channels occur with a combined efficiency of 76% for ground state HOD (+) at our lowest E (col), increasing to 94% for E (col) around 0. 33 eV, then falling at high E (col) to ~ 40%.

HCO (+)

DCO (+)

HOD (+)


Input: The HCO (+) and DCO (+) channels have a complicated dependence on the HOD (+) vibrational state.

HCO (+)

DCO (+)

HOD (+)


Input: Excitation of the OH or OD stretch modes enhances H (+) or D (+) transfer, respectively, and inhibits D (+) or H (+) transfer.

OH

OD

H (+)

D (+)

D (+)

H (+)


Input: Bend excitation preferentially enhances H (+) transfer, with no effect on D (+) transfer.

H (+)

D (+)


Input: There is no coupling of energy initially in any HOD (+) vibrational mode to recoil velocity of either of the product ions, even at low E (col) where vibrational excitation doubles or triples the energy available to products.

HOD (+)


Input: The results suggest that transfer of H or D atoms is enhanced if the atom in question has a high vibrational velocity, and that this effect offsets what is otherwise a general inhibition of reactivity by added energy.

H

D


Input: HOCO (+) + D and DOCO (+) + H products are also observed, but as minor channels despite being barrierless and exoergic.

HOCO (+)

D

DOCO (+)

H


Input: These channels appear to be complex mediated at low E (col), essentially vanish at intermediate E (col), then reappear with a direct reaction mechanism at high E (col).


Input: Density functional theory study on the reaction mechanism of synthesizing 1, 3-dimethyl-2-imidazolidinone by urea method.

1, 3-dimethyl-2-imidazolidinone

urea


Input: We report a first-principles density functional theory investigation on tailoring the fundamental reaction mechanism of synthesizing 1, 3-dimethyl-2-imidazolidinone (DMI) through the urea method with water serving as both solvent and catalyst.

1, 3-dimethyl-2-imidazolidinone

DMI

urea


Input: The nucleophilic cyclization reaction is implemented by two ammonia removal steps.

ammonia


Input: One-NH group of dimethylethylenediamine (DMEDA) first attacks the carbon atom of urea, eliminating one-NH3 group and forming an intermediate state CH3NHC2H4N (CH3) CONH2 (IMI).

NH

dimethylethylenediamine

DMEDA

carbon

urea

CH3NHC2H4N (CH3) CONH2


Input: IMI subsequently undergoes the cyclization process through a secondary ammonia removal via similar manner.

secondary ammonia


Input: Without water, the two ammonia removal steps are both slightly exothermic with high activation barriers (~ 50 kcal mol (-1)).

ammonia


Input: As water participated in the reaction, the kinetics of the two steps can be significantly improved, respectively.


Input: The role that water plays, beside as solvent, more importantly, is to serve as a proton exchange bridge.


Input: Due to the spatial configuration, the direct proton migration from the N atoms of ethylenediamine to urea is difficult to occur.

N

ethylenediamine

urea


Input: The water bridge facilitates the proton migration by shortening the migration distance.


Input: As a consequence, the activation barriers are considerably lowered down to ~ 30 kcal mol (-1), indicating a strong catalytic effect from water.


Input: In contrast, the three possible side reactions of IM (I), even catalyzed by water, have higher activation barriers due to strong steric inhibitive effect and consequently become difficult to occur at the same condition.


Input: The current computational understanding on the prototypical reaction to DMI can be extended to guide developing more efficient routes to synthesize imidazolidinone derivatives through the urea method.

DMI

imidazolidinone

urea


Input: Leveraging the cortical cholinergic system to enhance attention.


Input: Attentional impairments are found in a range of neurodegenerative and neuropsychiatric disorders.


Input: However, the development of procognitive enhancers to alleviate these impairments has been hindered by a lack of comprehensive hypotheses regarding the circuitry mediating the targeted attentional functions.


Input: Here we discuss the role of the cortical cholinergic system in mediating cue detection and attentional control and propose two target mechanisms for cognition enhancers: stimulation of prefrontal alpha 4 beta 2 * nicotinic acetylcholine receptors (nAChR) for the enhancement of cue detection and augmentation of tonic acetylcholine levels for the enhancement of attentional control.

acetylcholine

acetylcholine


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: A selective dopamine reuptake inhibitor improves prefrontal cortex-dependent cognitive function: potential relevance to attention deficit hyperactivity disorder.

dopamine


Input: Drugs used to treat attention deficit hyperactivity disorder (ADHD) improve prefrontal cortex (PFC)-dependent cognitive function.


Input: The majority of ADHD-related treatments act either as dual norepinephrine (NE) and dopamine (DA) reuptake inhibitors (psychostimulants) or selective NE reuptake inhibitors (SNRIs).

norepinephrine

dopamine


Input: Certain benztropine analogs act as highly selective DA reuptake inhibitors while lacking the reinforcing actions, and thus abuse potential, of psychostimulants.

benztropine


Input: To assess the potential use of these compounds in the treatment of ADHD, we examined the effects of a well-characterized benztropine analog, AHN 2-005, on performance of rats in a PFC-dependent delayed-alternation task of spatial working memory.

benztropine

AHN 2-005


Input: Similar to that seen with all drugs currently approved for ADHD, AHN 2-005 dose-dependently improved performance in this task.

AHN 2-005


Input: Clinically-relevant doses of psychostimulants and SNRIs elevate NE and DA preferentially in the PFC.


Input: Despite the selectivity of this compound for the DA transporter, additional microdialysis studies demonstrated that a cognition-enhancing dose of AHN 2-005 that lacked locomotor activating effects increased extracellular levels of both DA and NE in the PFC.

AHN 2-005


Input: AHN 2-005 produced a larger increase in extracellular DA in the nucleus accumbens, although the magnitude of this was well below that seen with motor activating doses of psychostimulants.

AHN 2-005


Input: Collectively, these observations suggest that benztropine analogs may be efficacious in the treatment of ADHD or other disorders associated with PFC dysfunction.

benztropine


Input: These studies provide a strong rationale for future research focused on the neural mechanisms contributing to the cognition-enhancing actions and the potential clinical utility of AHN 2-005 and related compounds.

AHN 2-005


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: The NMDA receptor as a target for cognitive enhancement.

NMDA


Input: NMDA receptors (NMDARs) play an important role in neural plasticity including long-term potentiation and long-term depression, which are likely to explain their importance for learning and memory.

NMDA


Input: Cognitive decline is a major problem facing an ageing human population, so much so that its reversal has become an important goal for scientific research and pharmaceutical development.


Input: Enhancement of NMDAR function is a core strategy toward this goal.


Input: In this review we indicate some of the major ways of potentiating NMDAR function by both direct and indirect modulation.


Input: There is good evidence that both positive and negative modulation can enhance function suggesting that a subtle approach correcting imbalances in particular clinical situations will be required.


Input: Excessive activation and the resultant deleterious effects will need to be carefully avoided.


Input: Finally we describe some novel positive allosteric modulators of NMDARs, with some subunit selectivity, and show initial evidence of their ability to affect NMDAR mediated events.


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Correlation of high urinary Smad1 level with glomerular hyperfiltration in type 2 diabetes mellitus.


Input: The aim of this study was to assess the relationship between urinary Smad1 and glomerular hyperfiltration (GHF) in type 2 diabetes mellitus (T2DM), and to explore the factors related to the urinary Smad1 in T2DM.


Input: The reference value of the estimated glomerular filtration rate (eGFR) was determined in 248 healthy individuals.


Input: 30 patients with GHF, 58 patients with norm-GFR T2DM, and 24 healthy patients who served as controls were recruited.


Input: Urinary Smad1, fasting plasma glucose (FPG), fasting serum C-Peptide (C-P), hemoglobin A1C (HbA1c), cystatin C, and other chemistry laboratory parameters of T2DM participants and controls were measured.

glucose


Input: Patients with GHF had higher levels of urinary Smad1 than the control group, and those with norm-GFR.


Input: For T2DM patients with body mass index, age, and gender adjustments, urinary Smad1 was positively correlated with FPG, HbA1C, and eGFR, but negatively correlated with fasting serum C-P.


Input: Multivariate linear regression analysis demonstrated that eGFR, HbA1C, and fasting serum C-P were independently associated with urinary Smad1.


Input: High levels of urinary Smad1 were found in GHF patients with T2DM, which may be another potential mechanism of GHF in relation to diabetic nephropathy.


Input: Comparison of antifungal activities of Vietnamese citrus essential oils.


Input: Citrus essential oils (EOs) are volatile compounds from citrus peels and widely used in perfumes, cosmetics, soaps and aromatherapy.


Input: In this study, inhibition of citrus EOs extracted from Vietnamese orange (Citrus sinensis), mandarin (Citrus reticulata Blanco), pomelo (Citrus grandis Osbeck) and lime (Citrus aurantifolia Swingle) on the growth of plant pathogenic fungi, Mucor hiemalis, Penicillium expansum and Fusarium proliferatum was investigated.


Input: The EOs of the citrus peels were obtained by cold-pressing method and the antifungal activity of EOs was evaluated using the agar dilution method.


Input: The results show that the EOs had significant antifungal activity.


Input: Lime EO was the best inhibitor of M. hiemalis and F. proliferatum while pomelo EO was the most effective against P. expansum.


Input: These results indicate that citrus EOs can be used as antifungal natural products in the food, pharmaceutical and cosmetic industries.


Input: Metastability in Pressure-Induced Structural Transformations of CdSe/ZnS Core/Shell Nanocrystals.

CdSe

ZnS


Input: The kinetics and thermodynamics of structural transformations under pressure depend strongly on particle size due to the influence of surface free energy.


Input: By suitable design of surface structure, composition, and passivation it is possible, in principle, to prepare nanocrystals in structures inaccessible to bulk materials.


Input: However, few realizations of such extreme size-dependent behavior exist.


Input: Here, we show with molecular dynamics computer simulation that in a model of CdSe/ZnS core/shell nanocrystals the core high-pressure structure can be made metastable under ambient conditions by tuning the thickness of the shell.

CdSe

ZnS


Input: In nanocrystals with thick shells, we furthermore observe a wurtzite to NiAs transformation, which does not occur in the pure bulk materials.

wurtzite

NiAs


Input: These phenomena are linked to a fundamental change in the atomistic transformation mechanism from heterogeneous nucleation at the surface to homogeneous nucleation in the crystal core.


Input: Radiolabeled mass-balance excretion and metabolism studies in laboratory animals: a commentary on why they are still necessary.


Input: The necessity of conducting traditional radiolabeled absorption, distribution, metabolism and excretion (ADME) studies in animals during development of new investigative agents has been questioned in a recent review.


Input: We present a compilation of the benefits of such studies in the understanding of the in vivo pharmacological activity and disposition of new drug candidates, including interpretation of preclinical toxicology findings, characterization of circulating metabolites, and determination of principal pathways of clearance.


Input: This understanding is valuable in anticipating the human disposition of the drugs and the planning of the clinical development program.


Input: Because of new technologies, evolving regulatory expectations, and increased scientific understanding of the disposition of drugs, the traditional design and timing of both animal and human ADME studies should be reviewed.


Input: Innovative " fit-for-purpose " studies may well be a better choice in a particular drug development program than a standard animal ADME " package ".


Input: However, we submit that, at this time, radiolabeled animal ADME studies still provide a definitive and irreplaceable component of our understanding of the in vivo actions and behaviors of drugs and should continue to be performed prior to the exposure of large numbers of human subjects to investigative drugs.


Input: Serotonergic involvement in the amelioration of behavioral abnormalities in dopamine transporter knockout mice by nicotine.

dopamine

nicotine


Input: Dopamine transporter knockout (DAT KO) mice exhibit elevated extracellular dopamine levels in brain regions that include the striatum and the nucleus accumbens, but not the prefrontal cortex.

Dopamine

dopamine


Input: DAT KO mice model some aspects of psychiatric disorders, including schizophrenia.


Input: Smoking is more common in patients with schizophrenia, suggesting that nicotine might ameliorate aspects of the behavioral abnormalities and/or treatment side effects seen in these individuals.


Input: We report nicotine-induced normalization of effects on locomotion and prepulse inhibition of acoustic startle (PPI) in DAT KO mice that require intact serotonin 5-HT1A systems.

nicotine

serotonin


Input: First, we observed that the marked hyperactivity displayed by DAT KO mice was reduced by administration of nicotine.

nicotine


Input: This nicotine effect was blocked by pretreatment with the non-specific nicotinic acetylcholine (nACh) receptor antagonist mecamylamine, or the 5-HT1A antagonist WAY100635.

nicotine

acetylcholine

mecamylamine


Input: Secondly, we examined the effects of nicotine on PPI in DAT KO mice.

nicotine


Input: Treatment with nicotine significantly ameliorated the PPI deficits observed in DAT KO mice.

nicotine


Input: The ameliorating action of nicotine on PPI deficits in DAT KO mice was blocked by mecamylamine, the alpha 7 nACh receptor antagonist methyllycaconitine or WAY100635, while the alpha 4 beta 2 nACh receptor antagonist dihydro-beta-erythroidinehydrobromide (DH beta E) produced only a non-significant trend toward attenuation of nicotine effects.

nicotine

mecamylamine

methyllycaconitine

dihydro-beta-erythroidinehydrobromide

DH beta E

nicotine


Input: Finally, we observed that administration of the 5-HT1A receptor agonist 8-OH-DPAT also ameliorated the deficit in PPI observed in DAT KO mice.


Input: This amelioration was antagonized by pretreatment with WAY100635.


Input: These data support the idea that nicotine might ameliorate some of the cognitive dysfunctions found in schizophrenia in a 5-HT1A-dependent fashion.

nicotine


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Two new diterpenes from Caesalpinia minax Hance.

diterpenes


Input: Two new cassane-type diterpenes, Caesalpinolide F (1) and Caesalpinolide G (2) were isolated from Caesalpinia minax Hance.

cassane

diterpenes

Caesalpinolide F

Caesalpinolide G


Input: Their structures were elucidated on the basis of 1D and 2D NMR, MS and CD analysis.


Input: Compounds 1 and 2 were tested against colon carcinoma (HCT-8) and breast cancer (MCF-7) human cancer cell lines, and showed mild cytotoxicity activities.


Input: Disposition of diiosononyl phthalate and its effects on sexual development of the male fetus following repeated dosing in pregnant rats.

diiosononyl phthalate


Input: Pregnant Sprague-Dawley rats received 50, 250, and 500 mg/kg/day diisononyl phthalate (DiNP) from GD 12 to 19 via corn oil gavage to study the dose response for effects on fetal male rat sexual development as well as metabolite disposition in the dam and fetus.

diisononyl phthalate

DiNP


Input: Monoisononyl phthalate (MiNP), mono (carboxy-isooctyl) phthalate (MCiOP), mono (hydroxyl-isononyl) phthalate (MHiNP), mono (oxo-isononyl) phthalate (MOiNP), and monoisononyl phthalate glucuronide (MiNP-G) were found in all measured tissues.

Monoisononyl phthalate

MiNP

mono (carboxy-isooctyl) phthalate

MCiOP

mono (hydroxyl-isononyl) phthalate

MHiNP

mono (oxo-isononyl) phthalate

MOiNP

monoisononyl phthalate glucuronide

MiNP-G


Input: MCiOP was the major metabolite, followed in decreasing order by MiNP, MHiNP, MOiNP, and MiNP-G.

MCiOP

MiNP

MHiNP

MOiNP

MiNP-G


Input: Percentage of dose absorbed decreased at 750 mg/kg/day.


Input: Testosterone concentration in the fetal testes was reduced at 250 and 750 mg/kg/day.

Testosterone


Input: Multinucleated germ cells were increased in the testes of rats at 250 and 750 mg/kg/day.


Input: The no observed effect level (NOEL) for this study was 50 mg/kg/day based on increased MNGs and reduced testes testosterone concentration in the fetal rat.

testosterone


Input: Quantitative prediction of CYP2B6 induction by estradiol during pregnancy: potential explanation for increased methadone clearance during pregnancy.

estradiol

methadone


Input: There is considerable evidence that pregnancy changes the disposition of drugs in an enzyme-and gestational stage-specific manner.


Input: On the basis of probe drug studies, the activity of CYP3A4 and CYP2D6 increases and CYP1A2 decreases during human pregnancy.


Input: However, no studies of CYP2B6 activity during human pregnancy have been conducted.


Input: In rodent models and in HepG2 cells, CYP2B enzymes have been shown to be regulated by estradiol.

estradiol


Input: Because estradiol concentrations increase by ~ 50-fold during human pregnancy, it was hypothesized that the increasing estradiol concentrations during human pregnancy would result in induction of CYP2B6 activity.

estradiol

estradiol


Input: Hepatocytes from three female donors were treated with estradiol, and the EC (50) and E (max) were measured for CYP2B6 mRNA and bupropion hydroxylation activity.

estradiol

bupropion


Input: The measured values were used to predict the magnitude of CYP2B6 induction during human pregnancy.


Input: At 100 nM total estradiol, a concentration achievable during the third trimester of pregnancy, CYP2B6 activity was predicted to increase by 1. 5-3-fold, based on increased CYP2B6 activity and mRNA.

estradiol


Input: When the E (max) and EC (50) values were compared with those for carbamazepine and rifampin, estradiol was found to be as potent an inducer of CYP2B6 as rifampin and carbamazepine.

carbamazepine

rifampin

estradiol

rifampin

carbamazepine


Input: These data suggest that, during human pregnancy, the increasing estradiol concentrations will result in increased clearance of drugs that have CYP2B6-mediated clearance pathways.

estradiol


Input: This could in part explain the observed increase in methadone clearance during pregnancy.

methadone


Input: Lipid rafts, synaptic transmission and plasticity: impact in age-related neurodegenerative diseases.


Input: The synapse is a crowded area.


Input: In the last years, the concept that proteins can be organized in different membrane domains according to their structure has emerged.


Input: Cholesterol-rich membrane domains, or lipid rafts, form an organized portion of the membrane that is thought to concentrate signaling molecules.

Cholesterol


Input: Accumulating evidence has shown that both the pre-synaptic and post-synaptic sites are highly enriched in lipid rafts, which are likely to organize and maintain synaptic proteins in their precise localization.


Input: Here we review recent studies highlighting the importance of lipid rafts for synaptic function and plasticity, as well as their relevance for age or disease-related cognitive impairment.


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Effects of clopidogrel and clarithromycin on the disposition of sibutramine and its active metabolites M1 and M2 in relation to CYP2B6 * 6 polymorphism.

clopidogrel

clarithromycin

sibutramine


Input: Plasma concentrations of sibutramine and its two active metabolites after single oral dose of sibutramine were determined in Korean healthy male subjects with different CYP2B6 genotypes (CYP2B6 * 1/* 1, * 1/* 6 and * 6/* 6), either alone or after four-day pretreatment with clopidogrel or clarithromycin.

sibutramine

sibutramine

clopidogrel

clarithromycin


Input: The pretreatment with clopidogrel and clarithromycin raised the mean area under the concentration-time curve (AUC) of sibutramine by 163% and 255%, respectively.

clopidogrel

clarithromycin

sibutramine


Input: Co-administration of clarithromycin, combined with CYP2B6 * 6/* 6 genotype, led to highest concentration of sibutramine.

clarithromycin

sibutramine


Input: The molar sum AUC (M1 + M2) was raised by 35% in the clopidogrel phase but not significantly affected by clarithromycin or CYP2B6 genotype.

clopidogrel

clarithromycin


Input: The CYP2B6 * 6/* 6 subjects in the clopidogrel phase showed the highest molar AUC (M1 + M2) among three genotype groups throughout the three phases.

clopidogrel


Input: The exposure of sibutramine and its metabolites seemed to be associated with the CYP2B6 genotype.

sibutramine


Input: The treatment of clopidogrel significantly altered the disposition of active metabolites as well as sibutramine, but clarithromycin only affects the disposition of sibutramine.

clopidogrel

sibutramine

clarithromycin

sibutramine


Input: These results suggest that the perturbation of CYP2B6 activity may contribute to the inter-individual variation of sibutramine drug responses although the clinical relevance is remained to be established.

sibutramine


Input: Leydig cell hyperplasia and Leydig cell tumour in postmenopausal women: report of two cases.


Input: Leydig cell hyperplasia and Leydig cell tumours of the ovary are rare.


Input: We present two cases in which patients had increased blood levels of testosterone and frank hirsutism.

testosterone


Input: Imaging showed minimal abnormalities.


Input: After adrenal disease had been ruled out, they underwent a bilateral oophorectomy.


Input: One case showed a Leydig cell hyperplasia, the other a Leydig cell tumour.


Input: An androgen producing tumour should be excluded in every woman with evidence of hirsutism or frank virilization and markedly elevated testosterone levels.

androgen

testosterone


Input: Adrenal disease with androgen hypersecretion can be suspected by detailed clinical, laboratory and radiologic imaging.

androgen


Input: Although DHEAS has a good sensitivity in the detection of adrenal origin of hyperandrogenism (and hence a good negative predictive value) it is not specific (specificity ranging from 85 to 98%).

DHEAS


Input: Imaging of the ovaries can be helpful but does not rule out ovarian disease if normal.


Input: Indeed, diffuse stromal Leydig cell hyperplasia and Leydig cell tumours (usually small) may escape imaging and in some cases diagnosis can only be made on pathology.


Input: As these clinical entities represent a diagnostic and therapeutic challenge, oophorectomy should be considered in postmenopausal women with hirsutism and elevated testosterone levels, after the exclusion of adrenal causes.

testosterone


Input: The procedure is relatively safe and effective.


Input: Follow-up remains indicated.


Input: Drug repurposing in pediatrics and pediatric hematology oncology.


Input: Drug' repurposing', that is, using old drugs for new indications, has been proposed as a more efficient strategy for drug development than the current standard of beginning with novel agents.


Input: In this review, we explore the scope of drug repurposing in pediatric hematology oncology and in pediatrics in general.


Input: Drugs commonly used in children were identified using the Harriet Lane Handbook (HLH) and searched in PubMed for different uses.


Input: Additional drugs were identified by searching PubMed and Google. com for' drug repurposing' or' drug repositioning'.


Input: Almost 10% of drugs with primary uses in pediatrics have been repurposed in pediatric hematology oncology or pediatrics.


Input: The observant clinician, pharmacologist and translational bioinformatician, as well as structural targeting, will have a role in discovering new repurposing opportunities.


Input: Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone.

estradiol

progesterone


Input: Results from clinical studies suggest that pregnancy alters hepatic drug metabolism in a cytochrome P450 (P450) isoform-specific manner, and rising concentrations of female hormones are potentially responsible for the changes.


Input: The objective of this study was to comprehensively characterize the effects of estrogen and progesterone on the expression and activity of major drug-metabolizing P450s.

estrogen

progesterone


Input: To this end, primary human hepatocytes were treated with estradiol and progesterone, and mRNA expression and activity levels of 10 different P450 isoforms were determined.

estradiol

progesterone


Input: The results showed that estradiol enhances CYP2A6, CYP2B6, and CYP3A4 expression, whereas progesterone induces CYP2A6, CYP2B6, CYP2C8, CYP3A4, and CYP3A5 expression.

estradiol

progesterone


Input: The induction was mainly observed when the average hormone concentrations were at the levels reached during pregnancy, suggesting that these effects are likely pregnancy-specific.


Input: Estradiol also increased enzyme activities of CYP2C9 and CYP2E1 without affecting the mRNA expression levels by unknown mechanisms.

Estradiol


Input: Taken together, our results show differential effects of estrogen and progesterone on P450 expression, suggesting involvement of different regulatory mechanisms in female hormone-mediated P450 regulation.

estrogen

progesterone


Input: Our findings potentially provide a basis in mechanistic understanding for altered drug metabolism during pregnancy.


Input: Towards the use of hydrogels in the treatment of limbal stem cell deficiency.


Input: Corneal blindness caused by limbal stem cell deficiency (LSCD) is a prevailing disorder worldwide.


Input: Clinical outcomes for LSCD therapy using amniotic membrane (AM) are unpredictable.


Input: Hydrogels can eliminate limitations of standard therapy for LSCD, because they present all the advantages of AM (i. e. biocompatibility, inertness and a biodegradable structure) but unlike AM, they are structurally uniform and can be easily manipulated to alter mechanical and physical properties.


Input: Hydrogels can be delivered with minimum trauma to the ocular surface and do not require extensive serological screening before clinical application.


Input: The hydrogel structure is also amenable to modifications which direct stem cell fate.


Input: In this focussed review we highlight hydrogels as biomaterial substrates which may replace and/or complement AM in the treatment of LSCD.


Input: Naringin induces death receptor and mitochondria-mediated apoptosis in human cervical cancer (SiHa) cells.

Naringin


Input: Cervical cancer is the second most common female cancer worldwide, and it remains a challenge to manage preinvasive and invasive lesions.


Input: Fruit-based cancer prevention entities, such as flavonoid and their derivatives, have demonstrated a marked ability to inhibit preclinical models of epithelial cancer cell growth and tumor formation.

flavonoid


Input: Here, we extend the role of naringin-mediated chemoprevention to that of cervical carcinogenesis.

naringin


Input: The present study sought to investigate the therapeutic potential effect of naringin on apoptosis in human cervical SiHa cancer cells.

naringin


Input: Viability of SiHa cells was evaluated by the MTT assay, apoptosis and mitochondrial transmembrane potential by flow cytometry, and pro-apoptotic related genes by Real-time quantitative PCR.

MTT


Input: Naringin showed a 50% inhibition of SiHa human cervical cancer cells at a concentration of 750 mu M.

Naringin


Input: SiHa cells exhibited apoptotic cell death, intranucleosomal DNA fragmentation, morphological changes and decline in the mitochondrial transmembrane potential.


Input: In addition, administration of naringin increased the expression of caspases, p53 and Bax, Fas death receptor and its adaptor protein FADD.

naringin


Input: These results suggest that the induction of apoptosis by naringin is through both death-receptor and mitochondrial pathways.

naringin


Input: Taken together, our results suggest that naringin might be an effective agent to treat human cervical cancer.

naringin


Input: Localisation and role of activin receptor-interacting protein 1 in mouse brain.


Input: Activin A, a stimulator of follicle-stimulating hormone secretion from the pituitary, acts as a neurotrophic and neuroprotective factor in the central nervous system.


Input: Activin receptor-interacting protein 1 (ARIP1) has been identified as a cytoplasmic protein that interacts with the type II receptor of activin (ActRII).


Input: However, the distribution pattern and function of ARIP1 are not well characterised in the brain.


Input: In the present study, we confirmed the existence of mRNA and protein of ARIP1 in the mouse brain, and found that ARIP1 was mainly localised at the hippocampus and hypothalamus in the cerebrum, granular layers in the cerebellum (especially in Purkinje cells of the cerebellum) and choroid epithelial cells by immunohistochemical staining.


Input: Furthermore, in contrast to the significant increase of activin A mRNA, ARIP1 mRNA and protein expression decreased in the mechanically lesioned brain of the mouse.


Input: Using neuroblastoma-derived Neuro-2a cells to investigate the function of ARIP1, we found that overexpression of ARIP1 down-regulated the activin A-induced signal transduction and significantly decreased the voltage-gated Na (+) current (I (Na)).

Na (+)


Input: These data indicate that ARIP1 is a key molecule for the regulation of the action of activin in neurones, and also that decreased ARIP1 expression in the lesioned brain may be beneficial to the neurotrophic and neuroprotective roles of activin A in recovery after brain injury.


Input: Powering the future of molecular artificial photosynthesis with light-harvesting metallosupramolecular dye assemblies.


Input: Chemical ingenuity will play a significant role in solving the greatest challenge currently facing society: providing clean and carbon neutral energy for all of humanity.


Input: Molecular artificial photosynthesis is an emerging technology based on principles learned from Nature where individual components perform the essential light-harvesting, charge-separation, and water splitting functions to store solar energy in the form of chemical bonds.


Input: This tutorial review focuses specifically on the application of metallosupramolecular self-assembly strategies to interface solar fuel catalysts with photosensitizers and construct light-harvesting antennae capable of achieving panchromatic absorption and directional energy concentration.


Input: Coronary microvascular function in patients with Cushing' s syndrome.


Input: The aim of the study was to evaluate patients with Cushing' s syndrome the coronary flow reserve (CFR), an index of coronary microvascular function.


Input: Fifteen newly diagnosed patients with Cushing' s syndrome (1 male/14 females; mean age 45 +/- 11 years), were selected for having no clinical evidence of ischemic heart disease.


Input: Twelve patients had pituitary-dependent Cushing' s disease and three had an adrenal adenoma.


Input: Fifteen subjects matched for age, sex, and major cardiovascular risk factors were used as controls.


Input: Coronary flow velocity in the left anterior descending coronary artery was investigated by transthoracic Doppler echocardiography at rest and during adenosine infusion.

adenosine


Input: CFR was obtained as the ratio hyperemic/resting diastolic flow velocity.


Input: A reduced coronary reserve (hyperemic/resting ratio <= 2. 5) was found in 5/15 Cushing patients and 4/15 controls.


Input: In all patients with abnormal CFR, epicardial coronary stenosis was excluded by multi-slice computed tomographic coronary angiography.


Input: CFR was inversely related to urinary cortisol in patients with endogenous hypercortisolism (Spearman' s rho =-0. 57, P = 0. 03), while no correlation was found in controls.

cortisol


Input: Coronary microvascular function, as assessed by CFR, is pathologically reduced in a considerable number of patients with Cushing' s syndrome without clinical symptoms of ischemic heart disease and in the absence of epicardial coronary artery lesions, as well as in controls matched for cardiovascular risk factors.


Input: The presence of comorbidities can explain this early coronary abnormality in both patients and controls.


Input: Whether urinary cortisol may be a predictor of coronary microvascular function in the setting of patients with Cushing' s syndrome, needs further investigation.

cortisol


Input: A rosette cooling cell: more effective container for solubilization of single-walled carbon nanotubes under probe-type ultrasonic irradiation.

carbon


Input: Probe-type ultrasonication has been employed for surfactant-aided solubilization, or individualization, of single-walled carbon nanotubes (SWNTs).

carbon


Input: The resulting solution can be used not only for spectroscopic analyses such as absorption, photoluminescence, and circular dichroism, but also for separation by density gradient ultracentrifugation, dielectrophoresis, chromatography, and polymer wrapping.


Input: In spite of its importance, the sonochemical processing of SWNTs has not been considered seriously.


Input: Herein, we report on a more efficient cooling cell for probe-type ultrasonication.


Input: As compared with a conventional cylindrical cell, the concentration of the SWNTs solubilized in water was found to be almost double in a rosette cooling cell after ultracentrifugation.


Input: The efficiency of a rosette cell can be attributed to the higher efficiency in circulation and cooling of the SWNT dispersion as well as enhancement of the cavitation process.


Input: Self-assembled monolayers with dynamicity stemming from (bio) chemical conversions: from construction to application.


Input: Surfaces with " dynamicity " whereby surface properties can be modulated by an external stimulus on user demand have been actively exploited for the past decade.


Input: These switchable surfaces with dynamic properties are widely used for a number of applications such as micro/nanoarrays, biomolecule immobilization, basic cell studies, and tissue engineering on a variety of materials.


Input: This minireview highlights the dynamic control of surface properties on self-assembled monolayers and focuses on dynamicity that stems from (bio) chemical conversions achieved by electrical potentials, photoillumination, chemical reagents, enzymes, and pH.


Input: Pharmacokinetic characterization of the novel TAZ modulator TM-25659 using a multicompartment kinetic model in rats and a possibility of its drug-drug interactions in humans.


Input: This study evaluated the pharmacokinetics of the novel TAZ modulator TM-25659 in rats following intravenous and oral administration at dose ranges of 0. 5-5 mg/kg and 2-10 mg/kg, respectively.


Input: Plasma protein binding, plasma stability, liver microsomal stability, CYP inhibition, and transport in Caco-2 cells were also evaluated.


Input: After intravenous injection, systemic clearance, steady-state volumes of distribution, and half-life were dose-independent, with values ranging from 0. 434-0. 890 mL. h (-1). kg (-1), 2. 02-4. 22 mL/kg, and 4. 60-7. 40 h, respectively.


Input: Mean absolute oral bioavailability was 50. 9% and was not dose dependent.


Input: Recovery of TM-25659 was 43. 6% in bile and < 1% in urine.


Input: In pharmacokinetic modeling studies, the three-compartment (3C) model was appropriate for understanding these parameters in rats.


Input: TM-25659 was stable in plasma.


Input: Plasma protein binding was approximately 99. 2%, and was concentration-independent.


Input: TM-25659 showed high permeation of Caco-2 cells and did not appear to inhibit CYP450.


Input: TM-25659 was metabolized in phase I and II steps in rat liver microsomes.


Input: In conclusion, the pharmacokinetics of TM-25659 was characterized for intravenous and oral administration at doses of 0. 5-5 and 2-10 mg/kg, respectively.


Input: TM-25659 was eliminated primarily by hepatic metabolism and urinary excretion.


Input: Inhibitory function of the dorsomedial hypothalamic nucleus on the hypothalamic-pituitary-adrenal axis response to an emotional stressor but not immune challenge.


Input: Accumulating evidence implicates the dorsomedial hypothalamic nucleus (DMH) in the regulation of autonomic and neuroendocrine stress responses.


Input: However, although projections from the DMH to the paraventricular hypothalamic nucleus (PVN), which is the critical site of the neuroendocrine stress axis, have been described, the impact of DMH neurones in the modulation of hypothalamic-pituitary-adrenal (HPA) axis activation during stress is not fully understood.


Input: The present study aimed to investigate the role of the DMH in HPA axis responses to different types of stimuli.


Input: Male Sprague-Dawley rats fitted with a chronic jugular venous catheter were exposed to either an emotional stressor (elevated platform-exposure) or immune challenge (systemic interleukin-1 beta administration).


Input: Bilateral electrolytic lesions of the DMH disinhibited HPA axis responses to the emotional stressor, as indicated by higher plasma adrenocorticotrophic hormone levels during and after elevated platform exposure in lesioned animals compared to sham-lesioned controls.


Input: Moreover, DMH-lesioned animals showed increased neuronal activation in the PVN, as indicated by a higher c-Fos expression after elevated-platform exposure compared to controls.


Input: By contrast, DMH-lesions had no effects on HPA axis responses to immune challenge.


Input: Taken together, our data suggest an inhibitory role of DMH neurones on stress-induced HPA axis activation that is dependent upon the nature of the stimulus being important in response to an emotional stressor but not to immune challenge.


Input: The interaction of amylin with other hormones in the control of eating.


Input: Twenty years of research established amylin as an important control of energy homeostasis.


Input: Amylin controls nutrient and energy fluxes by reducing energy intake, by modulating nutrient utilization via an inhibition of postprandial glucagon secretion and by increasing energy disposal via a prevention of compensatory decreases of energy expenditure in weight reduced individuals.


Input: Like many other gastrointestinal hormones, amylin is secreted in response to meals and it reduces eating by promoting meal-ending satiation.


Input: Not surprisingly, amylin interacts with many of these hormones to control eating.


Input: These interactions seem to occur at different levels because amylin seems to mediate the eating inhibitory effect of some of these gastrointestinal hormones, and the combination of some of these hormones seems to lead to a stronger reduction in eating than single hormones alone.


Input: Amylin' s effect on eating is thought to be mediated by a stimulation of specific amylin receptors in the area postrema.


Input: Secondary brain sites that were defined to mediate amylin action-and hence potential additional sites of interaction with other hormones-include the nucleus of the solitary tract, the lateral parabrachial nucleus, the lateral hypothalamic area and other hypothalamic nuclei.


Input: The focus of this review is to summarize the current knowledge of amylin interactions in the control of eating.


Input: In most cases, these interactions have only been studied at a descriptive rather than a mechanistic level and despite the clear knowledge on primary sites of amylin action, the interaction sites between amylin and other hormones are often unknown.


Input: Density functional study on the adsorption of the drug isoniazid onto pristine and B-doped single wall carbon nanotubes.

isoniazid

B

carbon


Input: The current study explores a new strategy to incorporate single wall carbon nanotubes (SWNTs)/doped SWNTs as carrier modules in target-specific administration of antitubercular chemotherapeutics through covalent and noncovalent functionalization onto the nanotube sidewall.

carbon


Input: Density functional studies illustrate that noncovalent functionalization of isoniazid (INH) is preferred over covalent attachment, exhibiting low adsorption energy values, HOMO-LUMO gap and comparison of quantum molecular descriptors performed in (5, 5) and (9, 0) SWNT systems.

isoniazid

INH


Input: Substitution doping of boron facilitates the adsorption of INH onto the otherwise inert nanotube.

boron

INH


Input: Frontier orbital analysis reveals reorientation of electronic charge in the nanotubes after functionalization, the effect being more pronounced in the case of doped nanotubes.


Input: The charge transfer is significant in covalent functionalization of INH via the B-dopant atom, whereas in noncovalent functionalization a small amount of charge transfer is noted.

INH

B


Input: Solvation studies demonstrate the dissolution of INH in B-doped (5, 5) and (9, 0) SWNTs to be higher compared to pristine nanotube-INH complexes.

INH

B

INH


Input: Functionalization of nanotubes via covalent and noncovalent means can foster pioneering prospects especially for experimental studies in this area of research.


Input: Protection by chrysin, apigenin, and luteolin against oxidative stress is mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate cysteine ligase in rat primary hepatocytes.

chrysin

apigenin

luteolin

heme

glutamate cysteine


Input: Chrysin, apigenin, and luteolin are flavones that differ in their number of hydroxyl groups in the B ring.

Chrysin

apigenin

luteolin

flavones

hydroxyl


Input: In this study, we investigated the protection by chrysin, apigenin, and luteolin against tert-butyl hydroperoxide (tBHP)-induced oxidative stress and the possible mechanisms involved in rat primary hepatocytes.

chrysin

apigenin

luteolin

tert-butyl hydroperoxide

tBHP


Input: Chrysin, apigenin, and luteolin dose-dependently up-regulated the protein expression of heme oxygenase 1 (HO-1) and glutamate cysteine ligase (GCL) catalytic (GCLC) and modifier subunit (GCLM) and increased the intracellular glutathione (GSH) content and the ratio of GSH to oxidized GSH.

Chrysin

apigenin

luteolin

heme

glutamate cysteine

glutathione

GSH

GSH

oxidized GSH


Input: Among the flavones studied, chrysin showed the greatest induction of HO-1, GCLC, and GCLM protein expression and GSH content.

chrysin

GSH


Input: Cellular reactive oxygen species production induced by tBHP was attenuated by pretreatment with chrysin, apigenin, and luteolin (P <. 05), and this protection was reversed by the GCL inhibitor l-buthionine-S-sulfoximine and the HO-1 inhibitor zinc protoporphyrin.

oxygen

tBHP

chrysin

apigenin

luteolin

l-buthionine-S-sulfoximine

zinc protoporphyrin


Input: Chrysin, apigenin, and luteolin activated extracellular signal-regulated protein kinase 2 (ERK2), nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, nuclear Nrf2-antioxidant responsive element (ARE) binding activity, and ARE-dependent luciferase activity.

Chrysin

apigenin

luteolin


Input: Both ERK2 and Nrf2 siRNAs attenuated chrysin-induced HO-1, GCLC, and GCLM protein expression.

chrysin


Input: Taken together, these results suggest that chrysin, apigenin, and luteolin inhibit tBHP-induced oxidative stress by up-regulating HO-1, GCLC, and GCLM gene transcription via the ERK2/Nrf2/ARE signaling pathways in rat primary hepatocytes.

chrysin

apigenin

luteolin

tBHP


Input: Alteration in plasma protein binding properties of propranolol and flurbiprofen during development of adjuvant-induced arthritis in rats.

propranolol

flurbiprofen


Input: Adjuvant-induced arthritis (AA) in the rat is used as a model for rheumatoid arthritis.


Input: In AA rats, the pharmacokinetics of various drugs is affected due to the alterations of plasma protein binding of drugs.


Input: We choose propranolol (PL) and flurbiprofen (FP) as model basic and acidic drugs, respectively, and investigated the effect of AA induction on their plasma protein binding at each developing stage of inflammation.

propranolol

flurbiprofen


Input: The plasma protein binding of PL and FP was dramatically changed due to reduced albumin and increased alpha 1-acid glycoprotein levels for at least 21 days after adjuvant treatment.


Input: Moreover, we illustrated the differences in protein binding in AA between both the drugs in each developing stage of inflammation.


Input: These results suggest that the changed plasma protein levels in AA rats accompanying the altered protein binding of drugs affect the pharmacokinetics of drugs which extensively bind to plasma protein under inflammatory condition.


Input: Determination of 10 ginsenosides in Panax ginseng of different harvest times based on HPLC fingerprints and principal component analysis.

ginsenosides


Input: A combinative method of HPLC fingerprinting and quantitative determination was successfully applied to monitor dynamic accumulation of ginsenosides in five-year-old Panax ginseng roots from different harvest times.

ginsenosides


Input: The optimal chromatographic conditions were achieved on a C18 column with gradient elution using acetonitrile and 1 mmol. L (-1) KH2PO4 buffer solution at 203 nm.


Input: The result indicated that the contents of total ginsenosides showed significant variations, and a decrease tendency appeared in the growth period of the fifth year.

ginsenosides


Input: Genotoxic damage in the oral mucosa cells of subjects carrying restorative dental fillings.


Input: A large proportion of the population carries restorative dental fillings containing either classic Hg-based amalgams and/or the more frequently used methacrylates.

Hg

amalgams

methacrylates


Input: Both Hg-and resin-based materials have been shown to be released into the buccal cavity and to be spread systemically.

Hg


Input: In addition, they induce toxic and genotoxic alterations in experimental test systems.


Input: Using the comet assay, we previously demonstrated that circulating lymphocytes of subjects with dental fillings have an increased DNA damage.


Input: Here, we analyzed the oral mucosa cells of 63 young subjects of both genders, by using both the comet assay and the micronucleus (MN) test and by monitoring cell death markers.


Input: The results obtained show that both amalgams and resin-based composite fillings can induce genotoxic damage in human oral mucosa cells, as convincingly and dose-dependently inferred from the results of the MN test and, more marginally, from comet assay data.

amalgams


Input: Lifestyle variables, also including alcohol intake and smoking habits, did not affect the genotoxic response and did not act as confounding factors.

alcohol


Input: Thus, we provide unequivocal evidence for the genotoxicity of both amalgams and resin-based dental fillings in humans not only by testing circulating lymphocytes but also by analyzing oral mucosa cells.

amalgams


Input: These findings are of particular relevance due to the circumstance that subjects with restorative materials are exposed continuously and for long periods of time.


Input: Anti-inflammatory and antioxidant activity of thymoquinone in a rat model of acute bacterial prostatitis.

thymoquinone


Input: Prostatitis plays a major role in morbidity and mortality related to prostate diseases.


Input: The aim of this study was to detect whether thymoquinone (TQ) could ameliorate oxidative damage and the proliferative response induced by Escherichia coli (E. coli) in rats.

thymoquinone


Input: A total of 42 adult male Wistar rats were used.


Input: The rats were randomly divided into seven groups (three treatment groups, three infected groups and one control group).


Input: Control group received saline and was killed 24 h after saline administration.


Input: Infected rats were killed after 24, 48 and 72 h following direct injection of E. coli into the prostate.


Input: Treatment groups were administered with 10 mg/kg dose of TQ intraperitoneally following E. coli injection and after 24 and 48 h following E. coli injection.


Input: The rats were killed at 24, 48 and 72 h after the first drug administration.


Input: Each group was compared with each other and with the control group.


Input: In addition, infected groups were compared with treatment groups.


Input: Our findings show that the treatment with TQ has a protective effect against bacterial prostatitis-induced tissue injury.


Input: Increase in malondialdehyde levels and histological damage caused by E. coli were improved markedly with TQ treatment.

malondialdehyde


Input: TQ treatment particularly increased the activity of glutathione peroxidase and decreased the activities of catalase and superoxide dismutase.

glutathione

superoxide


Input: These observations might be attributed, at least in part, to the antioxidant effect of TQ and suggest that it could be a clinically valuable agent in the prevention of acute prostatitis caused by E. coli.


Input: Toxicokinetics of methyleugenol in F344 rats and B6C3F 1 mice.

methyleugenol


Input: 1. Methyleugenol (MEG) has been used as a flavouring agent in food, as a fragrance in cosmetic products, and as an insect attractant.

Methyleugenol

MEG


Input: MEG was carcinogenic in both rats and mice following gavage administration.

MEG


Input: In this study we investigated plasma toxicokinetics of MEG in F344 rats and B6C3F 1 mice of both sexes following single gavage (37, 75, or 150 mg/kg) and intravenous (IV) (37 mg/kg) administration.

MEG


Input: 2. Following IV administration, MEG was rapidly distributed and cleared from the systemic circulation in both species and sexes.

MEG


Input: Absorption of MEG was rapid following gavage administration with secondary peaks in the plasma MEG concentration-versus-time profiles.

MEG

MEG


Input: C (max) and AUC (T) increased and the clearance decreased greater than proportional to the dose in rats and mice of both sexes.


Input: In general, rats had higher internal exposure to MEG than mice.

MEG


Input: 3. The results for AUC (T) and clearance suggest that perhaps the metabolism of MEG is saturated at higher doses tested in this study.

MEG


Input: Absolute bioavailability following gavage administration of 37 mg/kg was low in both rats (~ 4%) and mice (7-9%) of both sexes indicating extensive first-pass metabolism.


Input: There was no sex difference in plasma toxicokinetics of MEG following gavage administration both in rats and mice.

MEG


Input: Anti-inflammatory trends of 1, 3-diphenyl-2-propen-1-one derivatives.

1, 3-diphenyl-2-propen-1-one


Input: Chalcones (1, 3-Diphenyl-2-propen-1-one) are constituted by a three carbon alpha, beta-unsaturated carbonyl system.

Chalcones

1, 3-Diphenyl-2-propen-1-one

carbon alpha, beta-unsaturated carbonyl


Input: The biosynthesis of flavonoids and isoflavonoids is initiated by chalcones.

flavonoids

isoflavonoids

chalcones


Input: Notable pharmacological activities of chalcones and its derivatives include anti-inflammatory, antifungal, antibacterial, antimalarial, antituberculosis, antitumor, antimicrobial and antiviral effects respectively.

chalcones


Input: Owing to simplicity of the chemical structures and a huge variety of pharmacological actions exhibited, the entities derived from chalcones are subjected to extensive consideration.

chalcones


Input: This review article is an effort to sum up the anti-inflammatory activities of chalcone derived chemical entities.

chalcone


Input: Effect of chalcones on lipid peroxidation, heme oxygenase 1 (HO-1), cyclooxygenase (COX), interleukin 5 (IL-5), nitric oxide (NO) and expression of cell adhesion molecules (CAM) is summarized stepwise.

chalcones

heme

nitric oxide

NO


Input: Chalcones in Cancer: Understanding their Role in Terms of QSAR.

Chalcones


Input: II Part.


Input: Chalcones are a group of plant-derived polyphenolic compounds belonging to the flavonoids family and possess a wide variety of cytoprotective and modulatory functions.

Chalcones

polyphenolic

flavonoids


Input: In this research we tried to review the anticancer effect of chalcones derivatives and to evaluate new QSARs which will help in the understanding of the role of chalcones and of their analogs on cancer.

chalcones

chalcones


Input: Simultaneously a comparative study will be presented.


Input: Our QSAR results reveal that: 1) the clog P (hydrophobicity/hydrophilicity) parameter plays an important part in three QSAR relationships (linear model), 2) the steric factors such as molar volume MgVol, molar refractivity CMR or the substituents molar refractivity MR (linear) are important.


Input: Electronic effects are comparatively unimportant.


Input: These results compared to our previous findings on the QSAR of anti-proliferative chalcones support primarily the role of bulk.

chalcones


Input: Snake venom induced local toxicities: plant secondary metabolites as an auxiliary therapy.


Input: Snakebite is a serious medical and socio-economic problem affecting the rural and agricultural laborers of tropical and sub-tropical region across the world leading to high morbidity and mortality.


Input: In most of the snakebite incidences, victims usually end up with permanent tissue damage and sequelae with high socioeconomic and psychological impacts.


Input: Although, mortality has been reduced markedly due to anti-venom regimen, it is associated with several limitations.


Input: Snake venom metalloprotease, hyaluronidase and myotoxic phospholipase A2 are the kingpins of tissue necrosis and extracellular matrix degradation.


Input: Thus, inhibition of these enzymes is considered to be the rate limiting step in the management of snakebite.


Input: Unfortunately, tissue necrosis and extracellular matrix degradation persists even after the administration of anti-venom.


Input: At present, inhibitors from snake serum and plasma, several synthetic compounds and their analogs have been demonstrated to possess anti-snake venom activities, but the use of plant metabolites for this purpose has an added advantage of traditional knowledge and will make the treatment cheaper and more accessible to the affected population.


Input: Therefore, the clinical and research forums are highly oriented towards plant metabolites and interestingly, certain phytochemicals are implicated as the antibody elicitors against venom toxicity that can be exploited in designing effective anti-venoms.


Input: Based on these facts, we have made an effort to enlist plant based secondary metabolites with antiophidian abilities and their mechanism of action against locally acting enzymes/toxins in particular.


Input: The review also describes their functional groups responsible for therapeutic beneficial and certainly oblige in designing potent inhibitors against venom toxins.


Input: Mechanism-based modulator discovery for sirtuin-catalyzed deacetylation reaction.


Input: Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of evolutionarily conserved intracellular protein deacetylases that can catalyze the acetyl group removal from the specific N epsilon-acetyl-lysine (AcK) side chains on a variety of proteins from all kingdoms of life.

N epsilon-acetyl-lysine


Input: Yeast Sir2 was the first sirtuin identified, and so far seven sirtuins (i. e. SIRT1-7) have been found in mammals including humans.


Input: The sirtuin-catalyzed deacetylation reaction has captured tremendous interest during the past a few years because of (i) its increasingly demonstrated importance in many crucial biological processes such as gene transcription, metabolism, and aging, and thus its therapeutic potential for metabolic and age-related diseases and cancer, and (ii) its unique deacetylation chemistry.


Input: Specifically, the sirtuin-catalyzed AcK side chain deacetylation is not merely an amide hydrolysis reaction, instead is coupled to the nicotinamide cleavage from beta-nicotinamide adenine dinucleotide (beta-NAD + or NAD +) with the generation of three enzymatic products, i. e. the deacetylated protein species, nicotinamide, and 2'-O-acetyl-ADP-ribose (2'-O-AADPR).

amide

nicotinamide

beta-nicotinamide adenine dinucleotide

beta-NAD

NAD


Input: Here the author would like to review the past endeavors on developing mechanism-based sirtuin modulators (inhibitors and activators).


Input: The first part of this article will provide an updated mechanistic picture of the sirtuin-catalyzed deacetylation reaction.


Input: The second part will be focused on how the mechanistic knowledge has been exploited for the design of effective sirtuin modulators.


Input: Thiazolidinediones (TZDs) affect osteoblast viability and biomarkers independently of the TZD effects on aromatase.

Thiazolidinediones

TZDs

TZD


Input: Thiazolidinediones (TZDs) are insulin sensitizers used for treatment of diabetes.

Thiazolidinediones

TZDs


Input: We have previously reported that TZDs reduce estrogen synthesis by inhibiting aromatase activity in human granulosa cells (HGC).

TZDs

estrogen


Input: Multiple clinical trials demonstrated that TZDs increase the risk of fractures in postmenopausal women with type 2 diabetes.

TZDs


Input: We studied mouse osteoblasts alone or in a co-culture with HGC to determine whether TZD inhibition of aromatase plays a role in their effects on bone metabolism.

TZD


Input: Mouse osteoblasts were cultured with and without HGC, and incubated in a medium with or without testosterone, pioglitazone or rosiglitazone.

testosterone

pioglitazone

rosiglitazone


Input: Cell growth, oleic acid uptake, alkaline phosphatase activity, and osteocalcin production were measured.


Input: TZDs inhibited estradiol production by up to 84% in HGC/mouse osteoblast co-cultures.

TZDs

estradiol


Input: TZDs induced mouse osteoblast death and increased oleic acid uptake.

TZDs

oleic acid


Input: TZDs also inhibited alkaline phosphatase activity (58-75%, p < 0. 046) and osteocalcin production (52-75%, p < 0. 031).

TZDs


Input: For all the parameters, there were no significant differences between the osteoblast cultures alone and the HCG/osteoblast co-cultures.


Input: TZD effects on osteoblast viability, oleic acid uptake, alkaline phosphatase and osteocalcin production are independent of their effects on aromatase.

TZD


Input: New alloferon analogues: synthesis and antiviral properties.

alloferon


Input: We have extended our study on structure/activity relationship studies of insect peptide alloferon (H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH) by evaluating the antiviral effects of new alloferon analogues.

alloferon

H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH

alloferon


Input: We synthesized 18 alloferon analogues: 12 peptides with sequences shortened from N-or C-terminus and 6 N-terminally modified analogues H-X (1)-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH, where X (1) = Phe (13), Tyr (14), Trp (15), Phg (16), Phe (p-Cl) (17), and Phe (p-OMe) (18).

alloferon

N

C

N

Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH

Phe

Tyr

Trp

Phe (p-Cl)

Phe (p-OMe)


Input: We found that most of the evaluated peptides inhibit the replication of Human Herpesviruses or Coxsackievirus B2 in Vero, HEp-2 and LLC-MK (2) cells.


Input: Our results indicate that the compound [3-13]-alloferon (1) exhibits the strongest antiviral activity (IC (50) = 38 mu M) among the analyzed compound.


Input: Moreover, no cytotoxic activity against the investigated cell lines was observed for all studied peptides at concentration 165 mu M or higher.


Input: Sonochemical synthesis of hierarchical ZnO nanostructures.

ZnO


Input: This work is about fabrication of ZnO nanostructures (ZnO-NS) via a simple sonochemical method.

ZnO

ZnO


Input: The chemicals used for the synthesis of various shaped ZnO are Zn salt, sodium hydroxide and ammonia solution without other structure directing agent or surfactant needed.

ZnO

Zn

sodium hydroxide

ammonia solution


Input: This method is feasible and green, as it does not require high temperature and/or highly toxic chemicals.


Input: The shape of the ZnO-NS can be tuned by adjusting the ultrasound energy dissipated via varying the ultrasonication time from 5 to 60 min.

ZnO


Input: It was found that uniform ZnO nanorods with diameter around 50 nm were formed after 15 min of ultrasonication while flowerlike ZnO-NS was formed after 30 min.

ZnO

ZnO


Input: This method produces high quality ZnO-NS with controllable shapes, uniformity, and purity.

ZnO


Input: Objective and subjective cognitive enhancing effects of mixed amphetamine salts in healthy people.

amphetamine


Input: Psychostimulants such as mixed amphetamine salts (MAS, brand name Adderall) are widely used for cognitive enhancement by healthy young people, yet laboratory research on effectiveness has yielded variable results.

amphetamine

Adderall


Input: The present study assessed the effects of MAS in healthy young adults with an adequately powered double-blind cross-over placebo-controlled trial.


Input: We examined effects in 13 measures of cognitive ability including episodic memory, working memory, inhibitory control, convergent creativity, intelligence and scholastic achievement, with the goals of determining (1) whether the drug is at least moderately enhancing (Cohen' s d > =. 5) to some or all cognitive abilities tested, (2) whether its effects on cognition are moderated by baseline ability or COMT genotype, and (3) whether it induces an illusory perception of cognitive enhancement.


Input: The results did not reveal enhancement of any cognitive abilities by MAS for participants in general.


Input: There was a suggestion of moderation of enhancement by baseline ability and COMT genotype in a minority of tasks, with MAS enhancing lower ability participants on word recall, embedded figures and Raven' s Progressive Matrices.


Input: Despite the lack of enhancement observed for most measures and most participants, participants nevertheless believed their performance was more enhanced by the active capsule than by placebo.


Input: We conclude that MAS has no more than small effects on cognition in healthy young adults, although users may perceive the drug as enhancing their cognition.


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Vitamin D binding protein is a key determinant of 25-hydroxyvitamin D levels in infants and toddlers.

Vitamin D

25-hydroxyvitamin D


Input: Circulating 25-hydroxyvitamin D (25-OHD) levels vary among human populations.

25-hydroxyvitamin D


Input: Only limited information regarding determinants of these measures is available for infants and children, particularly in minority groups at greatest risk for vitamin D deficiency.

vitamin D


Input: We identified demographic determinants of circulating 25-OHD in a large cohort of minority children, and now extend our studies to examine potential roles of vitamin D binding protein (DBP) as a determinant of 25-OHD levels.

vitamin D


Input: Serum DBP level and common single nucleotide polymorphisms (SNPs) at positions 432 and 436 in the GC gene, encoding DBP, were examined.

nucleotide


Input: We confirmed self-reported ancestry using ancestry informative markers (AIMs), and included quantitative AIMs scores in the analysis.


Input: The multivariate model incorporated previously identified demographic and nutritional determinants of 25-OHD in this cohort, as well as GC SNPs and circulating DBP.


Input: Genetic variants in GC differed by self-reported ancestry.


Input: The 1f allele (D432/T436) was enriched in African Americans, occurring in 71%.


Input: Homozygosity for the 1f allele (DDTT) occurred in 53% of African Americans but only 6% of Caucasians and 13% of Hispanics.


Input: Circulating DBP was significantly correlated with 25-OHD.


Input: GC SNPs were associated with both circulating DBP and 25-OHD.


Input: It appears that progressive substitution of lysine for threonine at the 436 position results in lower circulating 25-OHD.

lysine

threonine


Input: Multivariate analysis revealed that genetic variance in GC significantly contributes to circulating DBP as well as 25-OHD.


Input: Moreover, the effect of GC SNPs on 25-OHD are evident after adjusting for their effects on circulating DBP.


Input: Thus in young children genetic variance of the common GC T436K SNP affects circulating levels of the DBP protein, which in turn affects circulating 25-OHD.


Input: However, the GC genotype also affects circulating 25-OHD independently of its effect on circulating DBP.


Input: These findings provide data that may be important in the interpretation of vitamin D status in children of varying ancestral backgrounds.


Input: The development of better photocatalysts through composition-and structure-engineering.


Input: Semiconductor photocatalysts that can effectively utilize solar irradiation hold great potential for harnessing renewable-energy sources, as well as for environmental protection and-remediation.


Input: Exploring advanced photocatalysts that have improved performance has been a central theme in photocatalysis research.


Input: Herein, we review the recent developments in the design-and fabrication of photocatalysts with an emphasis on composition-and structural control over multiple length scales.


Input: This Focus Review will be of value for researchers in the area of photocatalysis, in particular, in the aspects of material design that lead to the synthesis of better photocatalysts.


Input: Can the chemical reactivity of an ultimate carcinogen be related to its carcinogenicity?


Input: An application to propylene oxide.

propylene oxide


Input: In this article we report calculations of the activation free energy for a chemical reaction between propylene oxide and DNA, in particular with the guanine at the N7 position.

propylene oxide

guanine


Input: Calculations were performed using Hartree-Fock and MP2 methods in conjunction with flexible basis sets.


Input: The effects of solvation were considered using the Langevin dipoles and solvent reaction field methods.


Input: The calculated activation free energies are in good agreement with the experimental value of 25. 36 kcal/mol.


Input: Moreover, the reactivities of a series of ultimate carcinogens of the epoxy type toward DNA are shown to be related to their carcinogenicities.

epoxy


Input: Higher reactivity is generally associated with higher carcinogenicity, although transport properties, reactions with ultimate carcinogen scavengers, and the DNA correction mechanism are also very important.


Input: It is very likely that the window of reactivity rather than a high reactivity value is the relevant measure of carcinogenicity, since highly reactive ultimate carcinogens interact with water and proteins before they reach DNA.


Input: Negative regulation of osteoclast precursor differentiation by CD11b and beta 2 integrin-B-cell lymphoma 6 signaling.


Input: Negative regulation of osteoclastogenesis is important for bone homeostasis and prevention of excessive bone resorption in inflammatory and other diseases.


Input: Mechanisms that directly suppress osteoclastogenesis are not well understood.


Input: In this study we investigated regulation of osteoclast differentiation by the beta 2 integrin CD11b/CD18 that is expressed on myeloid lineage osteoclast precursors.


Input: CD11b-deficient mice exhibited decreased bone mass that was associated with increased osteoclast numbers and decreased bone formation.


Input: Accordingly, CD11b and beta 2 integrin signaling suppressed osteoclast differentiation by preventing receptor activator of NF-kappa B ligand (RANKL)-induced induction of the master regulator of osteoclastogenesis nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and of downstream osteoclast-related NFATc1 target genes.


Input: CD11b suppressed induction of NFATc1 by the complementary mechanisms of downregulation of RANK expression and induction of recruitment of the transcriptional repressor B-cell lymphoma 6 (BCL6) to the NFATC1 gene.


Input: These findings identify CD11b as a negative regulator of the earliest stages of osteoclast differentiation, and provide an inducible mechanism by which environmental cues suppress osteoclastogenesis by activating a transcriptional repressor that makes genes refractory to osteoclastogenic signaling.


Input: The role of long chain omega-3 polyunsaturated fatty acids in reducing lipid peroxidation among elderly patients with mild cognitive impairment: a case-control study.

omega-3 polyunsaturated fatty acids


Input: The present work explores the effect of dietary omega-3 polyunsaturated fatty acids (PUFAs) intake on lipid peroxidation among mild cognitive impairment (MCI) patients.

omega-3 polyunsaturated fatty acids

PUFAs


Input: The plasma lipid hydroperoxide (LPO) levels in 67 MCI patients were compared to those of 134 healthy elderly controls.

hydroperoxide


Input: Omega-3 PUFA intake was assessed using an interviewer-administered food frequency questionnaire.

Omega-3 PUFA


Input: Apolipoprotein E genotyping was performed using polymerase chain reaction and restriction enzyme digestion.


Input: The association between various confounders and lipid peroxidation was evaluated using regression analysis.


Input: The influence of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake on LPO level was investigated.

docosahexaenoic acid

DHA

eicosapentaenoic acid

EPA


Input: The results revealed that LPO levels were significantly higher in the MCI group than in the control group.


Input: Inverse correlations were found between DHA and EPA intake and LPO level among the MCI group.

DHA

EPA


Input: LPO levels decreased significantly with increasing DHA and EPA intake.

DHA

EPA


Input: In summary, the findings revealed that DHA and EPA can play a role in alleviating oxidative stress and reducing the risk of neurodegenerative diseases.

DHA

EPA


Input: Multidrug resistance-associated proteins are involved in the transport of the glutathione conjugates of the ultimate carcinogen of benzo [a] pyrene in human Caco-2 cells.

glutathione

benzo [a] pyrene


Input: A wide variety of contaminants are ingested through food, among them the pro-carcinogenic polycyclic aromatic hydrocarbon benzo [a] pyrene (BP) that is resorbed and partially metabolized in the enterocytes of the small intestine.

benzo [a] pyrene


Input: Previous in vitro studies have revealed that BP phenols are excreted as Phase II metabolites including glucuronides and sulfates.

BP phenols

sulfates


Input: This export is mediated by the breast cancer resistance protein (ABCG2).


Input: The ultimate carcinogenic Phase I BP metabolite anti-BP-7, 8-dihydrodiol-9, 10-epoxide (BPDE) can be detoxified by glutathione conjugate formation catalyzed by glutathione S-transferases.

BP-7, 8-dihydrodiol-9, 10-epoxide

BPDE

glutathione

glutathione S


Input: In the present study, differentiated human intestinal Caco-2 cells were used as a model for the human small intestine to investigate the detoxification of BPDE and excretion of stereoisomeric glutathione conjugates in the presence of an inhibitor of the glutathione-cleaving enzyme gamma-glutamyl transpeptidase at the cell surface.

BPDE

glutathione

glutathione


Input: The results indicate that the glutathione conjugates of BPDE are formed and excreted mainly to the apical and to a minor extent to the basolateral side of polarized Caco-2 monolayers.

glutathione

BPDE


Input: Inhibition studies revealed that the multidrug resistance-associated proteins (ABCCs) are involved in the transport of BPDE glutathione conjugates.

BPDE glutathione


Input: Stable ABCC1, ABCC2 and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that ABCC1 mediates the basolateral and ABCC2 the apical excretion of BPDE glutathione conjugates.

BPDE glutathione


Input: In conclusion, the ultimate carcinogen BPDE is detoxified via glutathione conjugation and subsequently excreted by Caco-2 cells in both apical and basolateral directions.

BPDE

glutathione