Input: Reduction of neuronal CoQ (10) status was accompanied by a progressive decrease in mitochondrial respiratory chain enzyme activities, with a 67. 5% decrease in cellular ATP production at 46% residual CoQ (10).

CoQ (10)

ATP

CoQ (10)


Input: Mitochondrial oxidative stress increased four-fold at 77% and 46% residual CoQ (10).

CoQ (10)


Input: A 40% increase in mitochondrial membrane potential was detected at 46% residual CoQ (10) with depolarisation following oligomycin treatment suggesting a reversal of complex V activity.

CoQ (10)


Input: This neuronal cell model provides insights into the effects of CoQ (10) deficiency on neuronal mitochondrial function and oxidative stress, and will be an important tool to evaluate candidate therapies for neurological conditions associated with CoQ (10) deficiency.

CoQ (10)

CoQ (10)


Input: Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay.


Input: In the human cell cycle, the Myt1 kinase is a crucial regulator of the G2/M transition.


Input: Because this membrane-associated kinase is hard to obtain and assay, there is a distinct lack of data so far.


Input: Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay.


Input: These compounds were tested in a binding assay together with a set of common kinase inhibitors against a full-length Myt1 expressed in a human cell line.


Input: Dasatinib exhibited nanomolar affinity whereas broad coverage inhibitors such as sunitinib and staurosporine derivatives did not show any effect.

Dasatinib

sunitinib

staurosporine


Input: We also carried out docking studies for the most potent compounds allowing further insights into the inhibitor interaction of this kinase.


Input: The glycoglycerolipids showed no significant effects in the binding assay, endorsing the idea of a mechanism of action distant from the active site.


Input: Nicotine improves performance in an attentional set shifting task in rats.

Nicotine


Input: A large number of studies in both humans and experimental animals have demonstrated nicotine-induced improvements in various aspects of cognitive function, including attention and memory.

nicotine


Input: The prefrontal cortex (PFC) is thought to be critically involved in the modulation of executive function and these attentional processes are enhanced by nicotine acting at nicotinic acetylcholine receptors.

nicotine

acetylcholine


Input: The involvement of nicotinic processes on cognitive flexibility in particular has not been specifically investigated.


Input: The effects of nicotine on attentional flexibility were therefore evaluated using the rodent attentional set shifting task in rats.

nicotine


Input: Nicotine injected both acutely and following repeated pre-exposure significantly improved both intradimensional and extradimensional set shifting performance in the task.

Nicotine


Input: Further investigation of the acute effects of nicotine demonstrated this improvement in attentional flexibility to be dose-dependent.

nicotine


Input: These results implicate the nicotinic receptor system in the mediation of processes underlying cognitive flexibility and suggest that nicotine improves attentional flexibility in rats, both within and between perceptual dimensions of a compound stimulus.

nicotine


Input: Nicotine-induced alterations in prefrontal circuitry may underlie these effects on cognitive flexibility.

Nicotine


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


Input: Co-learning facilitates memory in mice: a new avenue in social neuroscience.


Input: Social context affects brain function but our understanding of its neurobiology is at an early stage.


Input: The mere presence of one individual can alter the cognitive capacities of another and social learning has been demonstrated in many species, including the mouse.


Input: We asked several questions: 1.


Input: How can active engagement of two familiar mice in the same learning activity (co-learning) alter their memory?


Input: Under which environmental conditions (aversive vs non-aversive) can we expect the memory to be enhanced, impaired, or not affected?


Input: Can a genetic factor modify the co-learning effect on memory?


Input: More specifically, can co-learning correct memory deficits in autistic-like BTBR inbred mice with deficient sociability?


Input: We demonstrated that pairs of familiar inbred mice of the same or different genotypes (C57BL/6J and BTBR) that were habituated to new objects and their spatial location, had enhanced episodic memory in the spatial object recognition test, whereas individually-trained animals failed to solve this task.


Input: Notably, the co-learning effect was genotype-dependent.


Input: BTBR mice paired with BTBR cage-mates in the habituation session modestly ameliorated their performance in the object recognition test but co-learning with a familiar C57BL/6J mouse completely normalized episodic memory deficit.


Input: Next, we explored the co-learning effect on fear memory in these inbred strains.


Input: Interestingly, mice of both genotypes displayed significantly enhanced contextual fear memory once they had been conditioned together with BTBR animals.


Input: The same influence of BTBR presence was observed on cued fear memory in C57BL/6J mice, whereas a modest co-learning effect was found on cued fear conditioning in the BTBR strain.


Input: Taken together, we demonstrated for the first time the co-learning effect on cognitive capacities in mice, which can be modified by genetic background and environmental conditions.


Input: The possible implications of this methodological approach in social neuroscience are discussed.


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


Input: Passive stiffness of airway smooth muscle: the next target for improving airway distensibility and treatment for asthma?


Input: Reduced airway distensibility due to increased airway stiffness is a characteristic of asthma.


Input: Airway stiffness is determined by the property and structural organization of the various elements of the airway wall, and is often divided into active and passive components.


Input: Active stiffness is thought to be associated with activation of muscle cells in the airway wall.


Input: This component of stiffness can be inhibited when active force produced by the muscle is abolished.


Input: Passive stiffness, on the other hand, is thought to stem from non-muscle component of the airway wall, especially the collagen/elastin fibrous network of the extracellular matrix within which the muscle cells are embedded.


Input: In this brief review, the notion that passive stiffness is exclusively extracellular in origin is challenged.


Input: Recent evidence suggests that a substantial portion of the passive stiffness of an in vitro preparation of tracheal smooth muscle is calcium sensitive and is regulated by Rho-kinase, although the underlying mechanism and the details of regulation for the development of this intracellular passive stiffness are still largely unknown.

calcium


Input: To reduce airway stiffness different lines of attack must be tailored to different components of the stiffness.


Input: The regulatable passive stiffness is distinct from the relatively permanent stiffness of the extracellular matrix and the stiffness associated with active muscle contraction.


Input: To improve airway distensibility during asthma exacerbation, a comprehensive approach to reduce overall airway stiffness should therefore include a strategy for targeting the regulatable passive stiffness.


Input: Harmonization of description and classification of fetal observations: achievements and problems still unresolved: report of the 7th Workshop on the Terminology in Developmental Toxicology Berlin, 4-6 May 2011.


Input: This article summarizes the 7th Workshop on the Terminology in Developmental Toxicology held in Berlin, May 4-6, 2011.


Input: The series of Berlin Workshops has been mainly concerned with the harmonization of terminology and classification of fetal anomalies in developmental toxicity studies.


Input: The main topics of the 7th Workshop were knowledge on the fate of anomalies after birth, use of Version 2 terminology for maternal-fetal observations and non-routinely used species, reclassification of " grey zone " anomalies and categorization of fetal observations for human health risk assessment.


Input: The paucity of data on health consequences of the postnatal permanence of fetal anomalies is relevant and further studies are needed.


Input: The Version 2 terminology is an important step forward and the terms listed in this glossary are considered also to be appropriate for most observations in non-routinely used species.


Input: Continuation of the Berlin Workshops was recommended.


Input: Topics suggested for the next Workshop were grouping of fetal observations for reporting and statistical analysis.


Input: Natural anthocyanins from phytoresources and their chemical researches.

anthocyanins


Input: Anthocyanins are a class of naturally occurring polyphenols which have been most widely studied in recent decades for the rapid development of relative techniques.

Anthocyanins

polyphenols


Input: This article first reviews the various anthocyanin resources including fruits, flowers, vegetables and beverages.

anthocyanin


Input: Besides the direct extraction from natural resources, anthocyanins can also be obtained by semi-or total synthesis.

anthocyanins


Input: After the introduction of new representative anthocyanins found in the past few years and the major relationships between structures and stability, modern separation and analysis technologies in related studies were summarised, which play an important role in chemical researches of anthocyanins.

anthocyanins

anthocyanins


Input: Classification of Aurora kinase inhibitors by self-organizing map (SOM) and support vector machine (SVM).


Input: The Aurora kinase family (consisting of Aurora-A,-B and-C) is an important group of enzymes that controls several aspects of cell division in mammalian cells.


Input: In this study, 512 compounds of Aurora-A and-B inhibitors were collected.


Input: They were classified into three classes: dual Aurora-A and Aurora-B inhibitors, selective inhibitors of Aurora-A and selective inhibitors of Aurora-B by Self-Organizing Map (SOM) and Support Vector Machine (SVM).


Input: The prediction accuracies of the models (based on the training/test set splitting using SOM method) for the test set were 92. 2% for SOM1 and 93. 8% for SVM1, respectively.


Input: In addition, the extended connectivity fingerprints (ECFP _ 4) for all the molecules were calculated and structure-activity relationship of Aurora kinase inhibitors was summarized, which may be helpful to find the important structural features of inhibitors relating to the selectivity to Aurora kinases.


Input: Role of metabotropic glutamate receptor 1 in the basolateral amygdala-driven prefrontal cortical deactivation in inflammatory pain in the rat.

glutamate


Input: Plastic changes in the amygdala and limbic cortex networks have been widely shown in chronic pain.


Input: We have here investigated the role of group I metabotropic glutamate receptors (mGluRs) in the basolateral amygdala (BLA) pre-infra-limbic (PL-IL) divisions of the medial prefrontal cortex (mPFC) neuron connections after carrageenan-induced inflammatory pain in the rat.

glutamate


Input: Intra-plantar injection of carrageenan decreased either spontaneous or mechanically/electrically evoked activity of PL cortex pyramidal neurons which responded with excitation in a way prevented by CPCOOEt, a selective mGluR1 antagonist, though not by MPEP, a selective mGluR5 antagonist.

CPCOOEt

MPEP


Input: Accordingly, intra-BLA microinjection of DHPG, a group I mGluR agonist, caused PL cortex neuron activity depression, antagonized by CPCCOEt.

DHPG

CPCCOEt


Input: CPCOOEt, but not MPEP, reduced also carrageenan-induced mechanical allodynia.

CPCOOEt

MPEP


Input: The PL cortex cell deactivation in inflammatory pain condition was associated with increased GABA (conversely glutamate was decreased) in the PL/IL cortex.

GABA

glutamate


Input: The local application of bicuculline, a GABA (A) receptor selective antagonist, reduced mechanical allodynia.

bicuculline

GABA


Input: An over-expression of mGluR1, but not mGluR5, have been observed in the PL-IL cortex after inflammatory pain suggesting an increased mGluR1-dependent cross-talk among BLA and IL-PL cortex neurons in inflammatory pain conditions.


Input: This article is part of a Special Issue entitled' Metabotropic Glutamate Receptors'.

Glutamate


Input: Emerging role of AMP-activated protein kinase in endocrine control of metabolism in the liver.

AMP


Input: This review summarizes the emerging role of AMP-activated protein kinase (AMPK) in mediating endocrine regulation of metabolic fluxes in the liver.

AMP


Input: There are a number of hormones which, when acting on the liver, alter AMPK activation.


Input: Here we describe those hormones associated with activation and de-activation of AMPK and the potential mechanisms for changes in AMPK activation state.


Input: The actions of these hormones, in many cases, are consistent with downstream effects of AMPK signaling thus strengthening the circumstantial case for AMPK-mediated hormone action.


Input: In recent years, genetic mouse models have also been used in an attempt to establish the role of AMPK in hormone-stimulated metabolism in the liver.


Input: Few experiments have, however, firmly established a causal relationship between hormone action at the liver and AMPK signaling.


Input: Rectifying behavior of charge transfer complexes of tetrakis (dimethylamino) ethene with acceptor molecules: a theoretical study.

tetrakis (dimethylamino) ethene


Input: The effect of electric field induced electron transfer on the rectification properties of molecular rectifiers based on charge transfer complexes of tetrakis (dimethylamino) ethane (TDAE) with acceptor molecules was explored.

tetrakis (dimethylamino) ethane

TDAE


Input: The current-voltage curves and the rectification ratios (RR) for two different molecular rectifiers were obtained using a direct ab initio method at M06/LACVP (d) level of theory in the range from-2 to + 2 V.


Input: The highest RR of 25. 7 was determined for the complex of TDAE with 2-nitropyrene-4, 5, 9, 10-tetraone at 0. 5 V (D1), while another rectifier [complex of TDAE with 2, 7-dimethyl nitropyrene-4, 5, 9, 10-tetraone (D2)] showed a maximum RR of only 2. 9 at 0. 3 V.

TDAE

2-nitropyrene-4, 5, 9, 10-tetraone

TDAE

2, 7-dimethyl nitropyrene-4, 5, 9, 10-tetraone


Input: The electric field induced electron transfer occurring in D1 creates a one-way conducting channel consisting of two SOMOs involving the entire D1 complex.


Input: In the case of D2, no electron transfer occurs at the applied bias voltages due to the relatively high energy difference between HOMO and LUMO.


Input: Increased expression of P450scc and CYP17 in development of endogenous hyperandrogenism in a rat model of PCOS.


Input: The objective of the present study was to characterize the effect of insulin plus hCG on the expression of steroidogenic enzymes (P450scc and CYP17) in polycystic ovaries of rats.


Input: Changes in estrous cycle, ovarian morphology, hormonal levels, and protein levels by immunohistochemistry and western-blot were determined.


Input: Rats treated with insulin plus hCG displayed abnormal estrous cycles with increasing androgen biosynthesis.

androgen


Input: Meanwhile, insulin plus hCG resulted in multiple large cysts with diminished granulosa layers and increased thecal layers and stromal-interstitial tissue.


Input: Moreover, there was an increase in the expression of P450scc and CYP17 in thecal and stromal cells in our PCOS rat model compared with control rats.


Input: These results indicate that administration of insulin with hCG can synergistically result in endogenous hyperandrogenism which may partially upregulate the expression of steroidogenic enzymes in ovarian tissue.


Input: beta-Orcinol-type depsides from the lichen Thamnolia vermicularis.

beta-Orcinol


Input: A phytochemical investigation of a herb tea made from Thamnolia vermicularis led to the isolation of three new beta-orcinol-type depsides (1, 2 and 3), along with seven known compounds hypothamnolic acid (4), 3'-methylevenic acid (5), baeomycesic acid (6), squamatic acid (7), methyl 3'-methyllecanorate (8), barbatinic acid (9) and atranorin (10).

beta-orcinol

depsides

hypothamnolic acid

3'-methylevenic acid

baeomycesic acid

squamatic acid

methyl 3'-methyllecanorate

barbatinic acid

atranorin


Input: The structures of the new compounds were determined on the basis of spectroscopic evidence, including 1-D and 2-D NMR and ESI-MS techniques.


Input: AMPAKINE enhancement of social interaction in the BTBR mouse model of autism.

AMPAKINE


Input: Autism is a neurodevelopmental disorder in which the first diagnostic symptom is unusual reciprocal social interactions.


Input: Approximately half of the children diagnosed with an autism spectrum disorder also have intellectual impairments.


Input: General cognitive abilities may be fundamental to many aspects of social cognition.


Input: Cognitive enhancers could conceivably be of significant benefit to children and adults with autism.


Input: AMPAKINE compounds are a novel class of pharmacological agents that act as positive modulators of AMPA receptors to enhance excitatory glutamatergic neurotransmission.

AMPAKINE

AMPA


Input: This class of compounds was reported to improve learning and memory in several rodent and non-human primate tasks, and to normalize respiratory abnormalities in a mouse model of Rett syndrome.


Input: Here we evaluate the actions of AMPA compounds in adult male and female BTBR mice, a well characterized mouse model of autism.

AMPA


Input: Acute treatment with CX1837 and CX1739 reversed the deficit in sociability in BTBR mice on the most sensitive parameter, time spent sniffing a novel mouse as compared to time spent sniffing a novel object.


Input: The less sensitive parameter, time in the chamber containing the novel mouse versus time in the chamber containing the novel object, was not rescued by CX1837 or CX1739 treatment.


Input: Preliminary data with CX546, in which beta-cyclodextrin was the vehicle, revealed behavioral effects of the acute intraperitoneal and oral administration of vehicle alone.

beta-cyclodextrin


Input: To circumvent the artifacts introduced by the vehicle administration, we employed a novel treatment regimen using pellets of peanut butter for drug delivery.


Input: Absence of vehicle treatment effects when CX1837 and CX1739 were given in the peanut butter pellets, to multiple cohorts of BTBR and B6 control mice, confirmed that the pharmacologically-induced improvements in sociability in BTBR were not confounded by the administration procedures.


Input: The highest dose of CX1837 improved the cognitive deficit in novel object recognition in BTBR.


Input: No drug effects were detected on the high levels of repetitive self-grooming in BTBR.


Input: In open field tests, CX1837 and CX1739 did not induce hyperactivity or sedation in either strain.


Input: It is interesting to speculate that the ability of CX1837 and CX1739 to restore aspects of sociability in BTBR mice could utilize synaptic mechanisms regulating social cognition, suggesting a potential pharmacological target for interventions to treat symptoms of autism.


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


Input: Androgen insensitivity syndrome.

Androgen


Input: Androgen insensitivity syndrome (AIS) is a disorder caused by a mutation of the gene encoding the androgen receptor (AR; Xq11-q12).

Androgen

androgen


Input: The prevalence of AIS has been estimated to be one case in every 20, 000 to 64, 000 newborn males for the complete syndrome (CAIS), and the prevalence is unknown for the partial syndrome (PAIS).


Input: The symptoms range from phenotypically normal males with impaired spermatogenesis to phenotypically normal women with primary amenorrhea.


Input: Various forms of ambiguous genitalia have been observed at birth.


Input: The diagnosis is confirmed by determining the exact mutation in the AR gene.


Input: PAIS individuals require precise diagnosis as early as possible so that the sex can be assigned, treatment can be recommended, and they can receive proper genetic counseling.


Input: After birth, differential diagnosis should be performed using other forms of abnormal sexual differentiation of primary amenorrhea.


Input: The treatment of AIS is based on reinforcement sexual identity, gonadectomy planning, and hormone replacement therapy.


Input: The prognosis for CAIS is good if the testicular tissue is removed at the appropriate time.


Input: For PAIS, the prognosis depends on the ambiguity of the genitalia and physical and psychosocial adjustment to the assigned sex.


Input: Deep understanding of the interaction between thienorphine and UDP-glucuronosyltransferase (UGT) isoforms.

thienorphine

UDP


Input: Thienorphine has been demonstrated to be a potent, long-acting partial opioid agonist.

Thienorphine


Input: It is being developed as a good candidate to treat opioid dependence.


Input: The thienorphine' s glucuronide was detected after thienorphine was incubated with human liver microsomes (HLMs).

thienorphine

thienorphine


Input: Recombinant UGT isoforms screening experiment and enzyme kinetic study showed that UGT1A1 completely contributed to the glucuronidation of thienorphine.

thienorphine


Input: Among the tested UGT isoforms, UGT1A3 and UGT2B7 were inhibited by thienorphine, with other UGT isoforms negligibly influenced.

thienorphine


Input: The inhibition type is competitive, and inhibition kinetic parameters (K (i)) were 1. 65 and 5. 27 mu M for UGT1A3 and UGT2B7, respectively.


Input: However, due to low plasma concentration of thienorphine, in vivo drug-drug interaction might not occur.

thienorphine


Input: Adnexal torsion in children and adolescents: new trends to conservative surgical approach--our experience and review of literature.


Input: The purpose of this study is to discuss the surgical treatment for ovarian torsion in children and adolescents with a focus on the procedures of adnexal conservation surgery and its frequency in the literature of the last 10 years.


Input: We retrospectively reviewed the medical charts of 127 operative ovarian lesions including 30 ovarian torsions (23. 6%) treated in two pediatric centers over a 10-year period.


Input: Age at presentation, presenting symptoms, diagnostic studies, surgical procedure and pathological findings were analyzed.


Input: Mean age was 13. 7 years.


Input: Conservative surgery has been performed in 46. 7% of the cases and laparoscopic approach in 40%.


Input: Ovarian torsion occurred in 56. 7% on ovaries with functional lesion, in 23. 3% on normal adnexa and in 20% on ovaries with benign neoplasm.


Input: The article includes a literature review (2000-2010) and a statistical analysis which shows a slow increase in conservative surgery from 28 to 45%.


Input: Laparoscopic surgery accounts for 23. 5%.


Input: Literature review shows 40. 5% normal adnexa, 33. 2% non-neoplastic lesions, 25. 3% benign neoplasms and 1% malignant neoplasms.


Input: The surgical treatment of children and adolescents presenting adnexal torsion should be practiced as an emergency and it should be more conservative as possible in order to maximize the future reproductive potential.


Input: Silibinin protects H9c2 cardiac cells from oxidative stress and inhibits phenylephrine-induced hypertrophy: potential mechanisms.

Silibinin

phenylephrine


Input: Cardiac hypertrophy is the main response of the heart to various extrinsic and intrinsic stimuli, and it is characterized by specific molecular and phenotypic changes.


Input: Recent in vitro and in vivo studies indicate the involvement of reactive oxygen species in the hypertrophic response.

oxygen


Input: In this study, silibinin, a plant flavonolignan extracted from milk thistle with potent antioxidant activity, was evaluated for its effects in (a) preventing hydrogen peroxide (H2O2)-induced cellular damage and (b) blocking the phenylephrine-induced hypertrophic response.

silibinin

flavonolignan

hydrogen peroxide

phenylephrine


Input: Using the in vitro model of embryonic rat heart-derived H9c2 cells, we showed that silibinin has a rather safe profile as concentrations up to 200 mu M did not affect cell viability.

silibinin


Input: Pretreatment of H9c2 cells with silibinin resulted in better protection of H9c2 cells under conditions of H2O2-induced cellular stress compared to untreated cells as indicated by cell viability and DNA fragmentation assays.

silibinin


Input: Furthermore, silibinin attenuated the phenylephrine-induced hypertrophic response as evidenced by the measurement of cell surface, up-regulation of atrial natriuretic peptide and increase of cellular protein levels.

silibinin

phenylephrine


Input: Moreover, silibinin repressed the phenylephrine-induced phosphorylation of ERK1/2 kinases, while it appeared to inhibit the weakly activated by phenylephrine phosphorylation of Akt.

silibinin

phenylephrine

phenylephrine


Input: Based on our results, silibinin may attenuate the phenylephrine-induced hypertrophic response of H9c2 cells via antioxidant mechanisms involving mainly the inhibition of the intracellular signaling pathways mediated by ERK1/2 MAPKs and Akt.

silibinin

phenylephrine


Input: Modafinil effects on cognition and emotion in schizophrenia and its neurochemical modulation in the brain.

Modafinil


Input: Modafinil is a central nervous system wake promoting agent used for the treatment of excessive daytime sleeping.

Modafinil


Input: Its vigilance promoting properties and low abuse potential has intrigued the scientific community and has led to use it as a cognitive enhancer, before its neural functions were understood.


Input: Here, we review the effects of modafinil in human cognition and emotion and its specific actions on symptoms in patients with schizophrenia and whether these are consistently effective throughout the literature.

modafinil


Input: We also performed a systematic review on the effects of modafinil on neurotransmitter signalling in different areas of the brain in order to better understand the neuromechanisms of its cognitive and emotional enhancing properties.

modafinil


Input: A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions, with pro-mnemonic effects and problem solving improvements.

modafinil


Input: Emotional processing also appears to be enhanced by the drug, although to date there are only a limited number of studies.


Input: The systematic review on the neurochemical modulation of the modafinil suggests that its mnemonic enhancing properties might be the result of glutamatergic and dopaminergic increased neuronal activation in the hippocampus and in the prefrontal cortex respectively.

modafinil


Input: Other neurotransmitters were also activated by modafinil in various limbic brain areas, suggesting that the drug acts on these brain regions to influence emotional responses.

modafinil


Input: These reviews seek to delineate the neuronal mechanisms by which modafinil affects cognitive and emotional function.

modafinil


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


Input: Current understanding of TRPM7 pharmacology and drug development for stroke.


Input: The initial excitement and countless efforts to find a pharmacological agent that disrupts the excitotoxic pathway of ischemic neuronal death have only led to disappointing clinical trials.


Input: Currently, a thrombolytic agent called recombinant tissue plasminogen activator (rt-PA) is the only pharmacological treatment available for patients with acute ischemic stroke in most countries.


Input: Even though its efficacy has been confirmed repeatedly, rt-PA is considerably underused due to reasons including a short therapeutic window and repeated complications associated with its use.


Input: A search for alternative mechanisms that may operate dependently or independently with the well-established excitotoxic mechanism has led researchers to the discovery of newly described non-glutamate mechanisms.

glutamate


Input: Among the latter, transient receptor potential melastatin 7 (TRPM7) is one of the important nonglutamate mechanisms in stroke, which has been evaluated in both in-vitro and in-vivo.


Input: In this review, we will discuss the current state of pharmacological treatments of ischemic stroke and provide evidence that TRPM7 is a promising therapeutic target of stroke.


Input: Altered gene expression involved in insulin signaling pathway in type II diabetic osteoporosis rats model.


Input: It is well established that both estrogen loss and type II diabetes mellitus (DMII) can impair bone metabolism, but whether estrogen loss exacerbates the effects of DMII is unclear.

estrogen

estrogen


Input: Therefore, we determined if ovariectomy (OVX) of rats on a long-term high-fat/sugar diet and injection of a low dose of streptozotocin (DMII) decreased bone mineral density (BMD) more than OVX or DMII alone.

sugar

streptozotocin


Input: Bone insulin signaling is known to support bone metabolism; therefore, we also tested the hypothesis that OVX DMII rats (DOVX) would exhibit greater reductions in the expression of proteins important in insulin signaling, including IRS-1, IRS-2, and IGF-1.


Input: As hypothesized, BMD and plasma estrogen levels were decreased more in DOVX rats than in rats following OVX (NOVX) or DMII (DS) alone.

estrogen


Input: IGF-1 expression was decreased in the liver, kidney, skeletal muscle, and bone of DOVX, DS, and NOVX rats; however, the decrease was larger and occurred sooner in DOVX rats.


Input: While IRS-1 and IRS-2 decreased in most groups in all tissues examined, the expression patterns differed in both a group-and tissue-dependent fashion.


Input: In conclusion, these data demonstrate that estrogen loss and DMII induced by a high-fat/sugar diet interact to produce osteoporosis and support the hypothesis that the bone loss may be mediated at least in part by concurrent decreases in the insulin signaling proteins in bone.

estrogen

sugar


Input: Egis-11150: a candidate antipsychotic compound with procognitive efficacy in rodents.


Input: Classical antipsychotics, e. g. haloperidol, chlorpromazine, are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side-effects.

haloperidol

chlorpromazine


Input: The introduction of atypical antipsychotics such as risperidone, olanzapine and clozapine has obviated this problem, but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia.

risperidone

olanzapine

clozapine


Input: Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition.


Input: Here, we report the preclinical properties of a candidate antipsychotic, Egis-11150, that shows marked pro-cognitive efficacy.


Input: Egis-11150 displayed high affinity for adrenergic alpha (1), alpha (2c), 5-HT (2A) 5-HT 7, moderate affinity for adrenergic alpha (2a) and D 2 receptors.


Input: It was a functional antagonist on all of the above receptors, with the exception of 5-HT 7 receptors, where it was an inverse agonist.


Input: Phencyclidine-induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia.

Phencyclidine


Input: Passive-avoidance learning, novel object recognition and radial maze tests in rats were used to assess pro-cognitive activity, while phencyclidine-induced disruption of prepulse inhibition in mice was examined to test for effects on attention.

phencyclidine


Input: Egis-11150 (0. 01-0. 3 mg/kg, ip.) was effective in all of the preclinical models of schizophrenia examined.


Input: Moreover, a robust pro-cognitive profile was apparent.


Input: In summary, work in preclinical models indicates that Egis-11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia.


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


Input: Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model.

Propranolol


Input: Ageing is associated with a deterioration of cognitive performance and with increased risk of neurodegenerative disorders.


Input: Hypertension is the most-prevalent modifiable risk factor for cardiovascular morbidity and mortality worldwide, and clinical data suggest that hypertension is a risk factor for Alzheimer' s disease (AD).


Input: In the present study we tested whether propranolol, a beta-receptor antagonist commonly used as antihypertensive drug, could ameliorate the cognitive impairments and increases in AD-related markers shown by the senescence-accelerated mouse prone-8 (SAMP8).

propranolol


Input: Propranolol administration (5 mg/kg for 3 weeks) to 6-month-old SAMP8 mice attenuated cognitive memory impairments shown by these mice in the novel object recognition test.

Propranolol


Input: In the hippocampus of SAMP8 mice it has been found increases in A beta (42) levels, the principal constituent of amyloid plaques observed in AD, accompanied by both an increased expression of the cleaving enzyme BACE1 and a decreased expression of the degrading enzyme IDE.


Input: All these effects were reversed by propranolol treatment.

propranolol


Input: Tau hyperphosphorylation (PHF-1 epitope) shown by SAMP8 mice at this age was also decreased in the hippocampus of propranolol-treated mice, an effect probably related to a decrease in JNK1 expression.

propranolol


Input: Interestingly, propranolol also phosphorylated Akt in SAMP8 mice, which was associated with an increase of glycogen synthase kinase-3 beta phosphorylation, contributing therefore to the reductions in Tau hyperphosphorylation.

propranolol


Input: Synaptic pathology in SAMP8 mice, as shown by decreases in synaptophysin and BDNF, was also counteracted by propranolol treatment.

propranolol


Input: Overall, propranolol might be beneficial in age-related brain dysfunction and could be an emerging candidate for the treatment of other neurodegenerative diseases.

propranolol


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


Input: Metabolism and disposition of [14C] n-butyl-p-hydroxybenzoate in male and female Harlan Sprague Dawley rats following oral administration and dermal application.

[14C] n-butyl-p-hydroxybenzoate


Input: n-Butyl-p-hydroxybenzoate (n-butylparaben, BPB) is an antioxidant used in foods, pharmaceuticals and cosmetics.

n-Butyl-p-hydroxybenzoate

n-butylparaben

BPB


Input: This study investigated the disposition of ring-labelled [(14) C] BPB in Harlan Sprague Dawley rats, and in rat and human hepatocytes.

[(14) C] BPB


Input: BPB was rapidly cleared in hepatocytes from rat (t (1/2) = 3-4 min) and human (t (1/2) = 20-30 min).

BPB


Input: The major metabolites detected in rat hepatocytes were hydroxybenzoic acid and in human hepatocytes were hydroxybenzoic acid and hydroxyhippuric acid.

hydroxybenzoic acid

hydroxybenzoic acid

hydroxyhippuric acid


Input: [(14) C] BPB was administered to male rats orally at 10, 100 or 1000 mg/kg, intravenously at 10 mg/kg and dermally at 10 and 100 mg/kg; female rats were administered oral doses at 10 mg/kg.

[(14) C] BPB


Input: Oral doses of BPB were well-absorbed (> 83%) and eliminated chiefly in urine (83-84%); <= 1% of the radioactivity remained in tissues at 24 h or 72 h after dosing.

BPB


Input: About 4% and 8%, respectively, of 100 mg/kg dermal doses were absorbed in 24 h and 72 h, and about 50% of a 10 mg/kg dose was absorbed in 72 h.


Input: Metabolites detected in urine included those previously reported, BPB-glucuronide, BPB-sulfate, hydroxybenzoic acid and hydroxyhippuric acid, but also novel metabolites arising from ring hydroxylation followed by glucuronidation and sulfation.

BPB-glucuronide

BPB-sulfate

hydroxybenzoic acid

hydroxyhippuric acid


Input: Fertility and endocrine outcome after robot-assisted laparoscopic myomectomy (RALM).


Input: Introduction: Laparoscopic myomectomy has recently gained wide acceptance but this procedure remains technically highly demanding and concerns have been raised about the increased blood loss and an higher risk of postoperative uterine rupture of the pregnant uterus.


Input: Objective: The aim of the present study is to evaluate the fertility and endocrine outcome in women underwent robot-assisted laparoscopic myomectomy (RALM).


Input: Methods: Data from 48 RALM performed in our department between the years 2007 and 2011 have been collected.


Input: Conception rate, abortion rate, incidence of feto-maternal morbidity or severe pregnancy and labor-related complications were reported; FSH and AMH levels and ultrasound valuation of AFC has been made before and 6 months after operation.


Input: Number of cesarean sections and vaginal deliveries were described.


Input: Results: The average age of the patients was 35 years and median Body Mass Index was 23 kg/m (2) (range 18-35 kg/m (2)).


Input: Seven women (13%) became pregnant after RALM with eight pregnancies.


Input: One pregnancy is actually on going; there were six deliveries with caesarian section and one spontaneous delivery.


Input: No spontaneous abortions.


Input: No uterine ruptures occurred.


Input: No significant modification of ovarian function was found after myomectomy.


Input: Conclusion: RALM seems to have a favorable impact on the reproductive outcome of young patients with no impact on the ovarian function.


Input: Sour Cherry Seed Kernel Extract Increases Heme Oxygenase-1 Expression and Decreases Representation of CD3 + TNF-alpha + and CD3 + IL-8 + Subpopulations in Peripheral Blood Leukocyte Cultures from Type 2 Diabetes Patients.

Heme


Input: The present study evaluates a hypothesis that sour cherry (Prunus cerasus) seed extracts (SCE) modulate CD3 + T lymphocyte activity in ways predictive of potential for uses of SCE in management of inflammatory diseases.


Input: Peripheral blood mononuclear cells (PBMC) from 12 type 2 diabetes (T2DM) patients and eight healthy control subjects were cultured 24 h with 100 ng/ml lipopolysaccharide (LPS) to increase inflammatory signaling and co-incubated with 0. 5-100 micro g/ml SCE.


Input: Cultures were evaluated by two-color flow cytometry for percent representation of CD3 + IL8 + and CD3 + TNF-alpha + cells which express interleukin-8 (IL-8), and tumor necrosis factor-alpha, (TNF-alpha +) respectively, and by enzyme-linked immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1, known to be induced by SCE).

heme


Input: SCE dosage ranges of 0. 5-100 micro g/ml in cell cultures significantly suppressed LPS-increased CD3 + TNF-alpha + and CD3 + IL8 + representation from all participants (p < 0. 05), with greater pharmacological effect noted in suppression of CD3 + TNF-alpha + noted in cells from T2DM patients versus healthy control subjects.


Input: These effects correlated with increased HO-1 expression in SCE-treated PBMC from all subjects (p < 0. 05).


Input: Since TNF-alpha and IL-8 are diagnostic/prognostic biomarkers for many inflammatory syndromes, the capacity of SCE to down-regulate representation of cells that express them suggests potential for therapeutic use of SCE in T2DM and other diseases.


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


Input: Combined effects of treatment with vitamin C, vitamin E and selenium on the skin of diabetic rats.

vitamin C

vitamin E

selenium


Input: The aim of this study was to investigate the effects of vitamin C, vitamin E and selenium (Se) on the skin tissue of streptozotocin-induced diabetic rats.

vitamin C

vitamin E

selenium

Se

streptozotocin


Input: Swiss albino rats were divided into four groups: control, control + antioxidants, diabetic, diabetic + antioxidants groups.


Input: Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin.

streptozotocin


Input: Vitamin C (250 mg/kg), vitamin E (250 mg/kg) and Se (0. 2 mg/kg) were given by gavage technique to rats of one diabetic and one control group for 30 days.

Vitamin C

vitamin E

Se


Input: In the diabetic group, the levels of serum urea and creatinine, skin lipid peroxidation and nonenzymatic glycosylation levels increased, but skin glutathione levels decreased.

urea

creatinine

glutathione


Input: Treatment with vitamin C, vitamin E and Se reversed these effects.

vitamin C

vitamin E

Se


Input: The present study showed that vitamin C, vitamin E and Se exerted antioxidant effects and consequently may prevent skin damage caused by streptozotocin-induced diabetes.

vitamin C

vitamin E

Se

streptozotocin


Input: Dopamine D 2-agonist rotigotine effects on cortical excitability and central cholinergic transmission in Alzheimer' s disease patients.

Dopamine

rotigotine


Input: Dopamine is a neurotransmitter involved in several brain functions ranging from emotions control, movement organization to memory formation.

Dopamine


Input: It is also involved in the regulation of mechanisms of synaptic plasticity.


Input: However, its role in Alzheimer' s disease (AD) pathogenesis is still puzzling.


Input: Several recent line of research instead indicates a clear role for dopamine in both amyloid beta formation as well as in cognitive decline progression.

dopamine


Input: In particular it has been shown that dopamine D 2-like receptors (namely D 3 and D 2) could be mostly responsible for dopamine dysfunction in AD.

dopamine

dopamine


Input: Here we aimed to study the effects of the dopamine agonist Rotigotine on cortical excitability and on central cholinergic transmission in cases of AD.

dopamine

Rotigotine


Input: Rotigotine is a dopamine agonist with a pharmacological profile with high affinity for D 3 and D 2 receptors.

Rotigotine

dopamine


Input: We used paired pulse protocols assessing short intracortical inhibition (SICI) and intracortical facilitation (ICF) to asses cortical excitability over the primary motor cortex and Short Latency Afferent Inhibition (SLAI) protocols, to verify the effects of the drug on central cholinergic transmission in a group of AD patients compared to age-matched controls.


Input: We observed that rotigotine induces unexpected changes in both cortical excitability (increased) and central cholinergic transmission (restored) of AD patients.

rotigotine


Input: These unexpected effects might depend on the dopamine D 2-like receptors dysfunction previously described in AD brains.

dopamine


Input: The current findings could indicate that future strategies aimed to ameliorate symptoms of the related AD cognitive decline could also involve some dopaminergic drugs.


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


Input: Absorption of TAK-491, a new angiotensin II receptor antagonist, in animals.

angiotensin II


Input: The absorption process in animals of TAK-491, designed as ester-based prodrug with medoxomil moiety, was evaluated.

ester

medoxomil


Input: In the plasma of rats and dogs, TAK-536, the pharmacologically active metabolite, was present as the main component with hardly detectable concentrations of TAK-491 after oral administration of TAK-491.


Input: In the rat portal plasma, TAK-536 was also present as the main component with hardly detectable concentrations of TAK-491 after jejunal loop injection of TAK-491, suggesting TAK-491 was absorbed from small intestine and hydrolyzed almost completely during absorption.


Input: Caco-2 study indicated the permeability of TAK-491 was improved by prodrug modification and the compound could be mainly transferred as TAK-491.


Input: This is well consistent with the facts that the AUC and T (max) of TAK-536 after oral administration of TAK-491 were higher and shorter than those after oral administration of TAK-536 in dogs Hydrolysis of TAK-491 is observed not only by the intestinal and hepatic S9 fraction, but also by plasma and human serum albumin.


Input: However, medoxomil alcohol wasn' t detected during the hydrolysis of TAK-491.

medoxomil alcohol


Input: These metabolic features of TAK-491 were similar to olmesartan medoxomil, suggesting the hydrolytic pathway and enzymes for TAK-491 when catalyzing to TAK-536 would be the same as olmesartan medoxomil.

olmesartan medoxomil

olmesartan medoxomil


Input: Synthesis, characterization, screening and docking analysis of 4-anilinoquinazoline derivatives as tyrosine kinase inhibitors.

tyrosine


Input: We report here the design and synthesis of a series of 4-anilinoquinazoline derivatives, of which 7 compounds were crystallographically characterized, as epidermal growth factor receptor (EGFR) inhibitors by modifications on the aniline ring or at the 6-alkoxy site of the 6, 7-dimethoxy-4-anilinoquinazoline pharmacophore.

aniline

6, 7-dimethoxy-4-anilinoquinazoline


Input: The relative inhibition efficiency on EGFR of all as-prepared compounds were measured and ordered, and the IC50 values of nine highly active compounds were determined by ELISA.


Input: Docking studies indicated that all 4-anilinoquinazoline derivatives could be inserted into the ATP-binding pocket of the EGFR via indirect docking, and that the modifications at the 3'-position of the anilino group and 6-alkoxy site of the quinazoline ring have little interference with the formation of the two essential H-bonds between the N3 of the quinazoline ring and Thr766 through a water molecule, and the N1 of the quinazoline ring and N-H of Met769.

ATP

anilino

quinazoline

H

quinazoline

quinazoline

N-H


Input: The displacing of the phenyl at 4-position with pyridinyl dramatically reduces the activity of the quinazoline pharmacophore, the resulting derivative (10) being the least active compound.

phenyl

pyridinyl

quinazoline


Input: The docking results also showed that the formation of new H-bonds between the N-H of the ethylenediamine group linked to the 6-alkoxy site and Asp776/Cys773 in the binding pocket of EGFR makes compounds 19 (IC50 = 12. 1 +/- 1. 6 nM) and 20 (IC50 = 13. 6 +/- 0. 8 nM) the most potent EGFR inhibitors in this class and worthy of further modification to obtain more potent anticancer compounds.

H

N-H

ethylenediamine


Input: Small molecule modulation of nuclear receptor conformational dynamics: implications for function and drug discovery.


Input: Nuclear receptors are targets for a wide range of ligands, both natural and synthetic, that regulate their activity and provide a means to pharmacologically modulate the receptor.


Input: Recent emphasis in the nuclear receptor field has focused on selective nuclear receptor modulators, which can display graded transcriptional responses and tissue selective pharmacological responses that deviate from the prototypical agonist or antagonist.


Input: Understanding the molecular mechanism of action of these selective modulators will provide significant insight toward the development of the next generation of modulators.


Input: Although most nuclear receptor structural studies have primarily focused on obtaining ligand-receptor cocrystal structures, recent studies implicate an important role for protein dynamics in the mechanism of action of nuclear receptor ligands.


Input: Here we review nuclear receptor studies reporting how ligands modulate the conformational dynamics of the nuclear receptor ligand-binding domain (LBD).


Input: A particular emphasis is placed on protein NMR and hydrogen/deuterium exchange (HDX) techniques and how they provide complementary information that, when combined with crystallography, provide detailed insight into the function of nuclear receptors.

hydrogen

deuterium


Input: Gelucire 44/14 based immediate release formulations for poorly water-soluble drugs.


Input: Here, we aim to evaluate Gelucire 44/14 as non-ionic surface-active excipient to produce immediate-release solid dosage forms for poorly water-soluble drugs.


Input: Gelucires are polyethylene glycol (PEG) glycerides composed of mono-, di-and triglycerides and mono-and diesters of PEG.

polyethylene glycol

PEG

mono-, di-and triglycerides

PEG


Input: They are inert semi-solid waxy amphiphilic excipients with surface-active properties that spontaneously form a fine dispersion or emulsion upon contact with water.


Input: Monolithic Gelucire 44/14 structures are prone to prolonged erosion times, thereby slowing down drug dissolution.


Input: To overcome this issue, we combine either granulation or spray-drying, followed by compression into tablets, with an optimized composition of disintegration promoting agents.


Input: This formulation strategy allows obtaining nearly 100% drug release within 10 min dissolution time.


Input: Modeling the structure and proton transfer pathways of the mutant His-107-Tyr of human carbonic anhydrase II.

His

Tyr


Input: We present molecular modeling of the structure and possible proton transfer pathways from the surface of the protein to the zinc-bound water molecule in the active site of the mutant His-107-Tyr of human carbonic anhydrase II (HCAII).

zinc

His

Tyr


Input: No high-resolution structure or crystal structure is available till now for this particular mutant due to its lack of stability at physiological temperature.


Input: Our analysis utilizes as starting point a series of structures derived from high-resolution crystal structure of the wild type protein.


Input: While many of the structures investigated do not reveal a complete path between the zinc bound water and His-64, several others do indicate the presence of a transient connection even when His-64 is present in its outward conformation.

zinc

His

His


Input: Mutation at the residue 107 also reveals the formation of a new path into the active site.


Input: Competing contributions from His-64 sidechain rotation from its outward conformation are also evaluated in terms of optimal path analysis.

His


Input: No indication of a lower catalytic efficiency of the mutant is evident from our results under the condition of thermal stability of the mutant.


Input: Oxysterol generation and liver X receptor-dependent reverse cholesterol transport: not all roads lead to Rome.

Oxysterol

cholesterol


Input: Cell cholesterol metabolism is a tightly regulated process, dependent in part on activation of nuclear liver X receptors (LXRs) to increase expression of genes mediating removal of excess cholesterol from cells in the reverse cholesterol transport pathway.

cholesterol

cholesterol

cholesterol


Input: LXRs are thought to be activated predominantly by oxysterols generated enzymatically from cholesterol in different cell organelles.

oxysterols

cholesterol


Input: Defects resulting in slowed release of cholesterol from late endosomes and lysosomes or reduction in sterol-27-hydroxylase activity lead to specific blocks in oxysterol production and impaired LXR-dependent gene activation.

cholesterol

sterol

oxysterol


Input: This block does not appear to be compensated by oxysterol production in other cell compartments.

oxysterol


Input: The purpose of this review is to summarize current knowledge about oxysterol-dependent activation by LXR of genes involved in reverse cholesterol transport, and what these defects of cell cholesterol homeostasis can teach us about the critical pathways of oxysterol generation for expression of LXR-dependent genes.

oxysterol

cholesterol

cholesterol

oxysterol


Input: The mGlu 5 positive allosteric modulator LSN2463359 differentially modulates motor, instrumental and cognitive effects of NMDA receptor antagonists in the rat.

NMDA


Input: Metabotropic glutamate 5 (mGlu 5) receptors are known to functionally interact with N-methyl-d-aspartate (NMDA) receptors at both neuronal and behavioural levels, in a manner that may be of relevance to the treatment of schizophrenia.

glutamate

N-methyl-d-aspartate

NMDA


Input: We have previously described a novel mGlu 5 positive allosteric modulator (PAM), LSN2463359 and provided evidence of its ability to attenuate aspects of the behavioural response to administration of the competitive NMDA receptor antagonist, SDZ 220, 581.

NMDA

SDZ 220, 581


Input: In addition, LSN2463359 was found to selectively attenuate reversal learning deficits observed in the neurodevelopmental MAM E17 model but not in the acute phencyclidine (PCP) model.

phencyclidine

PCP


Input: In the present study, the interactions between this mGlu 5 PAM and the NMDA receptor were explored further by assessing the effects of LSN2463359 against some of the motor, instrumental and cognitive effects induced by the non-competitive NMDA receptor antagonists PCP and MK-801, the competitive NMDA receptor antagonist SDZ 220, 581 and the GluN2B selective NMDA receptor antagonist, Ro 63-1908.

NMDA

NMDA

PCP

NMDA

SDZ 220, 581

NMDA

Ro 63-1908


Input: LSN2463359 had either no or minor impact on locomotor hyperactivity induced by either PCP or SDZ 220, 581.

PCP

SDZ 220, 581


Input: However, in rats lever pressing for food rewards under a variable interval 30s schedule of instrumental responding, the drug clearly attenuated not only the suppression of response rate induced by SDZ 220, 581 but also the stimulation of response rate induced by Ro 63-1908.

SDZ 220, 581

Ro 63-1908


Input: In contrast, LSN2463359 failed to alter both of the instrumental effects induced by the open channel blockers PCP and MK-801.

PCP


Input: In addition, although PCP and SDZ 220, 581 induced similar deficits in a discrimination and reversal learning task, LSN2463359 was again only able to reverse the deficit induced by SDZ 220, 581.

PCP

SDZ 220, 581

SDZ 220, 581


Input: The results indicate that the interactions between mGlu 5 and NMDA receptors are dependent on both the mechanism of the blockade of the receptor and the behavioural domain under investigation.

NMDA


Input: Our work has implications for the preclinical use of NMDA receptor antagonists in the prediction of potential therapeutic efficacy in the search for novel treatments for schizophrenia.

NMDA


Input: Positive allosteric modulators of the mGlu 5 receptor certainly question the predictive validity of such approaches.


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


Input: In vitro characterisation of the novel positive allosteric modulators of the mGlu 5 receptor, LSN2463359 and LSN2814617, and their effects on sleep architecture and operant responding in the rat.


Input: The demonstrated functional interaction of metabotropic glutamate 5 (mGlu 5) receptors with N-methyl-d-aspartate (NMDA) receptors has prompted speculation that their activation may offer a potential treatment for aspects of schizophrenia.

glutamate

N-methyl-d-aspartate

NMDA


Input: Development of selective mGlu 5 agonists has been difficult, but several different positive allosteric modulator (PAM) molecules have now been identified.


Input: This study describes two novel mGlu 5 PAMs, LSN2463359 (N-(1-methylethyl)-5-(pyridin-4-ylethynyl) pyridine-2-carboxamide) and LSN2814617 [(7S)-3-tert-butyl-7-[3-(4-fluorophenyl)-1, 2, 4-oxadiazol-5-yl]-5, 6, 7, 8-tetrahydro [1, 2, 4] triazolo [4, 3-A] pyridine], which are useful tools for this field of research.

N-(1-methylethyl)-5-(pyridin-4-ylethynyl) pyridine-2-carboxamide

(7S)-3-tert-butyl-7-[3-(4-fluorophenyl)-1, 2, 4-oxadiazol-5-yl]-5, 6, 7, 8-tetrahydro [1, 2, 4] triazolo [4, 3-A] pyridine


Input: Both compounds are potent and selective potentiators of human and rat mGlu 5 receptors in vitro, displaying curve shift ratios of two to three fold in the concentration-response relationship to glutamate or the glutamate receptor agonist, DHPG, with no detectable intrinsic agonist properties.

glutamate

glutamate

DHPG


Input: Both compounds displaced the mGlu 5 receptor antagonist radioligand, [(3) H] MPEP in vitro and, following oral administration reached brain concentrations sufficient to occupy hippocampal mGlu 5 receptors as measured in vivo by dose-dependent displacement from the hippocampus of intravenously administered MPEPy.

[(3) H] MPEP

MPEPy


Input: In vivo EEG studies demonstrated that these mGlu 5 PAMs have marked wake-promoting properties but little in the way of rebound hypersomnolence.


Input: In contrast, the previously described mGlu 5 PAMs CDPPB and ADX47273 showed relatively poor evidence of in vivo target engagement in either receptor occupancy assays or EEG disturbance.

CDPPB


Input: Wake-promoting doses of LSN2463359 and LSN2814617 attenuated deficits in performance induced by the competitive NMDA receptor antagonist SDZ 220, 581 in two tests of operant behaviour: the variable interval 30 s task and the DMTP task.

NMDA

SDZ 220, 581


Input: These effects were lost if the dose of either compound extended into the range which disrupted performance in the baseline DMTP task.


Input: However, the improvements in response accuracy induced by the mGlu 5 potentiators in SDZ 220, 581-treated rats were not delay-dependent and, therefore, perhaps more likely reflected optimization of general arousal than specific beneficial effects on discrete cognitive processes.

SDZ 220, 581


Input: The systematic profiling of LSN2463359 and LSN2814617 alongside other previously described molecules will help determine more precisely how mGlu 5 potentiator pharmacology might provide therapeutic benefit.


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


Input: The development and application of small molecule modulators of SF3b as therapeutic agents for cancer.


Input: The identification of potent spliceosome modulators that demonstrate antitumor activity indicates that this complex may be a target for drug development.


Input: Several natural products have been demonstrated to bind to the SF3b1 subunit of this macromolecule and these agents modulate alternative RNA splicing.


Input: In this article we describe their biological properties, discuss the validity of the spliceosome as a therapeutic target, and propose that alteration of alternative splicing represents a viable approach for inducing tumor-selective cytotoxicity.


Input: Size of TiO (2) nanoparticles influences their phototoxicity: an in vitro investigation.

TiO (2)


Input: To uncover the size influence of TiO (2) nanoparticles on their potential toxicity, the cytotoxicity of different-sized TiO (2) nanoparticles with and without photoactivation was tested.

TiO (2)

TiO (2)


Input: It was demonstrated that without photoactivation, TiO (2) nanoparticles were inert up to 100 mu g/ml.

TiO (2)


Input: On the contrary, with photoactivation, the toxicity of TiO (2) nanoparticles significantly increased, which correlated well with the specific surface area of the particles.

TiO (2)


Input: Our results also suggest that the generation of hydroxyl radicals and reactive oxygen species (ROS)-mediated damage to the surface-adsorbed biomolecules could be the two major reasons for the cytotoxicity of TiO (2) nanoparticles after photoactivation.

hydroxyl

oxygen

TiO (2)


Input: Higher ROS generation from smaller particles was detected under both biotic and abiotic conditions.


Input: Smaller particles could adsorb more proteins, which was confirmed by thermogravimetric analysis.


Input: To further investigate the influence of the generation of hydroxyl radicals and adsorption of protein, poly (ethylene-alt-maleic anhydride) (PEMA) and chitosan were used to coat TiO (2) nanoparticles.

hydroxyl

poly (ethylene-alt-maleic anhydride)

PEMA

TiO (2)


Input: The results confirmed that surface coating of TiO (2) nanoparticles could reduce such toxicity after photoactivation, by hindering adsorption of biomolecules and generation of hydroxyl radical (. OH) during photoactivation.

TiO (2)

hydroxyl

. OH


Input: Fibroblast growth factor 23 inhibits extrarenal synthesis of 1, 25-dihydroxyvitamin D in human monocytes.

1, 25-dihydroxyvitamin D


Input: Vitamin D is a potent stimulator of monocyte innate immunity, and this effect is mediated via intracrine conversion of 25-hydroxyvitamin D (25OHD) to 1, 25-dihydroxyvitamin D (1, 25 (OH) (2) D).

Vitamin D

25-hydroxyvitamin D

1, 25-dihydroxyvitamin D

1, 25 (OH) (2) D


Input: In the kidney, synthesis of 1, 25 (OH) (2) D is suppressed by fibroblast growth factor 23 (FGF23), via transcriptional suppression of the vitamin D-activating enzyme 1 alpha-hydroxylase (CYP27B1).

1, 25 (OH) (2) D

vitamin D


Input: We hypothesized that FGF23 also suppresses CYP27B1 in monocytes, with concomitant effects on intracrine responses to 1, 25 (OH) (2) D.

1, 25 (OH) (2) D


Input: Healthy donor peripheral blood mononuclear cell monocytes (PBMCm) and peritoneal dialysate monocyte (PDm) effluent from kidney disease patients were assessed at baseline to confirm the presence of mRNA for FGF23 receptors (FGFRs), with Klotho and FGFR1 being more strongly expressed than FGFR2/3/4 in both cell types.


Input: Immunohistochemistry showed coexpression of Klotho and FGFR1 in PBMCm and PDm, with this effect being enhanced following treatment with FGF23 in PBMCm but not PDm.


Input: Treatment with FGF23 activated mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) pathways in PBMCm, demonstrating functional FGFR signaling in these cells.


Input: FGF23 treatment of PBMCm and PDm decreased expression of mRNA for CYP27B1.


Input: In PBMCm this was associated with downregulation of 25OHD to 1, 25 (OH) (2) D metabolism, and concomitant suppression of intracrine induced 24-hydroxylase (CYP24A1) and antibacterial cathelicidin (LL37).

1, 25 (OH) (2) D


Input: FGF23 suppression of CYP27B1 was particularly pronounced in PBMCm treated with interleukin-15 to stimulate synthesis of 1, 25 (OH) (2) D.

1, 25 (OH) (2) D


Input: These data indicate that FGF23 can inhibit extra-renal expression of CYP27B1 and subsequent intracrine responses to 1, 25 (OH) (2) D in two different human monocyte models.

1, 25 (OH) (2) D


Input: Elevated expression of FGF23 may therefore play a crucial role in defining immune responses to vitamin D and this, in turn, may be a key determinant of infection in patients with chronic kidney disease (CKD).

vitamin D


Input: A crown-ether loop-derivatized oligothiophene doubly attached on gold surface as cation-binding switchable molecular junction.

crown-ether

oligothiophene


Input: A crown-ether dithiol quaterthiophene is synthesized and immobilized on gold surface by double covalent fixation.

crown-ether dithiol quaterthiophene


Input: UV-vis spectroscopy and cyclic voltammetry show that the corresponding dithioester precursor can complex Pb (2 +) in solution and that this property is maintained for monolayers of the dithiol on gold.

dithioester

Pb (2 +)

dithiol


Input: Current-voltage measurements by eutectic GaIn drop contact on the monolayer show a significant increase (up to 1. 6 x 10 (3) times) of the current at low bias after Pb (2 +) complexation.

GaIn

Pb (2 +)


Input: Microindentation for in vivo measurement of bone tissue material properties in atypical femoral fracture patients and controls.


Input: Atypical femoral fractures (AFF) associated with long-term bisphosphonates (LTB) are a growing concern.

bisphosphonates


Input: Their etiology is unknown, but bone material properties might be deteriorated.


Input: In an AFF series, we analyzed the bone material properties by microindentation.


Input: Four groups of patients were included: 6 AFF, 38 typical osteoporotic fractures, 6 LTB, and 20 controls without fracture.


Input: Neither typical osteoporotic fractures nor controls have received any antiosteoporotic medication.


Input: A general laboratory workup, bone densitometry by dual-energy X-ray absorptiometry (DXA), and microindentation testing at the tibia were done in all patients.


Input: Total indentation distance (Total ID), indentation distance increase (IDI), and creep indentation distance (Creep ID) were measured (microns).


Input: Age-adjusted analysis of covariance (ANCOVA) was used for comparisons.


Input: Controls were significantly younger than fracture groups.


Input: Bisphosphonate exposure was on average 5. 5 years (range 5 to 12 years) for the AFF and 5. 4 years (range 5 to 8 years) for the LTB groups.

Bisphosphonate


Input: Total ID (microns) showed better material properties (lower Total ID) for controls 36 (+/- 6; mean +/- SD) than for AFF 46 (+/- 4) and for typical femoral fractures 47 (+/- 13), respectively.


Input: Patients on LTB showed values between controls and fractures, 38 (+/- 4), although not significantly different from any of the other three groups.


Input: IDI values showed a similar pattern 13 (+/- 2), 16 (+/- 6), 19 (+/- 3), and 18 (+/- 5).


Input: After adjusting by age, significant differences were seen between controls and typical (p < 0. 001) and atypical fractures (p = 0. 03) for Total ID and for IDI (p < 0. 001 and p < 0. 05, respectively).


Input: There were no differences in Creep ID between groups.


Input: Our data suggest that patients with AFF have a deep deterioration in bone material properties at a tissue level similar to that for the osteoporotic fracture group.


Input: The LTB group shows levels that are in between controls and both type of fractures, although not statistically different.


Input: These results suggest that bisphosphonate therapy probably does not put the majority of patients at risk for AFF.

bisphosphonate


Input: Biotransformation of serotonin derivatives by the larvae of common cutworm (Spodoptera litura).

serotonin


Input: Seven serotonin derivatives (1-7) were biotransformed using larvae of Spodoptera litura.

serotonin


Input: N-p-methoxy cinnamoyl serotonin (3) was converted into its O-demethylated compound, N-p-coumaroyl serotonin (2).

N-p-methoxy cinnamoyl serotonin

O

N-p-coumaroyl serotonin


Input: Furthermore, N-feruloyl serotonin (5) and N-isoferuloyl serotonin (6) were converted into, two new compounds, N-feruloyl serotonin-4'-O-beta-D-glucopyranoside (8) and N-isoferuloyl serotonin-3'-O-beta-D-glucopyranoside (9), respectively.

N-feruloyl serotonin

N-isoferuloyl serotonin

N-feruloyl serotonin-4'-O-beta-D-glucopyranoside

N-isoferuloyl serotonin-3'-O-beta-D-glucopyranoside


Input: These structures were established by IR, 1D-NMR and 2D-NMR spectral studies.


Input: New precursor of tetraterpenoids from the soft coral Sarcophyton glaucum.

tetraterpenoids


Input: One new precursor of tetraterpenoids, Sarglaucol (1), along with eight known compounds have been isolated from the soft coral Sarcophyton glaucum collected from the Sanya Bay, Hainan Island, China.

tetraterpenoids

Sarglaucol


Input: Their structures were elucidated through spectroscopic techniques including 1D-and 2D-NMR, and their relative configurations were also assigned by NMR and NOESY analysis.


Input: Compounds 1 showed weak antitumour activities.


Input: Theoretical study of the decomposition of ethyl and ethyl 3-phenyl glycidate.

ethyl and ethyl 3-phenyl glycidate


Input: The mechanism of the decomposition of ethyl and ethyl 3-phenyl glycidate in gas phase was studied by density functional theory (DFT) and MP2 methods.

ethyl and ethyl 3-phenyl glycidate


Input: A proposed mechanism for the reaction indicates that the ethyl side of the ester is eliminated as ethylene through a concerted six-membered cyclic transition state, and the unstable intermediate glycidic acid decarboxylates rapidly to give the corresponding aldehyde.

ethyl

ethylene

glycidic acid

aldehyde


Input: Two possible pathways for glycidic acid decarboxylation were studied: one via a five-membered cyclic transition state, and the other via a four-membered cyclic transition state.

glycidic acid


Input: The results of the calculations indicate that the decarboxylation reaction occurs via a mechanism with five-membered cyclic transition state.


Input: Coordination and bond activation in complexes of regioisomeric phenylpyridines with the nickel (II) chloride cation in the gas phase.

phenylpyridines

nickel (II) chloride


Input: Electrospray ionization of dilute solutions of phenylpyridines (phpy) in the presence of nickel (II) chloride leads to gaseous ions of the type [Ni (phpy) (m)] (2 +) with m = 3-5 and [NiCl (phpy) (n)] (+) with n = 1-3, which are characterized by various gas-phase experiments in combination with calculations using density functional theory.

phenylpyridines

phpy

nickel (II) chloride

[Ni (phpy) (m)] (2 +)

[NiCl (phpy) (n)] (+)


Input: Of the regioisomeric phpy' s, 2-phpy behaves drastically different compared to 3-and 4-phpy.

phpy

3-and 4-phpy


Input: Ion mobility mass spectrometry allows a differentiation of the gaseous ions and an elucidation of characteristic properties of the metal complexes.


Input: For 2-phpy, C-H bond activation in the [NiCl (phpy) (2)] (+) complex is significant, whereas this route is almost suppressed for the corresponding complexes of 3-and 4-phpy and only occurs at elevated energies.

C-H

[NiCl (phpy) (2)] (+)

3-and 4-phpy


Input: Show me your license, please: deregulation of centriole duplication mechanisms that promote amplification.


Input: Centrosomes are organelles involved in generating and organizing the interphase microtubule cytoskeleton, mitotic spindles and cilia.


Input: At the centrosome core are a pair of centrioles, structures that act as the duplicating elements of this organelle.


Input: Centrioles function to recruit and organize pericentriolar material which nucleates microtubules.


Input: While centrioles are relatively simple in construction, the mechanics of centriole biogenesis remain an important yet poorly understood process.


Input: More mysterious still are the regulatory mechanisms that oversee centriole assembly.


Input: The fidelity of centriole duplication is critical as defects in either the assembly or number of centrioles promote aneuploidy, primary microcephaly, birth defects, ciliopathies and tumorigenesis.


Input: In addition, some pathogens employ mechanisms to promote centriole overduplication to the detriment of the host cell.


Input: This review summarizes our current understanding of this important topic, highlighting the need for further study if new therapeutics are to be developed to treat diseases arising from defects of centrosome duplication.


Input: A significant dose-dependent relationship between mercury exposure from dental amalgams and kidney integrity biomarkers: A further assessment of the Casa Pia children' s dental amalgam trial.

mercury


Input: Dental amalgams are a commonly used dental restorative material.


Input: Amalgams are about 50% mercury (Hg), and Hg is known to significantly accumulate in the kidney.

mercury

Hg

Hg


Input: It was hypothesized that because Hg accumulates in the proximal tubules (PTs), glutathione-S-transferases (GST)-alpha (suggestive of kidney damage at the level of PT) would be expected to be more related to Hg exposure than GST-pi (suggestive of kidney damage at the level of the distal tubules).

Hg

glutathione

S

Hg


Input: Urinary biomarkers of kidney integrity were examined in children of 8-18 years old, with and without dental amalgam fillings, from a completed clinical trial (parent study).


Input: Our study determined whether there was a significant dose-dependent correlation between increasing Hg exposure from dental amalgams and GST-alpha and GST-pi as biomarkers of kidney integrity.

Hg


Input: Overall, the present study, using a different and more sensitive statistical model than the parent study, revealed a statistically significant dose-dependent correlation between cumulative exposure to Hg from dental amalgams and urinary levels of GST-alpha, after covariate adjustment; where as, a nonsignificant relationship was observed with urinary levels of GST-pi.

Hg


Input: Furthermore, it was observed that urinary GST-alpha levels increased by about 10% over the 8-year course of the study among individuals with an average exposure to amalgams among the study subjects from the amalgam group, in comparison with study subjects with no exposure to dental amalgams.


Input: The results of our study suggest that dental amalgams contribute to ongoing kidney damage at the level of the PTs in a dose-dependent fashion.


Input: Emergency Do Not Consume/do Not Use concentrations for potassium permanganate in drinking water.

potassium permanganate


Input: Over the past decade, regulatory authorities and water purveyors have become increasingly concerned with accidental or intentional adulteration of municipal drinking water.


Input: Emergency response guidelines, such as the' Do Not Consume' or use concentration limits derived herein, can be used to notify the public in such cases.


Input: Potassium permanganate (KMnO (4)) is used to control iron concentrations and to reduce the levels of nuisance materials that affect odor or taste of finished drinking water.

Potassium permanganate

KMnO (4)


Input: Manganese (Mn) is recognized an essential nutrient, permanganate (MnO4 (-)) and manganous (Mn (+ 2)) ions are caustic, and the acute toxicity of KMnO (4) is defined by its oxidant/irritant properties and by the toxicity of Mn.

Manganese

Mn

permanganate

MnO4 (-)

manganous

Mn (+ 2)

KMnO (4)

Mn


Input: Ingestion of small amounts (4-20 mg/kg) of aqueous KMnO (4) solutions that are above 200 mg/L causes gastrointestinal distress, while bolus ingestion has caused respiratory arrest following coagulative necrosis and hemorrhage in the esophagus, stomach, or liver.

KMnO (4)


Input: Dilute KMnO (4) solutions (1-100 mg/L) are used as a topical antiseptics and astringents, but > 1: 5000 (200 mg/L) dilutions can irritate or discolor sensitive mucous membranes and direct skin or ocular contact with concentrated KMnO (4) can perforate tissues.

KMnO (4)

KMnO (4)


Input: Based on clinical experience with 200 mg/L KMnO (4), a Do Not Consume concentration of 7 mg/L KMnO (4) (equivalent to 2 mg Mn/L) is recommended.

KMnO (4)

KMnO (4)

Mn


Input: Recognizing limited empirical data from which to calculate an ocular reference value, a skin contact' Do Not Use' concentration of 30 mg Mn/L is recommended based on the skin irritation in some patients after a 10-min contact with 100 mg KMnO4/L.

Mn


Input: Cresyl saligenin phosphate makes multiple adducts on free histidine, but does not form an adduct on histidine 438 of human butyrylcholinesterase.

Cresyl saligenin phosphate

histidine

histidine


Input: Cresyl saligenin phosphate (CBDP) is a suspected causative agent of " aerotoxic syndrome ", affecting pilots, crew members and passengers.

Cresyl saligenin phosphate

CBDP


Input: CBDP is produced in vivo from ortho-containing isomers of tricresyl phosphate (TCP), a component of jet engine lubricants and hydraulic fluids.

CBDP

tricresyl phosphate

TCP


Input: CBDP irreversibly inhibits butyrylcholinesterase (BChE) in human plasma by forming adducts on the active site serine (Ser-198).

CBDP

serine

Ser


Input: Inhibited BChE undergoes aging to release saligenin and o-cresol.

saligenin

o-cresol


Input: The active site histidine (His-438) was hypothesized to abstract o-hydroxybenzyl moiety from the initial adduct on Ser-198.

histidine

His

o-hydroxybenzyl

Ser


Input: Our goal was to test this hypothesis.


Input: Mass spectral analysis of CBDP-inhibited BChE digested with Glu-C showed an o-hydroxybenzyl adduct (+ 106amu) on lysine 499, a residue far from the active site, but not on His-438.

CBDP

Glu

o-hydroxybenzyl

lysine

His


Input: Nevertheless, the nitrogen of the imidazole ring of free l-histidine formed a variety of adducts upon reaction with CBDP, including the o-hydroxybenzyl adduct, suggesting that histidine-CBDP adducts may form on other proteins.

nitrogen

imidazole

l-histidine

CBDP

o-hydroxybenzyl

histidine

CBDP


Input: Training your brain: Do mental and physical (MAP) training enhance cognition through the process of neurogenesis in the hippocampus?


Input: New neurons are produced each day in the hippocampus through the process of neurogenesis.


Input: Both mental and physical training can modify this process by increasing the number of new cells that mature into functional neurons in the adult brain.


Input: However, the mechanisms whereby these increases occur are not necessarily the same.


Input: Physical activity, especially aerobic exercise greatly increases the number of new neurons that are produced in the hippocampal formation.


Input: In contrast, mental training via skill learning increases the numbers that survive, particularly when the training goals are challenging.


Input: Both manipulations can increase cognitive performance in the future, some of which are reportedly mediated by the presence of new neurons in the adult hippocampus.


Input: Based on these data, we suggest that a combination of mental and physical training, referred to here as MAP training, is more beneficial for neuronal recruitment and overall mental health than either activity alone.


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


Input: Organochlorine pesticide levels and risk of Alzheimer' s disease in north Indian population.

Organochlorine


Input: Alzheimer' s disease (AD) could result from a multifactorial process involving both genetic predisposition and exposure to environmental factors like pesticides.


Input: A case control study of 70 patients of AD and 75 controls was done to examine the association between organochlorine pesticides (OCPs) and risk of AD.

organochlorine


Input: OCPs (hexachlorocyclohexane (HCH), aldrin, dieldrin, endosulfan, pp'-dichlorodiphenyldichloroethylene (pp'-DDE), op'-DDE, pp'-dichlorodiphenyltrichloroethane (pp'-DDT), op'-DDT, pp'-dichlorodiphenyldichloroethane (pp'-DDD) and op'-DDD) were extracted from blood and quantitatively estimated using gas chromatography.

hexachlorocyclohexane

HCH

aldrin

dieldrin

endosulfan

pp'-dichlorodiphenyldichloroethylene

pp'-DDE

op'-DDE

pp'-dichlorodiphenyltrichloroethane

pp'-DDT

op'-DDT

pp'-dichlorodiphenyldichloroethane

pp'-DDD

op'-DDD


Input: A Mann-Whitney U test revealed significant difference in beta-HCH levels (U = 1237. 00, W = 4087. 00, z =-6. 296, p = 0. 000, r =-0. 71), dieldrin levels (U = 1449. 00, W = 4299. 00, z =-5. 809, p = 0. 000, r =-0. 68) and pp'-DDE levels (U = 2062. 00, W = 4912. 00, z =-2. 698, p = 0. 007, r =-0. 59) between AD patients and controls.

beta-HCH

dieldrin

pp'-DDE


Input: In conclusion, this study supports epidemiological studies that associate exposure to pesticides with increased risk of AD, and we identified the specific pesticides beta-HCH, dieldrin and pp'-DDE that are associated with the risk of AD in the north Indian population.

beta-HCH

dieldrin

pp'-DDE


Input: However, further research is needed to establish the potential role of these OCPs as an etiologic agent for AD case.


Input: Therapeutic efficacy of silymarin from milk thistle in reducing manganese-induced hepatic damage and apoptosis in rats.

manganese


Input: Oxidative stress has been proposed as a possible mechanism involved in manganese (Mn) toxicity.

manganese

Mn


Input: Using natural antioxidants against metal-induced hepatotoxicity is a modern approach.


Input: The present study investigated the beneficial role of silymarin, a natural flavonoid, in Mn-induced hepatotoxicity focusing on histopathology and biochemical approaches.

flavonoid

Mn


Input: Male Wistar rats were exposed orally to manganese chloride (20 mg/mL) for 30 days followed by intraperitoneal cotreatment with silymarin (100 mg/kg).

manganese chloride


Input: Exposure to Mn resulted in a significant elevation of the plasma marker enzyme activities and bilirubin level related to liver dysfunction of reactive oxygen species (ROS) production and hepatic oxidative stress indices.

Mn

bilirubin

oxygen


Input: This metal reduced the activities of superoxide dismutase, catalase and glutathione peroxidase and nonenzymatic antioxidant levels such as reduced glutathione, total sulfhydryl groups and vitamin C.

superoxide

glutathione

glutathione

sulfhydryl

vitamin C


Input: In addition, it caused hepatic hemorrhage, cellular degeneration and necrosis of hepatocytes as indicated by liver histopathology and DNA fragmentation studies.


Input: Coadministration of silymarin alleviated Mn oxidative damage effects by inhibiting ROS generation.

Mn


Input: Histological studies also supported the beneficial role of silymarin against Mn-induced hepatic damages.

Mn


Input: Combining all, results suggested that silymarin could protect hepatic tissues against Mn-induced oxidative stress probably through its antioxidant activity.

Mn


Input: Therefore, its supplementation could provide a new approach for the reduction in hepatic complication due to Mn poisoning.

Mn


Input: Effect of copper overload on the survival of HepG2 and A-549 human-derived cells.

copper


Input: We investigated the effect of copper (Cu) overload (20-160 micro M/24 h) in two cell lines of human hepatic (HepG2) and pulmonary (A-549) origin by determining lipid and protein damage and the response of the antioxidant defence system.

copper

Cu


Input: A-549 cells were more sensitive to Cu overload than HepG2 cells.

Cu


Input: A marked increase was observed in both the cell lines in the nitrate plus nitrite concentration, protein carbonyls and thiobarbituric acid reactive substances (TBARS).

nitrate

nitrite

carbonyls

thiobarbituric acid


Input: The TBARS increase was consistent with an increment in saturated fatty acids at the expense of polyunsaturated acids in a Cu concentration-dependent fashion.

saturated fatty acids

Cu


Input: Antioxidant enzymes were stimulated by Cu overload.

Cu


Input: Superoxide dismutase activity increased significantly in both the cell lines, with greater increases in HepG2 than in A-549 cells.

Superoxide


Input: A marked increase in ceruloplasmin and metallothionein content in both the cell types was also observed.


Input: Dose-dependent decreases in alpha-tocopherol and ferric reducing ability were observed.

alpha-tocopherol

ferric


Input: Total glutathione content was lower in A-549 cells and higher in HepG2.

glutathione


Input: Calpain and caspase-3 were differentially activated in a dose-dependent manner under copper-induced reactive oxygen species production.

copper

oxygen


Input: We conclude that Cu exposure of human lung-and liver-derived cells should be considered a reliable experimental system for detailed study of mechanism/mechanisms by which Cu overload exerts its deleterious effects.

Cu

Cu


Input: A human hemi-cornea model for eye irritation testing: quality control of production, reliability and predictive capacity.


Input: We have developed a 3-dimensional human hemi-cornea which comprises an immortalized epithelial cell line and keratocytes embedded in a collagen stroma.


Input: In the present study, we have used MTT reduction of the whole tissue to clarify whether the production of this complex 3-D-model is transferable into other laboratories and whether these tissues can be constructed reproducibly.

MTT


Input: Our results demonstrate the reproducible production of the hemi-cornea model according to standard operation procedures using 15 independent batches of reconstructed hemi-cornea models in two independent laboratories each.


Input: Furthermore, the hemi-cornea tissues have been treated with 20 chemicals of different eye-irritating potential under blind conditions to assess the performance and limitations of our test system comparing three different prediction models.


Input: The most suitable prediction model revealed an overall in vitro-in vivo concordance of 80% and 70% in the participating laboratories, respectively, and an inter-laboratory concordance of 80%.


Input: Sensitivity of the test was 77% and specificity was between 57% and 86% to discriminate classified from non-classified chemicals.


Input: We conclude that additional physiologically relevant endpoints in both epithelium and stroma have to be developed for the reliable prediction of all GHS classes of eye irritation in one stand alone test system.


Input: High levels of arachidonic acid and peroxisome proliferator-activated receptor-alpha in breast cancer tissues are associated with promoting cancer cell proliferation.

arachidonic acid


Input: Fatty acids are endogenous ligands of peroxisome proliferator-activated receptor-alpha (PPAR alpha), which is linked to the regulation of fatty acid uptake, lipid metabolism and breast cancer cell growth.

Fatty acids

fatty acid


Input: This study was designed to screen candidate fatty acids from breast cancer tissue and to investigate the effects of these candidate fatty acids on PPAR alpha expression, cell growth and cell cycle progression in breast cancer cell lines.

fatty acids

fatty acids


Input: One breast cancer tissue and one reference tissue were each taken from 30 individual breasts to examine for fatty acid composition and PPAR alpha expression.

fatty acid


Input: The cancer cell lines MDA-MB-231 (ER-), MCF-7 (ER + + + +) and BT-474 (ER + +) were used to explore the mechanisms regulating cell proliferation.


Input: We found that arachidonic acid (AA) and PPAR alpha were highly expressed in the breast cancer tissues.

arachidonic acid


Input: AA stimulated the growth of all three breast cancer cells in a time-and dose-dependent manner.


Input: The growth stimulatory effect of AA was associated with PPAR alpha activation, and the most potent effect was found in MCF-7 cells.


Input: The stimulation of cell proliferation by AA was accompanied by the increased expression of cyclin E, a reduced population of G1 phase cells, and a faster G1/S phase transition.


Input: In contrast, AA had no effects on the levels of CDK2, CDK4, cyclin D1, p27, Bcl-2 and Bax.


Input: Our results demonstrate that high levels of AA and PPAR alpha expression in human breast cancer tissues are associated with ER-overexpressed breast cancer cell proliferation, which is involved in activating PPAR alpha, stimulating cyclin E expression, and promoting faster G1/S transition.


Input: Vitamin E deficiency impairs the somatostatinergic receptor-effector system and leads to phosphotyrosine phosphatase overactivation and cell death in the rat hippocampus.

Vitamin E

phosphotyrosine


Input: Vitamin E plays an essential role in maintaining the structure and function of the nervous system, and its deficiency, commonly associated with fat malabsorption diseases, may reduce neuronal survival.

Vitamin E


Input: We previously demonstrated that the somatostatinergic system, implicated in neuronal survival control, can be modulated by alpha-tocopherol in the rat dentate gyrus, increasing cyclic adenosine monophosphate response element binding protein phosphorylation.

alpha-tocopherol

cyclic adenosine monophosphate


Input: To gain a better understanding of the molecular actions of tocopherols and examine the link among vitamin E, somatostatin and neuronal survival, we have investigated the effects of a deficiency and subsequent administration of tocopherol on the somatostatin signaling pathway and neuronal survival in the rat hippocampus.

tocopherols

vitamin E

somatostatin

tocopherol

somatostatin


Input: No changes in somatostatin expression were detected in vitamin-E-deficient rats.

somatostatin

vitamin-E


Input: These rats, however, showed a significant increase in the somatostatin receptor density and dissociation constant, which correlated with a significant increase in the protein levels of somatostatin receptors.

somatostatin

somatostatin


Input: Nevertheless, vitamin E deficiency impaired the ability of the somatostatin receptors to couple to the effectors adenylyl cyclase and phosphotyrosine phosphatase by diminishing Gi protein functionality.

vitamin E

somatostatin

adenylyl

phosphotyrosine


Input: Furthermore, vitamin E deficiency significantly increased phosphotyrosine phosphatase activity and PTP eta expression, as well as PKC delta activation, and decreased extracellular-signal-regulated kinase phosphorylation.

vitamin E

phosphotyrosine


Input: All these changes were accompanied by an increase in neuronal cell death.


Input: Subsequent alpha-tocopherol administration partially or completely reversed all these values to control levels.

alpha-tocopherol


Input: Altogether, our results prove the importance of vitamin E homeostasis in the somatostatin receptor-effector system and suggest a possible mechanism by which this vitamin may regulate the neuronal cell survival in the adult hippocampus.

vitamin E

somatostatin


Input: Emergence of zebrafish models in oncology for validating novel anticancer drug targets and nanomaterials.


Input: The in vivo zebrafish models have recently attracted great attention in molecular oncology to investigate multiple genetic alterations associated with the development of human cancers and validate novel anticancer drug targets.


Input: Particularly, the transparent zebrafish models can be used as a xenotransplantation system to rapidly assess the tumorigenicity and metastatic behavior of cancer stem and/or progenitor cells and their progenies.


Input: Moreover, the zebrafish models have emerged as powerful tools for an in vivo testing of novel anticancer agents and nanomaterials for counteracting tumor formation and metastases and improving the efficacy of current radiation and chemotherapeutic treatments against aggressive, metastatic and lethal cancers.


Input: Skin phototoxicity of cosmetic formulations containing photounstable and photostable UV-filters and vitamin A palmitate.

vitamin A palmitate


Input: The aim of this study was to evaluate the in vitro skin phototoxicity of cosmetic formulations containing photounstable and photostable UV-filters and vitamin A palmitate, assessed by two in vitro techniques: 3T3 Neutral Red Uptake Phototoxicity Test and Human 3-D Skin Model In Vitro Phototoxicity Test.

vitamin A palmitate


Input: For this, four different formulations containing vitamin A palmitate and different UV-filters combinations, two of them considered photostable and two of them considered photounstable, were prepared.

vitamin A palmitate


Input: Solutions of each UV-filter and vitamin under study and solutions of four different combinations under study were also prepared.


Input: The phototoxicity was assessed in vitro by the 3T3 NRU phototoxicity test (3T3-NRU-PT) and subsequently in a phototoxicity test on reconstructed human skin model (H3D-PT).


Input: Avobenzone presented a pronounced phototoxicity and vitamin A presented a tendency to a weak phototoxic potential.

Avobenzone

vitamin A


Input: A synergistic effect of vitamin A palmitate on the phototoxicity of combinations containing avobenzone was observed.

vitamin A palmitate

avobenzone


Input: H3D-PT results did not confirm the positive 3T3-NRU-PT results.


Input: However, despite the four formulations studied did not present any acute phototoxicity potential, the combination 2 containing octyl methoxycinnamate (OMC), avobenzone (AVB) and 4-methylbenzilidene camphor (MBC) presented an indication of phototoxicity that should be better investigated in terms of the frequency of photoallergic or chronic phototoxicity in humans, once these tests are scientifically validated only to detect phototoxic potential with the aim of preventing phototoxic reactions in the general population, and positive results cannot predict the exact incidence of phototoxic reactions in humans.

octyl methoxycinnamate

OMC

avobenzone

AVB

4-methylbenzilidene camphor

MBC


Input: Improved procedures for in vitro skin irritation testing of sticky and greasy natural botanicals.


Input: Skin irritation evaluation is an important endpoint for the safety assessment of cosmetic ingredients required by various regulatory authorities for notification and/or import of test substances.


Input: The present study was undertaken to investigate possible protocol adaptations of the currently validated in vitro skin irritation test methods based on reconstructed human epidermis (RhE) for the testing of plant extracts and natural botanicals.


Input: Due to their specific physico-chemical properties, such as lipophilicity, sticky/buttery-like texture, waxy/creamy foam characteristics, normal washing procedures can lead to an incomplete removal of these materials and/or to mechanical damage to the tissues, resulting in an impaired prediction of the true skin irritation potential of the materials.


Input: For this reason different refined washing procedures were evaluated for their ability to ensure appropriate removal of greasy and sticky substances while not altering the normal responses of the validated RhE test method.


Input: Amongst the different procedures evaluated, the use of a SDS 0. 1% PBS solution to remove the sticky and greasy test material prior to the normal washing procedures was found to be the most suitable adaptation to ensure efficient removal of greasy and sticky in-house controls without affecting the results of the negative control.

SDS


Input: The predictive capacity of the refined SDS 0. 1% washing procedure, was investigated by using twelve oily and viscous compounds having known skin irritation effects supported by raw and/or peer reviewed in vivo data.

SDS


Input: The normal washing procedure resulted in 8 out of 10 correctly predicted compounds as compared to 9 out of 10 with the refined washing procedures, showing an increase in the predictive ability of the assay.


Input: The refined washing procedure allowed to correctly identify all in vivo skin irritant materials showing the same sensitivity as the normal washing procedures, and further increased the specificity of the assay from 5 to 6 correct predictions out of 7 non irritants as compared to the normal washing procedures.


Input: In addition, when exposed to non-irritant oily and viscous materials, tissues rinsed with 0. 1% SDS generally showed increased viabilities accompanied by decreased variabilities as compared to the normal washing procedures.

SDS


Input: Similar results were obtained when testing typical in-house natural botanical ingredients.


Input: In conclusion, the use of a refined washing procedure making use of SDS 0. 1% in PBS was found a suitable procedure to ensure efficient removal of greasy and sticky materials, leading to an increased predictive capacity and decreased variability of the tissue responses while maintaining its sensitivity and not affecting untreated tissues morphology and viability.

SDS


Input: Photochromic materials: more than meets the eye.


Input: Photochromic materials are a family of compounds which can undergo reversible photo-switches between two different states or isomers with remarkably different properties.


Input: Inspired by their smart photo-switchable characteristics, a variety of light-driven functional materials have been exploited, such as ultrahigh-density optical data storage, molecular switches, logic gates, molecular wires, optic/electronic devices, sensors, bio-imaging and so on.


Input: This review commences with a brief description of exciting progress in this field, from systems in solution to modified functional surfaces.


Input: Further development of these photo-switchable systems into practical applications as well as existing challenges are also discussed and put in prospect.


Input: Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats.

glutamate

sodium lactate


Input: Rats with chronic inhibition of GABA synthesis by infusion of l-allyglycine, a glutamic acid decarboxylase inhibitor, into their dorsomedial/perifornical hypothalamus are anxious and exhibit panic-like cardio-respiratory responses to treatment with intravenous (i. v.) sodium lactate (NaLac) infusions, in a manner similar to what occurs in patients with panic disorder.

GABA

l-allyglycine

glutamic acid

sodium lactate

NaLac


Input: We previously showed that either NMDA receptor antagonists or metabotropic glutamate receptor type 2/3 receptor agonists can block such a NaLac response, suggesting that a glutamate mechanism is contributing to this panic-like state.

NMDA

glutamate

NaLac

glutamate


Input: Using this animal model of panic, we tested the efficacy of CBiPES and THIIC, which are selective group II metabotropic glutamate type 2 receptor allosteric potentiators (at 10-30 mg/kg i. p.), in preventing NaLac-induced panic-like behavioral and cardiovascular responses.

CBiPES

THIIC

glutamate

NaLac


Input: The positive control was alprazolam (3mg/kg i. p.), a clinically effective anti-panic benzodiazepine.

alprazolam

benzodiazepine


Input: As predicted, panic-prone rats given a NaLac challenge displayed NaLac-induced panic-like cardiovascular (i. e. tachycardia and hypertensive) responses and " anxiety " (i. e. decreased social interaction time) and " flight " (i. e. increased locomotion)-associated behaviors; however, systemic injection of the panic-prone rats with CBiPES, THIIC or alprazolam prior to the NaLac dose blocked all NaLac-induced panic-like behaviors and cardiovascular responses.

NaLac

NaLac

CBiPES

THIIC

alprazolam

NaLac

NaLac


Input: These data suggested that in a rat animal model, selective group II metabotropic glutamate type 2 receptor allosteric potentiators show an anti-panic efficacy similar to alprazolam.

glutamate

alprazolam


Input: High multivitamin intakes during pregnancy and postweaning obesogenic diets interact to affect the relationship between expression of PPAR genes and glucose regulation in the offspring.

glucose


Input: High multivitamin intake (HV) during pregnancy increases body fat and weight and alters glucose and fatty acid metabolism in Wistar rat offspring.

glucose

fatty acid


Input: This study investigated the expression of peroxisome-proliferator activated receptors (PPARs) genes involved in regulation of glucose and fatty acid metabolism in their tissues.

glucose

fatty acid


Input: Dams received the AIN-93G diet with either the regular (RV) or 10-fold multivitamins (HV) during pregnancy.


Input: Male offspring were weaned to either the RV diet (RV-RV and HV-RV) or an obesogenic diet (RV-Ob and HV-Ob).