Input: Stabilization of fenofibrate in low molecular weight hydroxypropylcellulose matrices produced by hot-melt extrusion.


Input: The objective of this study was to improve the dissolution rate and to enhance the stability of a poorly water-soluble and low glass-trasition temperature (T (g)) model drug, fenofibrate, in low molecular weight grades of hydroxypropylcellulose matrices produced by hot-melt extrusion (HME).

fenofibrate


Input: Percent drug loading had a significant effect on the extrudability of the formulations.


Input: Dissolution rate of fenofibrate from melt extruded pellets was faster than that of the pure drug (p < 0. 05).

fenofibrate


Input: Incorporation of sugars within the formulation further increased the fenofibrate release rates.

sugars

fenofibrate


Input: Differential scanning calorimetry results revealed that the crystalline drug was converted into an amorphous form during the HME process.


Input: Fenofibrate is prone to recrystallization due to its low T (g).

Fenofibrate


Input: Various polymers were evaluated as stabilizing agents among which polyvinylpyrrolidone 17PF and amino methacrylate copolymer exhibited a significant inhibitory effect on fenofibrate recrystallization in the hot-melt extrudates.

polyvinylpyrrolidone

amino methacrylate

fenofibrate


Input: Subsequently immediate-release fenofibrate tablets were successfully developed and complete drug release was achieved within 5 min.

fenofibrate


Input: The dissolution profile was comparable to that of a currently marketed formulation.


Input: The hot-melt extruded fenofibrate tablets were stable, and exhibited an unchanged drug release profile after 3-month storage at 40 degrees C/75% RH.

fenofibrate


Input: PTPN14 interacts with and negatively regulates the oncogenic function of YAP.


Input: The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis.


Input: The pivotal effector of this pathway is YAP, a transcriptional co-activator amplified in mouse and human cancers where it promotes epithelial-to-mesenchymal transition and malignant transformation.


Input: Here, we report a novel regulatory mechanism for the YAP oncogenic function via direct interaction with non-receptor tyrosine phosphatase 14 (PTPN14) through the WW domain of YAP and the PPxY domain of PTPN14.

tyrosine


Input: We also found that YAP is a direct substrate of PTPN14.


Input: In addition, luciferase reporter assay showed that the inhibition of the YAP transcriptional co-activator function by PTPN14 is mediated through their protein interactions and may result from an increase in the inactive cytoplasmic form of YAP.


Input: Last, knockdown of PTPN14 induces the nuclear retention of YAP and increases the YAP-dependent cell migration.


Input: In summary, our results indicate a potential regulatory role of PTPN14 on YAP and demonstrate a novel mechanism in YAP regulation.


Input: The autophagy-associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells.


Input: The aggressiveness of glioblastoma multiforme (GBM) is defined by local invasion and resistance to therapy.


Input: Within established GBM, a subpopulation of tumor-initiating cells with stem-like properties (GBM stem cells, GSCs) is believed to underlie resistance to therapy.


Input: The metabolic pathway autophagy has been implicated in the regulation of survival in GBM.


Input: However, the status of autophagy in GBM and its role in the cancer stem cell fraction is currently unclear.


Input: We found that a number of autophagy regulators are highly expressed in GBM tumors carrying a mesenchymal signature, which defines aggressiveness and invasion, and are associated with components of the MAPK pathway.


Input: This autophagy signature included the autophagy-associated genes DRAM1 and SQSTM1, which encode a key regulator of selective autophagy, p62.


Input: High levels of DRAM1 were associated with shorter overall survival in GBM patients.


Input: In GSCs, DRAM1 and SQSTM1 expression correlated with activation of MAPK and expression of the mesenchymal marker c-MET.


Input: DRAM1 knockdown decreased p62 localization to autophagosomes and its autophagy-mediated degradation, thus suggesting a role for DRAM1 in p62-mediated autophagy.


Input: In contrast, autophagy induced by starvation or inhibition of mTOR/PI-3K was not affected by either DRAM1 or p62 downregulation.


Input: Functionally, DRAM1 and p62 regulate cell motility and invasion in GSCs.


Input: This was associated with alterations of energy metabolism, in particular reduced ATP and lactate levels.

ATP

lactate


Input: Taken together, these findings shed new light on the role of autophagy in GBM and reveal a novel function of the autophagy regulators DRAM1 and p62 in control of migration/invasion in cancer stem cells.


Input: Selective activation of either mGlu2 or mGlu3 receptors can induce LTD in the amygdala.


Input: Group II metabotropic glutamate (mGlu) receptors are known to induce a long-term depression (LTD) of synaptic transmission in many brain regions including the amygdala.

glutamate


Input: However the roles of the individual receptor subtypes, mGlu2 and mGlu3, in LTD are not well understood.


Input: In particular, it is unclear whether activation of mGlu3 receptors is sufficient to induce LTD at synapses in the CNS.


Input: In the present study, advantage was taken of a Wistar rat strain not expressing mGlu2 receptors (Ceolin et al., 2011) to investigate the function of mGlu3 receptors in the amygdala.


Input: In this preparation, the group II agonist, DCG-IV induced an LTD of the cortical, but not the intra-nuclear, synaptic input to the lateral amygdala.


Input: This LTD was concentration dependent and was blocked by the group II mGlu receptor antagonist, LY341495.


Input: To investigate further the role of mGlu3 receptors, we used LY395756 (an mGlu2 agonist and mGlu3 antagonist), which acts as a pure mGlu3 receptor antagonist in this rat strain.


Input: This compound alone had no effect on basal synaptic transmission, but blocked the LTD induced by DCG-IV.


Input: Furthermore, we found that DCG-IV also induces LTD in mGlu2 receptor knock-out (KO) mice to a similar extent as in wild-type mice.


Input: This confirms that the activation of mGlu3 receptors alone is sufficient to induce LTD at this amygdala synapse.


Input: To address whether mGlu2 activation alone is also sufficient to induce LTD at this synapse we used LY541850 (the active enantiomer of LY395756) in wild-type mice.


Input: LY541850 induced a substantial LTD showing that either receptor alone is capable of inducing LTD in this pathway.


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

Glutamate


Input: Effect of water extracts from edible myrtaceae plants on uptake of 2-(n-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose in TNF-alpha-treated FL83B mouse hepatocytes.

2-(n-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose


Input: This study investigated the glucose uptake activity of the water extracts from the leaves and fruit of edible Myrtaceae plants, including guava (Psidium guajava Linn.), wax apples [Syzygium samarangense (Blume) Merr. and L. M. Perry], Pu-Tau [Syzygium jambo (L.) Alston], and Kan-Shi Pu-Tau (Syzygium cumini Linn.) in FL83B mouse hepatocytes.

glucose


Input: The fluorescent dye 2-(n-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose was used to estimate the uptake ability of the cells.

2-(n-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose


Input: Glucose uptake test showed that pink wax apple fruit extract (PWFE) exhibits the highest glucose uptake activity, at an increment of 21% in the insulin-resistant FL83B mouse hepatocytes as compared with the TNF-alpha-treated control group.

Glucose

glucose


Input: Vescalagin was isolated using column chromatography of PWFE.

Vescalagin


Input: This compound, at the concentration of 6. 25 micro g/mL, exhibits the same glucose uptake improvement in insulin-resistant cells as PWFE at a 100-micro g/mL dose.

glucose


Input: We postulate that vescalagin is an active component in PWFE that may alleviate the insulin resistance in mouse hepatocytes.

vescalagin


Input: Two new C-15 enolic acyl phragmalin-type limonoids from Chukrasia tabularis var. velutina.

enolic acyl phragmalin

limonoids


Input: Two new C-15 enolic acyl phragmalin-type limonoid orthoesters, chukvelutilide G (1) and chukrasine F (2), were isolated from the stem barks of Chukrasia tabularis var. velutina.

enolic acyl phragmalin

limonoid orthoesters

chukvelutilide G

chukrasine F


Input: Their structures were elucidated by their extensive high resolution-electrospray ionization mass spectrometry (HR-ESI-MS), one-and two-dimensional spectroscopic analysis, including heteronuclear single quantum coherence (HSQC), HMBC and NOESY experiments.


Input: A new xanthone from the bark of Calophyllum thorelii.

xanthone


Input: A new xanthone, calothorexanthone, together with five known compounds, garbogiol, 1, 4, 8-trihydroxyxanthone, delta-tocotrienol, 1, 7-dihydroxyxanthone and globuxanthone, was isolated from a petroleum ether extract of the bark of Calophyllum thorelii.

xanthone

calothorexanthone

garbogiol

1, 4, 8-trihydroxyxanthone

delta-tocotrienol

1, 7-dihydroxyxanthone

globuxanthone


Input: Their structures were established on the basis of spectroscopic methods, mainly one-and two-dimensional NMR.


Input: Antioxidant activity of the isolated compounds was tested using DPPH free radical scavenging assay and some exhibited remarkable effects with IC50 of 13. 63-17. 46 micro g mL (-1).

DPPH


Input: TRAPPC9-related autosomal recessive intellectual disability: report of a new mutation and clinical phenotype.


Input: Intellectual disability (ID) with autosomal recessive (AR) inheritance is believed to be common; however, very little is known about causative genes and genotype-phenotype correlations.


Input: The broad genetic heterogeneity of AR-ID, and its usually nonsyndromic nature make it difficult to pool multiple pedigrees with the same underlying genetic defect to achieve consistent nosology.


Input: Nearly all autosomal genes responsible for recessive cognitive disorders have been identified in large consanguineous families from the Middle East, and nonsense mutations in TRAPPC9 have been reported in a total of 5.


Input: Although several recurrent phenotypic abnormalities are described in some of these patients, the associated phenotype is usually referred to as nonsyndromic.


Input: By means of single-nucleotide polymorphism-array first and then by exome sequencing, we identified a new pathogenic mutation in TRAPPC9 in two Italian sisters born to healthy and apparently nonconsanguineous parents.


Input: It consists of a homozygous splice site mutation causing exon skipping with frameshift and premature termination, as confirmed by mRNA sequencing.


Input: By detailed phenotypic analysis of our patients, and by critical literature review, we found that homozygous TRAPPC9 loss-of-function mutations cause a distinctive phenotype, characterized by peculiar facial appearance, obesity, hypotonia (all signs resembling a Prader-Willi-like phenotype), moderate-to-severe ID, and consistent brain abnormalities.


Input: MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.


Input: Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options.


Input: We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals.


Input: Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein.


Input: To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route.


Input: Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps.


Input: Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology.


Input: Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30 +/- 10 non-overlapping injections per animal.


Input: Vector DNA was detectable in all samples tested and ranged from < 1 to > 3000 vector genome copies per cell.


Input: RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium.


Input: Left ventricular function remained unchanged over a 3-month follow-up.


Input: These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM.


Input: This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.


Input: Preparation and cyclodextrin assisted dissolution rate enhancement of itraconazolium dinitrate salt.

itraconazolium dinitrate


Input: The poor solubility of itraconazole (ITR) results in its variable oral absorption and bioavailability and has also proven to be a major setback in developing an efficient oral delivery system.

itraconazole

ITR


Input: To improve its solubility and dissolution profile, itraconazolium dinitrate salt (ITRDNT) was prepared and characterized using various spectral and thermal techniques.

itraconazolium dinitrate

ITRDNT


Input: The morphology of the salt was studied using optical and scanning electron microscopy (SEM).


Input: Broth microdilution assay demonstrated antifungal efficacy of ITRDNT similar to ITR against four different fungal strains namely, Asparagillus fumigatus, Microsporum canis, Microsporum gypsum and Trichophyton rubrum.

ITRDNT

ITR


Input: The salt exhibited better solubility profile than ITR in water and a number of pharmaceutical solvents.

ITR


Input: Dissolution studies revealed the total amount of drug released from ITRDNT in 3 h was four times greater than that of ITR.

ITRDNT

ITR


Input: To further improve dissolution characteristics, the physical mixtures of ITR and ITRDNT with two cyclodextrins, beta-cyclodextrin (beta-CD) and HP-beta-cyclodextrin (HP-beta-CD) were prepared and their molar ratios were optimized.

ITR

ITRDNT

beta-cyclodextrin

beta-CD

HP-beta-cyclodextrin

HP-beta-CD


Input: It was observed that about 75% of drug was released in 30 min from 1: 3 molar ratio of ITRDNT and HP-beta-CD physical mixture, which was distinctly higher than ITR commercial capsules (70%).

ITRDNT

HP-beta-CD

ITR


Input: Owing to its facile and economical preparation and substantially better in vitro release profile, the ITRDNT and its CD physical mixtures could be better and cost effective alternatives to ITR and commercial ITR capsules.

ITRDNT

ITR

ITR


Input: " Vitamin E " fortified parenteral lipid emulsions: Plackett-Burman screening of primary process and composition parameters.

Vitamin E


Input: The objective of this study was to screen the effect of eight formulations and process parameters on the physical attributes and stability of " Vitamin E "-rich parenteral lipid emulsions.

Vitamin E


Input: Screening was performed using a 12-run, 8-factor, 2-level Plackett-Burman design.


Input: This design was employed to construct polynomial equations that identified the magnitude and direction of the linear effect of homogenization pressure, number of homogenization cycles, primary and secondary emulsifiers, pre-homogenization temperature, oil loading, and ratio of vitamin E to medium-chain triglycerides (MCT) in the oil phase on particle size, polydispersity index, short-term stability, and outlet temperature of manufactured emulsions.

vitamin E

triglycerides


Input: The viscosity of vitamin E was reduced from 3700 (100%) to 64 mPa. s (30%) by MCT addition.

vitamin E


Input: As viscosity is critical for efficient emulsification, vitamin/MCT ratio was the most significant contributor for the stability of emulsions.


Input: Particle size increased from 236 to 388 nm, and percentage vitamin remaining emulsified after 48 h dropped from 100 to 73% with increase in vitamin/MCT ratio from 30/70 to 70/30.


Input: Significant decrease in particle size and PI, and an increase in outlet temperature were also observed with increase in homogenization pressure and number of homogenization cycles.


Input: Emulsifiers and oil loading, however, had insignificant effect on the responses.


Input: Overall, stable submicron emulsions at vitamin/MCT ratio of 30/70 could be prepared at 25, 000 psi and 25 cycles in ambient conditions.


Input: The identification of these parameters by a well-constructed design demonstrated the utility of screening studies in the " Quality by Design " approach to pharmaceutical product development.


Input: The effect of process parameters on audible acoustic emissions from high-shear granulation.


Input: Product quality in high-shear granulation is easily compromised by minor changes in raw material properties or process conditions.


Input: It is desired to develop a process analytical technology (PAT) that can monitor the process in real-time and provide feedback for quality control.


Input: In this work, the application of audible acoustic emissions (AAEs) as a PAT tool was investigated.


Input: A condenser microphone was placed at the top of the air exhaust on a PMA-10 high-shear granulator to collect AAEs for a design of experiment (DOE) varying impeller speed, total binder volume and spray rate.


Input: The results showed the 10 Hz total power spectral densities (TPSDs) between 20 and 250 Hz were significantly affected by the changes in process conditions.


Input: Impeller speed and spray rate were shown to have statistically significant effects on granulation wetting, and impeller speed and total binder volume were significant in terms of process end-point.


Input: The DOE results were confirmed by a multivariate PLS model of the TPSDs.


Input: The scores plot showed separation based on impeller speed in the first component and spray rate in the second component.


Input: The findings support the use of AAEs to monitor changes in process conditions in real-time and achieve consistent product quality.


Input: mGlu3 receptor and astrocytes: partners in neuroprotection.


Input: Astrocytes are currently studied intensively because of their now highlighted relevance as key players with neurons that modulate a wide range of central functions, from synaptic plasticity and synaptogenesis to regulation of metabolic and neuroinflammatory processes.


Input: Since the discovery of mGlu3 receptors on astrocytes, accumulating evidence supports a role of these receptors not only in maintaining synaptic homeostasis and treating psychiatric disorders but also in promoting astrocyte survival in several pathologic conditions.


Input: This review focuses on providing up-to-date knowledge regarding effects of activating astroglial mGlu3 receptors on psychiatric disorders, astrocyte and neuronal survival, and neurodegenerative diseases.


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


Input: Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice.


Input: Human studies suggest that a variety of prenatal stressors are related to high risk for cognitive and behavioral abnormalities associated with psychiatric illness (Markham and Koenig, 2011).


Input: Recently, a downregulation in the expression of GABAergic genes (i. e., glutamic acid decarboxylase 67 and reelin) associated with DNA methyltransferase (DNMT) overexpression in GABAergic neurons has been regarded as a characteristic phenotypic component of the neuropathology of psychotic disorders (Guidotti et al., 2011).

glutamic acid


Input: Here, we characterized mice exposed to prenatal restraint stress (PRS) in order to study neurochemical and behavioral abnormalities related to development of schizophrenia in the adult.


Input: Offspring born from non-stressed mothers (control mice) showed high levels of DNMT1 and 3a mRNA expression in the frontal cortex at birth, but these levels progressively decreased at post-natal days (PND) 7, 14, and 60.


Input: Offspring born from stressed mothers (PRS mice) showed increased levels of DNMTs compared to controls at all time-points studied including at birth and at PND 60.


Input: Using GAD67-GFP transgenic mice, we established that, in both control and PRS mice, high levels of DNMT1 and 3a were preferentially expressed in GABAergic neurons of frontal cortex and hippocampus.


Input: Importantly, the overexpression of DNMT in GABAergic neurons was associated with a decrease in reelin and GAD67 expression in PRS mice in early and adult life.


Input: PRS mice also showed an increased binding of DNMT1 and MeCP2, and an increase in 5-methylcytosine and 5-hydroxymethylcytosine in specific CpG-rich regions of the reelin and GAD67 promoters.

CpG


Input: Thus, the epigenetic changes in PRS mice are similar to changes observed in the post-mortem brains of psychiatric patients.


Input: Behaviorally, adult PRS mice showed hyperactivity and deficits in social interaction, prepulse inhibition, and fear conditioning that were corrected by administration of valproic acid (a histone deacetylase inhibitor) or clozapine (an atypical antipsychotic with DNA-demethylation activity).

valproic acid

clozapine


Input: Taken together, these data show that prenatal stress in mice induces abnormalities in the DNA methylation network and in behaviors indicative of a schizophrenia-like phenotype.


Input: Thus, PRS mice may be a valid model for the investigation of new drugs for schizophrenia treatment targeting DNA methylation.


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


Input: Presynaptic mGlu7 receptors control GABA release in mouse hippocampus.

GABA


Input: The functional role of presynaptic release-regulating metabotropic glutamate type 7 (mGlu7) receptors in hippocampal GABAergic terminals was investigated.

glutamate


Input: Mouse hippocampal synaptosomes were preloaded with [(3) H] D-gamma-aminobutyric acid ([(3) H] GABA) and then exposed in superfusion to 12 mM KCl.

[(3) H] D-gamma-aminobutyric acid

[(3) H] GABA

KCl


Input: The K (+)-evoked [(3) H] GABA release was inhibited by the mGlu7 allosteric agonist N, N'-dibenzyhydryl-ethane-1, 2-diamine dihydrochloride (AMN082, 0. 001-10 mu M), as well as by the group III mGlu receptor agonist l-(+)-2-amino-4-phosphonobutyric acid [(l)-AP4, 0. 01-1 mM].

K (+)

[(3) H] GABA

N, N'-dibenzyhydryl-ethane-1, 2-diamine dihydrochloride

l-(+)-2-amino-4-phosphonobutyric acid


Input: The mGlu8 receptor agonist (S)-3, 4-dicarboxyphenylglycine [(S)-3, 4-DCPG, 10-100 nM] was ineffective.

(S)-3, 4-dicarboxyphenylglycine

(S)-3, 4-DCPG


Input: AMN082 and (l)-AP4-induced effects were recovered by the mGlu7 negative allosteric modulator (NAM) 6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo [4, 5-c] pyridin-4 (5H)-one hydrochloride (MMPIP).

6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo [4, 5-c] pyridin-4 (5H)-one hydrochloride

MMPIP


Input: AMN082 also inhibited in a MMPIP-sensitive manner the K (+)-evoked release of endogenous GABA.

MMPIP

K (+)

GABA


Input: AMN082 and the adenylyl cyclase (AC) inhibitor MDL-12, 330A reduced [(3) H] GABA exocytosis in a 8-Br-cAMP-sensitive.

MDL-12, 330A

[(3) H] GABA


Input: AMN082-inhibitory effect was additive to that caused by (-) baclofen, but insensitive to the GABA (B) antagonist 3-[[(3, 4-Dichlorophenyl) methyl] amino] propyl] diethoxymethyl) phosphinic acid (CGP52432).

(-) baclofen

GABA

3-[[(3, 4-Dichlorophenyl) methyl] amino] propyl] diethoxymethyl) phosphinic acid


Input: Conversely, (-) baclofen-induced inhibition of GABA exocytosis was insensitive to MMPIP.

(-) baclofen

GABA

MMPIP


Input: Finally, the forskolin-evoked [(3) H] GABA release was reduced by AMN082 or (-) baclofen but abolished when the two agonists were added concomitantly.

forskolin

[(3) H] GABA

(-) baclofen


Input: Mouse hippocampal synaptosomal plasmamembranes posses mGlu7 receptor proteins; confocal microscopy analysis unveiled that mGlu7 proteins colocalize with syntaxin-1A (Stx-1A), with vesicular GABA transporter (VGAT)-proteins and with GABA (B) receptor subunit proteins.

GABA

GABA


Input: We propose that presynaptic inhibitory mGlu7 heteroreceptors, negatively coupled to AC-dependent intraterminal pathway, exist in mouse hippocampal GABA-containing terminals, where they colocalize, but do not functionally cross-talk, with GABA (B) autoreceptors.

GABA

GABA


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


Input: RETRACTED: Effects of crude diesel oil on the enzymatic defenses of the Great sturgeon, Huso huso.


Input: RETRACTED.


Input: A new method for preparing pentacyclic triterpene rich Centella asiatica extracts.

pentacyclic triterpene


Input: This study evaluated microwave-assisted extraction (MAE) for four pentacyclic triterpenes as well as developed a method for preparing a pentacyclic triterpenene rich extract from Centella asiatica.

pentacyclic triterpenes

pentacyclic triterpenene


Input: MAE was capable of increasing the yield of the pentacyclic triterpenes up to twice that produced by the heat reflux method, and it was also much less time consuming.

pentacyclic triterpenes


Input: The optimal conditions of MAE employed were extraction with absolute ethanol as solvent, an irradiation power of 600 W, at 75 degrees C, four irradiation cycles and four extraction times.

ethanol


Input: Here, we provide a simple method for the preparation of the pentacyclic triterpene rich C. asiatica extracts, which contained not less than 65% w/w total pentacyclic triterpenes.

pentacyclic triterpene

pentacyclic triterpenes


Input: The method involved a macroporous resin (Diaion (R) HP-20) column eluted with ethanol and a decolourisation step with activated charcoal.

ethanol


Input: Discovery and structural characterization of a phospholamban-binding cyclic peptide and design of novel inhibitors of phospholamban.


Input: The interplay between cardiac sarcoplasmic Ca (2 +) ATPase and phospholamban is a key regulating factor of contraction and relaxation in the cardiac muscle.

Ca (2 +)


Input: In heart failure, aberrations in the inhibition of sarcoplasmic Ca (2 +) ATPase by phospholamban are associated with anomalies in cardiac functions.

Ca (2 +)


Input: In experimental heart failure models, modulation of the interaction between these two proteins has been shown to be a potential therapeutic approach.


Input: The aim of our research was to find molecules able to interfere with the inhibitory activity of phospholamban on sarcoplasmic Ca (2 +) ATPase.

Ca (2 +)


Input: For this purpose, a portion of phospholamban was synthesized and used as target for a phage-display peptide library screening.


Input: The cyclic peptide C-Y-W-E-L-E-W-L-P-C-A was found to bind to phospholamban (1-36) with high specificity.


Input: Its functional activity was tested in Ca (2 +) uptake assays utilizing preparations from cardiac sarcoplasmic reticulum.

Ca (2 +)


Input: By synthesizing and testing a series of alanine point-mutated cyclic peptides, we identified which amino acid was important for the inhibition of the phospholamban function.

alanine

amino acid


Input: The structures of active and inactive alanine-mutated cyclic peptides, and of phospholamban (1-36), were determined by NMR.

alanine


Input: This structure-activity analysis allowed building a model of phospholamban-cyclic peptide complex.


Input: Thereafter, a simple pharmacophore was defined and used for the design of small molecules.


Input: Finally, examples of such molecules were synthesized and characterized as phospholamban inhibitors.


Input: A possible explanation for the population size discrepancy in tuna (genus Thunnus) estimated from mitochondrial DNA and microsatellite data.


Input: A recent study using both mitochondrial DNA (mtDNA) and microsatellite data reported on a population size discrepancy in the eastern tiger salamander where the effective population size (N (e)) estimate of the former exceeded that of the latter.


Input: That study suggested, among other hypotheses, that homoplasy of microsatellite alleles is responsible for the discrepancy.


Input: In this investigation, we report 10 new cases of a similar discrepancy in five species of tuna.


Input: These cases derive from our Bayesian inferences using data from Pacific Bluefin Tuna (Thunnus orientalis) and Yellowfin Tuna (Thunnus albacares), as well as from published estimates of genetic diversity for additional populations of Yellowfin Tuna and three other tuna species.


Input: Phylogenetic character analyses of inferred genealogies of Pacific Bluefin and Yellowfin Tuna reveal similar reduced levels of mtDNA and microsatellite homoplasy.


Input: Thus, the discrepancy between inferred population sizes from mtDNA and microsatellite data in tuna is most likely not an artifact of the chosen mutation models used in the microsatellite analyses, but may reflect behavioral differences between the sexes such as female-biased philopatry and male-biased dispersal.


Input: This explanation now warrants critical testing with more local populations of tuna and with other animal and plant groups that have different life histories.


Input: Organ accumulation in mice after inhalation of single or mixed essential oil compounds.


Input: Essential oils are composed of multiple components.


Input: It is thought that the effect of essential oils is due to specific component ratios, which may differ from the original ratio when the essential oil is absorbed.


Input: However, very little detailed research exists in this area.


Input: We studied the distribution of essential oil components after inhalation of single and mixed components in mice.


Input: This research was done using four main components of Alpinia zerumbet (Pers.) B.


Input: L.


Input: Burtt. and R.


Input: M.


Input: Sm.: alpha-pinene, p-cymene, 1, 8-cineole, and limonene.

alpha-pinene

p-cymene

1, 8-cineole

limonene


Input: After inhalation of single or mixed components for 90 min, component levels in the brain and liver of mice were measured.


Input: The results indicated that the amount of alpha-pinene in the brain and liver was twofold greater after mixed-component inhalation than that after single-component inhalation.

alpha-pinene


Input: In a comparison of the components of the mixed inhalation, the ratio of alpha-pinene increased to about three times that of 1, 8-cineole.

alpha-pinene

1, 8-cineole


Input: It is thought that the absorption via the nasal mucus greatly influences this phenomenon.


Input: The results of this investigation of the bodily distribution of essential oil volatile components may provide clues for elucidating their action.


Input: Antiangiogenic effects of p-coumaric acid in human endothelial cells.

p-coumaric acid


Input: p-Coumaric acid, a hydroxy derivative of cinnamic acid, has been known to possess antioxidant and anticancer activities.

p-Coumaric acid

hydroxy

cinnamic acid


Input: Despite its potential contribution to chemopreventive effects, the mechanism by which p-coumaric acid exerts its antiangiogenic actions remains elusive.

p-coumaric acid


Input: In this study, we revealed that p-coumaric acid inhibited the sprouting of endothelial cells in rat aortic rings and inhibited the tube formation and migration of endothelial cells.

p-coumaric acid


Input: We observed that p-coumaric acid could downregulate mRNA expression levels of the key angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor.

p-coumaric acid


Input: Also, we demonstrated that p-coumaric acid inhibited both the AKT and ERK signaling pathways, which are known to be crucial for angiogenesis.

p-coumaric acid


Input: Using a mouse model, we also showed that p-coumaric acid effectively suppressed tumor growth in vivo by lowering hemoglobin contents.

p-coumaric acid


Input: Collectively, these findings indicate that p-coumaric acid possesses potent anticancer properties due to the inhibition of angiogenesis in vivo.

p-coumaric acid


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


Input: Fatty acid composition of selected macrophytes.

Fatty acid


Input: The content of total lipids and the fatty acid (FA) profile were determined for eight macroalgae (Cystoseira abies-marina, Fucus spiralis, Chaetomorpha pachynema, Codium elisabethae, Porphyra sp., Osmundea pinnatifida, Pterocladiella capillacea and Sphaeroccoccus coronopifolius).

fatty acid


Input: Total lipids were extracted using a solvent mixture of methanol/chloroform (2/1, v/v) and further derivatised to FA methyl esters (FAME).

methanol

chloroform

FA methyl esters

FAME


Input: The analyses of FAME samples were performed by gas chromatography coupled to a flame ionisation detector.

FAME


Input: The total lipid content ranged from 0. 06 to 3. 54 g (per 100 g).


Input: The most abundant saturated FA were palmitic (C16: 0) and myristic (C14: 0), while oleic (C18: 1 n-9) was the dominant monounsaturated acid.

palmitic

C16: 0

myristic

C14: 0

oleic

C18: 1

monounsaturated acid


Input: All seaweeds contained linoleic FA (C18: 2 n-6).

linoleic FA

C18: 2


Input: The alpha-linolenic (C18: 3 n-3) and eicosapentaenoic (20: 5 n-3) acids were present only in Porphyra sp.

alpha-linolenic

C18: 3

eicosapentaenoic


Input: (3. 34% +/- 0. 13) and C. pachynema (0. 47% +/- 0. 12), respectively.


Input: The n-6/n-3 and h/H ratios were low, suggesting a high nutritional value of the algae studied.

H


Input: Improvement in solubility and bioavailability of puerarin by mechanochemical preparation.

puerarin


Input: An efficient and solvent-free procedure was developed to improve the solubility and bioavailability of the poorly water-soluble drug puerarin by mechanochemical technology.

puerarin


Input: The stable inclusion complex of puerarin and 2-hydroxypropyl-beta-cyclodextrin (HPCD) was prepared by a ball mill under the following conditions: equimolar ratio of puerarin to HPCD; rotational speed of 250 rpm; milling time of 90 min; steel balls of 22 mm diameter.

puerarin

HPCD

HPCD


Input: The solid complex was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffractometry (XRD), and fourier transformation-infrared spectroscopy (FT-IR).


Input: Mechanochemical action could result in enhanced molecular encapsulation, homogeneous distribution and amorphization of the drug.


Input: In comparison to puerarin, a 1. 64-fold increase in absolute bioavailability was obtained.

puerarin


Input: The solubility of the inclusion complex was 25. 33-fold higher and the drug release amount reached 79. 44% at 15 min, 2. 76-fold higher.


Input: Design and evaluation of a self-microemulsifying drug delivery system for apigenin.

apigenin


Input: Objective of this study was to prepare, characterize and evaluate a self-microemulsifying drug delivery system (SMEDDS) with the aim to improve the solubility and dissolution of apigenin.

apigenin


Input: Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of apigenin loaded SMEDDS was optimized by a simplex lattice experiment design.

apigenin


Input: The optimal formulation of SMEDDS obtained was comprised of 60% Cremophor ((R)) EL, 30% Transcutol ((R)) HP and 10% Capryol (TM) 90.

Transcutol

Capryol


Input: The equilibrium solubility of apigenin in SMEDDS was about 15 mg/g, and it could increase the solubility of apigenin in water for about 7500 folds.

apigenin

apigenin


Input: Apigenin loaded SMEDDS could turn into microemulsion when diluted with distilled water and the droplets were spherical under transmission electron microscope (TEM), the average particle size was 17. 1 nm and zeta potential-5. 18 mV.

Apigenin


Input: In vitro dissolution studies showed about 95% of apigenin was released within 10 min.

apigenin


Input: All of the results showed that SMEDDS could enhance the solubility and dissolution of apigenin, and would be a potential carrier to improve the oral absorption of apigenin, a poorly water soluble drug.

apigenin

apigenin


Input: Improvement of liver function in humans using a mixture of schisandra fruit extract and sesamin.

sesamin


Input: This was a randomized, parallel, and placebo-controlled study.


Input: Forty subjects were divided into a test group and a placebo group.


Input: The study was focused on the potential effects of a mixture of Schisandra fruit extract and sesamin (hereinafter called' SCH') in the subjects with borderline high levels (40-60 U/L) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST).

sesamin

SCH

alanine

aspartate


Input: Twenty subjects taking SCH (four tablets per day) and 20 subjects taking a placebo (four tablets per day) were studied.

SCH


Input: The effects of SCH on ALT, AST, total bilirubin, direct bilirubin, free radical levels, total antioxidant status, glutathione peroxidase, glutathione reductase, and the lag time for low-density lipoprotein oxidation were determined.

SCH

bilirubin

bilirubin

glutathione

glutathione


Input: The total test period was 5 months.


Input: Intervention of SCH clearly reduced the levels of ALT and AST, but it made no change in the total bilirubin and direct bilirubin.

SCH

bilirubin

bilirubin


Input: Intake of SCH also greatly increased the antioxidant capacity and decreased the values of thiobarbituric acid reactive substances, total free radicals, and superoxide anion radicals in the plasma.

SCH

thiobarbituric acid

superoxide


Input: The activities of glutathione peroxidase and reductase in the erythrocytes were significantly increased.

glutathione


Input: In addition, the lag time for low-density lipoprotein oxidation, an inflammatory marker, was evidently increased.


Input: Fatty liver was found to have been significantly improved in this study.


Input: SCH proved to have the effects of antioxidation and improving liver function.

SCH


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


Input: Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer.


Input: Most solid tumors are characterized by a metabolic shift from glucose oxidation to glycolysis, in part due to actively suppressed mitochondrial function, a state that favors resistance to apoptosis.

glucose


Input: Suppressed mitochondrial function may also contribute to the activation of hypoxia-inducible factor 1 alpha (HIF1 alpha) and angiogenesis.


Input: We have previously shown that the inhibitor of pyruvate dehydrogenase kinase (PDK) dichloroacetate (DCA) activates glucose oxidation and induces apoptosis in cancer cells in vitro and in vivo.

pyruvate

dichloroacetate

DCA

glucose


Input: We hypothesized that DCA will also reverse the' pseudohypoxic' mitochondrial signals that lead to HIF1 alpha activation in cancer, even in the absence of hypoxia and inhibit cancer angiogenesis.

DCA


Input: We show that inhibition of PDKII inhibits HIF1 alpha in cancer cells using several techniques, including HIF1 alpha luciferase reporter assays.


Input: Using pharmacologic and molecular approaches that suppress the prolyl-hydroxylase (PHD)-mediated inhibition of HIF1 alpha, we show that DCA inhibits HIF1 alpha by both a PHD-dependent mechanism (that involves a DCA-induced increase in the production of mitochondria-derived alpha-ketoglutarate) and a PHD-independent mechanism, involving activation of p53 via mitochondrial-derived H (2) O (2), as well as activation of GSK3 beta.

prolyl

DCA

DCA

alpha-ketoglutarate

H (2) O (2)


Input: Effective inhibition of HIF1 alpha is shown by a decrease in the expression of several HIF1 alpha regulated gene products as well as inhibition of angiogenesis in vitro in matrigel assays.


Input: More importantly, in rat xenotransplant models of non-small cell lung cancer and breast cancer, we show effective inhibition of angiogenesis and tumor perfusion in vivo, assessed by contrast-enhanced ultrasonography, nuclear imaging techniques and histology.


Input: This work suggests that mitochondria-targeting metabolic modulators that increase pyruvate dehydrogenase activity, in addition to the recently described pro-apoptotic and anti-proliferative effects, suppress angiogenesis as well, normalizing the pseudo-hypoxic signals that lead to normoxic HIF1 alpha activation in solid tumors.

pyruvate


Input: Macrophage cathepsin K promotes prostate tumor progression in bone.


Input: Bone marrow macrophages (BMMs) share common progenitors with osteoclasts and are critical components of bone-tumor microenvironment; however, their function in prostate tumor growth in the skeleton has not been explored.


Input: BMMs are the major source of inflammatory factors and proteases, including cysteine protease cathepsin K (CTSK).

cysteine


Input: In this study, utilizing mice deficient in CTSK, we demonstrate the critical involvement of this potent collagenase in tumor progression in bone.


Input: We present the evidence that tumor growth and progression in the bone are impaired in the absence of CTSK.


Input: Most importantly, we show for the first time that BMM-supplied CTSK may be involved in CCL2-and COX-2-driven pathways that contribute to tumor progression in bone.


Input: Together, our data unravel novel roles for CTSK in macrophage-regulated processes, and provide evidence for close interplay between inflammatory, osteolytic and tumor cell-driven events in the bone-tumor microenvironment.


Input: Single non-ionic surfactant based self-nanoemulsifying drug delivery systems: formulation, characterization, cytotoxicity and permeability enhancement study.


Input: Single non-ionic surfactant based self-nanoemulsifying drug delivery system (SNEDDS) was formulated and characterised for poor water soluble drug, Atorvastatin calcium.

Atorvastatin calcium


Input: Capmul MCM oil showing highest solubility for Atorvastatin calcium was selected as oil phase.

Atorvastatin calcium


Input: Self-nanoemulsifying capacity of Cremophor RH 40, Cremophor EL, Tween 20, Tween 60, Tween 80 and Labrasol were tested for the selected oil.

Tween 20

Tween 60

Tween 80


Input: In vitro dissolution studies were performed and were characterized by t85% and dissolution efficiency (DE).


Input: Cytotoxicity of the formulations and permeation enhancement of the drug across caco-2 cell monolayer was assessed.


Input: Capmul MCM was found to be better nanoemulsified in decreasing order of Cremophor RH 40 > Cremophor EL > Tween 20 > Tween 60 > Tween 80.

Tween 20

Tween 60

Tween 80


Input: Values of droplet size (range 11-83 nm), polydispersity index (range 0. 07-0. 65); zeta potential (range-3. 97 to-19. 0) and cloud point (60-85 degrees C) before and after drug loading proves the uniformity and stability of the formulations.


Input: SNEDDS formulated with Tween 20 surfactant showed enhanced dissolution with t85% and DE values at 10 min and 78. 70, respectively.

Tween 20


Input: None of the formulation showed cytotoxicity at the concentration tested.


Input: Tween 20 based SNEDDS enhanced permeation of the drug as compared with pure drug across cell lines.

Tween 20


Input: It can be concluded that SNEDDS can be formulated by using single non-ionic surfactant system for enhance dissolution and absorption of poorly soluble drug, Atorvastatin calcium.

Atorvastatin calcium


Input: Does the light influence astaxanthin production in Xanthophyllomyces dendrorhous?

astaxanthin


Input: Astaxanthin (C40H52O4) is an important natural pigment that has considerable promising applications in human health.

Astaxanthin


Input: Until now, many efforts were made aimed to develop economically sustainable bioprocesses alternative to the chemical synthesis, to satisfy the increasing demand of this ketocarotenoid from feed, food and cosmetic industries.


Input: The extraction of natural astaxanthin from the yeast Xanthophyllomyces dendrorhous till now seems to be rather expensive if compared with chemically synthesized astaxanthin.

astaxanthin

astaxanthin


Input: In this article, astaxanthin production by Xanthophyllomyces dendrorhous under two different conditions was studied: a first effort was made using a conventional reactor while a second using an enlightened one.

astaxanthin


Input: This research was aimed also to optimise astaxanthin production by testing the influence of the light and of some nutrient sources.

astaxanthin


Input: From fermentation tests, an astaxanthin yield ranging about 970 micro g g (-1) was obtained after fed batch cultivation in the conventional reactor.

astaxanthin


Input: In the enlightened reactor lower values, about 930 micro g g (-1), were found.


Input: Silibinin triggers apoptosis and cell-cycle arrest of SGC7901 cells.

Silibinin


Input: Silibinin, a flavonoid compound, has shown to be of chemopreventive potential against many cancers.

Silibinin

flavonoid


Input: However, its efficacy against gastric cancer has not been well elucidated.


Input: Here, we assessed the activity of Silibinin on apoptosis and cell-cycle arrest in human gastric cells culture system using SGC-7901 as the model.

Silibinin


Input: Silibinin treatment could inhibit the cell growth and cause a prominent G2 phase arrest and apoptosis in dose-and time-dependent manner.

Silibinin


Input: In mechanistic studies, Silibinin decreased the protein level of p34cdc2, which might be the possible molecular mechanism of Silibinin efficacy on the growth inhibition in SGC-7901 cells.

Silibinin

Silibinin


Input: In addition, Silibinin caused an increase in p53 and p21 protein level as well as mRNA levels.

Silibinin


Input: Interestingly, Silibinin-induced apoptosis in SGC-7901 cells was independent of caspases activation.

Silibinin


Input: These results indicated that Silibinin is a cell-cycle regulator and apoptosis inducer in human gastric carcinoma SGC-7901 cells and might be used as a candidate chemopreventive agent for gastric carcinoma prevention and intervention.

Silibinin


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


Input: Acetylation and deacetylation--novel factors in muscle wasting.


Input: We review recent evidence that acetylation and deacetylation of cellular proteins, including transcription factors and nuclear cofactors, may be involved in the regulation of muscle mass.


Input: The level of protein acetylation is balanced by histone acetyltransferases (HATs) and histone deacetylases (HDACs) and studies suggest that this balance is perturbed in muscle wasting.


Input: Hyperacetylation of transcription factors and nuclear cofactors regulating gene transcription in muscle wasting may influence muscle mass.


Input: In addition, hyperacetylation may render proteins susceptible to degradation by different mechanisms, including intrinsic ubiquitin ligase activity exerted by HATs and by dissociation of proteins from cellular chaperones.


Input: In recent studies, inhibition of p300/HAT expression and activity and stimulation of SIRT1-dependent HDAC activity reduced glucocorticoid-induced catabolic response in skeletal muscle, providing further evidence that hyperacetylation plays a role in muscle wasting.


Input: It should be noted, however, that although several studies advocate a role of hyperacetylation in muscle wasting, apparently contradictory results have also been reported.


Input: For example, muscle atrophy caused by denervation or immobilization may be associated with reduced, rather than increased, protein acetylation.


Input: In addition, whereas hyperacetylation results in increased degradation of certain proteins, other proteins may be stabilized by increased acetylation.


Input: Thus, the role of acetylation and deacetylation in the regulation of muscle mass may be both condition-and protein-specific.


Input: The influence of HATs and HDACs on the regulation of muscle mass, as well as methods to modulate protein acetylation, is an important area for continued research aimed at preventing and treating muscle wasting.


Input: The effects of an antiosteoporosis herbal formula containing epimedii herba, ligustri lucidi fructus and psoraleae fructus on density and structure of rat long bones under tail-suspension, and its mechanisms of action.


Input: An innovative anti-osteoporosis herbal formula containing Epimedii Herba, Ligustri Lucidi Fructus and Psoraleae Fructus (ELP) has been previously shown its bone protecting effects in ovariectomized osteoporotic rats and also in post-menopausal osteopenic women.


Input: This study aimed to investigate the efficacy of ELP against bone loss during physical inactivity or weightlessness.


Input: A hindlimb unloading tail-suspended rat model was used for studying the effects of ELP on bone mineral density (BMD) and bone micro-architecture.


Input: For in vitro mechanistic studies, rat mesenchymal stem cells (MSCs) and mouse macrophage cells (RAW264. 7) were used for studying the effects of ELP on osteogenic/adipogenic differentiations and osteoclastogenesis, respectively.


Input: Our data illustrated that ELP had a significant preventive effect against bone loss induced by tail-suspension (TS) at day 28 (p < 0. 01) as indicated in the reduction in BMD loss and the preservation of bone micro-architecture.


Input: ELP could significantly promote the osteogenesis and suppress the adipogenesis (p < 0. 05) in MSCs.


Input: Besides, significant inhibition of osteoclast formation (p < 0. 01) was found in ELP-treated RAW264. 7 cells upon receptor activator of nuclear factor kappa-B ligand induction.


Input: Our study presents the first scientific evidence that ELP had a significant preventive effect against bone loss induced by TS through the actions of enhancing osteogenesis, suppressing adipogenesis and osteoclastogenesis.


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


Input: Two new alkaloid galactosides from the kernel of Prinsepia uniflora.

alkaloid galactosides


Input: Two new alkaloid galactosides have been isolated from the kernel of Prinsepia uniflora.

alkaloid galactosides


Input: Their structures were elucidated as 5-[(alpha-D-galactopyranosyloxy) methyl]-1H-pyrrole-2-carbaldehyde (1) and 6-[(alpha-D-galactopyranosyloxy) methyl]-3-pyridinol (2) by various spectroscopic means including HR-ESI-MS, IR, 1D and 2D NMR.

5-[(alpha-D-galactopyranosyloxy) methyl]-1H-pyrrole-2-carbaldehyde

6-[(alpha-D-galactopyranosyloxy) methyl]-3-pyridinol


Input: The determined structures were characterized with a unit of galactose which is rarely seen in the previously isolated pyrrole and pyridinol compounds.

galactose

pyrrole

pyridinol


Input: mGlu2/3 and mGlu5 receptors: potential targets for novel antidepressants.


Input: Major depressive disorder is among the most prevalent forms of mental illness.


Input: All currently available antidepressant medications have stemmed from study of the mechanisms of serendipitously discovered drugs, and only 30-50% of patients exhibit remission and frequently at least 3-4 weeks are required for manifestation of significant therapeutic effects.


Input: To overcome these drawbacks, discovering novel neuronal mechanisms of pathophysiology of depression as well as more effective treatments are necessary.


Input: This review focuses on the metabotropic glutamate (mGlu) receptors and their potential for drug targets for the treatment of depression.

glutamate


Input: In particular, accumulating evidence has indicated the potential importance and usefulness of agents acting on mGlu2/3 and mGlu5 receptors.


Input: Preclinical and clinical evidence of mGlu2/3 receptor ligands and mGlu5 receptor antagonists are described.


Input: Moreover, their potential in clinic will be discussed in the context of neuronal mechanisms of ketamine, an agent recently demonstrated a robust effect for patients with treatment-resistant depression.

ketamine


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

Glutamate


Input: Combining GLP-1 receptor agonists with insulin: therapeutic rationales and clinical findings.


Input: Due to the increasing prevalence of type 2 diabetes mellitus (T2DM), the emergent trend towards diagnosis in younger patients and the progressive nature of this disease, many more patients than before now require insulin to maintain glycaemic control.


Input: However, there is a degree of inertia among physicians and patients regarding the initiation and intensification of insulin therapy, in part due to concerns about the associated weight gain and increased risk of hypoglycaemia.


Input: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and suppress glucagon secretion in a glucose-dependent manner, thus conferring glycaemic control with a low incidence of hypoglycaemia.

glucose


Input: GLP-1RAs also promote weight loss, and have beneficial effects on markers of beta cell function, lipid levels, blood pressure and cardiovascular risk markers.


Input: However, the durability of their effectiveness is unknown and, compared with insulin, the antihyperglycaemic efficacy of GLP-1RAs is limited.


Input: The combination of a GLP-1RA and insulin might thus be highly effective for optimal glucose control, ameliorating the adverse effects typically associated with insulin.

glucose


Input: Data from clinical studies support the therapeutic potential of GLP-1RA-insulin combination therapy, typically showing beneficial effects on glycaemic control and body weight, with a low incidence of hypoglycaemia and, in established insulin therapy, facilitating reductions in insulin dose.


Input: In this review, the physiological and pharmacological rationale for using GLP-1RA and insulin therapies in combination is discussed, and data from clinical studies that have assessed the efficacy and safety of this treatment strategy are outlined.


Input: Metabonomic Study of Genkwa Flos-induced Hepatotoxicity and Effect of Herb-Processing Procedure on Toxicity.


Input: A urinary metabonomic approach based on ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS) was developed to study the metabolic disturbances caused by the administration of Genkwa Flos (GF) to rats.


Input: Potential biomarkers of GF-induced toxic effects were screened out and identified, and the underlying toxicological mechanism as well as the detoxification of vinegar-processing procedure on this herb was discussed.


Input: Urine samples were analyzed by the established UPLC-MS method.


Input: With the help of serum biochemistry and histopathology results, metabolic disturbances induced by the exposure to GF and the detoxification of processing procedure were confirmed.


Input: The differences in the metabolic profiles of healthy and treated rats were clearly discriminated with the principal component analysis of the chromatographic data.


Input: Eight significantly changed metabolites were identified and interpreted as biomarkers for the hepatotoxicity and detoxification of processing procedure.


Input: This study indicated that a UPLC-MS-based metabonomic analysis of urine samples could be considered as a promising tool to predict the hepatotoxicity induced by the GF and the detoxification of traditional vinegar-processing procedure on this herb.


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


Input: Group III and subtype 4 metabotropic glutamate receptor agonists: discovery and pathophysiological applications in Parkinson' s disease.

glutamate


Input: Restoring the balance between excitatory and inhibitory circuits in the basal ganglia, following the loss of dopaminergic (DA) neurons of the substantia nigra pars compacta, represents a major challenge to treat patients affected by Parkinson' s disease (PD).


Input: The imbalanced situation in favor of excitation in the disease state may also accelerate excitotoxic processes, thereby representing a potential target for neuroprotective therapies.


Input: Reducing the excitatory action of glutamate, the major excitatory neurotransmitter in the basal ganglia, should lead to symptomatic improvement for PD patients and may promote the survival of DA neurons.

glutamate


Input: Recent studies have focused on the modulatory action of metabotropic glutamate (mGlu) receptors on neurodegenerative diseases including PD.

glutamate


Input: Group III mGlu receptors, including subtypes 4, 7 and 8, are largely expressed in the basal ganglia.


Input: Recent studies highlight the use of selective mGlu4 receptor positive allosteric modulators (PAMs) for the treatment of PD.


Input: Here we review the effects of newly-designed group-III orthosteric agonists on neuroprotection, neurorestoration and reduction of l-DOPA induced dyskinesia in animal models of PD.

l-DOPA


Input: The combination of orthosteric mGlu4 receptor selective agonists with PAMs may open new avenues for the symptomatic treatment of PD.


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

Glutamate


Input: Nucleophosmin is essential for c-Myc nucleolar localization and c-Myc-mediated rDNA transcription.


Input: The transcription factor c-Myc has a critical role in cell proliferation and growth.


Input: The control of ribosome biogenesis by c-Myc through the regulation of transcription mediated by all three RNA polymerases is essential for c-Myc-driven proliferation.


Input: Specifically, in the nucleolus, c-Myc has been shown to be recruited to ribosomal DNA and activate RNA polymerase (pol) I-mediated transcription of ribosomal RNA (rRNA) genes.


Input: In addition, c-Myc accumulates in nucleoli upon inhibition of the proteasome, suggesting nucleolar localization also has a role in c-Myc proteolysis.


Input: Nucleophosmin (NPM), a predominantly nucleolar protein, is also critical in ribosome biogenesis and, like c-Myc, is found overexpressed in many types of tumors.


Input: Previously, we demonstrated that NPM directly interacts with c-Myc and controls c-Myc-induced hyperproliferation and transformation.


Input: Here, we show that NPM is necessary for the localization of c-Myc protein to nucleoli, whereas c-Myc nucleolar localization is independent of p53, Mdm2 and ARF.


Input: Conversely, high transient NPM expression enhances c-Myc nucleolar localization, leading to increased c-Myc proteolysis.


Input: In addition, NPM is necessary for the ability of c-Myc to induce rRNA synthesis in the nucleolus, and constitutive NPM overexpression stimulates c-Myc-mediated rRNA synthesis.


Input: Taken together, these results demonstrate an essential role for NPM in c-Myc nucleolar localization and c-Myc-mediated rDNA transcription.


Input: Opposing functions of Fbxw7 in keratinocyte growth, differentiation and skin tumorigenesis mediated through negative regulation of c-Myc and Notch.


Input: The tumor suppressor Fbxw7 (also known as Sel-10, hCdc4, hAgo, or Fbw7) is an F-box protein that functions as the substrate-recognition subunit of an SCF ubiquitin ligase complex and targets a group of oncoproteins for degradation.


Input: We now show that Fbxw7 regulates the proliferation and differentiation of keratinocytes by mediating the degradation of c-Myc and Notch proteins.


Input: Fbxw7-deficient keratinocytes showed an increased proliferative capacity that was dependent on the accumulation of c-Myc but not on that of Notch.


Input: Fbxw7 deficiency also resulted in the premature differentiation of keratinocytes in a manner dependent on both c-Myc and Notch.


Input: Although Fbxw7-deficient keratinocytes proliferated excessively in vitro, loss of Fbxw7 did not predispose keratinocytes to the formation of squamous cell carcinoma in vivo induced by the expression of oncogenic Ras, possibly because the stem cell population of keratinocytes becomes exhausted as a result of enhanced Notch activity.


Input: Indeed, suppression of Notch signaling by additional ablation of RBP-J in Fbxw7-deficient keratinocytes conferred a more aggressive tumorigenic capacity.


Input: Collectively, these results indicate that Fbxw7 controls the proliferation and differentiation of keratinocytes, and that it exerts both inhibitory and stimulatory actions in skin carcinogenesis by counteracting the proliferation-promoting effect of c-Myc and the tumor-suppressive effect of Notch, respectively.


Input: Risk factors for Parkinson' s disease may differ in men and women: an exploratory study.


Input: Although several environmental and genetic risk or protective factors have been associated with Parkinson' s disease (PD), their interactions overall and in men and women separately remain unknown.


Input: We used the medical records-linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995.


Input: Each incident case was matched by age (+/- 1 year) and sex to a general population control.


Input: We considered the following 12 risk or protective factors: personal history of head trauma, pesticide use, immunologic diseases, anemia, hysterectomy (in women only), cigarette smoking, coffee consumption, and education; and family history of parkinsonism, essential tremor, dementia, or psychiatric disorders.


Input: We used recursive partitioning analyses to explore interactions overall and in men and women separately and used logistic regression analyses to test for interactions.


Input: In the overall group, we observed the independent effects of anemia, lack of coffee consumption (never vs. ever), and head trauma; however, the findings were different in men and women.


Input: In men, we observed the independent effects of lack of coffee consumption (never vs. ever), head trauma, and pesticide use, and a suggestive synergistic interaction between immunologic diseases and family history of dementia.


Input: By contrast, in women, anemia was the most important factor and we observed a suggestive synergistic interaction between anemia and higher education.


Input: Risk factors for PD and their interactions may differ in men and women.


Input: Solid lipid nanoparticles and nanosuspension of adefovir dipivoxil for bioavailability improvement: formulation, characterization, pharmacokinetic and biodistribution studies.

adefovir dipivoxil


Input: The present study was aimed at developing colloidal formulations like solid lipid nanoparticles (SLN) and nanosuspension (NS) for improving bioavailability of adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor which displays poor oral bioavailability.

adefovir dipivoxil

nucleoside


Input: SLNs were prepared by solvent injection method while NS was prepared by pearl milling method.


Input: The prepared formulations were characterized for physicochemical parameters such as particle size, zeta potential, drug content, X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC).


Input: Pharmacokinetic and biodistribution studies were performed in mice to evaluate in vivo fate of the formulations.


Input: The SLNs showed particle size of 267 +/- 18 nm and entrapment efficiency of 73. 5 +/- 2. 12%.


Input: The particle size obtained for NS was 393 +/- 13 nm against 710 +/- 70 mu m for bulk drug, which led to significant improvement in saturation solubility.


Input: DSC and XRD studies of NS and SLN showed reduction in crystallinity while in vitro studies showed improved dissolution rate in both cases.


Input: Pharmacokinetics studies of orally administered formulations in mice exhibited higher plasma concentration compared to plain drug.


Input: Biodistribution studies showed higher accumulation of drug in liver, kidneys, intestine and stomach.


Input: The higher concentration of AD in liver after 24 hr highlights its potential advantage for effective treatment of chronic hepatitis infection.


Input: The relative bioavailability for adefovir NS and SLN were 52. 46% and 78. 23% respectively compared to 34. 34% bioavailability obtained after administration of adefovir micro suspension (AMS), indicating suitability of both nanoparticulate formulations for improving bioavailability.

adefovir

adefovir


Input: SLNs were found to performed better as compared to NS for improving the bioavailability of AD.


Input: A new bromobenzyl methyl sulphoxide from marine red alga Symphyocladia latiuscula.

bromobenzyl methyl sulphoxide


Input: A new bromophenol, 2, 3, 6-tribromo-4, 5-dihydroxybenzyl methyl sulphoxide, was isolated from the EtOH extract of the marine alga Symphyocladia latiuscula.

bromophenol

2, 3, 6-tribromo-4, 5-dihydroxybenzyl methyl sulphoxide

EtOH


Input: Its structure was confirmed by spectroscopic methods (1D-and 2D-NMR, HR-ESI-MS).


Input: This new bromophenol showed moderate antifungal activity against Candida albicans with MIC value of 37. 5 micro g mL (-1).

bromophenol


Input: Aromadendrine, a new component of the flavonoid pattern of Olea europaea L. and its anti-inflammatory activity.

Aromadendrine

flavonoid


Input: Leaves of Olea europaea, cultivar Nocellara del Belice, were examined with respect to the medium-polar fraction, obtained by an ethyl acetate extraction of the whole extract.

ethyl acetate


Input: In the medium polar fraction, we isolated the two hydroxy-phenyl-ethyl alcohols (hydroxyl-tyrosol and tyrosol) that are the main component of olives.

hydroxy-phenyl-ethyl alcohols

hydroxyl-tyrosol

tyrosol


Input: In addition, we isolated a flavonoidic compound, aromadendrine, a dihydroflavonol yet known but quite rare in nature.

flavonoidic

aromadendrine

dihydroflavonol


Input: It is the first time that aromadendrine is isolated in O. europaea and we studied the aromadendrine biological activity.

aromadendrine

aromadendrine


Input: In particular, the ability of aromadendrine to reduce the inflammation induced in normal keratinocytes using an in vitro cell model was evaluated.

aromadendrine


Input: The results of the present research indicate aromadendrine as a novel component in O. europaea with effective activity against skin inflammation.

aromadendrine


Input: Ibuprofen ion-exchange fiber complex: improved dissolution and gastric tolerance based on ion exchange.

Ibuprofen


Input: The purpose of the present study is to develop a novel method to improve the dissolution of water-insoluble drug ibuprofen and the gastric tolerance of this non-steroidal anti-inflammatory drug which has potentially serious gastrointestinal side effects.

ibuprofen


Input: This method is based on ion exchange of ion-exchange fibers.


Input: Water-insoluble drug ibuprofen was dispersed in deionized water, and then the ion-exchange fibers in OH (-) type was immersed in it.

ibuprofen

OH (-)


Input: Ibuprofen and the active groups of the ion-exchange fibers combined into ion pairs based on the acid-base reaction.

Ibuprofen


Input: This drug carrier did not release drugs in deionized water, but in water solution containing other ions it would release the drugs into the solution by ion exchange.


Input: Confirmed by the X-ray diffraction and the scanning electron microscopy, the ibuprofen combined onto the ion-exchange fibers was in a highly molecular level dispersed state.

ibuprofen


Input: The improved dissolution of ibuprofen ion-exchange fiber complexes is likely to originate from this ibuprofen' s highly dispersed state.

ibuprofen

ibuprofen


Input: Due to this, ibuprofen' s highly dispersed state, ibuprofen ion-exchange fiber complexes significantly decreases the gastrointestinal side effects of ibuprofen by avoiding the solid ibuprofen' s educing.

ibuprofen

ibuprofen

ibuprofen

ibuprofen


Input: The present study showed that ibuprofen ion-exchange fiber complexes have the two-fold advantages.

ibuprofen


Input: One is to improve the dissolution of ibuprofen.

ibuprofen


Input: The other is to decrease the ibuprofen' s gastrointestinal toxicity.

ibuprofen


Input: A modern approach for controlled transdermal delivery of diflunisal: optimization and in vivo evaluation.

diflunisal


Input: The purpose of the present work was to elaborate an optimized transdermal therapeutic system for diflunisal.

diflunisal


Input: Selection of suitable ingredients was done via solubility and phase behavior studies.


Input: Composition of microemulsion (ME) systems consisting of butyl lactate, Brij ((R)) 97, Transcutol ((R)) and water was optimized using augmented simplex lattice mixture design.

butyl lactate

Brij

Transcutol


Input: The independent variables selected were the percentages of butyl lactate, surfactant mixture and water.

butyl lactate


Input: The dependent variables were refractive index, pH, conductivity, viscosity, drug solubility in the ME formulation and the ex vivo skin permeation flux.


Input: Mathematical equations and response surface plots were used to relate the dependent and independent variables.


Input: The statistical validity of the polynomials was established.


Input: Optimized formulation factors were selected by desirability approach.


Input: The optimized ME formulation was converted into gel using Carbomer ((R)) 934.

Carbomer


Input: The microemulsion based gel (MBG) showed better spreadability and 5. 07-fold increase in the transdermal flux than Carbomer ((R)) 934 gel.

Carbomer


Input: The in vivo antihyperalgesia assay performed on mice showed significant reduction of the licking time in the treated group compared to the control group.


Input: This demonstrated the reliability of the simplex lattice statistical design for predicting optimum ME formulation.


Input: The developed MBG proved its in vivo efficiency for transdermal delivery of diflunisal.

diflunisal


Input: Antimicrobial and antioxidant properties of Betula aetnensis Rafin.


Input: (Betulaceae) leaves extract.


Input: This study aimed to evaluate the antimicrobial effects, the radical scavenging activity (by DPPH and ABTS tests) and the antioxidant capacity (by beta-carotene bleaching test) of Betula aetnensis leaves extract.

DPPH

ABTS

beta-carotene


Input: The antimicrobial activity was tested against 14 Gram-positive clinical strains, 2 ATCC Gram-positive strains, 10 Gram-negative clinical strains and 4 Gram-negative ATCC strains.


Input: Streptococcus pyogenes Ery-S and Ery-R1 were the most sensitive.


Input: Betula aetnensis was considerably active against three bacterial strains, namely Haemophilus influenzae ATCC 49247, Amp-R1 and Moraxella catarrhalis ATCC 25238.


Input: Standard ATCC strains of Gram-positive bacteria were more sensitive than Gram-negative.


Input: Betula aetnensis showed also an interesting reducing power with TEAC values of 9. 7 and a good inhibition of linoleic acid oxidation with an IC50 value of 22. 0 micro g mL (-1) after 30 min of incubation.

linoleic acid


Input: The total phenol and flavonoid contents were determined with the purpose to evaluate the relationship with the observed bioactivities.

phenol

flavonoid


Input: Feroniellides C-E, new apotirucallane triterpenoids from the stem bark of Feroniella lucida.

Feroniellides C-E

apotirucallane triterpenoids


Input: Bioassay-directed isolation of Feroniella lucida stem bark yielded three new apotirucallane triterpenoids named feroniellides C-E.

apotirucallane triterpenoids

feroniellides C-E


Input: The structures of the new compounds were established by extensive analysis of spectroscopic data.


Input: Of triterpenoids examined, feroniellides D and E revealed anticancer activity against KB and HeLa cells with IC50 values in range of 3. 4-14. 2 micro g mL (-1), which are significantly more potent than feroniellides A-C (IC50 25. 5-60. 0 micro g mL (-1)).

triterpenoids

feroniellides D and E

feroniellides A-C


Input: The present investigation suggests that an isovalerate moiety in feroniellides D and E is possibly associated with exerting cytotoxicity against cancer cells.

isovalerate

feroniellides D and E


Input: Nanostructural difference of water-soluble pectin and chelate-soluble pectin among ripening stages and cultivars of Chinese cherry.


Input: Nanostructure of water-soluble pectin (WSP) and chelate-soluble pectin (CSP) of two Chinese cherry (Prunus pseudocerasus L.) cultivars (soft cultivar' Caode' and crisp cultivar' Bende') with two different ripening stages were characterised using atomic force microscopy.


Input: Both cultivars shared some common values of chain widths for WSP or CSP, and both pectins shared several values of chain widths including 37, 55 and 61 nm.


Input: The results indicate that different cultivars shared similar components of pectin, and cultivar textural difference might be related to the interaction between pectin and other cherry components or the dissociation of pectin.


Input: During ripening, the wide WSP and CSP gradually dissociate in width.


Input: The results demonstrated that the changes of WSP and CSP of Chinese cherry in widths were a dissociation process.


Input: Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments.

chloride


Input: In cortical and hippocampal neurons, cation-chloride cotransporters (CCCs) control the reversal potential (EGABA) of GABAA receptor-mediated current and voltage responses and, consequently, they modulate the efficacy of GABAergic inhibition.

chloride


Input: Two members of the CCC family, KCC2 (the major neuron-specific K-Cl cotransporter; KCC isoform 2) and NKCC1 (the Na-K-2Cl cotransporter isoform 1 which is expressed in both neurons and glial cells) have attracted much interest in studies on GABAergic signaling under both normal and pathophysiological conditions, such as epilepsy.


Input: There is tentative evidence that loop diuretic compounds such as furosemide and bumetanide may have clinically relevant antiepileptic actions, especially when administered in combination with conventional GABA-mimetic drugs such as phenobarbital.


Input: Furosemide is a non-selective inhibitor of CCCs while at low concentrations bumetanide is selective for NKCCs.


Input: Search for novel antiepileptic drugs (AEDs) is highly motivated especially for the treatment of neonatal seizures which are often resistant to, or even aggravated by conventional AEDs. This review shows that the antiepileptic effects of loop diuretics described in the pertinent literature are based on widely heterogeneous mechanisms ranging from actions on both neuronal NKCC1 and KCC2 to modulation of the brain extracellular volume fraction.


Input: A promising strategy for the development of novel CCC-blocking AEDs is based on prodrugs that are activated following their passage across the blood-brain barrier.


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


Input: Celiac disease in subjects with type 1 diabetes mellitus: a prevalence study in western Sicily (Italy).


Input: The association between celiac disease and type 1 diabetes mellitus is well known.


Input: Up to now, celiac disease prevalence in children and adults with type 1 diabetes in Sicily has not been reported.


Input: The aim of this study was to assess the prevalence of celiac disease in patients with type 1 diabetes mellitus who come from a defined geographical area in western Sicily and to investigate the clinical features of these subjects.


Input: The records of 492 consecutive patients with type 1 diabetes mellitus referred in a period of 5 years were analyzed.


Input: During the period of the survey, out of 492 patients with type 1 diabetes, 22 (4. 5%) had a previous diagnosis of celiac disease.


Input: There were 14 females and 8 males; these patients showed a mean age of 13 years at diabetes onset.


Input: Diagnosis of celiac disease was often simultaneous or subsequent to that of diabetes.


Input: Autoimmune thyroiditis was coexisting in 8 patients (36%).


Input: Our data confirm, in a Sicilian population, the not unusual association between celiac disease and type 1 diabetes, although prevalence rate is lower than in others Italian studies.


Input: Autoimmune thyroiditis is present with high prevalence in these patients.


Input: Celiac disease diagnosis often followed onset of type 1 diabetes, particularly in female subjects with a young age at diabetes onset; therefore, in these subjects, an active search for the presence of celiac disease is warranted for many years after appearance of diabetes.


Input: Cytotoxic and leishmanicidal properties of garcinielliptone FC, a prenylated benzophenone from Platonia insignis.


Input: Garcinielliptone FC (GFC), a natural prenylated benzophenone, was extracted from Platonia insignis Mart.

Garcinielliptone FC

GFC

prenylated benzophenone


Input: (Clusiaceae), a native plant commonly known as bacuri and used in traditional Brazilian medicine for the treatment of skin diseases.


Input: The aim of this study was to evaluate the cytotoxic and leishmanicidal effects of GFC using in vitro models.

GFC


Input: The experimental data demonstrated that the polyisoprenylated benzophenone GFC possesses cytotoxic and leishmanicidal activities.

polyisoprenylated benzophenone GFC


Input: A new acylated flavone glycoside with antioxidant and radical scavenging activities from Teucrium polium leaves.

acylated flavone glycoside


Input: The antioxidant properties of six flavones from Teucrium polium L., one of them isolated for the first time, have been established through the determination of their abilities to inhibit free radicals using DPPH, ABTS radicals and ORAC test.

flavones

DPPH

ABTS


Input: The structure of the new metabolite has been elucidated by 1-D (1H, 13C and DEPT) and 2-D (COSY, TOCSY, HSQC, CIGAR) NMR experiments and by ESI Q-TOF HRMS analysis.


Input: Flavones 1-3 presented an efficacious activity towards the stable DPPH radical.

Flavones

DPPH


Input: Analogously, compounds 2 and 3 resulted significantly active also versus ABTS cation radical.

ABTS


Input: On the basis of the comparable bioactivity of luteolin-based compounds, the presence of an ortho-dihydroxy substitution in the flavone B-ring is supposed to be the structural feature responsible for the antioxidant activity.

luteolin

ortho-dihydroxy

flavone


Input: Composition and antioxidant capacity of the essential oil of leaves of Vitex megapotamica (Sprengel) Moldenke.


Input: This study is designed to examine the chemical composition and antioxidant activity of the essential oil of Vitex megapotamica.


Input: Gas chromatography-mass spectrometry analysis resulted in the detection of 27 components, representing 92. 36% of the total oil composition.


Input: The main components in the oil were butylated hydroxytoluene (BHT) (34. 17%), phytol (12. 66%), alpha-caryophyllene (11. 84%), delta-elemene (10. 65%), beta-caryophyllene (7. 82%), gamma-elemene (4. 24%) and germacrene D (2. 82%).

butylated hydroxytoluene

BHT

phytol

alpha-caryophyllene

delta-elemene

beta-caryophyllene

gamma-elemene

germacrene D


Input: The antioxidant activity of the oil was evaluated in terms of their free-radical scavenging activity against 1, 1-diphenyl-2-picrylhydrazyl.

1, 1-diphenyl-2-picrylhydrazyl


Input: The oil showed percentage inhibition of 35. 62% and 75. 25% at concentrations of 76 and 101. 6 mg mL (-1), respectively.


Input: BHT (36. 30%) was also determined by HPLC-DAD in the hexane fraction from the leaves.

BHT

hexane


Input: To the best of our knowledge, this is the first study of the composition and antioxidant activity of the essential oil of the species V. megapotamica.


Input: Inhibitory action on rat uterine muscle contraction in vitro and acute toxicity in rats of the Thai traditional preparation Prasaplai.


Input: The activity of an aqueous extract of Prasaplai, a Thai traditional medicine, was studied on the isolated rat uterus in the oestrus stage.


Input: The results showed that the extract inhibited the contraction induced by a submaximal dose of acetylcholine (2. 04 x 10 (-4) mg mL (-1)), oxytocin (1. 54 x 10 (-4) mg mL (-1)) and prostaglandin E2 (PGE2) (6. 00 x 10 (-4) mg mL (-1)).

acetylcholine

oxytocin

prostaglandin E2


Input: The inhibition was concentration-dependent and reversible by tissue washing.


Input: The IC50 of Prasaplai extracts expressed as milligram of powdered preparation per millilitre of perfusion solution for acetylcholine, oxytocin and PGE2 were 11. 70, 10. 00 and 5. 75 mg mL (-1), respectively.

acetylcholine

oxytocin


Input: These data reveal that Prasaplai has an antispasmodic effect against uterine contraction by different mechanisms and corroborate the traditional use in the treatment of dysmenorrhoea.


Input: Oral administration of single dose of the water extract, calculated as powdered Prasaplai up to 20 g kg (-1) in rats, showed no sign and symptom of acute toxicity, and no rat died even at the maximum dose.


Input: A new caryolane sesquiterpene from Heteropappus altaicus (Willd.) Novopokr.

caryolane sesquiterpene


Input: A new caryolane sesquiterpene, 1 beta-methoxycaryol-9-one (1), along with eight known compounds (2-9), was isolated from the whole plant of Heteropappus altaicus.

caryolane sesquiterpene

1 beta-methoxycaryol-9-one


Input: The structures were elucidated on the basis of comprehensive 1D-and 2D-NMR analysis and high-resolution mass spectrometry.


Input: The 13C-NMR data of compound 2 are reported for the first time.


Input: An antileishmanial prenyloxy-naphthoquinone from roots of Plumbago zeylanica.

prenyloxy-naphthoquinone


Input: Leishmania donovani, an obligate intracellular parasite of genus Leishmania causes visceral leishmaniasis that affects millions of people worldwide, especially in the Indian subcontinent and East Africa.


Input: Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions due to efficacy and cost effectiveness but the growing incidence of their resistance has seriously hampered their use.


Input: This study discloses strong in vitro antileishmanial activity of 2-methyl-5-(3'-methyl-but-2'-enyloxy)-[1, 4] naphthoquinone (1), a prenyloxy-naphthoquinone isolated and characterised from roots of the plant Plumbago zeylanica (family-Plumbaginaceae).

2-methyl-5-(3'-methyl-but-2'-enyloxy)-[1, 4] naphthoquinone

prenyloxy-naphthoquinone


Input: The observed EC50 for the compound 1 against promastigote and amastigote forms of L. donovani was significantly (p < 0. 001) lower than miltefosine, a reference drug.

miltefosine


Input: In context to limited treatment options and growing resistance for available drugs, compound 1 offers a greater prospect towards antileishmanial drug discovery and development.


Input: Isolation and structure determination of new siderophore tsukubachelin B from Streptomyces sp.

tsukubachelin B


Input: The new siderophore tsukubachelin B (1) was isolated from the iron-deficient culture medium of the newly isolated strain Streptomyces sp.

tsukubachelin B

iron


Input: The chemical structure of tsukubachelin B (1) was established via interpretation of 2D nuclear magnetic resonance and electrospray ionization-mass spectroscopic data.

tsukubachelin B


Input: The structure of tsukubachelin B (1) comprises 6 mol of amino acids, including 2 mol of serine and 1 mol each of ornithine, N-alpha-methyl-N-delta-hydroxy-N-delta-formylornithine, N-alpha-methyl-N-delta-hydroxyornithine, and cyclic N-hydroxyornithine.

tsukubachelin B

amino acids

serine

ornithine

N-alpha-methyl-N-delta-hydroxy-N-delta-formylornithine

N-alpha-methyl-N-delta-hydroxyornithine

cyclic N-hydroxyornithine


Input: Hierarchical clustering analysis of blood plasma lipidomics profiles from mono-and dizygotic twin families.


Input: Twin and family studies are typically used to elucidate the relative contribution of genetic and environmental variation to phenotypic variation.


Input: Here, we apply a quantitative genetic method based on hierarchical clustering, to blood plasma lipidomics data obtained in a healthy cohort consisting of 37 monozygotic and 28 dizygotic twin pairs, and 52 of their biological nontwin siblings.


Input: Such data are informative of the concentrations of a wide range of lipids in the studied blood samples.


Input: An important advantage of hierarchical clustering is that it can be applied to a high-dimensional' omics' type data, whereas the use of many other quantitative genetic methods for analysis of such data is hampered by the large number of correlated variables.


Input: For this study we combined two lipidomics data sets, originating from two different measurement blocks, which we corrected for block effects by' quantile equating'.


Input: In the analysis of the combined data, average similarities of lipidomics profiles were highest between monozygotic (MZ) cotwins, and became progressively lower between dizygotic (DZ) cotwins, among sex-matched nontwin siblings and among sex-matched unrelated participants, respectively.


Input: Our results suggest that (1) shared genetic background, shared environment, and similar age contribute to similarities in blood plasma lipidomics profiles among individuals; and (2) that the power of quantitative genetic analyses is enhanced by quantile equating and combination of data sets obtained in different measurement blocks.


Input: Measles virus selectively blind to signaling lymphocyte activation molecule as a novel oncolytic virus for breast cancer treatment.


Input: Oncolytic viruses hold much promise as novel therapeutic agents that can be combined with conventional therapeutic modalities.


Input: Measles virus (MV) is known to enter cells using the signaling lymphocyte activation molecule (SLAM), which is expressed on cells of the immune system.


Input: Although human breast cancer cell lines do not express SLAM, we found that a wild-type MV (HL strain) efficiently infected various breast cancer cell lines, causing cell death.


Input: Based on this finding, we used reverse genetics to generate a recombinant MV selectively unable to use SLAM (rMV-SLAMblind).


Input: The rMV-SLAMblind lacked infectivity for SLAM-positive lymphoid cells, while retaining oncolytic activity against breast cancer cells.


Input: We showed that, unlike the MV vaccine strains, rMV-SLAMblind used PVRL4 (polio virus receptor-related 4) as a receptor to infect breast cancer cells and not the ubiquitously expressed CD46.


Input: Consistent with this, rMV-SLAMblind infected CD46-positive primary normal human cells at a much-reduced level, whereas a vaccine strain of the Edmonston lineage (rMV-Edmonston) efficiently infected and killed them.


Input: The rMV-SLAMblind showed antitumor activity against human breast cancer xenografts in immunodeficient mice.


Input: The oncolytic activity of rMV-SLAMblind was significantly greater than that of rMV-Edmonston.


Input: To assess the in vivo safety, three monkeys seronegative for MV were inoculated with rMV-SLAMblind, and no clinical symptoms were documented.


Input: On the basis of these results, rMV-SLAMblind could be a promising candidate as a novel oncolytic virus for breast cancer treatment.


Input: Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPL (S447X)) gene therapy for lipoprotein lipase deficiency: an open-label trial.


Input: We describe the 2-year follow-up of an open-label trial (CT-AMT-011-01) of AAV1-LPL (S447X) gene therapy for lipoprotein lipase (LPL) deficiency (LPLD), an orphan disease associated with chylomicronemia, severe hypertriglyceridemia, metabolic complications and potentially life-threatening pancreatitis.


Input: The LPL (S447X) gene variant, in an adeno-associated viral vector of serotype 1 (alipogene tiparvovec), was administered to 14 adult LPLD patients with a prior history of pancreatitis.


Input: Primary objectives were to assess the long-term safety of alipogene tiparvovec and achieve a <E2F6> 40% reduction in fasting median plasma triglyceride (TG) at 3-12 weeks compared with baseline.

triglyceride


Input: Cohorts 1 (n = 2) and 2 (n = 4) received 3 x 10 (11) gc kg (-1), and cohort 3 (n = 8) received 1 x 10 (12) gc kg (-1).


Input: Cohorts 2 and 3 also received immunosuppressants from the time of alipogene tiparvovec administration and continued for 12 weeks.


Input: Alipogene tiparvovec was well tolerated, without emerging safety concerns for 2 years.


Input: Half of the patients demonstrated a <E2F6> 40% reduction in fasting TG between 3 and 12 weeks.


Input: TG subsequently returned to baseline, although sustained LPL (S447X) expression and long-term changes in TG-rich lipoprotein characteristics were noted independently of the effect on fasting plasma TG.


Input: Anti-diabetic Activity of Swertiamarin is due to an Active Metabolite, Gentianine, that Upregulates PPAR-gamma Gene Expression in 3T3-L1 cells.

Swertiamarin

Gentianine


Input: We have previously shown the anti-diabetic effects of swertiamarin; however, pharmacokinetic analysis showed that swertiamarin had a plasma half-life of 1. 3 h.

swertiamarin

swertiamarin


Input: Gentianine is an active metabolite of swertiamarin that possesses a pharmacophoric moiety.

Gentianine

swertiamarin


Input: The aim of this study was to explore the possibility whether the anti-diabetic effect of swertiamarin is due to gentianine.

swertiamarin

gentianine


Input: Swertiamarin treatment had no significant effect on adipogenesis, or the mRNA expression of PPAR-gamma and GLUT-4; however, there was a significant increase in the mRNA expression of adiponectin.

Swertiamarin


Input: On the other hand, treatment with gentianine significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of PPAR-gamma, GLUT-4 and adiponectin.

gentianine


Input: These findings suggest, for the first time, that the anti-diabetic effect of swertiamarin is due to gentianine, an active metabolite of swertiamarin.

swertiamarin

gentianine

swertiamarin


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


Input: Chronic treatment with selective I2-imidazoline receptor ligands decreases the content of pro-apoptotic markers in rat brain.

imidazoline


Input: Selective I (2)-imidazoline receptor ligands induce neuroprotection through various molecular mechanisms including blockade of N-methyl-D-aspartate (NMDA) receptors.

imidazoline

N-methyl-D-aspartate

NMDA


Input: To investigate new neuroprotective mechanisms associated with I (2)-imidazoline receptors, the effects of selective (2-styryl-2-imidazoline (LSL 61122), 2-(2-benzofuranyl)-2-imidazoline (2-BFI), 2-(4, 5-dihydroimidazol-2-yl) quinoline hydrochloride (BU-224)) and non-selective (idazoxan) I (2)-drugs on canonical apoptotic pathways were assessed in rat brain cortex.

imidazoline

LSL 61122

2-(4, 5-dihydroimidazol-2-yl) quinoline hydrochloride

idazoxan


Input: The acute treatment with LSL 61122 (10 mg/kg) reduced the content of mitochondrial (pro-apoptotic) Bax (-33%) and cytochrome c (-31%), which was prevented by idazoxan, an I (2)-receptor antagonist.

LSL 61122

idazoxan


Input: The sustained stimulation of I (2)-imidazoline receptors with selective drugs (10 mg/kg, every 12 h for seven days) was associated with down-regulation of key components of the extrinsic (Fas receptor:-20%; Fas associated protein with death domain (FADD) adaptor:-47-54%) and/or intrinsic (Bax:-20-23%; cytochrome c:-22-28%) apoptotic signalling and/or up-regulation of survival anti-apoptotic factors (p-Ser194 FADD/FADD ratio: + 1. 6-2. 5-fold; and/or Bcl-2/Bax ratio: + 1. 5-fold), which in the long-term could dampen cell death in the brain.

imidazoline


Input: Similar chronic treatments with LSL 60101 (the imidazole analogue of 2-BFI) and idazoxan (a mixed I (2)/alpha (2)-ligand) did not induce significant alterations of pro-or anti-apoptotic proteins.

LSL 60101

imidazole

idazoxan


Input: The disclosed anti-apoptotic mechanisms of selective I (2)-imidazoline drugs may work in concert with other molecular mechanisms of neuroprotection (e. g. blockade of NMDA receptors) that are engaged by I (2)-ligands.

imidazoline


Input: A new furolactone-type lignan from Lycium chinense.

furolactone

lignan


Input: The phytochemical investigation of extracts from the root barks of Lycium chinense yielded a new furolactone-type lignan, lyciumin (1).

lyciumin


Input: Its structure and absolute configurations were established on the basis of spectral data, particularly by the use of 1D NMR, 2D shift-correlated NMR pulse sequences ((1) H-(1) H COSY, HSQC, HMBC and ROESY) and CD spectra.

(1) H

(1) H


Input: How inhibition influences seizure propagation.


Input: Inhibitory neuron behaviour is of fundamental importance to epileptic pathophysiology.


Input: When inhibition is compromised, such as by GABAergic blockade (Curtis et al., 1970; Connors, 1984; Traub and Miles, 1991) or by shifts in GABAergic reversal potential (Huberfeld et al., 2007), epileptiform discharges occur far more readily.


Input: Other studies have shown enhanced inhibition in vivo in the surrounding cortical territories associated with both focal pathological and physiological activity (Prince and Wilder, 1967; Dichter and Spencer, 1969a, b; Goldensohn and Salazar, 1986; Traub and Miles, 1991; Liang and Jones, 1997; Liang et al., 1998; Schwartz and Bonhoeffer, 2001).


Input: This gave rise to the concept of an " inhibitory restraint ".


Input: This concept can explain the often confusing anatomical reorganizations seen in chronically epileptic brains (Sloviter, 1987; Cossart et al., 2001), indicating which changes might be pro-epileptic, and which oppose the epileptic state.


Input: It also may explain key electrophysiological features of epileptic seizures.


Input: Here we describe current knowledge about the restraint, gleaned mainly from acute pharmacological experiments in animals, both in vivo and in vitro, and speculate how this may alter our understanding of human seizure activity in clinical practice.


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


Input: Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice.

serotonin


Input: Excessive fear is a hallmark of several emotional and mental disorders such as phobias and panic disorders.


Input: Considerable attention is focused on defining the neurobiological mechanisms of the extinction of conditioned fear memory in an effort to identify mechanisms that may hold clinical significance for remediating aberrant fear memory.


Input: Serotonin modulates the acquisition and retention of conditioned emotional memory, and the serotonin 2A receptor (5HT2AR) may be one of the postsynaptic targets mediating such effects.

Serotonin

serotonin


Input: Here we tested the hypothesis that the 5HT2AR regulates the consolidation and extinction of fear memory in male C57BL/6J mice.


Input: The influence of 5HT2ARs on memory consolidation was further confirmed with a novel object recognition task.


Input: With a trace fear conditioning paradigm, administration of the 5HT2AR agonist TCB-2 (1. 0 mg/kg, i. p.) before the extinction test facilitated the acquisition of extinction of fear memory as compared to vehicle treatment.


Input: In contrast, administration of the 5HT2AR antagonist MDL 11, 939 (0. 5 mg/kg, i. p.) delayed the acquisition of extinction of fear memory.

MDL 11, 939


Input: Further, the post-conditioning administration of TCB-2 enhanced contextual and cued fear memory, possibly by facilitating the consolidation of fear memory.


Input: Administration of TCB-2 also facilitated the acquisition of extinction of fear memory in delay fear conditioned mice.


Input: Stimulation or blockade of 5HT2ARs did not affect the encoding or retrieval of conditioned fear memory.


Input: Finally, administration of TCB-2 right after training in an object recognition task enhanced the consolidation of object memory.


Input: These results suggest that stimulation of 5HT2ARs facilitates the consolidation and extinction of trace and delay cued fear memory and the consolidation of object memory.


Input: Blocking the 5HT2AR impairs the acquisition of fear memory extinction.


Input: The results support the view that serotonergic activation of the 5HT2AR provides an important modulatory influence on circuits engaged during extinction learning.


Input: Taken together these results suggest that the 5HT2AR may be a potential therapeutic target for enhancing hippocampal and amygdala-dependent memory.


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


Input: Deep brain stimulation, histone deacetylase inhibitors and glutamatergic drugs rescue resistance to fear extinction in a genetic mouse model.


Input: Anxiety disorders are characterized by persistent, excessive fear.


Input: Therapeutic interventions that reverse deficits in fear extinction represent a tractable approach to treating these disorders.


Input: We previously reported that 129S1/SvImJ (S1) mice show no extinction learning following normal fear conditioning.


Input: We now demonstrate that weak fear conditioning does permit fear reduction during massed extinction training in S1 mice, but reveals specific deficiency in extinction memory consolidation/retrieval.


Input: Rescue of this impaired extinction consolidation/retrieval was achieved with d-cycloserine (N-methly-d-aspartate partial agonist) or MS-275 (histone deacetylase (HDAC) inhibitor), applied after extinction training.

d-cycloserine

N-methly-d-aspartate


Input: We next examined the ability of different drugs and non-pharmacological manipulations to rescue the extreme fear extinction deficit in S1 following normal fear conditioning with the ultimate aim to produce low fear levels in extinction retrieval tests.


Input: Results showed that deep brain stimulation (DBS) by applying high frequency stimulation to the nucleus accumbens (ventral striatum) during extinction training, indeed significantly reduced fear during extinction retrieval compared to sham stimulation controls.