Input: Models to predict intestinal absorption of therapeutic peptides and proteins.


Input: Prediction of human intestinal absorption is a major goal in the design, optimization, and selection of drugs intended for oral delivery, in particular proteins, which possess intrinsic poor transport across intestinal epithelium.


Input: There are various techniques currently employed to evaluate the extension of protein absorption in the different phases of drug discovery and development.


Input: Screening protocols to evaluate protein absorption include a range of preclinical methodologies like in silico, in vitro, in situ, ex vivo and in vivo.


Input: It is the careful and critical use of these techniques that can help to identify drug candidates, which most probably will be well absorbed from the human intestinal tract.


Input: It is well recognized that the human intestinal permeability cannot be accurately predicted based on a single preclinical method.


Input: However, the present social and scientific concerns about the animal well care as well as the pharmaceutical industries need for rapid, cheap and reliable models predicting bioavailability give reasons for using methods providing an appropriate correlation between results of in vivo and in vitro drug absorption.


Input: The aim of this review is to describe and compare in silico, in vitro, in situ, ex vivo and in vivo methods used to predict human intestinal absorption, giving a special attention to the intestinal absorption of therapeutic peptides and proteins.


Input: Serotonin receptor 2A (HTR2A) gene polymorphism predicts treatment response to venlafaxine XR in generalized anxiety disorder.

Serotonin

venlafaxine XR


Input: Generalized anxiety disorder (GAD) is a chronic psychiatric disorder with significant morbidity and mortality.


Input: Antidepressant drugs are the preferred choice for treatment; however, treatment response is often variable.


Input: Several studies in major depression have implicated a role of the serotonin receptor gene (HTR2A) in treatment response to antidepressants.

serotonin


Input: We tested the hypothesis that the genetic polymorphism rs7997012 in the HTR2A gene predicts treatment outcome in GAD patients treated with venlafaxine XR.

venlafaxine XR


Input: Treatment response was assessed in 156 patients that participated in a 6-month open-label clinical trial of venlafaxine XR for GAD.

venlafaxine XR


Input: Primary analysis included Hamilton Anxiety Scale (HAM-A) reduction at 6 months.


Input: Secondary outcome measure was the Clinical Global Impression of Improvement (CGI-I) score at 6 months.


Input: Genotype and allele frequencies were compared between groups using chi (2) contingency analysis.


Input: The frequency of the G-allele differed significantly between responders (70%) and nonresponders (56%) at 6 months (P = 0. 05) using the HAM-A scale as outcome measure.


Input: Similarly, using the CGI-I as outcome, the G-allele was significantly associated with improvement (P = 0. 01).


Input: Assuming a dominant effect of the G-allele, improvement differed significantly between groups (P = 0. 001, odds ratio = 4. 72).


Input: Similar trends were observed for remission although not statistically significant.


Input: We show for the first time a pharmacogenetic effect of the HTR2A rs7997012 variant in anxiety disorders, suggesting that pharmacogenetic effects cross diagnostic categories.


Input: Our data document that individuals with the HTR2A rs7997012 single nucleotide polymorphism G-allele have better treatment outcome over time.


Input: Future studies with larger sample sizes are necessary to further characterize this effect in treatment response to antidepressants in GAD.


Input: Pollutant concentrations in placenta.


Input: Unborn children are exposed to environmental pollutants via the placenta, and there is a causal relationship between maternal intake of pollutants and fetal exposure.


Input: Placental examination is an effective way for acquiring data for estimating fetal exposure.


Input: We analyzed the concentrations of 104 congeners of persistent organic pollutants, seven organotin compounds, five heavy metals, and methylmercury in 130 randomly selected placentas.

methylmercury


Input: Additionally, we examined similarities between pollutant concentrations by analyzing correlations between their placental concentrations.


Input: Our results yield new information for conducting contaminant risk assessments for the prenatal period.


Input: Out of the 117 individual persistent organic pollutants or metals assayed, 46 could be detected in more than half of the placentas.


Input: Moreover, dichlorodiphenyldichloroethylene (p, p'-DDE) was found in all placentas.

dichlorodiphenyldichloroethylene

p, p'-DDE


Input: The data indicates that fetal exposure to dioxins and furans (PCDD/Fs), polychlorinated biphenyls (PCBs), p, p'-DDE, and methylmercury depends on the mother' s parity, and age.

dioxins

furans

PCDD

polychlorinated biphenyls

PCBs

p, p'-DDE

methylmercury


Input: We also conclude that sources of the above four pollutants are similar but differ from the sources of polybrominated diphenyl ethers.

polybrominated diphenyl ethers


Input: Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment.


Input: The fish ingredient N3-docosahexaenoic acid 22: 6 n-3 (DHA) stimulates brain development.

N3-docosahexaenoic acid

DHA


Input: On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system.

methylmercury

MeHg


Input: In this Context the IQ score in children is considered as an aggregate measure of in utero brain development.


Input: To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children.

DHA

DHA


Input: For MeHg the maternal intake was converted into its accumulation in the maternal body.

MeHg


Input: The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score.


Input: Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified.

MeHg

DHA


Input: For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA.

MeHg

DHA


Input: In the case of long-living predators a negative effect up to 10 points on the IQ score was found.


Input: The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content.

DHA

MeHg


Input: Tissues distribution of heavy metals and erythrocytes antioxidant status in rats exposed to Nigerian bonny light crude oil.


Input: The harmful effects of folkloric uses of Nigerian bonny light crude oil (BLCO) in ailments management may outweigh the expected beneficial effects.


Input: We investigated the levels of heavy metal concentrations in the tissues as well as the effect of BLCO on the antioxidant status of erythrocytes of rats after oral exposure to 0, 200 and 800 mg/kg BLCO for 7 days.


Input: Analysis of heavy metal concentrations in BLCO showed that Zn > Fe > Pb > Cu > Ni.

Zn

Fe

Pb

Cu

Ni


Input: The trend of accumulation of the metals in the tissues is blood-Fe > Pb > Zn whereas Cu and Ni levels were not affected; Liver-Ni > Zn > Fe > Cu > Pb and Testes-Ni > Cu > Pb > Zn > Fe.

Fe

Pb

Zn

Cu

Ni

Ni

Zn

Fe

Cu

Pb

Ni

Cu

Pb

Zn

Fe


Input: The order of concentration of the metals in the tissues is as follows: iron-blood > liver > testes; zinc-liver > blood > testes; lead-blood > liver > testes; copper-testes > liver > blood; nickel-liver > testes > blood.

iron

zinc

copper

nickel


Input: Activities of the antioxidant enzymes of erythrocytes such as superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase increased significantly in a dose-dependent manner with significant elevation in hydrogen peroxide and malondialdehyde levels, whereas glutathione level was not significantly decreased in BLCO-treated animals.

superoxide

glutathione S

glutathione

hydrogen peroxide

malondialdehyde

glutathione


Input: Collectively, the results showed that BLCO induces oxidative damage to erythrocytes of rats.


Input: Pharmacogenetic predictors for EGFR-inhibitor-associated skin toxicity.


Input: The aim of this study was to investigate pharmacogenetic determinants of skin rash associated with epidermal growth factor receptor (EGFR) inhibitor treatment.


Input: A total of 109 prospectively sampled cancer patients, receiving the first treatment with an EGFR inhibitor, were genotyped for functional EGFR polymorphisms and tagging variants in genes involved in receptor downstream signaling.


Input: Skin rash was absent in 26 (23. 9%) patients and associated with shorter overall survival compared with patients presenting skin rash (P = 0. 005).


Input: The EGFR polymorphisms, 497G/A (P = 0. 008), and the haplotypes of the promoter variants, EGFR-216G/T and-191C/A (P = 0. 029), were associated with the appearance of skin rash.


Input: In addition, a common haplotype in the PIK3CA gene was associated with skin rash (P = 0. 045) and overall survival (P = 0. 009).


Input: In conclusion, genetic variation within the EGFR gene and its downstream signaling partner PIK3CA might predict EGFR-inhibitor-related skin rash.


Input: Volatile compound in cut and un-cut flowers of tetraploid Freesia hybrida.


Input: The flower volatile compounds (FVCs) of two tetraploid Freesia hybrida (pink-yellow and yellow) cultivars and their cut flowers were analysed by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry.


Input: Twelve FVCs were identified in the pink-yellow cultivar, with linalool as the major compound; 30 FVCs were identified in the yellow cultivar, with linalool and terpineol as the two major compounds.

linalool

linalool

terpineol


Input: The FVCs (> 1%) of the two cut flower cultivars were very similar to that of the un-cut flowers, and no significant difference was observed.


Input: Volatile organic compounds of Schenella pityophilus.


Input: Volatile organic compounds of Schenella pityophilus have been identified via solid-phase microextraction-gas chromatography-mass spectrometry analysis.


Input: Ten compounds have been identified, in which 3-methylthio-1-propene was the most significant component.


Input: Some other components were previously identified in Tuber aestivum and Tuber melanosporum.


Input: Diclavatol and tetronic acids from Penicillium griseoroseum.

Diclavatol

tetronic acids


Input: In our continuous studies on the chemistry of the endophytic fungus Penicillium griseoroseum, an endophyte isolated from fruits of Coffea arabica, we isolated clavatol, a dimethylated tetraketide, and its dimer which appears to be a novel natural compound.

clavatol

dimethylated tetraketide


Input: The studies also resulted in the identification of two known tetronic acids, viridicatic acid and terrestric acid, found in ethyl acetate and n-butanol extracts.

tetronic acids

viridicatic acid

terrestric acid

ethyl acetate

n-butanol


Input: Spectroscopic studies using 1-D and 2-D NMR and MS/MS analysis were performed to determine the structures of these compounds, first reported by this Penicillium.


Input: Two other tetronic acids congeners were identified through HPLC/MS/MS studies, based on fragmentation pattern of ions produced from ionised tetronic acids, and UV light absorptions.

tetronic acids

tetronic acids


Input: A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus.


Input: Adenovirus serotype 5 (Ad5) is frequently used as an effective vector for induction of therapeutic transgenes in cancer gene therapy or of tumor cell lysis in oncolytic virotherapy.


Input: Ad5 can infect target cells through binding with the coxsackie and adenovirus receptor (CAR).


Input: Thus, the infectious ability of Ad5-based vectors depends on the CAR expression level in target cells.


Input: There are conventional methods to evaluate the CAR expression level in human target cells, including flow cytometry, western blotting and immunohistochemistry.


Input: Here, we show a simple system for detection and assessment of functional CAR expression in human tumor cells, using the green fluorescent protein (GFP)-expressing telomerase-specific replication-competent adenovirus OBP-401.


Input: OBP-401 infection induced detectable GFP expression in CAR-expressing tumor cells, but not in CAR-negative tumor cells, nor in CAR-positive normal fibroblasts, 24 h after infection.


Input: OBP-401-mediated GFP expression was significantly associated with CAR expression in tumor cells.


Input: OBP-401 infection detected tumor cells with low CAR expression more efficiently than conventional methods.


Input: OBP-401 also distinguished CAR-positive tumor tissues from CAR-negative tumor and normal tissues in biopsy samples.


Input: These results suggest that GFP-expressing telomerase-specific replication-competent adenovirus is a very potent diagnostic tool for assessment of functional CAR expression in tumor cells for Ad5-based antitumor therapy.


Input: Chemical composition and antioxidant activity of the essential oil of Tabernaemontana catharinensis A.


Input: DC. leaves.


Input: The essential oils obtained by hydrodistillation from the leaves of Tabernaemontana catharinensis had their composition analysed by GC-MS.


Input: A total of 18 substances were identified, consisting of a complex mixture of sesquiterpenes (83. 52%), monoterpenes (5. 46%) and triterpenes (4. 56%).

sesquiterpenes

monoterpenes

triterpenes


Input: The main components in the oil were beta-caryophyllene (56. 87%), alpha-cadinol (12. 52%), 8S, 13-cedran-diol (5. 41%), alpha-terpineol (3. 99%), beta-eudesmol (2. 54%), caryophyllene oxide (2. 51%) and ethyl iso-allocholate (2. 03%) along with beta-cubebene, gamma-cadinene, cubenol, 1, 8-cineol, o-cymene, curcumenol, spathulenol, friedeline and beta-sitosterol as minor constituents.

beta-caryophyllene

alpha-cadinol

8S, 13-cedran-diol

alpha-terpineol

beta-eudesmol

caryophyllene oxide

ethyl iso-allocholate

beta-cubebene

gamma-cadinene

cubenol

1, 8-cineol

o-cymene

curcumenol

spathulenol

friedeline

beta-sitosterol


Input: An antioxidant property was tested with the oil obtained by means of 1, 1-diphenyl-2-picrylhydrazyl assay; the oil presented interesting radical scavenging activity.

1, 1-diphenyl-2-picrylhydrazyl


Input: To the best of our knowledge, this is the first study of the composition and antioxidant activity of essential oil from the T. catharinensis collected from Brazil.


Input: Green tea extract alleviates arsenic-induced biochemical toxicity and lipid peroxidation in rats.

arsenic


Input: The present work was undertaken to evaluate the protective effect of an aqueous extract of green tea (GT, Camellia sinensis) leaves against arsenic (NaAsO2)-induced biochemical toxicity and lipid peroxidation production in experimental rats.

arsenic


Input: The treatment with arsenic exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine).

arsenic

alanine

aspartate

bilirubin

cholesterol

urea

creatinine


Input: But the co-administration of GT has increased the level of plasmatic concentration of biochemical parameters.


Input: Exposure of rats to arsenic caused also a significant increase in liver, kidney and testicular thiobarbituric acid reactive substances compared to control.

arsenic

thiobarbituric acid


Input: However, the co-administration of GT was effective in reducing its level.


Input: To conclude, our data suggest that arsenic exposure enhanced an oxidative stress by disturbing the tissue antioxidant defense system, but the GT co-administration alleviates the toxicity induced by arsenic exposure.

arsenic

arsenic


Input: Changes in carbohydrate metabolism, oxidative stress and loss of cortisol secretion in adrenocortica l cells of Oreochromis niloticus exposed in vitro to endosulfan.

carbohydrate

cortisol

endosulfan


Input: The effects of endosulfan, an organochlorine pesticide regularly used in Niger Delta ecological zone, were examined and also its effects on various biochemical parameters in the serum of Oreochromis niloticus, a dominant fish species in Nigeria.

endosulfan

organochlorine


Input: One hundred and fifty juveniles of O. niloticus were used for the toxicity study.


Input: Lethal concentration of 50% mortality of sample (LC50) was determined using semi-static method.


Input: From the result of the LC50 determination, lower concentrations of endosulfan were prepared for sublethal test.

endosulfan


Input: Five fish per test concentration in three replicates were exposed to varying concentrations of endosulfan.

endosulfan


Input: Glucose level and the enzyme activities were measured spectrophotometrically at the end of 28 days of exposure.

Glucose


Input: Glucose levels and glutathione-S-transferase activities were significantly (p < 0. 05) higher than the control and the concentrations increased with increasing concentration of the toxicant and exposure duration.

Glucose

glutathione

S


Input: Cortisol secretion was significantly (p = 0. 05) lower in the treated fish than the control.

Cortisol


Input: These findings indicated that endosulfan altered all the investigated parameters, which is an indication of their suitability as markers for fish and other aquatic organism toxicity study.

endosulfan


Input: Determination of aflatoxin M1 in milk by high-performance liquid chromatography in Mashhad (north east of Iran).

aflatoxin M1


Input: The aim of this study was to evaluate aflatoxin M1 (AFM1) contamination in milk samples in Mashhad in Iran.

aflatoxin M1


Input: A total of 60 milk samples were collected from retail stores of five regions in June 2011.


Input: The occurrence and concentration range of AFM1 in the samples were investigated by high-performance liquid chromatography method.


Input: AFM1 was found in 100% of the examined milk samples by average concentration of 16. 16 ng/L and the contamination level ranging between 2 and 64 ng/L.


Input: The concentration of AFM1 in all the samples was lower than the Iranian national standard and Food and Drug Administration limit (500 ng/L), and only in one (1. 6%) of the samples, the concentration of AFM1 was greater than the maximum tolerance limit (50 ng/L) accepted by European Union and Codex Alimentarius Commission.


Input: Statistical evaluation showed no significant difference between the mean concentrations of AFM1 in milk samples taken from different regions (p > 0. 05).


Input: CNS distribution of metabotropic glutamate 2 and 3 receptors: transgenic mice and [(3) H] LY459477 autoradiography.

glutamate

[(3) H] LY459477


Input: Group II metabotropic glutamate (mGlu) receptor agonists were efficacious in randomized clinical research trials for schizophrenia and generalized anxiety disorder.

glutamate


Input: The regional quantification of mGlu (2) and mGlu (3) receptors remains unknown.


Input: A selective and structurally novel mGlu (2/3) receptor agonist, 2-amino-4-fluorobicyclo [3. 1. 0] hexane-2, 6-dicarboxylic acid (LY459477) was tritiated and the distribution of mGlu (2) and mGlu (3) receptors was studied in transgenic mice lacking either mGlu (2), mGlu (3) or both receptors.

2-amino-4-fluorobicyclo [3. 1. 0] hexane-2, 6-dicarboxylic acid


Input: LY459477 is an agonist with 1-2 nM potency for rodent and human mGlu (2) and mGlu (3) receptors.


Input: The functional selectivity of LY459477 was demonstrated by over 640-fold selectivity and the displacement binding selectivity was greater than 320-fold for all glutamate receptors except mGlu (6) (~ 230-fold).

glutamate


Input: More than 1000-fold selectivity was demonstrated for all non-glutamate receptors known to be targeted by antipsychotic drugs.

glutamate


Input: Like atypical antipsychotic drugs, LY459477 reversed in vitro electrophysiological effects of a serotonergic hallucinogen and behavioral effects of phencyclidine or amphetamine.

phencyclidine

amphetamine


Input: There was virtually no binding of [(3) H] LY459477 to any brain region in mice with a deletion of both mGlu (2) and mGlu (3) receptors.

[(3) H] LY459477


Input: Regions enriched in mGlu (2) receptors included the medial prefrontal cortex, select hippocampal regions, the medial mammillary nucleus, the medial habenula, and the cerebellar granular cell layer.


Input: Regions enriched in mGlu (3) receptors were the dorsolateral entorhinal cortex, the hippocampal CA1 field, the piriform cortex, the substantia nigra, the thalamic reticular nucleus, and primary sensory thalamic nuclei.


Input: These findings suggest [(3) H] LY459477 should be a useful tool to further define the role of mGlu (2) and mGlu (3) receptors throughout the brain with respect to major neuropsychiatric syndromes.

[(3) H] LY459477


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

Glutamate


Input: Formulation, in vitro and in vivo evaluation of transdermal patches containing risperidone.

risperidone


Input: The efficacy of oral risperidone treatment in prevention of schizophrenia is well known.

risperidone


Input: However, oral side effects and patient compliance is always a problem for schizophrenics.


Input: In this study, risperidone was formulated into matrix transdermal patches to overcome these problems.

risperidone


Input: The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated.

eudragit RL 100

eudragit RS 100


Input: The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin.

risperidone


Input: Among the tested preparations, formulations with 20% risperidone, 3: 2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1. 87 +/- 0. 09 mg/cm (2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential.

risperidone

ERL 100

ERS 100


Input: The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison.

risperidone

risperidone


Input: The calculated relative bioavailability of risperidone transdermal patch was 115. 20% with prolonged release of drug.

risperidone


Input: Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation.


Input: This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.

risperidone


Input: Defining " epileptogenesis " and identifying " antiepileptogenic targets " in animal models of acquired temporal lobe epilepsy is not as simple as it might seem.


Input: The " latent period " between brain injury and clinical epilepsy is widely regarded to be a seizure-free, pre-epileptic state during which a time-consuming cascade of molecular events and structural changes gradually mediates the process of " epileptogenesis. " The concept of the " latent period " as the duration of " epileptogenesis " implies that epilepsy is not an immediate result of brain injury, and that anti-epileptogenic strategies need to target delayed secondary mechanisms that develop sometime after an initial injury.


Input: However, depth recordings made directly from the dentate granule cell layers in awake rats after convulsive status epilepticus-induced injury have now shown that whenever perforant pathway stimulation-induced status epilepticus produces extensive hilar neuron loss and entorhinal cortical injury, hyperexcitable granule cells immediately generate spontaneous epileptiform discharges and focal or generalized behavioral seizures.


Input: This indicates that hippocampal injury caused by convulsive status epilepticus is immediately epileptogenic and that hippocampal epileptogenesis requires no delayed secondary mechanism.


Input: When latent periods do exist after injury, we hypothesize that less extensive cell loss causes an extended period during which initially subclinical focal seizures gradually increase in duration to produce the first clinical seizure.


Input: Thus, the " latent period " is suggested to be a state of " epileptic maturation, " rather than a prolonged period of " epileptogenesis, " and therefore the antiepileptogenic therapeutic window may only remain open during the first week after injury, when some delayed cell death may still be preventable.


Input: Following the perhaps unavoidable development of the first focal seizures (" epileptogenesis "), the most fruitful therapeutic strategy may be to interrupt the process of " epileptic maturation, " thereby keeping focal seizures focal.


Input: This article is part of the Special Issue entitled' New Targets and Approaches to the Treatment of Epilepsy'.


Input: Chemical composition and antibacterial activity of the volatile oil from seeds of Artemisia annua L. from Iran.


Input: The composition of essential oil of the seeds of Artemisia annua L. was analysed by GC-MS.


Input: Overall, 16 volatile components were identified on the basis of their mass spectra characteristics and retention indices representing 95. 5% of the total oil.


Input: Trans-3 (10)-caren-4-ol (22. 3%), artemisia ketone (18. 6%), 1, 8-cineole (14. 9%), delta-selinene (13. 0%) and alpha-pinene (8. 2%) were the major compounds.

Trans-3 (10)-caren-4-ol

artemisia ketone

1, 8-cineole

delta-selinene

alpha-pinene


Input: Oxygenated monoterpenes were the main compounds with 51. 6% followed by sesquiterpene hydrocarbons (13. 3%), monoterpene hydrocarbons (9. 9%) and other compounds (8. 3%).

monoterpenes

sesquiterpene hydrocarbons

monoterpene hydrocarbons


Input: The essential oil was highly active against Escherichia coli and Enterococcus faecalis.


Input: Exposure to contaminants exacerbates oxidative stress in amphipod Monoporeia affinis subjected to fluctuating hypoxia.


Input: Fitness and survival of an organism depend on its ability to mount a successful stress response when challenged by exposure to damaging agents.


Input: We hypothesized that co-exposure to contaminants may exacerbate oxidative stress in hypoxia-challenged benthic animals compromising their ability to recover upon reoxygenation.


Input: This was tested using the amphipod Monoporeia affinis exposed to hypoxia followed by reoxygenation in sediments collected in polluted and pristine areas.


Input: In both sediment types, oxygen radical absorbance capacity (ORAC) and antioxidant enzyme activities [superoxide dismutase (SOD) and catalase (CAT)] increased during hypoxia, suggesting that M. affinis has a strategy of preparation for oxidative stress that facilitates recovery after a hypoxic episode.

oxygen

superoxide


Input: Exposure to contaminants altered this anticipatory response as indicated by higher baselines of ORAC and SOD during hypoxia and no response upon reoxygenation.


Input: This coincided with significantly elevated oxidative damage evidenced by a marked reduction in glutathione redox status (ratio of reduced GSH/oxidized GSSG) and an increase in lipid peroxidation (TBARS levels).

glutathione

reduced GSH

oxidized GSSG


Input: Moreover, RNA: DNA ratio, a proxy for protein synthetic activity, decreased in concert with increased TBARS, indicating a linkage between oxidative damage and fitness.


Input: Finally, inhibited acetylcholinesterase (AChE) activity in animals exposed to contaminated sediments suggested a neurotoxic impact, whereas significant correlations between AChE and oxidative biomarkers may indicate connections with redox state regulation.


Input: The oxidative responses in pristine sediments suggested a typical scenario of ROS production and removal, with no apparent oxidative damage.


Input: By contrast, co-exposure to contaminants caused greater increase in antioxidants, lipid peroxidation, and slowed recovery from hypoxia as indicated by CAT, GSH/GSSG, TBARS and AChE responses.

GSH

GSSG


Input: These results support the hypothesized potential of xenobiotics to hamper ability of animals to cope with fluctuating hypoxia.


Input: They also emphasize the importance of understanding interactions between antioxidant responses to different stressors and physiological mechanisms of oxidative damage.


Input: Simultaneous determination of glucoraphanin and sulforaphane in Brassica oleracea seeds by high-performance liquid chromatography with evaporative light-scattering detector.

glucoraphanin

sulforaphane


Input: In this article, a novel and efficient analysis method is described to simultaneously and quantitatively determine glucoraphanin and its major degradation product sulforaphane by reversed-phase high-performance liquid chromatography (HPLC) coupled with an evaporative light-scattering detector (ELSD).

glucoraphanin

sulforaphane


Input: This method was validated according to the regulatory guidelines with respect to precision, accuracy and linearity.


Input: The HPLC-ELSD method was successfully used to assess the contents of glucoraphanin and sulforaphane in varieties of Brassica oleracea seeds.

glucoraphanin

sulforaphane


Input: The developed analytical method not only avoids the underestimation of total glucoraphanin content, but also provides a reduction in analysis time and good efficiency and sensitivity compared to with conventional HPLC methods.

glucoraphanin


Input: RETRACTED: Detection of acute toxicity test of crude diesel oil on Beluga, Huso huso.


Input: RETRACTED.


Input: The PP1 binding code: a molecular-lego strategy that governs specificity.


Input: Ser/Thr protein phosphatase 1 (PP1) is a single-domain hub protein with nearly 200 validated interactors in vertebrates.

Ser

Thr


Input: PP1-interacting proteins (PIPs) are ubiquitously expressed but show an exceptional diversity in brain, testis and white blood cells.


Input: The binding of PIPs is mainly mediated by short motifs that dock to surface grooves of PP1.


Input: Although PIPs often contain variants of the same PP1 binding motifs, they differ in the number and combination of docking sites.


Input: This molecular-lego strategy for binding to PP1 creates holoenzymes with unique properties.


Input: The PP1 binding code can be described as specific, universal, degenerate, nonexclusive and dynamic.


Input: PIPs control associated PP1 by interference with substrate recruitment or access to the active site.


Input: In addition, some PIPs have a subcellular targeting domain that promotes dephosphorylation by increasing the local concentration of PP1.


Input: The diversity of the PP1 interactome and the properties of the PP1 binding code account for the exquisite specificity of PP1 in vivo.


Input: Serratin a new metabolite obtained from Serratia marcescens, a bacterium isolated from the microflora associated with banana plantations.

Serratin


Input: When cultures of Serratia marcescens, an enterobacteria isolated from the microflora associated with banana plantations incubated at 27 degrees C in a yeast-calcium carbonate-dextrose solid medium (10 g of yeast extract, 20 g dextrose, 15 g bacteriological agar, 20 g calcium carbonate and 1000 mL distilled water) were extracted with chloroform and purified by column chromatography, we obtained a new colourless bacterial metabolite which according to spectroscopic data proved to be serratin.

calcium carbonate

dextrose

dextrose

calcium carbonate

chloroform

serratin


Input: MTBP suppresses cell migration and filopodia formation by inhibiting ACTN4.


Input: Murine double minute (MDM2) binding protein (MTBP) has been implicated in cancer progression.


Input: Here, we demonstrate one mechanism by which MTBP inhibits cancer metastasis.


Input: Overexpression of MTBP in human osteosarcoma cell lines lacking wild-type p53 did not alter primary tumor growth in mice, but significantly inhibited metastases.


Input: MTBP downregulation increased the migratory potential of MDM2 (-/-) p53 (-/-) mouse embryonic fibroblasts, suggesting that MTBP inhibited cell migration independently of the Mdm2-p53 pathway.


Input: Co-immunoprecipitation and mass spectrometric analysis identified alpha-actinin-4 (ACTN4) as an MTBP-interacting protein.


Input: Endogenous MTBP interacted with and partially colocalized with ACTN4.


Input: MTBP overexpression inhibited cell migration and filopodia formation mediated by ACTN4.


Input: Increased cell migration by MTBP downregulation was inhibited by concomitant downregulation of ACTN4.


Input: MTBP also inhibited ACTN4-mediated F-actin bundling.


Input: We furthermore demonstrated that nuclear localization of MTBP was dispensable for inhibiting ACTN4-mediated cell migration and filopodia formation.


Input: Thus, MTBP suppresses cell migration, at least partially, by inhibiting ACTN4 function.


Input: Our study not only provides a mechanism of metastasis suppression by MTBP, but also suggests MTBP as a potential biomarker for cancer progression.


Input: Phytochemical composition of polar fraction of Stachys germanica L. subsp.


Input: salviifolia (Ten.) Gams, a typical plant of Majella National Park.


Input: In this study, we report the isolation and identification of several compounds present in the polar fraction of Stachys germanica L. subsp.


Input: salviifolia (Ten.) Gams, collected in the protected area of Majella National Park.


Input: In particular, we have isolated and identified harpagide, 7-beta-hydroxy-harpagide, ajugol, 5-allosyloxy-aucubin, verbascoside and, for the first time in this genus, arbutin.

harpagide

ajugol

verbascoside

arbutin


Input: Pharmacokinetic and pharmacodynamic evaluation of floating microspheres of metformin hydrochloride.

metformin hydrochloride


Input: Metformin hydrochloride (MH), a biguanide antidiabetic, is the drug of choice in obese patients.

Metformin hydrochloride

biguanide


Input: It is well absorbed from the upper part of gastrointestinal tract and has oral bioavailability of 50% to 60%.


Input: The objective of this study was to formulate MH into floating microspheres in order to increase its residence time at the site of absorption and thus improve its bioavailability; and to extend the duration of action along with possibilities of dose reduction.


Input: Microspheres were prepared by emulsion solvent evaporation method and evaluated for particle size, entrapment efficiency, buoyancy, and in vitro release; and further characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry.


Input: The pharmacokinetic and pharmacodynamic evaluation of selected formulation was carried out in male Wistar diabetic rats.


Input: The data was statistically analyzed by unpaired t-test.


Input: A 3. 5-fold increase in relative bioavailability was observed.


Input: The prolongation of half-life (t (1/2)) from 4. 5 +/- 2. 41 h to 14. 12 +/- 4. 81 h indicated extended duration of action.


Input: Oral glucose tolerance test (OGTT) was analyzed by one-way analysis of variance followed by Dunnet multiple comparison test, a significant decrease (p < 0. 05) in the blood glucose levels was observed when formulations were compared with control rats.

glucose

glucose


Input: Hence, MH floating microspheres were tested at 50 mg/kg and 100 mg/kg body weight, OGTT data showed nonsignificant difference (p > 0. 05).


Input: In conclusion, an effective oral antidiabetics treatment can be achieved by formulating MH into floating microspheres which results in increase in bioavailability along with extended duration of action resulting in possible reduction in dose.


Input: Pharmacological evidence of functional inhibitory metabotrophic glutamate receptors on mouse arousal-related cholinergic laterodorsal tegmental neurons.

glutamate


Input: Cholinergic neurons of the pontine laterodorsal tegmentum (LDT) are importantly involved in neurobiological mechanisms governing states of arousal such as sleep and wakefulness as well as other appetitive behaviors, such as drug-seeking.


Input: Accordingly, mechanisms controlling their excitability are important to elucidate if we are to understand how these LDT neurons generate arousal states.


Input: Glutamate mediates the vast majority of excitatory synaptic transmission in the vertebrate CNS and while presence of glutamate input in the LDT has been shown and ionotropic responses to glutamate have been reported in the LDT, characterization of metabotropic responses is lacking.

Glutamate

glutamate

glutamate


Input: Therefore, electrophysiological responses and changes in levels of intracellular Ca (2 +) in mouse cholinergic LDT neurons following application of specific mGluR agonists and antagonists were examined.

Ca (2 +)


Input: Unexpectedly, both the mGluR (5) specific agonist, CHPG, and the group II mGluR (mGlu (2/3)) agonist, LY379268 (LY), induced a TTX-insensitive outward current/hyperpolarization.

CHPG

TTX


Input: Both outward currents were significantly reduced by the mGluR antagonist MCPG and the CHPG-induced current was blocked by the specific mGluR (5) antagonist MTEP.

MCPG

CHPG

MTEP


Input: Concurrent Ca (2 +) imaging revealed that while CHPG actions did include release of Ca (2 +) from CPA/thapsigargin-sensitive intracellular stores, actions of LY did not.

Ca (2 +)

CHPG

Ca (2 +)

CPA

thapsigargin


Input: Both CHPG-and LY-induced outward currents were mediated by a TEA-sensitive potassium conductance.

CHPG

TEA

potassium


Input: The large-conductance, Ca (2 +)-dependent potassium (BK) channel blocker, iberiotoxin, attenuated CHPG actions.

Ca (2 +)

potassium

CHPG


Input: Consistent with actions on the BK conductance, CHPG enhanced the amplitude of the fast component of the after hyperpolarizing potential, concurrent with a reduction in the firing rate.

CHPG


Input: We conclude that stimulation of mGluR (5) and group II (mGluR (2/3)) elicits postsynaptically-mediated outward currents/hyperpolarizations in cholinergic LDT neurons.


Input: Effects of glutamatergic input would be, thus, expected not only to be excitation via stimulation of ionotropic glutamate receptors and mGluR (1), but also inhibition via actions at mGluR (5) and mGluR (2/3) on these neurons.

glutamatergic


Input: As these two processes counteract each other, these surprising findings necessitate revision of predictions regarding the net level of excitation generated by glutamate input to cholinergic LDT cells and, by extension, the functional outcome of glutamate transmission on processes which these neurons regulate.

glutamate

glutamate


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

Glutamate


Input: A potent Chk1 inhibitor is selectively cytotoxic in melanomas with high levels of replicative stress.


Input: There are few effective treatments for metastatic melanoma.


Input: Checkpoint kinase 1 (Chk1) inhibitors are being trialled for their efficacy in enhancing conventional chemotherapeutic agents, but their effectiveness as single agents is not known.


Input: We have examined the effectiveness of two novel Chk1 selective inhibitors, AR323 and AR678, in a panel of melanoma cell lines and normal cell types.


Input: We demonstrate that these drugs display single-agent activity, with IC50s in the low nanomolar range.


Input: The drugs produce cytotoxic effects in cell lines that are most sensitive to these drugs, whereas normal cells are only sensitive to these drugs at the higher concentrations where they have cytostatic activity.


Input: The cytotoxic effect is the consequence of inhibition of S-phase Chk1, which drives cells prematurely from late S phase into an aberrant mitosis and results in either failure of cytokinesis or cell death through an apoptotic mechanism.


Input: The sensitivity to the Chk1 inhibitors was correlated with the level of endogenous DNA damage indicating replicative stress.


Input: Chk1 inhibitors are viable single-agent therapies that target melanoma cells with high levels of endogenous DNA damage.


Input: This sensitivity suggests that Chk1 is a critical component of an adaptation to replicative stress in these cells.


Input: It also suggests that markers of DNA damage may be useful in identifying the melanomas and potentially other tumour types that are more likely to be sensitive to Chk1 inhibitors as single agents.


Input: Development and characterization of coated-microparticles based on whey protein/alginate using the Encapsulator device.


Input: The aim of this study is to prepare whey protein (WP)-based microparticles (MP) using the Encapsulator ((R)) device.


Input: The viscosity dependence of the extrusion device required to mix WP with a food-grade and less viscous polymer.


Input: Mixed WP/ALG MP were obtained with the optimized WP/alginate (ALG) ratio (62/38).


Input: These particles were further coated with WP or ALG using non-traumatic and solvent-free coating process developed in this study.


Input: Size and morphology of coated and uncoated MP were determined.


Input: Then, swelling and degradation (WP release) of formulations were investigated in pH 1. 2 and 7. 5 buffers and in simulated gastric and intestinal fluids (SGF, SIF) and compared to pure ALG and pure WP particle behaviours.


Input: At pH 1. 2, pure ALG shrank and pure WP swelled, whereas the sizes of mixed WP/ALG matrix were stable.


Input: In SGF, WP/ALG MP resisted to pepsin degradation compare to pure WP particles due to ALG shrinkage which limited pepsin diffusion within particles.


Input: Coating addition with WP or ALG slowed down pepsin degradation.


Input: At pH 7. 5, WP/ALG particles were rapidly degraded due to ALG sensitivity but the addition of a WP coating limited effectively the swelling and the degradation of MP.


Input: In SIF, pancreatin accelerated MP degradation but ALG-coated MP exhibited interesting robustness.


Input: These results confirmed the interest and the feasibility to produce coated WP-based MP which could be a potential orally controlled release drug delivery system.


Input: Secondary metabolites from Marchantia paleacea calluses and their allelopathic effects on Arabidopsis seed growth.


Input: Rapid-growth Marchantia paleacea calluses were induced on MSK2 medium through surface sterilisation of the capsula.


Input: Ten known compounds including two steroids (1-2), six bibenzyls (3, 5-9), a flavonoid (10), and a terpenoid (4) were isolated from these calluses.

steroids

bibenzyls

flavonoid

terpenoid


Input: The allelopathic effect of the six bibenzyls was assessed in Arabidopsis thaliana.

bibenzyls


Input: Results revealed that bibenzyls could inhibit seedling growth in a dose-dependent manner.

bibenzyls


Input: Preparation and in vitro/in vivo evaluation of a ketoprofen orally disintegrating/sustained release tablet.

ketoprofen


Input: Context: Orally disintegrating tablets (ODTs) with sustained release profiles are a new generation of ODTs called orally disintegrating/sustained release tablets (ODSRTs), which are convenient in use and able to slowly release drugs to maintain effective blood concentrations over a prolonged period of time.


Input: Ketoprofen, one of non-steroidal anti-inflammatory drugs, is an ideal model drug for ODSRTs.

Ketoprofen


Input: Methods: We designed a simple two-step process to develop novel ketoprofen orally disintegrating/sustained release tablets (KODSRTs).

ketoprofen


Input: Firstly, sustained release ketoprofen fine granules were developed by spray drying the aqueous dispersions composed of Eudragit RS-30D, Starch 1500 and PEG 6000.

ketoprofen

Eudragit RS-30D

PEG 6000


Input: The optimal parameters of spray drying were 100 degrees C for inlet air temperature and 1. 5 mL/min for feed rate.


Input: Subsequently, the obtained granules were directly compressed into KODSRTs after mixing with lactose, mannitol and a superdisintegrant, crosslinked polyvinylpyrrolidone (PVPP).

lactose

mannitol

polyvinylpyrrolidone

PVPP


Input: The characteristics of KODSRTs, especially their potential for extended drug release, were evaluated.


Input: Results: Results of an in vitro release test demonstrated that KODSRTs could slowly release ketoprofen for 24 h after disintegrating within 30 s.

ketoprofen


Input: Extended release properties of KODSRTs were decided by the ketoprofen sustained release fine granules in tablets.

ketoprofen


Input: Besides, the disintegration time of KODSRTs depended on the percentage of PVPP in tablets.

PVPP


Input: In vivo pharmacokinetic studies in beagles also showed that KODSRTs possessed a significantly extended release profile compared with ketoprofen normal capsules.

ketoprofen


Input: Conclusion: KODSRTs were successfully prepared using a simple two-step process: spray drying and direct compression.


Input: The receptor tyrosine kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target.

tyrosine


Input: Deregulation of the receptor tyrosine kinase Axl has been implicated in the progression of several human cancers.

tyrosine


Input: However, the role of Axl in prostate cancer remains poorly understood, and the therapeutic efficacy of Axl targeting remains untested.


Input: In this report we identified Axl as a new therapeutic target for prostate cancer.


Input: Axl is consistently overexpressed in prostate cancer cell lines and human prostate tumors.


Input: Interestingly, the blockage of Axl gene expression strongly inhibits proliferation, migration, invasion and tumor growth.


Input: Furthermore, inhibition of Axl expression by small interfering RNA regulates a transcriptional program of genes involved in cell survival, strikingly all connected to the nuclear factor-kappa B pathway.


Input: Additionally, blockage of Axl expression leads to inhibition of Akt, IKK alpha and I kappa B alpha phosphorylation, increasing I kappa B alpha expression and stability.


Input: Furthermore, induction of Akt phosphorylation by insulin-like growth factor 1 in Axl knockdown cells restores Akt activity and proliferation.


Input: Taken together, our results establish an unambiguous role for Axl in prostate cancer tumorigenesis with implications for prostate cancer treatment.


Input: Oncogenic K-ras expression is associated with derangement of the cAMP/PKA pathway and forskolin-reversible alterations of mitochondrial dynamics and respiration.

cAMP

forskolin


Input: The Warburg effect in cancer cells has been proposed to involve several mechanisms, including adaptation to hypoxia, oncogenes activation or loss of oncosuppressors and impaired mitochondrial function.


Input: In previous papers, it has been shown that K-ras transformed mouse cells are much more sensitive as compared with normal cells to glucose withdrawal (undergoing apoptosis) and present a high glycolytic rate and a strong reduction of mitochondrial complex I.

glucose


Input: Recent observations suggest that transformed cells have a derangement in the cyclic adenosine monophosphate/cAMP-dependent protein kinase (cAMP/PKA) pathway, which is known to regulate several mitochondrial functions.

cyclic adenosine monophosphate

cAMP

cAMP


Input: Herein, the derangement of the cAMP/PKA pathway and its impact on transformation-linked changes of mitochondrial functions is investigated.

cAMP


Input: Exogenous stimulation of PKA activity, achieved by forskolin treatment, protected K-ras-transformed cells from apoptosis induced by glucose deprivation, enhanced complex I activity, intracellular adenosine triphosphate (ATP) levels, mitochondrial fusion and decreased intracellular reactive oxygen species (ROS) levels.

forskolin

glucose

adenosine triphosphate

ATP

oxygen


Input: Several of these effects were almost completely prevented by inhibiting the PKA activity.


Input: Short-time treatment with compounds favoring mitochondrial fusion strongly decreased the cellular ROS levels especially in transformed cells.


Input: These findings support the notion that glucose shortage-induced apoptosis, specific of K-ras-transformed cells, is associated to a derangement of PKA signaling that leads to mitochondrial complex I decrease, reduction of ATP formation, prevalence of mitochondrial fission over fusion, and thereby opening new approaches for development of anticancer drugs.

glucose

ATP


Input: A new chromone from the leaves of Melaleuca cajuputi Powell.

chromone


Input: A new chromone, 5, 7-dihydroxy-2-(hydroxymethyl)-6, 8-dimethyl-chromen-4-one, named melachromone, together with 12 known compounds, including chromones, anthraquinone, flavonoids, flavonoid glycosides, benzene derivatives, ellagic acids and terpenes, were isolated from the leaves of Melaleuca cajuputi Powell.

chromone

5, 7-dihydroxy-2-(hydroxymethyl)-6, 8-dimethyl-chromen-4-one

melachromone

chromones

anthraquinone

flavonoids

flavonoid glycosides

benzene

ellagic acids

terpenes


Input: Their structures were characterised by spectroscopic methods.


Input: Functional selectivity induced by mGlu 4 receptor positive allosteric modulation and concomitant activation of Gq coupled receptors.


Input: Metabotropic glutamate receptors (mGlus) are a group of Family C Seven Transmembrane Spanning Receptors (7TMRs) that play important roles in modulating signaling transduction, particularly within the central nervous system.

glutamate


Input: mGlu (4) belongs to a subfamily of mGlus that is predominantly coupled to G (i/o) G proteins.


Input: We now report that the ubiquitous autacoid and neuromodulator, histamine, induces substantial glutamate-activated calcium mobilization in mGlu (4)-expressing cells, an effect which is observed in the absence of co-expressed chimeric G proteins.

histamine

glutamate

calcium


Input: This strong induction of calcium signaling downstream of glutamate activation of mGlu (4) depends upon the presence of H (1) histamine receptors.

calcium

glutamate

histamine


Input: Interestingly, the potentiating effect of histamine activation does not extend to other mGlu (4)-mediated signaling events downstream of G (i/o) G proteins, such as cAMP inhibition, suggesting that the presence of G (q) coupled receptors such as H (1) may bias normal mGlu (4)-mediated G (i/o) signaling events.

histamine

cAMP


Input: When the activity induced by small molecule positive allosteric modulators of mGlu (4) is assessed, the potentiated signaling of mGlu (4) is further biased by histamine toward calcium-dependent pathways.

histamine

calcium


Input: These results suggest that G (i/o)-coupled mGlus may induce substantial, and potentially unexpected, calcium-mediated signaling events if stimulation occurs concomitantly with activation of G (q) receptors.

calcium


Input: Additionally, our results suggest that signaling induced by small molecule positive allosteric modulators may be substantially biased when G (q) receptors are co-activated.


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

Glutamate


Input: Two new triterpenoid saponins from the husks of Xanthoceras sorbifolia.

triterpenoid saponins


Input: Two new oleanane triterpenoid saponins, xanthohuskisides A (1) and B (2), were isolated from the husks of Xanthoceras sorbifolia.

oleanane triterpenoid saponins

xanthohuskisides


Input: The structures of these two compounds were established as 3-O-beta-D-glucopyranosyl (1 --> 6)-[beta-D-glucopyranosyl (1 --> 2)]-beta-D-glucopyranosyl, 28-O-beta-D-glucopyranosyl (1 --> 6)-[alpha-L-rhamnopyranosyl (1 --> 2)]-beta-D-glucopyranosyl 16-deoxybarringtogenol C (1) and 3-O-beta-D-glucopyranosyl (1 --> 6)-[beta-D-glucopyranosyl (1 --> 2)]-beta-D-glucopyranosyl, 28-O-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranosyl 16-deoxybarringtogenol C (2), respectively, based on the analysis on their spectral data including NMR and HR-ESI-MS.

3-O-beta-D-glucopyranosyl (1 --> 6)-[beta-D-glucopyranosyl (1 --> 2)]-beta-D-glucopyranosyl, 28-O-beta-D-glucopyranosyl (1 --> 6)-[alpha-L-rhamnopyranosyl (1 --> 2)]-beta-D-glucopyranosyl 16-deoxybarringtogenol C

3-O-beta-D-glucopyranosyl (1 --> 6)-[beta-D-glucopyranosyl (1 --> 2)]-beta-D-glucopyranosyl, 28-O-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranosyl 16-deoxybarringtogenol C


Input: The growth inhibitory activities of compounds 1 and 2 were assayed, and 2 showed moderate activity against U937 cell line with the IG (50) value of 82. 85 +/- 1. 58 micro M.


Input: Yes and Lyn play a role in nuclear translocation of the epidermal growth factor receptor.


Input: The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in human cancers.


Input: Cetuximab is an anti-EGFR antibody that has been approved for use in oncology.


Input: Previously we investigated mechanisms of resistance to cetuximab using a model derived from the non-small cell lung cancer line NCI-H226.


Input: We demonstrated that cetuximab-resistant clones (Ctx (R)) had increased nuclear localization of the EGFR.


Input: This process was mediated by Src family kinases (SFKs), and nuclear EGFR had a role in resistance to cetuximab.


Input: To better understand SFK-mediated nuclear translocation of EGFR, we investigated which SFK member (s) controlled this process as well as the EGFR tyrosine residues that are involved.

tyrosine


Input: Analyses of mRNA and protein expression indicated upregulation of the SFK members Yes (v-Yes-1 yamaguchi sarcoma viral oncogene) and Lyn (v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog) in all Ctx (R) clones.


Input: Further, immunoprecipitation analysis revealed that EGFR interacts with Yes and Lyn in Ctx (R) clones, but not in cetuximab-sensitive (Ctx (S)) parental cells.


Input: Using RNAi interference, we found that knockdown of either Yes or Lyn led to loss of EGFR translocation to the nucleus.


Input: Conversely, overexpression of Yes or Lyn in low nuclear EGFR-expressing Ctx (S) parental cells led to increased nuclear EGFR.


Input: Chromatin immunoprecipitation (ChIP) assays confirmed nuclear EGFR complexes associated with the promoter of the known EGFR target genes B-Myb and iNOS.


Input: Further, all Ctx (R) clones exhibited upregulation of B-Myb and iNOS at the mRNA and protein levels.


Input: siRNAs directed at Yes or Lyn led to decreased binding of EGFR complexes to the B-Myb and iNOS promoters based on ChIP analyses.


Input: SFKs have been shown to phosphorylate EGFR on tyrosines 845 and 1101 (Y845 and Y1101), and mutation of Y1101, but not Y845, impaired nuclear entry of the EGFR.


Input: Taken together, our findings demonstrate that Yes and Lyn phosphorylate EGFR at Y1101, which influences EGFR nuclear translocation in this model of cetuximab resistance.


Input: Effects of sinensetin on lipid metabolism in mature 3T3-L1 adipocytes.

sinensetin


Input: Sinensetin is a rare polymethoxylated flavone found in certain citrus fruits.

Sinensetin

polymethoxylated flavone


Input: In this study, we investigated the effects of sinensetin on lipid metabolism in mature 3T3-L1 adipocytes.

sinensetin


Input: Sinensetin decreased the expression of sterol regulatory element-binding protein 1c (SREBP1c), suggesting its antiadipogeneic property via downreguation of SREBP1c.

Sinensetin

sterol


Input: Also, sinensetin increased the phosphorylation of protein kinase A and hormone-sensitive lipase, indicating its lipolytic property via a cAMP-mediated signaling pathway.

sinensetin

cAMP


Input: Moreover, sinensetin inhibited insulin-stimulated glucose uptake by decreasing the phosphorylation of insulin receptor substrate and Akt.

sinensetin

glucose


Input: Furthermore, sinensetin increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase.

sinensetin

AMP

acetyl-CoA


Input: It also upregulated mRNA expression of carnitine palmitoyltransferase-1a, suggesting that sinensetin enhances fatty acid beta-oxidation through the AMPK pathway.

carnitine

sinensetin


Input: Taken together, these results suggest that sinensetin may have potential as a natural agent for prevention/improvement of obesity.

sinensetin


Input: The marine alga Gelidium amansii promotes the development and complexity of neuronal cytoarchitecture.


Input: Neurotrophic factors are vital not only to support neuronal development but also to protect mature neurons from atrophy in neurodegenerative diseases.


Input: As an effort to explore natural sources that possess neurotrophic activity, we screened common marine algae for their neuritogenic activity in the developing rat hippocampal neurons in culture.


Input: Of the 22 seaweed species examined, ethanol extracts of Gelidium amansii (GAE) exhibited potent neuritogenic activity, followed by Undaria pinnatifida and Sargassum fulvellum extracts.

ethanol


Input: The effects of GAE were dose dependent with an optimum concentration of 15 micro g/mL.


Input: The GAE significantly promoted the initial neuronal differentiation from the stage I into the stage II and increased the indices of axonal and dendritic development such as the length, the numbers of primary processes, and branching frequencies by a minimum of twofold compared with the vehicle control.


Input: These results show that marine algae are promising candidates for neurotrophic potentials.


Input: New immunosuppressive cyclomyrsinol diterpenes from Euphorbia kopetdaghi Prokh.

cyclomyrsinol diterpenes


Input: Aceton: chloroform (1: 2) extracts of the aerial parts of Euphorbia kopetdaghi Prokh.

Aceton

chloroform


Input: (Euphorbiaceae) were investigated for its diterpenoids and afforded three new five-membered ring, pentacyclic myrisinane polyester comprised of 3, 5, 10-O-triacetyl-8-O-isobutanoyl-14-O-benzoylcyclomyrsinol (1), 3, 5, 10, 14-O-tetraacetyl-8-O-(2'-methyl butanoyl)-cyclomyrsinol (2) and 3, 5, 10, 14-O-tetracetyl-8-O-isobutanoylcyclomyrsinol (3).

diterpenoids

pentacyclic myrisinane polyester

3, 5, 10-O-triacetyl-8-O-isobutanoyl-14-O-benzoylcyclomyrsinol

3, 5, 10, 14-O-tetraacetyl-8-O-(2'-methyl butanoyl)-cyclomyrsinol

3, 5, 10, 14-O-tetracetyl-8-O-isobutanoylcyclomyrsinol


Input: The structures were elucidated based on (13) C-and (1) H-NMR as well as 2D-NMR, IR and different MS spectra and the immunomodulation activity for compound 1 was evaluated through lymphocyte proliferation assay, IL-2 assay, oxidative burst of phagocytic leukocytes and through their cytotoxicity on two cell lines.

(13) C

(1) H


Input: Compound 1 showed significant suppressive activity against phytohemagglutinin-activated T-cell proliferation with an IC (50) of 1. 83 micro g mL (-1), IL-2 suppressive activity with an IC (50) of 19. 0 micro g mL (-1) and oxidative burst suppressive activity with an IC (50) of 1. 6 micro g mL (-1) and ignorable cytotoxic effect on the CC-1 rat hepatocyte and 3T3-L1 mouse fibroblast cell-lines.


Input: Molecular crosstalk between a chemical and a biological stressor and consequences on disease manifestation in rainbow trout.


Input: The aim of the present study was to examine the molecular and organism reaction of rainbow trout, Oncorhynchus mykiss, to the combined impact of two environmental stressors.


Input: The two stressors were the myxozoan parasite, Tetracapsuloides bryosalmonae, which is the etiological agent of proliferative kidney disease (PKD) and a natural stressor to salmonid populations, and 17 beta-estradiol (E2) as prototype of estrogen-active chemical stressors in the aquatic environment.

17 beta-estradiol

estrogen


Input: Both stressors, the parasite and estrogenic contaminants, co-exist in Swiss rivers and are discussed as factors contributing to the decline of Swiss brown trout populations over the last decades.


Input: Using a microarray approach contrasting parasite-infected and non-infected rainbow trout at low or high estrogen levels, it was observed that molecular response patterns under joint exposure differed from those to the single stressors.

estrogen


Input: More specifically, three major response patterns were present: (i) expression responses of gene transcripts to one stressor are weakened by the presence of the second stressor; (ii) expression responses of gene transcripts to one stressor are enhanced by the presence of the second stressor; (iii) expression responses of gene transcripts at joint treatment are dominated by one of the two stressors.


Input: Organism-level responses to concurrent E2 and parasite treatment-assessed through measuring parasite loads in the fish host and cumulative mortalities of trout-were dominated by the pathogen, with no modulating influence of E2.


Input: The findings reveal function-and level-specific responses of rainbow trout to stressor combinations, which are only partly predictable from the response to the single stressors.


Input: Intraspecific chemical variability of essential oil from leaves of Cupressus atlantica Gaussen, an endemic and endangered coniferous species in Morocco.


Input: The composition of essential oils isolated from leaves of 11 natural populations of Cupressus atlantica, an endemic and endangered coniferous species from Morocco, was investigated by GC-MS.


Input: In total, 42 essential oil components were identified, accounting for 73. 1-97. 7% of the total oil.


Input: Monoterpene (25. 2-84. 9%) and sesquiterpene hydrocarbons (12. 2-46. 8%) were the principal subclasses of compounds, with alpha-pinene (15-65. 4%), germacrene D (5. 9-30. 5%), delta-3-carene (2-16. 6%) and gamma-cadinene (1. 3-9. 8%) as the main constituents.

Monoterpene

sesquiterpene hydrocarbons

alpha-pinene

germacrene D

gamma-cadinene


Input: The results of the oil composition were analysed by hierarchical cluster and principal component analysis that established three main groups of essential oils.


Input: These oils were differentiated by the content of the major constituents (alpha-pinene, germacrene D, delta-3-carene and gamma-cadinene), geographical location and climatic characteristics.

alpha-pinene

germacrene D

gamma-cadinene


Input: The biogenesis of active protein phosphatase 2A holoenzymes: a tightly regulated process creating phosphatase specificity.


Input: Protein phosphatase type 2A (PP2A) enzymes constitute a large family of Ser/Thr phosphatases with multiple functions in cellular signaling and physiology.

Ser

Thr


Input: The composition of heterotrimeric PP2A holoenzymes, resulting from the combinatorial assembly of a catalytic C subunit, a structural A subunit, and regulatory B-type subunit, provides the essential determinants for substrate specificity, subcellular targeting, and fine-tuning of phosphatase activity, largely explaining why PP2A is functionally involved in so many diverse physiological processes, sometimes in seemingly opposing ways.


Input: In this review, we highlight how PP2A holoenzyme biogenesis and enzymatic activity are controlled by a sophisticatedly coordinated network of five PP2A modulators, consisting of alpha 4, phosphatase 2A phosphatase activator (PTPA), leucine carboxyl methyl transferase 1 (LCMT1), PP2A methyl esterase 1 (PME-1) and, potentially, target of rapamycin signaling pathway regulator-like 1 (TIPRL1), which serve to prevent promiscuous phosphatase activity until the holoenzyme is completely assembled.

leucine carboxyl methyl

methyl

rapamycin


Input: Likewise, these modulators may come into play when PP2A holoenzymes are disassembled following particular cellular stresses.


Input: Malfunctioning of these cellular control mechanisms contributes to human disease.


Input: The potential therapeutic benefits or pitfalls of interfering with these regulatory mechanisms will be briefly discussed.


Input: Effects of the total alkaloidal extract of Murraya koenigii leaf on oxidative stress and cholinergic transmission in aged mice.


Input: Alzheimer' s disease (AD) is characterized by signs of major oxidative stress and the loss of cholinergic cells.


Input: The present study was designed to investigate the role of the total alkaloidal extract from Murraya koenigii (MKA) leaves on age related oxidative stress and the cholinergic pathway in aged mice.


Input: Ascorbic acid (100 mg/kg, p. o.) was used as a standard drug.

Ascorbic acid


Input: The MKA improved the level of protective antioxidants such as glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase (GRD), superoxide dismutase (SOD) and catalase (CAT) in brain homogenate at higher doses (20 and 40 mg/kg, p. o.).

glutathione

reduced glutathione

GSH

glutathione

superoxide


Input: Moreover, a dose dependent decline was noted in lipid peroxidation (LPO) and the nitric oxide assay (NO) at all doses of MKA (10, 20 and 40 mg/kg, p. o.).

nitric oxide


Input: Interestingly, significant progress was noted with the supplementation of MKA by an improvement of the acetylcholine (ACh) levels and a reduction in the acetylcholinesterase (AChE) activity in aged mouse brain.

acetylcholine

ACh


Input: In addition, a significant elevation of serum albumin (ALBU), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and total protein as well as a decline in creatinine, total cholesterol, urea nitrogen and glucose levels with MKA also ameliorated the hepatic and renal functions in normal ageing process.

alanine

aspartate

creatinine

cholesterol

urea nitrogen

glucose


Input: The results showed the possible utility of Murraya koenigii leaves in neuroprotection against neurodegenerative disorders such as Alzheimer' s disease.


Input: Quercetin reduces high-fat diet-induced fat accumulation in the liver by regulating lipid metabolism genes.

Quercetin


Input: To understand the molecular mechanisms underlying the influence of quercetin on the physiological effects of hyperlipidemia, we investigated its role in the prevention of high-fat diet (HFD)-induced obesity and found that it regulated hepatic gene expression related to lipid metabolism.

quercetin


Input: Quercetin supplementation in mice significantly reduced the HFD-induced gains in body weight, liver weight, and white adipose tissue weight compared with the mice fed only with HFD.

Quercetin


Input: It also significantly reduced HFD-induced increases in serum lipids, including cholesterol, triglyceride, and thiobarbituric acid-reactive substance (TBARS).

cholesterol

triglyceride

thiobarbituric acid


Input: Consistent with the reduced liver weight and white adipose tissue weight, hepatic lipid accumulation and the size of lipid droplets in the epididymal fat pads were also reduced by quercetin supplementation.

quercetin


Input: To further investigate how quercetin may reduce obesity, we analyzed lipid metabolism-related genes in the liver.

quercetin


Input: Quercetin supplementation altered expression profiles of several lipid metabolism-related genes, including Fnta, Pon1, Pparg, Aldh1b1, Apoa4, Abcg5, Gpam, Acaca, Cd36, Fdft1, and Fasn, relative to those in HFD control mice.

Quercetin


Input: The expression patterns of these genes observed by quantitative reverse transcriptase-polymerase chain reaction were confirmed by immunoblot assays.


Input: Collectively, our results indicate that quercetin prevents HFD-induced obesity in C57B1/6 mice, and its anti-obesity effects may be related to the regulation of lipogenesis at the level of transcription.

quercetin


Input: Effects of Bixa orellana L. seeds on hyperlipidemia.


Input: Bixa orellana L., urucum, or urucu, a native tropical tree of Central and South American rain forests is used to treat various diseases in popular medicine.


Input: In Cear a, Northeast of Brazil, the seeds of urucum have been used for the treatment of high lipid blood levels.


Input: The present study investigated the effects of the aqueous extract from Bixa orellana seeds (AEBO) in mice with hyperlipidemia induced by tyloxapol, fructose and ethanol.

tyloxapol

fructose

ethanol


Input: In hyperlipidemia induced by Triton WR1339, 400 and 800 mg/kg AEBO reduced triglycerides (TG) serum levels at 24 h and 48 h.

Triton WR1339

triglycerides


Input: In the study of hypertriglyceridemia induced by fructose, AEBO in doses of 400 mg/kg and 800 mg/kg reduced TG levels by 48. 2% and 48. 7%, respectively.

fructose


Input: Finally, the ethanol experimental model with 400 mg/kg AEBO promoted a reduction of 33. 6% of TG levels, while the 800 mg/kg concentration reduced hypertriglyceridemia in 62. 2%.

ethanol


Input: In conclusion, the aqueous extract of the seeds of Bixa orellana was capable of reversing the hypertriglyceridemia induced by Triton, fructose and ethanol, demonstrating a hypolipidemic effect.

Triton

fructose

ethanol


Input: However, further studies are necessary to discover the precise mechanism of action.


Input: Sarmentosamide, a novel hexadienamide from Thai soil actinomycetes.

Sarmentosamide

hexadienamide


Input: A new hexadienamide derivative named sarmentosamide (1) was identified from the culture of Streptomyces sp.

sarmentosamide


Input: SBI108 isolated from Thai soil under an herb.


Input: The structure was elucidated on the basis of spectroscopic data, and the absolute configuration was determined by chemical degradation.


Input: A comparative study of phytochemical composition of genetically and non-genetically modified soybean (Glycine max L.) and evaluation of antitumor activity.


Input: Colon cancer is one of the major causes of cancer mortality worldwide.


Input: The analysed feeds, containing non-genetically modified (GM) soybean and Roundup Ready soybean, showed a different polyphenolic content and lipophilic composition.

polyphenolic


Input: Non-GM soybean extract possessed twice the polyphenolic content of GM soybean and the highest number of sterols.

polyphenolic

sterols


Input: Among them, gamma-sitosterol was found to be the major constituent.

gamma-sitosterol


Input: Methanolic extract of non-GM soybean extract was more potent than GM soybean extract against colon carcinoma cell line LoVo using MTT assay, while the second one showed a slightly higher anti-inflammatory activity.

MTT


Input: The findings add to epidemiological evidence for the therapeutic effects of soy foods in colorectal carcinoma.


Input: Isolation of a p-hydroxyphenyl anhydride from the leaves of Diphysa carthagenensisw.

p-hydroxyphenyl anhydride


Input: Diphysidione (1), a new p-hydroxyphenyl anhydride, and vitexin (2) were isolated from the leaves of Diphysa carthagenensis.

Diphysidione

p-hydroxyphenyl anhydride

vitexin


Input: The structure of the new metabolite was characterised as 4-(4-hydroxy-phenyl)-3H-pyran-2, 6-dione using 1D and 2D NMR spectroscopy.

4-(4-hydroxy-phenyl)-3H-pyran-2, 6-dione


Input: Electroporation-mediated gene transfer directly to the swine heart.


Input: In vivo gene transfer to the ischemic heart via electroporation holds promise as a potential therapeutic approach for the treatment of heart disease.


Input: In the current study, we investigated the use of in vivo electroporation for gene transfer using three different penetrating electrodes and one non-penetrating electrode.


Input: The hearts of adult male swine were exposed through a sternotomy.


Input: Eight electric pulses synchronized to the rising phase of the R wave of the electrocardiogram were administered at varying pulse widths and field strengths following an injection of either a plasmid encoding luciferase or one encoding green fluorescent protein.


Input: Four sites on the anterior wall of the left ventricle were treated.


Input: Animals were killed 48 h after injection and electroporation and gene expression was determined.


Input: Results were compared with sites in the heart that received plasmid injection but no electric pulses or were not treated.


Input: Gene expression was higher in all electroporated sites when compared with injection only sites demonstrating the robustness of this approach.


Input: Our results provide evidence that in vivo electroporation can be a safe and effective non-viral method for delivering genes to the heart, in vivo.


Input: Combination of group I mGlu receptors antagonist with dopaminergic agonists strengthens the synaptic transmission at corticostriatal synapses in culture.


Input: Restoring synaptic plasticity in neurodegenerative diseases could prevent neuronal degeneration, as well as motor and cognitive disorders.


Input: In Parkinson' s disease, synaptic plasticity at corticostriatal synapses is altered.


Input: Dendrites of striatal medium spiny neurons (MSNs) receive dopaminergic inputs from the substantia nigra and glutamatergic cortical afferents.


Input: Because both glutamate and dopamine are required to induce and sustain MSNs plasticity, the particular molecular mechanisms involved at this synaptic triad are difficult to understand.

glutamate

dopamine


Input: In the present work, we established a convenient in vitro model of the corticostriatal synapse to study synaptic plasticity.


Input: We focused on long-term depression involving group I metabotropic glutamate (mGlu) receptors.

glutamate


Input: We found that in striatal neurons co-cultured with cortical neurons, the absence of dopaminergic stimuli favored the excess of glutamatergic drive from cortical neuron terminals, thus resulting in a constitutive depression of the corticostriatal glutamatergic transmission.


Input: Indeed, concomitant blockade of group I mGlu receptors and activation of dopaminergic receptors stably reduced the depression of the synaptic transmission.


Input: Thus the dependence on glutamate and dopamine balance of the corticostriatal synapse responsiveness validates the accuracy of this manageable in vitro model to depict the molecular pathways involved in the plasticity at corticostriatal synapses and to test restorative therapeutic approaches in Parkinson' s disease.

glutamate

dopamine


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

Glutamate


Input: Heavy metals content by ICP-OES in Sarda sarda, Sardinella aurita and Lepidopus caudatus from the Strait of Messina (Sicily, Italy).


Input: In this study copper, nickel, lead, cadmium, arsenic, chromium and vanadium content was measured in the muscles and gills of 24 fishes (Sarda sarda, Sardinella aurita and Lepidopus caudatus) caught in the Strait of Messina, by inductively coupled plasma-optical emission spectroscopy with microwave digestion techniques.

copper

nickel

cadmium

arsenic

chromium

vanadium


Input: In general, it was found that arsenic was higher than other analytes in all fish species, particularly its content was much higher in S. aurita than in the other two exemplary species.

arsenic


Input: Lead and cadmium were always detected with values below the legal limits (CE no. 1881/2006 and subsequent modification CE no. 629/2008).

cadmium


Input: A new abietane diterpenoid from Salvia xanthocheila Boiss.

abietane diterpenoid


Input: From the chloroform extract of aerial part of Salvia xanthocheila Boiss. one new abietane diterpenoid, xantoquinone (5 alpha, 6 alpha-dimethoxy-7, 11, 14-trioxoabieta-8, 12-diene) and one known oleanene triterpenoid namely 1 beta, 3 beta-dihydroxy-12-oleanene were isolated.

chloroform

abietane diterpenoid

xantoquinone

5 alpha, 6 alpha-dimethoxy-7, 11, 14-trioxoabieta-8, 12-diene

oleanene triterpenoid

1 beta, 3 beta-dihydroxy-12-oleanene


Input: The structure of the new terpenoid was elucidated by comprehensive spectroscopic analysis including electron ionisation-mass spectra, (1) H NMR, (13) C NMR, distortionless enchancement by polarisation transfer, H, H correlation spectroscopy, heteronuclear multiple-quantum coherence and heteronuclear multiple-bond correlation.

terpenoid

(1) H

(13) C

H

H


Input: A new amide and a new monoterpene from the seeds of Clausena lansium.

amide

monoterpene


Input: A new amide (2) and a new monoterpene (6) were isolated from the seeds of Clausena lansium together with four known ones (1, 3-5).

amide

monoterpene


Input: The structures of the new compounds were elucidated by extensive spectroscopic analyses.


Input: The absolute configurations of 1, 2 and 6 were determined by optical rotation and the modified Mosher' s method.


Input: New triterpenoids from Morus alba L. stem bark.

triterpenoids


Input: Two lupeol-type pentacyclic triterpenoids characterised as lup-20 (29)-en-3 beta-ol-27-oic acid (moruslupenoic acid A) and lup-12, 20 (29)-dien-3 beta-ol-26-oic acid (moruslupenoic acid B) and lanst-5, 24-dien-3 beta-yl acetate (moruslanosteryl acetate) along with the known triterpenoidal phytoconstituents alpha-amyrin acetate, beta-amyrin-beta-D-glucopyranoside and betulinic acid have been isolated from the stem bark of Morus alba L.

lupeol

pentacyclic triterpenoids

lup-20 (29)-en-3 beta-ol-27-oic acid

moruslupenoic acid A

lup-12, 20 (29)-dien-3 beta-ol-26-oic acid

moruslupenoic acid B

lanst-5, 24-dien-3 beta-yl acetate

moruslanosteryl acetate

alpha-amyrin acetate

beta-amyrin-beta-D-glucopyranoside

betulinic acid


Input: (Moraceae).


Input: The structures of the isolated phytoconstituents were established on the basis of spectral data analysis and chemical means.


Input: Synergy between L-DOPA and a novel positive allosteric modulator of metabotropic glutamate receptor 4: implications for Parkinson' s disease treatment and dyskinesia.

L-DOPA

glutamate


Input: Group III metabotropic glutamate (mGlu) receptors are localized in presynaptic terminals within basal ganglia (BG) circuitry that become hyperactive due to dopamine depletion in Parkinson' s disease (PD).

glutamate

dopamine


Input: For this reason, group III mGlu receptors, in particular mGlu4, have been considered as key strategic targets for non-dopaminergic pharmacological treatments aimed at modulating these synapses, without producing the well known side-effects of l-DOPA, in particular the highly disabling l-DOPA-induced dyskinesia (LID).

l-DOPA

l-DOPA


Input: Herein we add physiological and functional support to this hypothesis using Lu AF21934, a novel selective and brain-penetrant mGlu4 receptor positive allosteric modulator (PAM) tool compound.

Lu AF21934


Input: By in vitro electrophysiological recordings we demonstrate that Lu AF21934 inhibits corticostriatal synaptic transmission and enhances the effect of the orthosteric mGlu4 receptor-preferred agonist LSP1-2111.

Lu AF21934


Input: In na i ve rats, Lu AF21934 dose-dependently (10 and 30 mg/kg) alleviated haloperidol-induced catalepsy.

Lu AF21934

haloperidol


Input: In hemiparkinsonian rats (unilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta), Lu AF21934 alone did not affect akinesia at the doses tested (10 and 30 mg/kg).

Lu AF21934


Input: However, when Lu AF21934 was combined with sub-threshold doses of l-DOPA (1 and 5 mg/kg), it acted synergistically in alleviating akinesia in a dose-dependent manner and, notably, also reduced the incidence of LID but not its severity.

Lu AF21934

l-DOPA


Input: Interestingly, these effects occurred at Lu AF21934 brain free concentrations that showed functional activity in in vitro screens (calcium flux and electrophysiology assays).

Lu AF21934

calcium


Input: These results support the potential for antiparkinsonian clinical use of a combined treatment consisting in l-DOPA and a mGlu4 receptor PAM to reduce efficacious l-DOPA doses (generally known as l-DOPA sparing), while maintaining the same benefit on PD motor troubles, and at the same time minimizing the development of LID.

l-DOPA

l-DOPA

l-DOPA


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

Glutamate


Input: New triterpenoids from the stem bark of Hypodaphnis zenkeri.

triterpenoids


Input: A new pentacyclic triterpenoid and three new derivatives based on the taraxer-14-ene skeleton with a C-28 attached a carboxylic acid group have been isolated from the stem bark of Hypodaphnis zenkeri, together with six known compounds.

pentacyclic triterpenoid

carboxylic acid


Input: The new product was identified as 2 alpha, 3 alpha-dihydroxytaraxer-14-en-28-oic acid (1).

2 alpha, 3 alpha-dihydroxytaraxer-14-en-28-oic acid


Input: Its derivatives, 2 alpha, 3 alpha-diacetyltaraxer-14-en-28-oic acid (2), 2 alpha, 3 alpha-di-O-carbonyl-2 alpha, 3 alpha-dihydroxytaraxer-14-en-28-oic acid (3) and 2 alpha, 3 alpha-dipropionyltaraxer-14-en-28-oic acid (4) were obtained by semisynthesis.

2 alpha, 3 alpha-diacetyltaraxer-14-en-28-oic acid

2 alpha, 3 alpha-di-O-carbonyl-2 alpha, 3 alpha-dihydroxytaraxer-14-en-28-oic acid

2 alpha, 3 alpha-dipropionyltaraxer-14-en-28-oic acid


Input: The known compounds were identified as 3 beta-hydroxytaraxer-14-en-28-oic acid or aleuritolic acid (5) (McPhail, A. T., McPhail, D. R., Wani, M. C., Wall, M. E. & A. W., Nicholas, A. W. (1989). Identity of maprounic acid with aleuritolic acid. Revision of the structure of maprounic acid: X-ray crystal structure of p-bromobenzyl acetylmaprounate. Journal Natural Products, 52, 212), 3 alpha-hydroxytaraxer-14-en-28-oic acid or isoaleuritolic acid (6), 3 alpha-acetyltaraxer-14-en-28-oic acid acetate or aleuritolic acid acetate (7) (Chaudhuri, S. K., Fullas, F., Brown, D. M., Wani, M. C., Wall, M. E., Cai, L., ... Kinghorn, A. D. (1995). Isolation and structural elucidation of pentacyclic triterpenoids from Maprounea africana. Journal of Natural Products, 58, 1-9), 3-oxo-taraxer-14-ene or taraxerone (8) beta-sitosterol (9) and stigmasterol (10) (Kamboj & Saluja, 2011), together with fatty acids.

3 beta-hydroxytaraxer-14-en-28-oic acid

aleuritolic acid

maprounic acid

aleuritolic acid

maprounic acid

p-bromobenzyl acetylmaprounate

3 alpha-hydroxytaraxer-14-en-28-oic acid

isoaleuritolic acid

3 alpha-acetyltaraxer-14-en-28-oic acid acetate

aleuritolic acid acetate

taraxerone

beta-sitosterol

stigmasterol


Input: Their structures were established on the basis of spectroscopic studies and chemical transformations.


Input: A new flavonol from Oxytropis ochrocephala Bunge.

flavonol


Input: A new acylated flavonoid, 3-O-rhamnocitrin-6-O-benzoyl-beta-D-glucopyranoside (1), together with five known flavonoids, rhamnocitrin (2), pratensein (3), (3R)-7, 3'-dihydroxy-2', 4'-dimethoxyisoflavan (4), (3R)-7, 2'-dihydroxy-3', 4'-dimethoxyisoflavan (5) and isoliquiritigenin (6), was isolated from Oxytropis ochrocephala Bunge.

acylated flavonoid

3-O-rhamnocitrin-6-O-benzoyl-beta-D-glucopyranoside

flavonoids

rhamnocitrin

pratensein

(3R)-7, 3'-dihydroxy-2', 4'-dimethoxyisoflavan

(3R)-7, 2'-dihydroxy-3', 4'-dimethoxyisoflavan

isoliquiritigenin


Input: The structural elucidation of the isolated compounds was primarily based on HRESIMS, IR and 1-D-and 2-D-NMR analyses.


Input: Continuous infusion of 20-hydroxyecdysone increased mass of triceps brachii in C57BL/6 mice.


Input: Phytoecdysteroids have been attributed with numerous pharmacological properties in animals, including increasing muscle mass, and 20-hydroxyecdysone (20E) is one of the most abundant phytoecdysteroids produced by plants.

Phytoecdysteroids

phytoecdysteroids


Input: In this study, the physiological and gene expression effects of 20E were analyzed in C57BL/6 mice given a continuous infusion of saline or 20E (5 mg/kg/day) for 5 or 15 days using subcutaneously implanted Alzet (R) osmotic pumps.


Input: The masses of the total body, muscle groups and organs were determined.


Input: There was a significant increase (p = 0. 01) in the mass of triceps brachii in mice treated with 20E for 5 days (115 +/- 8 mg) compared with mice treated with saline for 5 days (88 +/- 3 mg), however, there were no differences in the other measured parameters.


Input: To determine potential mechanisms of 20E in skeletal muscle, Illumina' s Mouse Whole Genome-6 v2. 0 Expression BeadChips were used to evaluate changes in gene expression of the triceps brachii after 20E infusion.


Input: Ingenuity Pathways Analysis was used to identify genes with the most evidence for differential expression, of which, 16 genes involved in the skeletal and muscular system were identified.


Input: Overall, the data suggest that 20E does not have potent anabolic properties, however, a muscle-specific increase was observed and genes were identified to provide an explanation for the muscle accretion.


Input: Antihyperglycemic and antihyperlipidemic activities of ethanolic extract of Zygophyllum album in streptozotocin-induced diabetic mice.

streptozotocin


Input: Zygophyllum album has been mentioned in Tunisian system of folk medicine to be of value in the treatment of diabetes mellitus.


Input: The present study was designed to investigate the possible antihyperglycemic effects of ethanolic extracts of the whole plant of Z. album on blood glucose, plasma insulin, serum lipids and hepatic glycogen and metabolism enzymes of carbohydrate in streptozotocin (STZ)-induced diabetic mice.

glucose

carbohydrate

streptozotocin

STZ


Input: Administration of the ethanolic extract from plant (100 and 300 mg/kg body weight) for 14 days resulted in significant reduction in plasma glucose, cholesterol, triglycerides, low-density lipoprotein, very-low-density liprotein, hepatic glucokinase and glycogen in STZ diabetic mice.

glucose

cholesterol

triglycerides

STZ


Input: In addition to that, significant increase in plasma high-density lipoprotein, hepatic phosphofructokinase and glucose-6 phosphate dehydrogenase was observed in STZ diabetic mice.

glucose-6 phosphate

STZ


Input: After administration of the ethanolic extract, the increased level of plasma insulin is not significant in diabetic mice.


Input: In conclusion, the present results showed that the ethanolic extract of Z. album possesses significant antihyperglycemic and antihyperlipidemic effects in experimental model of diabetes mellitus.


Input: Continuous production of drug nanoparticle suspensions via wet stirred media milling: a fresh look at the Rehbinder effect.


Input: Nanoparticles of BCS Class II drugs are produced in wet stirred media mills operating in batch or recirculation mode with the goal of resolving the poor water-solubility issue.


Input: Scant information is available regarding the continuous production of drug nanoparticles via wet media milling.


Input: Griseofulvin and Naproxen were milled in both recirculation mode and multi-pass continuous mode to study the breakage dynamics and to determine the effects of suspension flow rate.

Griseofulvin

Naproxen


Input: The evolution of the median particle size was measured and described by an empirical breakage model.


Input: We found that these two operation modes could produce drug nanosuspensions with similar particle size distributions (PSDs).


Input: A reduced suspension flow rate slowed the breakage rate and led to a wider PSD and more differentiation between the two operation modes.


Input: The latter part of this study focused on the roles of stabilizers (hydroxypropyl cellulose and sodium lauryl sulfate) and elucidation of the so-called Rehbinder effect (reduction in particle strength due to adsorbed stabilizers such as polymers and surfactants).

hydroxypropyl

sodium lauryl sulfate


Input: Milling the drugs in the absence of the stabilizers produced primary nanoparticles and their aggregates, while milling with the stabilizers produced smaller primary nanoparticles with minimal aggregation.


Input: Using laser diffraction, BET nitrogen adsorption, scanning electron microscopy imaging, and a microhydrodynamic analysis of milling, this study, for the first time, provides sufficient evidence for the existence of the Rehbinder effect during the milling of drugs.

nitrogen


Input: Not only do the polymers and surfactants allow proper stabilization of the nanoparticles in the suspensions, but they also do facilitate drug particle breakage.


Input: Egr-1 mediates epidermal growth factor-induced downregulation of E-cadherin expression via Slug in human ovarian cancer cells.


Input: Loss of the cell adhesion protein E-cadherin increases the invasive capability of ovarian cancer cells.


Input: We have previously shown that epidermal growth factor (EGF) downregulates E-cadherin and induces ovarian cancer cell invasion through the H (2) O (2)/p38 MAPK-mediated upregulation of the E-cadherin transcriptional repressor Snail.

H (2) O (2)


Input: However, the molecular mechanisms underlying the EGF-induced downregulation of E-cadherin are not fully understood.


Input: In the current study, we demonstrated that treatment of two ovarian cancer cell lines, SKOV3 and OVCAR5, with EGF induced the expression of the transcription factor Egr-1, and this induction was abolished by small interfering RNA (siRNA)-mediated depletion of the EGF receptor.


Input: EGF-induced Egr-1 expression required the activation of the ERK1/2 and PI3K/Akt signaling pathways and was unrelated to EGF-induced H (2) O (2) production and activation of the p38 MAPK pathway.

H (2) O (2)


Input: Moreover, depletion of Egr-1 with siRNA abolished the EGF-induced downregulation of E-cadherin and increased cell invasion.


Input: Interestingly, siRNA depletion of Egr-1 attenuated the EGF-induced expression of Slug, but not that of Snail.


Input: Moreover, chromatin immunoprecipitation (ChIP) analysis showed that Slug is a target gene of Egr-1.


Input: These results provide evidence that Egr-1 is a mediator that is involved in the EGF-induced downregulation of E-cadherin and increased cell invasion.


Input: Our results also demonstrate that EGF activates two independent signaling pathways, which are the H (2) O (2)/p38 MAPK-mediated upregulation of Snail expression and the Egr-1-mediated upregulation of Slug expression.

H (2) O (2)


Input: These two signaling pathways contribute to the EGF-induced downregulation of E-cadherin, which subsequently increases the invasive capability of ovarian cancer cells.


Input: Anti-oncogenic potential of the eIF4E-binding proteins.


Input: The eIF4E-binding proteins (4E-BPs) are inhibitors of protein synthesis that sequester the mRNA cap-binding protein eIF4E and consequently block cell growth and proliferation.


Input: In most tumors however, their inhibitory function is compromised by major oncogenic signaling pathways.


Input: Recently, thanks to the generation of mouse genetic models, considerable progress has been made in elucidating the involvement of 4E-BPs and their unique target, eIF4E, in the process of carcinogenesis.


Input: Increasing evidence indicates that an' addiction' to protein synthesis emerges in cancer cells, highlighting the potential that 4E-BPs have as targets for therapeutics.


Input: In this review, we summarize the biochemical function, regulation and anti-oncogenic activity of the 4E-BPs.


Input: Macrophage immunomodulatory activity of a purified polysaccharide isolated from Ganoderma atrum.


Input: The objective of this study was to evaluate the immunomodulatory effects of the purified Ganoderma atrum polysaccharide (PSG-1) on murine macrophage cell line RAW264. 7.


Input: Phagocytotic assay by fluorescein isothiocyanate-dextran internalization showed that PSG-1 stimulated the phagocytosis of macrophages.

fluorescein isothiocyanate


Input: G. atrum polysaccharide increased the production of NO, and the level of mRNA expression of inducible nitric oxide synthase in a dose-response manner.

NO

nitric oxide


Input: G. atrum polysaccharide also dose-dependently induced the release of TNF-alpha and interleukin-1 beta.


Input: Generation of reactive oxygen species was promoted by PSG-1, as determined by flow cytometry.

oxygen


Input: Moreover, PSG-1 induced nuclear factor-kappa B activation by elevation of p65 nuclear translocation, suggesting that PSG-1 probably stimulated macrophage activities by activating the nuclear factor-kappa B pathway.


Input: Prevention of hydrogen peroxide-induced red blood cells lysis by Ilex paraguariensis aqueous extract: participation of phenolic and xanthine compounds.

hydrogen peroxide

phenolic

xanthine


Input: The fresh leaves and stems of Ilex paraguariensis (Aquifoliaceae) are employed to prepare the commercial product used in North-eastern Argentina, Southern Brazil and Eastern Paraguay named yerba mat e.


Input: The presence of polyphenols and xanthines, which present antioxidant activity, has been described in I. paraguariensis.

polyphenols

xanthines


Input: In living organism, reactive oxygen species can cause tissue damage affecting erythrocyte membranes leading to hemolysis.

oxygen


Input: The aim of this work was to evaluate the protective effect of an aqueous extract of I. paraguariensis (green leaves) on the hemolysis of red blood cells induced by hydrogen peroxide and to correlate this activity with the enzymatic activity related to hydrogen peroxide metabolism.

hydrogen peroxide

hydrogen peroxide


Input: The antioxidant activity of chlorogenic acid and caffeine was also analysed to evaluate their contribution to the activity of the crude extract.

chlorogenic acid

caffeine


Input: The extract as well as the isolated compounds protected red blood cells from hemolysis.


Input: This effect was related to a catalase-like activity.


Input: This study could contribute to the knowledge of the antioxidant activity of I. paraguariensis in view of the great quantities of yerba mat e consumed by the population.


Input: Anti-hyperglycemic effect of fermented ginseng in type 2 diabetes mellitus mouse model.


Input: Ginseng has shown an efficacy in preventing and managing various health conditions.


Input: This study aimed to evaluate the effect of the fermented ginseng extract (FGE) in type 2 diabetes mellitus murine model.


Input: FGE was provided to male C57BL/ksJ-db/db mice for 8 weeks at 0. 1% (w/w) dose in contrast to water for the control group.


Input: Potential anti-diabetic mechanisms were investigated with blood glucose, serum insulin, serum adiponectin, hemoglobin A1c (HbA1c), glucose tolerance, insulin secretion assay, quantitative real-time polymerase chain reaction, and hematoxylin-eosin staining.

glucose

hematoxylin

eosin


Input: Compared with the control group, the FGE group had lower levels of blood glucose after 6 and 9 h fasting, HbA1c, and the area under the curve in an oral glucose tolerance test and higher levels of adiponectin and serum insulin (p < 0. 05).

glucose

glucose


Input: The FGE group had higher levels of peroxisome proliferator-activated receptor gamma 2 and glucose transporter protein 2 mRNAs, a lower level of tumor necrosis factor-alpha (TNF-alpha) (p < 0. 05), and less lymphocytes in pancreas than the control group had.

glucose


Input: The FGE exerted anti-diabetic effects in type 2 diabetic mice.


Input: A simple method of microneedle array fabrication for transdermal drug delivery.


Input: The outermost layer of skin, stratum corneum, being lipophilic limits the passive transport of hydrophilic and large molecular weight drugs.


Input: Microfabrication technology has been adapted to fabricate micron scale needles, which are minimally invasive, yet able to deliver the drugs across this barrier layer.


Input: In this study, we fabricated microneedles from a biocompatible polymer, namely, poly (ethylene glycol) diacrylate.

poly (ethylene glycol) diacrylate


Input: A simple lithographical approach was developed for microneedle array fabrication.


Input: Several factors including polymerization time, ultraviolet light intensity and distance from light source were studied for their effects on microneedle formation.


Input: The microneedle length and tip diameter can be controlled by varying these factors.


Input: The microneedles were shown to be able to penetrate cadaver pig skin.


Input: Model drug rhodamine B was encapsulated in the range of 50 micro g to 450 micro g per microneedle array.

rhodamine B


Input: The fabricated microneedles containing rhodamine B increased the permeability by four times than the control.

rhodamine B


Input: Altogether, we demonstrated that the microneedle arrays can be fabricated through a simple single-step process and needles were mechanically strong to penetrate skin, increasing the permeability of encapsulated drug through skin.


Input: Effects of estradiol in adult neurogenesis and brain repair in zebrafish.

estradiol


Input: The brain of the adult teleost fish exhibits intense neurogenic activity and an outstanding capability for brain repair.


Input: Remarkably, the brain estrogen-synthesizing enzyme, aromatase B, is strongly expressed, particularly in adult fishes, in radial glial cells, which act as progenitors.

estrogen


Input: Using zebrafish, we tested the hypothesis that estrogens affect adult neurogenesis and brain regeneration by modulating the neurogenic activity of radial glial cells.

estrogens


Input: To investigate this, the estrogenic environment was modified through inhibition of aromatase activity, blockade of nuclear estrogen receptors, or estrogenic treatments.

estrogenic


Input: Estrogens significantly decreased cell proliferation and migration at the olfactory bulbs/telencephalon junction and in the mediobasal hypothalamus.


Input: It also appears that cell survival is reduced at the olfactory bulbs/telencephalon junction.


Input: We also developed a model of telencephalic lesion to assess the role of aromatase and estrogens in brain repair.

estrogens


Input: Proliferation increased rapidly immediately after the lesion in the parenchyma of the injured telencephalon, while proliferation at the ventricular surface appeared after 48 h and peaked at 7 days.


Input: At this time, most proliferative cells express Sox2, however, none of these Sox2 positive cells correspond to aromatase B-positive radial glial cells.


Input: Interestingly, aromatase B expression was significantly reduced 48 h and 7 days after the injury, but surprisingly, at 72 h after lesion, aromatase B expression appeared de novo expressed in parenchyma cells, suggesting a role for this ectopic expression of aromatase in brain repair mechanisms.


Input: Altogether these data suggest that estrogens modulate adult, but not reparative neurogenesis, in zebrafish.

estrogens