Input: The thalamic paraventricular nucleus (PVT), reported to participate in arousal and motivated behaviors, contains abundant receptors for thyrotropin-releasing hormone (TRH), a neuropeptide also known to modulate arousal and mood.

thyrotropin

TRH


Input: To test the hypothesis that TRH could influence the excitability of PVT neurons, whole call patch clamp recordings obtained in rat brain slice preparations were evaluated during bath applied TRH.

TRH

TRH


Input: In the majority of neurons tested, TRH induced reversible TTX-resistant membrane depolarization.

TRH

TTX


Input: Under voltage-clamp, TRH induced a concentration-dependent G protein-mediated inward current.

TRH


Input: The mean net TRH-induced current exhibited a decrease in membrane conductance.

TRH


Input: Further analyses identified two concurrent conductances contributing to the TRH-induced response.

TRH


Input: One conductance featured a Na (+)-independent and K (+)-dependent net current that displayed rectification and was suppressed by micromolar concentrations of Ba (2 +) and two GIRK antagonists, tertiapin Q and SCH 23390.

Na (+)

K (+)

Ba (2 +)

SCH 23390


Input: The second conductance featured a Na (+)-dependent net inward current with an I-V relationship that exhibited double rectification with a negative slope conductance below-40 mV.

Na (+)


Input: This conductance was suppressed by nonselective TRPC channel blockers 2-APB, flufenamic acid and ML204, enhanced by La (3 +) in a subpopulation of cells, and unchanged by the TRPV1 antagonist capsazepine or a Na (+)/Ca (2 +) exchanger blocker KB-R7943.

flufenamic acid

La (3 +)

capsazepine

Na (+)

Ca (2 +)


Input: TRH also enhanced hyperpolarization-activated low threshold spikes, a feature that was sensitive to pretreatment with either 2-APB or ML204.

TRH


Input: Collectively, the data imply that TRH enhances excitability in PVT neurons via concurrently decreasing a G-protein-gated inwardly rectifying K (+) conductance and activating a cationic conductance with characteristics reminiscent of TRPC-like channels, possibly involving TRPC4/C5 subunits.

TRH

K (+)


Input: The Prevalence, Maintenance and Relevance of GPCR Oligomerization.


Input: Over the past decade ideas and experimental support for the hypothesis that G protein-coupled receptors may exist as dimeric or oligomeric complexes moved initially from heresy to orthodoxy, to the current situation in which the capacity of such receptors to interact is generally accepted but the prevalence, maintenance and relevance of such interactions to both pharmacology and function remain unclear.


Input: A vast body of data obtained following transfection of cultured cells is still to be translated to native systems and, even where this has been attempted, results often remain controversial and contradictory.


Input: This review will consider approaches that are currently being applied, why these might be challenging to interpret and suggest means to overcome these limitations.


Input: Attack of the nervous system by Clostridium perfringens Epsilon toxin: From disease to mode of action on neural cells.


Input: Epsilon toxin (ET), produced by Clostridium perfringens types B and D, ranks among the four most potent poisonous substances known so far.


Input: ET-intoxication is responsible for enterotoxaemia in animals, mainly sheep and goats.


Input: This disease comprises several manifestations indicating the attack of the nervous system.


Input: This review aims to summarize the effects of ET on central nervous system.


Input: ET binds to endothelial cells of brain capillary vessels before passing through the blood-brain barrier.


Input: Therefore, it induces perivascular oedema and accumulates into brain.


Input: ET binding to different brain structures and to different component in the brain indicates regional susceptibility to the toxin.


Input: Histological examination has revealed nerve tissue and cellular lesions, which may be directly or indirectly caused by ET.


Input: The naturally occurring disease caused by ET-intoxication can be reproduced experimentally in rodents.


Input: In mice and rats, ET recognizes receptor at the surface of different neural cell types, including certain neurons (e. g. the granule cells in cerebellum) as well as oligodendrocytes, which are the glial cells responsible for the axons myelination.


Input: Moreover, ET induces release of glutamate and other transmitters, leading to firing of neural network.

glutamate


Input: The precise mode of action of ET on neural cells remains to be determined.


Input: Investigation of in vivo metabolic profile of Abelmoschus Manihot based on pattern recognition analysis.


Input: ETHNOPHARMACOLOGICAL RELEVANCE:: Abelmoschus manihot (L.) Medik. var.


Input: manihot is one of the most commonly used Chinese medicines and has played an important role in treating chronic glomerulonephritis and diabetic nephropathy.


Input: AIM OF THE STUDY:: Metabolites identification of traditional Chinese medicine (TCM) is a complex and time-consuming process due to the complicity of TCM and subsequent large number of detected ions.


Input: In this paper, UPLC-MS combined with pattern recognition analysis approach were used to simplify and quicken the identification of the metabolites of Abelmoschus Manihot.


Input: MATERIALS AND METHODS:: Rat urine samples were collected before (as control sample) and after Abelmoschus Manihot administration.


Input: Pattern recognition analysis method was used to differentiate components between Abelmoschus Manihot-treated group and its controlled comparison.


Input: These components could be considered as Abelmoschus Manihot-related metabolites in vivo.


Input: RESULTS:: LC-MS based metabolomics could be an advanced tool to help us find metabolites with regards to its capacity of processing large datasets, differentiating and classifying of sample groups, as well as its indiscriminative nature of biomarker and metabolite identification.


Input: Using this method, seven metabolites were identified, which are flavonoid aglycone glucuronidation, sulfatation, and methylation metabolites.

flavonoid


Input: CONCLUSION:: Our results showed that UPLC-MS based-pattern recognition analysis approach can be used to quickly identify Abelmoschus Manihot related metabolites in biological fluids.


Input: Furthermore, this work demonstrates the potential application of combining the UPLC-MS approach with the metabolomics approach in identifying the metabolites of TCM.


Input: Structure-Based DNA-Targeting Strategies with Small Molecule Ligands for Drug Discovery.


Input: Nucleic acids are the molecular targets of many clinical anticancer drugs.


Input: However, compared with proteins, nucleic acids have traditionally attracted much less attention as drug targets in structure-based drug design, partially because limited structural information of nucleic acids complexed with potential drugs is available.


Input: Over the past several years, enormous progresses in nucleic acid crystallization, heavy-atom derivatization, phasing, and structural biology have been made.


Input: Many complicated nucleic acid structures have been determined, providing new insights into the molecular functions and interactions of nucleic acids, especially DNAs complexed with small molecule ligands.


Input: Thus, opportunities have been created to further discover nucleic acid-targeting drugs for disease treatments.


Input: This review focuses on the structure studies of DNAs complexed with small molecule ligands for discovering lead compounds, drug candidates, and/or therapeutics.


Input: Loss of Kruppel-like Factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2).


Input: Kr u ppel-like Factor 3 (KLF3) is a transcriptional regulator that we have shown to be involved in the regulation of adipogenesis in vitro.


Input: Here we report that KLF3 null mice are lean and protected from diet-induced obesity and glucose intolerance.

glucose


Input: On a chow diet, plasma levels of leptin are decreased, and adiponectin is increased.


Input: Despite significant reductions in body weight and adiposity, wildtype and knockout animals show equivalent energy intake, expenditure and excretion.


Input: To investigate the molecular events underlying these observations, we used microarray analysis to compare gene expression in Klf3 (+/+) and Klf3 (-/-) tissues.


Input: We found that mRNA expression of Fam132a, which encodes a newly identified insulin-sensitizing adipokine, adipolin, is significantly upregulated in the absence of KLF3.


Input: We confirmed that KLF3 binds the Fam132a promoter in vitro and in vivo and that this leads to repression of promoter activity.


Input: Further, plasma adipolin levels were significantly increased in Klf3 (-/-) mice compared to wild-type littermates.


Input: Boosting levels of adipolin via targeting of KLF3 offers a novel potential therapeutic strategy for the treatment of insulin resistance.


Input: Characterization of Recombinantly Expressed Rat and Monkey Intestinal Alkaline Phosphatases: In Vitro Studies and In Vivo Correlations.


Input: Intestinal alkaline phosphatases (IALPs) are widely expressed in the brush border of epithelial cells of the intestinal mucosa.


Input: Although their physiological role is unclear, they are very significant when it comes to the release of bioactive parent from orally dosed phosphate prodrugs.

phosphate


Input: Such prodrugs can be resistant to cleavage by IALP, or alternatively undergo rapid cleavage leading to the release and precipitation of the less soluble parent.


Input: Because purified IALPs from pre-clinical species are not commercially available, and species differences have not been investigated to date, an effort was made to recombinantly express, purify and characterize rat and cynomolgus monkey IALP (rIALP).


Input: Specifically, rIALP-catalyzed cleavage of five prodrugs (fosphenytoin, clindamycin phosphate, dexamethasone phosphate, ritonavir phosphate and ritonavir oxymethyl phosphate) was tested in vitro and parent exposure was assessed in vivo (rat only) following an oral dose of each prodrug.

fosphenytoin

clindamycin phosphate

dexamethasone phosphate

ritonavir phosphate

ritonavir oxymethyl phosphate


Input: It was determined that the rate of phosphate cleavage in vitro varied widely; direct phosphates were more resistant to bioconversion, whereas faster conversion was observed with oxymethyl linked prodrugs.

phosphate

phosphates

oxymethyl


Input: Overall, the rat rIALP-derived data were qualitatively consistent with in-vivo data; prodrugs that were readily cleaved in vitro rendered higher parent drug exposure in vivo.


Input: Of the five prodrugs tested, one (ritonavir phosphate) showed no conversion in vitro and minimal parent exposure in vivo.

ritonavir phosphate


Input: Finally, the apparent Km values obtained for fosphenytoin and clindamycin phosphate in vitro suggest that IALP is not likely to be saturated at therapeutic doses.

fosphenytoin

clindamycin phosphate


Input: Regulation of Lipid Metabolism by Glucocorticoids and 11 beta-HSD1 in Skeletal Muscle.


Input: The prevalence of insulin resistance and type 2 diabetes mellitus are rising dramatically and as a consequence there is an urgent need to understand the pathogenesis underpinning these conditions to develop new and more efficacious treatments. We have tested the hypothesis that glucocorticoid-mediated changes in insulin sensitivity may be associated with changes in lipid flux.


Input: Furthermore, pre-receptor modulation of glucocorticoid availability by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) may represent a critical regulatory step. Dexamethasone decreased lipogenesis in both murine C2C12 and human LHC-NM2 myotubes.

11 beta-hydroxysteroid

Dexamethasone


Input: Inactivating p-Ser-79/218 of acetyl-CoA carboxylase 1/2 (ACC1/2) and activating p-Thr-172 of AMP-activated protein kinase (AMPK) were both increased following dexamethasone treatment in C2C12 myotubes.

Ser

acetyl-CoA

Thr

AMP

dexamethasone


Input: By contrast, dexamethasone increased beta-oxidation.

dexamethasone


Input: Selective 11 beta-HSD1 inhibition blocked the 11-dehydrocorticosterone (11DHC)-mediated decrease in lipogenic, and increase in lipolytic gene expression.


Input: Lipogenic gene expression was decreased, whilst lipolytic and beta-oxidative genes expression increased in corticosterone (CORT) and 11DHC treated wild-type mice, and CORT (but not 11DHC) treated 11 beta-HSD1 (-/-) mice.

corticosterone

CORT

CORT


Input: Furthermore, CORT and 11DHC treated wild-type mice, and CORT (but not 11DHC) treated 11 beta-HSD1 (-/-) mice had increased p-Ser-79/218 ACC1/2, p-Thr-172 AMPK and intramyocellular diacylglyderide content. In summary, we have shown that glucocorticoids have potent actions upon intramyocellular lipid homeostasis by decreasing lipid storage, increasing lipid mobilisation and utilisation and increasing diacylglyderide content.

CORT

CORT

Ser

Thr

diacylglyderide

diacylglyderide


Input: It is plausible that dysregulated intramyocellular lipid metabolism may underpin GC-induced insulin resistance of skeletal muscle.


Input: LXR Mediates Enhanced Hepatic Gluconeogenic Gene Expression in Adult Male Rat MPR Offspring.


Input: Epidemiological studies demonstrate that the link between impaired fetal development and glucose intolerance in later life is exacerbated by postnatal catch-up growth.

glucose


Input: Maternal protein restriction (MPR) during pregnancy and lactation in the rat has been previously demonstrated to lead to impaired glucose tolerance in adulthood, however the effects of protein restoration during weaning on glucose homeostasis are largely unknown.

glucose

glucose


Input: Recent in vitro studies have identified that the Liver X Receptor-alpha (LXR alpha) maintains glucose homeostasis by inhibiting critical genes involved in gluconeogenesis including G6Pase, 11 beta-HSD1 and PEPCK.

glucose


Input: Therefore, we hypothesized MPR with postnatal catch-up growth would impair LXR alpha in vivo, which in turn would lead to augmented gluconeogenic LXR alpha-target gene expression and glucose intolerance.

glucose


Input: To examine this hypothesis, pregnant Wistar rats were fed a control (20%) protein diet (C) or a low (8%) protein diet during pregnancy and switched to a control diet at birth (LP).


Input: At four months, the LP offspring had impaired glucose tolerance.

glucose


Input: In additional, LP offspring had decreased LXR alpha expression, while hepatic expression of 11 beta-HSD1 and G6Pase were significantly higher.


Input: This was concomitant with decreased binding of LXR alpha to the putative LXRE on 11 beta-HSD1 and G6Pase.


Input: Finally, we demonstrated that the acetylation of Histone H3 [K9, 14] surrounding the transcriptional start site of hepatic LXR alpha was decreased in LP offspring, suggesting MPR-induced epigenetic silencing of the LXR alpha promoter.


Input: In summary, our study demonstrates for the first time the important role of LXR alpha in mediating enhanced hepatic gluconeogenic gene expression and consequent glucose intolerance in adult MPR offspring.

glucose


Input: Prevalence of MAGI in patients with type 2 diabetes mellitus.


Input: Background.


Input: MAGI is an acronym that identifies the " male accessory gland inflammations/infections ", a potential cause of male infertility.


Input: Type 2 diabetes mellitus (DM2) prevalence is going to increase among men of reproductive age.


Input: Due to the high prevalence of these two conditions, we could suppose that they might appear together in the same patient.


Input: Aim.


Input: To evaluate MAGI prevalence in patients with DM2 in fertile age.


Input: Subjects and Methods.


Input: A cross-sectional study carried out on patients with DM2 of fertile age.


Input: All patients underwent andrological evaluation for the identification of conventional MAGI diagnostic criteria.


Input: Results.


Input: DM2 patients showed a frequency of MAGI about 43%, significantly lower (p < 0. 05) than in infertile patients of the same age without diabetes, which showed a MAGI overall frequency of 61%.


Input: Among examined diabetic patients the prevalence of MAGI did not significantly differ between patients attending for diabetes care problems (glycemic control) and patients with andrological disorders.


Input: Finally, no significant difference in seminal inflammatory signs frequency was detected between patients with DM2 and infertile patients without diabetes.


Input: Finally, the correlation analysis showed a significant direct correlation between duration of diabetes and glycemic control with the prevalence of MAGI.


Input: Conclusion.


Input: MAGI prevalence in DM2 is lower than the one detected in age matched infertile non-diabetic patients, however, as in infertile patients, there is a high frequency of seminal inflammatory signs.


Input: Moreover, the observed prevalence among diabetic patients with diabetes care problems and diabetic patients with andrological problems is not statistically different.


Input: beta-Arrestin-Dependent Activation of the Cofilin Pathway Is Required for the Scavenging Activity of the Atypical Chemokine Receptor D6.


Input: Chemokines promote the recruitment of leukocytes to sites of infection and inflammation by activating conventional heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs).


Input: Chemokines are also recognized by a set of atypical chemokine receptors (ACRs), which cannot induce directional cell migration but are required for the generation of chemokine gradients in tissues.


Input: ACRs are presently considered " silent receptors " because no G protein-dependent signaling activity is observed after their engagement by cognate ligands.


Input: We report that engagement of the ACR D6 by its ligands activates a beta-arrestin1-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin through the Rac1-p21-activated kinase 1 (PAK1)-LIM kinase 1 (LIMK1) cascade.


Input: This signaling pathway is required for the increased abundance of D6 protein at the cell surface and for its chemokine-scavenging activity.


Input: We conclude that D6 is a signaling receptor that exerts its regulatory function on chemokine-mediated responses in inflammation and immunity through a distinct signaling pathway.


Input: Lanostane Triterpenoids from the Mushroom Naematoloma fasciculare.

Lanostane Triterpenoids


Input: In our continuing search for structurally interesting and bioactive metabolites from Korean wild mushrooms, bioassay-guided fractionation and a chemical investigation of the MeOH extracts of the fruiting bodies of the mushroom Naematoloma fasciculare resulted in the isolation of four new lanostane triterpenoids (1-4), together with 11 known compounds (5-15).

MeOH

lanostane triterpenoids


Input: The structures of 1-5 were determined by a combination of 1D and 2D NMR and HRMS.


Input: The absolute configuration of the 3-hydroxy-3-methylglutaryl group as a side chain in 1 and 2 was determined by the alkaline methanolysis method.


Input: The full NMR data assignment of the known compound fasciculol G (5) is reported for the first time.

fasciculol G


Input: Compounds 1-15 were tested for their antiproliferative activities against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) and evaluated for their inhibitory effects on nitric oxide production in a lipopolysaccharide-activated murine microglial cell line.

nitric oxide


Input: Isotopic Spectra of the Hydroxyl Radical.

Hydroxyl


Input: Rotational spectra of OH and its isotopologues have been precisely measured using high efficiency Terahertz (THz) sources.

OH


Input: The measurements are compared with existing data and are useful for global modeling.


Input: For the first time microwave measurements of the $\Lambda $-doubling transitions of $^ {17} $OH isotopologue are combined with THz data successfully.

$^ {17} $OH


Input: Precise rotational, fine-structure and hyperfine structure parameters for the $^ {17} $OH isotopologue are reported.

$^ {17} $OH


Input: An isotopically independent Dunham model for all isotopologues of $^ 2\Pi $OH v $< $3 is presented.

OH


Input: An Antioxidative Carbohydrate Polymer from Enhydra fluctuans and Its Interaction with Bovine Serum Albumin.

Carbohydrate


Input: Enhydra fluctuans leaves are traditionally sold on Indian markets for various health benefits.


Input: However no phytochemical study on its high molecular weight compound has so far been performed.


Input: Chemical, chromatographic, ESI-TOF-MS and NMR analyses of the water extracted carbohydrate polymer (CP) of E. fluctuans leaves showed the presence of a 24 kDa arabinogalactan having a (1, 3)-linked beta-D-Galp main chain, substituted at O-6 by (1, 6)-linked beta-D-Galp side chains.

carbohydrate

beta-D-Galp

beta-D-Galp


Input: The latter residues were substituted at O-3 by (1, 3)-, (1, 5)-and (1, 3, 5)-linked alpha-L-Araf chains, and nonreducing end-units of alpha-L-Araf and beta-D-Galp.

alpha-L-Araf

alpha-L-Araf

beta-D-Galp


Input: This polymer contained esterified phenolic acids.

esterified phenolic acids


Input: Biochemical analysis revealed similarity in antioxidative potential between the identified carbohydrate polymer and known standard antioxidants.

carbohydrate


Input: The highly branched side chains and the phenolic acid residues of the arabinogalactan might be the functional sites.

phenolic acid


Input: Fluorimetric and ultraviolet spectrometric analyses showed that the studied carbohydrate polymer can form complex with bovine serum albumin having binding constant K = 2. 42 x 10 (6)/M and changes its microenvironment.

carbohydrate


Input: Thus, traditional aqueous extraction method provides a carbohydrate polymer, which stimulates a fair biological response: this could represent an interesting approach in phytotherapeutic treatments.

carbohydrate


Input: Monolithic Barrier-All-Around High Electron Mobility Transistor with Planar GaAs Nanowire Channel.

GaAs


Input: High quality growth of planar GaAs nanowires (NWs) with widths as small as 35 nm is realized by comprehensively mapping the parameter space of group III flow, V/III ratio, and temperature as the size of the NWs scale down.

GaAs


Input: Using a growth mode modulation scheme for the NW and thin film barrier layers, monolithically integrated AlGaAs barrier-all-around planar GaAs NW high electron mobility transistors (NW-HEMTs) are achieved.

AlGaAs

GaAs


Input: The peak extrinsic transconductance, drive current, and effective electron velocity are 550 micro S/micro m, 435 micro A/micro m, and ~ 2. 9 x (10) ^ 7 cm/s, respectively, at 2V supply voltage with a gate length of 120 nm.


Input: The excellent DC performance demonstrated here shows the potential of this bottom-up planar NW technology for low-power high-speed very-large-scale-integration (VLSI) circuits.


Input: Involvement of serotonin 5-HT3 receptors in the modulation of noradrenergic transmission by serotonin reuptake inhibitors: a microdialysis study in rat brain.

serotonin

serotonin


Input: RATIONALE: Selective serotonin reuptake inhibitors (SSRIs), in addition to being able to enhance serotonergic neurotransmission, are able to modulate other brain systems involved in depression.

serotonin


Input: OBJECTIVES: This study evaluates the neurochemical effect of the SSRI citalopram on brain noradrenergic activity and the serotonin receptor involved in this effect.

serotonin


Input: METHODS: Dual-probe microdialysis in the locus coeruleus (LC) and prefrontal cortex (PFC) was performed in freely awake rats.


Input: RESULTS: Systemic citalopram (10 mg/kg, i. p.) increased noradrenaline (NA) in the LC (E max = 141 +/- 13%) and simultaneously decreased NA in the PFC (Emax =-46 +/- 7%).

citalopram

noradrenaline


Input: In the local presence into the LC of the alpha 2-adrenoceptor antagonist RS79948 (1 mu M), systemic citalopram increased NA in the LC (Emax = 157 +/- 25%) and PFC (Emax = 175 +/- 24%).

citalopram


Input: Local citalopram (0. 1-100 mu M) into the LC induced NA increase in the LC (Emax = 210 +/- 25%) and decrease in the PFC (Emax =-38 +/- 9%).

citalopram


Input: Local LC citalopram effect was abolished by LC presence of the 5-HT3 receptor antagonist MDL72222 (1 mu M) but not the 5-HT1/2 receptor antagonist methiothepin (1 mu M).

citalopram

methiothepin


Input: Systemic citalopram in the LC presence of MDL72222 did not modify NA in the LC but increased NA in the PFC (Emax = 158 +/- 26%).

citalopram


Input: Local citalopram into the PFC enhanced NA (Emax = 376 +/- 18%) in the area, which was prevented by MDL72222.

citalopram


Input: CONCLUSIONS: The SSRI citalopram modulates central noradrenergic neurotransmission by activation, through endogenous serotonin, of 5-HT3 receptors expressed in the somatodendritic (LC) and terminal (PFC) areas, which subsequently promote an enhancement of local NA.

citalopram

serotonin


Input: Therefore, 5-HT3 receptors and somatodendritic alpha 2-adrenoceptors in the LC play an important role in the global effect of SSRIs.


Input: A glucocorticoid education group meeting: an effective strategy for improving self-management to prevent adrenal crisis.


Input: OBJECTIVE: To assess self-management in patients receiving glucocorticoid replacement therapy for primary or secondary adrenal failure before and 6 months after a glucocorticoid education group meeting.


Input: METHODS: All patients with primary or secondary adrenal insufficiency, treated at the department of Medicine, Division of Endocrinology were invited by their endocrinologist to participate in a three-hour glucocorticoid education group meeting, consisting of a lecture about the disease and glucocorticoid doses adjustments in case of stress, followed by an instruction how to inject hydrocortisone intramusculary.

hydrocortisone


Input: Finally, all participants could practice the intramuscular injection and discuss their experience with (imminent) adrenal crises with other patients and the health care providers.


Input: Two weeks before the meeting and 6 months after the meeting, patients were asked to fill out a questionnaire about how they would act in 6 different conditions (e. g. febrile illness or vomiting).


Input: RESULTS: Of the 405 patients who were invited, 246 patients (61%) participated.


Input: At baseline the response by the participants on the questionnaire was 100% (N = 246) and at follow-up 74% (N = 183).


Input: At follow-up, significantly more participants (p = < 0. 005) gave the correct answers how to act in the different situations (e. g. self administration of a glucocorticoid injection and phone contact in case of vomiting/diarrhoea without fever).


Input: Moreover, the use of self-management tools, such as having a' medicine passport (travel document with information about disease and medication) (p = 0. 007) or SOS medallion (p = 0. 0007)' increased.


Input: CONCLUSION: A glucocorticoid education group meeting for patients with adrenal failure seems helpful to improve self-management and proper use of stress-related glucocorticoid dose adjustment.


Input: A tuneable array of unique steady-state microfluidic gradients.


Input: We report an on-chip gradient generator that has been designed, modelled, fabricated, and characterized to facilitate temporal tuning of several unique gradients in parallel for multiple applications.


Input: This design allows for steady state programming of the intensities across multiple orders of magnitude while producing exponential, linear, and logarithmic gradient profiles.


Input: The magnitude of the gradients is controlled through regulating the ratio of the two on-chip flow inlets without the need for valves or other active mixers.


Input: On-chip binding of biotin by a fluorescent streptavidin complex creates a diffusive barrier that regulates access to the gradient inlets, providing a second orthogonal mechanism for regulating the microgradient intensities.

biotin


Input: The device is also characterized using an on-chip enzymatic reaction to produce an array of tuneable product concentrations within the various microchannels.


Input: Statistical optimization of a multivariate fermentation process for enhancing antibiotic activity of Streptomyces sp.


Input: Antibiotic activity against various gram positive bacteria including Staphylococcus aureus and Enterococcus was ascertained from a soil-isolated microbial strain Streptomyces sp.


Input: The antibiotic activity of the strain was maximized by using a dual-stage, multivariate statistical optimization framework based on the response surface methodology considering a lab-scale fermentation process.


Input: Multiple nutrient constituents of the fermentation broth were jointly optimized in the first stage, while the fermentation culture conditions were optimized in the subsequent stage.


Input: Based on the empirical models derived from the dual-stage statistical optimization framework, 39. 79% of cumulative enhancement in the antibiotic activity was obtained (analytically) at the concurrent optimal settings (Optimal nutrient composition for the first stage of optimization: 29. 82 glucose, 7. 6 peptone, 4. 678 MgCl2 and 0. 5005 g/l casamino acid; and optimal fermentation condition for the second stage of optimization: incubation period 47. 55 h; incubation temperature 29. 15 degrees C; and pH 8. 36).

glucose


Input: The analytically depicted enhancement in the antibiotic activity was validated experimentally.


Input: Renal and hepatotoxic alterations in adult mice on inhalation of specific mixture of organic solvents.


Input: This study was aimed at investigating alterations in renal and hepatic toxicity induced by exposing to a combination of three solvents, namely, benzene, toluene and xylene in adult mice.

benzene

toluene

xylene


Input: The mice were divided into three groups (control, low-dose-treated (450 ppm) and high-dose (675 ppm) groups) using randomization methods.


Input: The treated groups were exposed to vapours of a mixture of benzene, toluene and xylene at doses of 450 and 675 ppm, for 6 h day (-1) for a short-term of 7-day exposure period.

benzene

toluene

xylene


Input: The study revealed that the solvent exposure resulted in an increase in the weight of liver and kidney as compared to the control.


Input: Biochemical analyses indicated a significant decline in the activities of superoxide dismutase and catalase in both the treated groups, with concomitant increase in lipid peroxidation.

superoxide


Input: Liver aminotransferases (alanine aminotransferase and aspartate aminotransferase) were elevated with significant alterations in the levels of protein, creatinine and cholesterol in these tissues upon solvent exposure.

alanine

aspartate

creatinine

cholesterol


Input: Correlated with these changes, serum thyroid hormones T3 and T4 were also significantly altered.


Input: This study, therefore, demonstrates that inhalation of vapours from the solvent mixture resulted in significant dose-dependent biochemical and functional changes in the vital tissues (liver and kidney) studied.


Input: The study has specific relevance since humans are increasingly being exposed to such solvents due to increased industrial use in such combinations.


Input: A prospective, randomised, investigator-blind, controlled, clinical study on the clinical efficacy and tolerability of two highly purified hMG preparations administered subcutaneously in women undergoing IVF.


Input: Abstract The aim of this multicentre, prospective, randomised, investigator blind, controlled clinical trial was to evaluate the clinical efficacy and tolerability of a highly purified human menopausal gonadotrophin (hMG) preparation (Merional-HG) when administered to patients undergoing controlled ovarian stimulation (COS) for in-vitro fertilisation (IVF) procedure enrolled in hospital departments.


Input: One hundred fifty-seven patients were randomised in two parallel groups: 78 started COS with Merional-HG and 79 with Menopur.


Input: Results of the study showed that both highly purified hMG preparations were equivalent in terms of number of oocytes retrieved (primary endpoint: 8. 8 +/- 3. 9 versus 8. 4 +/- 3. 8, p = 0. 54).


Input: In the patients treated with Merional-HG, we observed a higher occurrence of mature oocytes (78. 3% versus 71. 4%, p = 0. 005) and a reduced quantity of gonadotrophins administered per cycle (2. 556 +/- 636 IU versus 2. 969 +/- 855 IU, p < 0. 001).


Input: Fertilisation, cleavage, implantation rates and the number of positive beta-human chorionic gonadotrophin (hCG; pregnancy) tests and the clinical pregnancy rate were comparable in the two groups.


Input: Both treatments were well tolerated.


Input: In conclusion, the results of this study support the efficacy and safety of Merional-HG administered subcutaneously for assisted reproduction techniques.


Input: Efficiency of Merional-HG appears to be higher due to reduced quantity of drug used and the higher yield of mature oocytes retrieved.


Input: Cysteine-conjugated metabolite of ginger component [6]-shogaol serves as a carrier of [6]-shogaol in cancer cells and in mice.

Cysteine


Input: Shogaols, a series of major constituents in dried ginger (Zingiber officinale), show high anti-cancer potencies.

Shogaols


Input: Previously, we reported that a major metabolite resulting from the mercapturic acid pathway, 5-cysteinyl-[6]-shogaol (M2), showed comparable growth inhibitory effects towards cancer cells to [6]-shogaol (6S).

mercapturic acid


Input: Here we probe the mechanism by which M2 exerts its bioactivity.


Input: We utilized a series of chemical stability tests in conjunction with bioassays to show that thiol-conjugates display chemopreventative potency by acting as carriers of active ginger component 6S.

thiol


Input: M2 chemical degradation to 6S was observed in an environment most resembling physiological conditions, with a pH of 7. 4 at 37 degrees C.


Input: The metabolic profiles of M2 in cancer cells HCT-116 and H-1299 resembled those of 6S, indicating that its biotransformation route was initiated by deconjugation.


Input: Further, the presence of excess glutathione significantly delayed 6S and M2 metabolism and counteracted cell death induced by 6S and M2, suggesting that increasing available free thiols exogenously both promoted formation of 5-glutathionyl-[6]-shogaol (M13) and inhibited the production of free 6S from M2 deconjugation, resulting in delayed 6S cell entry and bioactivity.

glutathione

thiols


Input: Given the chemopreventative properties of M2 and our observations in vitro, we investigated its metabolism in mice.


Input: M2 and 6S showed similar metabolic profiles in mouse urine and fecal samples.


Input: Six new thiol-conjugated metabolites (M16-M21), together with previously reported ones, were identified by LC/MS.

thiol


Input: In particular, the increase of 5-N-acetylcystenyl-[6]-shogaol (M5) and its 3-demethylated product (M16) abundance in mouse feces after treatment with M2 indicate that in addition to acting as a carrier of 6S, M2 is also directly acetylated to M5, which is further demethylated to M16 in vivo.


Input: In conclusion, cysteine-conjugated metabolite of [6]-shogaol M2 exerts its bioactivity by acting as a carrier of 6S in both cancer cells and in mice.

cysteine


Input: Three-Dimensional Self-Assembly of Chalcopyrite Copper Indium Diselenide Nanocrystals into Oriented Films.

Chalcopyrite Copper Indium Diselenide


Input: CuInSe2, which is one of the highest efficiency thin-film solar cell active layer materials, has been an attractive target for nanocrystal synthesis and manipulation.


Input: Here, we report unprecedented, simultaneous control of the synthesis and self-assembly behavior of CuInSe2 nanocrystals.


Input: These nanocrystals are solution-processable, monodisperse tetragonal bipyramids that exhibit photoconductivity and self-assemble into crystallographically oriented thin films.


Input: Structural characterization indicates that these nanocrystals are tetragonal phase, as is used in high-efficiency, second-generation, thin-film solar cells.


Input: Elemental analysis indicates that approximately 1: 1: 2 Cu/In/Se stoichiometry can be achieved, and that the elemental composition can be adjusted from copper-rich to indium-rich with reaction time.

Cu

In

Se

copper

indium


Input: Ginsenjilinol, a new protopanaxatriol-type saponin with inhibitory activity on LPS-activated NO production in macrophage RAW 264. 7 cells from the roots and rhizomes of Panax ginseng.

Ginsenjilinol

protopanaxatriol

saponin

NO


Input: One new dammarane triterpene saponin named ginsenjilinol (1) was isolated from the roots and rhizomes of Panax ginseng C. A.

dammarane triterpene saponin

ginsenjilinol


Input: Mey., together with two known saponins ginsenoside Rf (2) and ginsenoside Re5 (= panajaponol A, 3).

saponins ginsenoside Rf

ginsenoside Re5

panajaponol A


Input: Based on IR, HR-ESI-MS, and 1D as well as 2D NMR ((1) H-(1) H COSY, NOESY, HSQC, and HMBC) spectral data, the chemical structure of the new saponin was elucidated as 3 beta, 12 beta, 20S, 26-tetrahydroxydammar-24E-en-6 alpha-O-beta-d-glucopyranosyl-(1 --> 2)-O-beta-d-glucopyranoside.

(1) H

(1) H

saponin

3 beta, 12 beta, 20S, 26-tetrahydroxydammar-24E-en-6 alpha-O-beta-d-glucopyranosyl-(1 --> 2)-O-beta-d-glucopyranoside


Input: The ability of the isolated saponins to inhibit nitric oxide production by lipopolysaccharide-activated RAW 264. 7 cells was also assayed.

saponins

nitric oxide


Input: All of the isolated saponins exhibited the significant activity in a concentration-dependent manner at concentrations of 60-200 mu M with the half maximal inhibitory concentration (IC50) values of 70. 96 +/- 2. 05 mu M for 1, 74. 14 +/- 2. 65 mu M for 2, and 79. 83 +/- 1. 78 mu M for 3, respectively, whereas indomethacin had an IC50 of 63. 75 +/- 3. 33 mu M as a positive control drug.

saponins

indomethacin


Input: Parent-only vs. parent-child (family-focused) approaches for weight loss in obese and overweight children: a systematic review and meta-analysis.


Input: Families are recommended as the agents of change for weight loss in overweight and obese children; family approaches are more effective than those that focus on the child alone.


Input: However, interventions that focus on parents alone have not been summarized.


Input: The objective of this review was to assess the effectiveness of interventions that compared a parent-only (PO) condition with a parent-child (PC) condition.


Input: Four trials using a similar between-group background approaches to overweight and obese children' s weight loss met the inclusion criteria, but only one trial reported sufficient data for meta-analysis.


Input: Further information was obtained from authors.


Input: Meta-analysis showed no significant difference in z-BMI from baseline to end of treatment between the conditions (three trials) or to end of follow up (two trials).


Input: The trials were at risk of bias and no single trial was at lower risk of bias than others.


Input: There is an absence of high quality evidence regarding the effect of parent-only interventions for weight loss in children compared to parent-child interventions, but current evidence suggests the need for further investigation.


Input: Two new cytotoxic iridoid esters from the rhizomes and roots of Patrinia heterophylla Bunge.

iridoid esters


Input: Two new iridoid esters, named patriheterdoid B, C, have been isolated from the rhizomes and roots of Patrinia heterophylla Bunge.

iridoid esters

patriheterdoid B, C


Input: Their structures were elucidated by extensive spectroscopic technologies.


Input: Together with patriheterdoid B, C, two known analogues have been isolated and identified by means of mass spectrometry and (1) H and (13) C NMR spectrometry.

patriheterdoid B, C

(1) H

(13) C


Input: These compounds showed cytotoxic activity against SGC-7901, PC3 cell lines.


Input: Bio-inspired, Calcium-free Alginate Hydrogels with Tunable Physical and Mechanical Properties and Improved Biocompatibility.

Calcium


Input: Alginate hydrogels are for various biomedical applications including tissue engineering, cell therapy, and drug delivery.


Input: However, it is not easy to control swelling, or viscoelastic and biophysical properties of alginate hydrogels prepared by conventional crosslinking methods (ionic interaction using divalent cations).


Input: In this study, we describe a bio-inspired approach for preparing divalent ion-free alginate hydrogels that exhibit tunable physical and mechanical properties and improved biocompatibility due to the absence of cations in the gel matrices.


Input: We conjugated dopamine, a minimalized adhesive motif found in the holdfast pads of mussels, to alginate backbones (alginate-catechol) and the tethered catechols underwent oxidative crosslinking.

dopamine

catechol

catechols


Input: This resulted in divalent cation-free alginate hydrogels.


Input: The swelling ratios and moduli of the alginate-catechol hydrogels are readily tunable, which is difficult to achieve in ionic bond-based alginate hydrogels.

catechol


Input: Furthermore, alginate-catechol hydrogels enhanced the survival of various human primary cells including stem cells in the three-dimensional gel matrix, indicating that intrinsic cytotoxicity caused by divalent cations becomes negligible when employing catechol oxidation for alginate crosslinking.

catechol

catechol


Input: The inflammatory response in vivo was also significantly attenuated compared to conventional alginate hydrogels with calcium crosslinking.

calcium


Input: This biomimetic approach for the preparation of alginate hydrogels may provide a novel platform technology to develop tunable, functional, biocompatible three-dimensional scaffolds for tissue engineering and cell therapy.


Input: Antiangiogenetic effects of anthranoids from Alternaria sp., an endophytic fungus in a Thai medicinal plant Erythrina variegata.

anthranoids


Input: Endophytic fungi are known as a prolific source for the discovery of structurally interesting and biologically active secondary metabolites, some of which are promising candidates for drug development.


Input: In the present study, three anthranoids were isolated from an Alternaria sp. endophytic fungus and evaluated for their antiangiogenic activity in a rat aortic sprouting assay, an ex vivo model of angiogenesis.

anthranoids


Input: Of these three compounds, altersolanol (2) was further characterized and found to show a promising activity in ex vivo, in vitro and in vivo angiogenesis asssays.

altersolanol


Input: Using human umbilical vein endothelial cells as an in vitro model, the angiogenic effect of 2 was found to occur via suppression of all three main functions of endothelial cells, namely proliferation, tube formation and migration.


Input: Puerarin stimulates proliferation and differentiation and protects against cell death in human osteoblastic MG-63 cells via ER-dependent MEK/ERK and PI3K/Akt activation.

Puerarin


Input: Puerarin, the main isoflavone glycoside found in the Chinese herb radix of Pueraria lobata (Willd.) Ohwi, has received increasing attention because of its possible role in the prevention of osteoporosis.

Puerarin

isoflavone glycoside


Input: Previously, we showed that puerarin could inhibit the bone absorption of osteoclasts and promote long bone growth in fetal mouse in vitro.

puerarin


Input: Further study confirmed that puerarin stimulated proliferation and differentiation of osteoblasts in rat.

puerarin


Input: However, the mechanisms underlying its actions on human bone cells have not been well defined.


Input: Here we show that puerarin increases proliferation and differentiation and opposes cisplatin-induced apoptosis in human osteoblastic MG-63 cells containing two estrogen receptor (ER) isoforms.

puerarin

cisplatin

estrogen


Input: Puerarin promotes proliferation by altering cell cycle distribution whereas puerarin-mediated survival may be associated with up-regulation of Bcl-xL expression.

Puerarin

puerarin


Input: Treatment with the ER antagonist ICI 182, 780 abolishes the above actions of puerarin on osteoblast-derived cells.

ICI 182, 780

puerarin


Input: Using small interfering double-stranded RNA technology, we further demonstrate that the effects of puerarin on proliferation, differentiation and survival are mediated by both ER alpha and ER beta.

puerarin


Input: Moreover, we also demonstrate that puerarin functions at least partially through activation of MEK/ERK and PI3K/Akt signaling.

puerarin


Input: This agent also shows much weaker effect on breast epithelial cell growth than that of estrogen.

estrogen


Input: Therefore, puerarin will be a promising agent that prevents or retards osteoporosis.

puerarin


Input: Bone Morphogenetic Protein-7 inhibits silica-induced pulmonary fibrosis in rats.

silica


Input: Bone morphogenetic protein-7 (BMP-7) has been shown to inhibit liver and renal fibrosis in in vivo and in vitro studies.


Input: There is no study to investigate BMP-7' s role in the development of pulmonary fibrosis induced by silica.

silica


Input: In the current study, we used the rat model to explore the potential antifibrotic role of BMP-7 and its underlying mechanism in silica-induced pulmonary fibrosis.

silica


Input: Sixty Wistar rats were randomly assigned into three groups.


Input: Control group received saline, silica group received silica and BMP-7 treated group received silica and BMP-7.

silica

silica

silica


Input: BMP-7 was administered to silica-treated rats intraperitoneally at a dose of 300 mu g/kg/injection from day 8 to day 30 every other day.

silica


Input: After the animals were sacrificed on day 15 and 30, hydroxyproline levels, the protein expressions of BMP/Smad and TGF-beta/Smad signaling, and histopathology in lung tissues were analyzed.

hydroxyproline


Input: The hydroxyproline contents in BMP-7 treated groups were significantly lower than the silica groups (P < 0. 05).

hydroxyproline

silica


Input: Histopathological results showed BMP-7 could reduce the progression of silica induced fibrosis.

silica


Input: Furthermore, the expression of p-Smad1/5/8, a marker of BMP/Smad signaling, was significantly up-regulated in BMP-7 treated groups (P < 0. 05) compared with the silica groups.

silica


Input: On the contrary, the expression of p-Smad2/3, a marker for TGF-beta/Smad signaling, reduced significantly in BMP-7-treated groups compared with silica groups (P < 0. 05).

silica


Input: In conclusion, the pulmonary fibrosis induced by silica in rats was significantly reduced with the therapeutic treatment of BMP-7.

silica


Input: The antifibrotic effect of BMP-7 could be related to the activation of BMP/Smad signaling and inhibition of TGF-beta/Smad pathways.


Input: Ghrelin receptor is activated by naringin and naringenin, constituents of a prokinetic agent Poncirus fructus.

naringin

naringenin


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Poncirus fructus (PF), also known as a dried immature fruit of Poncirus trifoliata (L.) Raf, has long been traditionally used for the various gastrointestinal disorders in Eastern Asia.


Input: AIM OF STUDY: The aqueous extract of PF (PF-W) has the strong prokinetic effect, yet the underlying mechanism is still elusive.


Input: The present study investigated whether PF-W has any effect on motilin receptor or ghrelin receptor, since these receptors enhance intestinal motility when activated.


Input: MATERIALS AND METHODS: The effect of PF-W and its components on motilin or ghrelin receptor was determined by calcium imaging and whole-cell patch clamp methods.

calcium


Input: RESULTS: PF-W activates the ghrelin receptor, but not the motilin receptor, resulting in a transient increase of intracellular calcium levels.

calcium


Input: Furthermore, among various constituents of PF, only naringin and naringenin evoked the intracellular calcium augmentation via the ghrelin receptor.

naringin

naringenin

calcium


Input: Moreover, cortistatin-8-a ghrelin receptor inhibitor-specifically blocked naringin-and naringenin-induced calcium increases.

naringin

naringenin

calcium


Input: In addition, naringin and naringenin induced inward currents in ghrelin receptor-expressing cells under whole-cell patch clamp configuration.

naringin

naringenin


Input: CONCLUSION: PF-W activates the ghrelin receptor, and naringin and naringenin are key constituents responsible for the activation of ghrelin receptor.

naringin

naringenin


Input: Therefore, the present study suggests that the ghrelin receptor is a molecular entity responsible for the strong prokinetic activity of PF-W.


Input: Gene flow vs. pollution pressure: Genetic diversity of Mytilus galloprovincialis in eastern Adriatic.


Input: Environmental pollution may modify all the evolutionary processes involved in shaping the genetic patterns of exposed populations.


Input: In order to evaluate the pollution impact on the genetic diversity of Mediterranean mussel Mytilus galloprovincialis ten populations inhabiting differently polluted sites along the eastern Adriatic coast, from pristine bays to heavily trafficked harbours, were studied.


Input: Pollution pressure was assessed through an integrated study of biological effects and responses across different levels of biological organization.


Input: Eight microsatellite markers were analysed to assess genetic diversity of investigated populations.


Input: Both the principal component analysis (PCA) of the biomarker data set as well as the biomarker response index (BRI) confirmed substantial pollution pressure at the highly polluted sites, and very low pollution exposure at the three reference sites.


Input: Very shallow genetic differentiation was found in respect to maritime distances or pollution status, and this was attributed to a high gene flow among the populations.


Input: However, populations inhabiting polluted sites exhibited higher levels of genetic diversity and evolutionary mechanisms underlying this phenomenon are discussed.


Input: When a good taste turns bad: Neural mechanisms underlying the emergence of negative affect and associated natural reward devaluation by cocaine.

cocaine


Input: An important feature of cocaine addiction in humans is the emergence of negative affect (e. g., dysphoria, irritability, anhedonia), postulated to play a key role in craving and relapse.

cocaine


Input: Indeed, the DSM-IV recognizes that social, occupational and/or recreational activities become reduced as a consequence of repeated drug use where previously rewarding experiences (e. g., food, job, family) become devalued as the addict continues to seek and use drug despite serious negative consequences.


Input: Here, research in the Carelli laboratory is reviewed that examined neurobiological mechanisms that may underlie these processes using a novel animal model.


Input: Oromotor responses (taste reactivity) were examined as rats learned that intraoral infusion of a sweet (e. g., saccharin) predicts impending but delayed access to cocaine self-administration.

saccharin

cocaine


Input: We showed that rats exhibit aversive taste reactivity (i. e., gapes/rejection responses) during infusion of the sweet paired with impending cocaine, similar to aversive responses observed during infusion of quinine, a bitter tastant.

cocaine

quinine


Input: Critically, the expression of this pronounced aversion to the sweet predicted the subsequent motivation to self-administer cocaine.

cocaine


Input: Electrophysiology studies show that this shift in palatability corresponds to an alteration in nucleus accumbens (NAc) cell firing; neurons that previously responded with inhibition during infusion of the palatable sweet shifted to excitatory activity during infusion of the cocaine-devalued tastant.

cocaine


Input: This excitatory response profile is typically observed during infusion of quinine, indicating that the once palatable sweet becomes aversive following its association with impending but delayed cocaine, and NAc neurons encode this aversive state.

quinine

cocaine


Input: We also review electrochemical studies showing a shift (from increase to decrease) in rapid NAc dopamine release during infusion of the cocaine-paired tastant as the aversive state developed, again, resulting in responses similar to quinine infusion.

dopamine

cocaine

quinine


Input: Collectively, our findings suggest that cocaine-conditioned cues elicit a cocaine-need state that is aversive, is encoded by a distinct subset of NAc neurons and rapid dopamine signaling, and promotes cocaine-seeking behavior.

cocaine

cocaine

dopamine

cocaine


Input: Finally, we present data showing that experimentally induced abstinence (30 days) exacerbates this natural reward devaluation by cocaine, and this effect is correlated with a greater motivation to lever press during extinction.

cocaine


Input: Dissecting the neural mechanisms underlying these detrimental consequences of addiction is critical since it may lead to novel treatments that ameliorate negative affective states associated with drug use and decrease the drive (craving) for the drug.


Input: This article is part of a Special Issue entitled' NIDA 40th Anniversary Issue'.


Input: Cognitive Function During Nicotine Withdrawal: Implications for Nicotine Dependence Treatment.

Nicotine

Nicotine


Input: Nicotine withdrawal is associated with deficits in neurocognitive function including sustained attention, working memory, and response inhibition.

Nicotine


Input: Several convergent lines of evidence suggest that these deficits may represent a core dependence phenotype and a target for treatment development efforts.


Input: A better understanding of the mechanisms underlying withdrawal-related cognitive deficits may lead to improve nicotine dependence treatment.

nicotine


Input: We begin with an overview of the neurocognitive effects of withdrawal in rodent and human models, followed by discussion of the neurobehavioral mechanisms that are thought to underlie these effects.


Input: We then review individual differences in withdrawal-related neurocognitive effects including genetics, gender, and psychiatric comorbidity.


Input: We conclude with a discussion of the implications of this research for developing improved therapies, both pharmacotherapy and behavioral treatments, that target cognitive symptoms of nicotine withdrawal.

nicotine


Input: Design, synthesis and biological evaluation of indeno [1, 2-d] thiazole derivatives as potent histone deacetylase inhibitors.

indeno [1, 2-d] thiazole


Input: Novel indeno [1, 2-d] thiazole hydroxamic acids were designed, synthesized, and evaluated for histone deacetylases (HDACs) inhibition and antiproliferative activities on tumor cell lines.

indeno [1, 2-d] thiazole hydroxamic acids


Input: Most of the tested compounds exhibited HDAC inhibition and antiproliferative activity against both MCF7 and HCT116 cells with GI50 values in the sub-micromolar range.


Input: Among them, compound 6o showed good inhibitory activity against pan-HDAC with IC50 value of 0. 14 mu M and significant growth inhibition on MCF7 and HCT116 cells with GI50 values of 0. 869 and 0. 535 mu M, respectively.


Input: Evaluation of 2'-alpha-fluorine modified nucleoside phosphonates as potential inhibitors of HCV polymerase.

nucleoside phosphonates


Input: Ribonucleoside phosphonate analogues containing 2'-alpha-fluoro modifications were synthesized and their potency evaluated against HCV RNA polymerase.

Ribonucleoside phosphonate


Input: The diphosphophosphonate (triphosphate equivalent) adenine and cytidine analogues displayed potent inhibition of the HCV polymerase in the range of 1. 9-2. 1 mu M, but only modest cell-based activity in the HCV replicon.

diphosphophosphonate

triphosphate

adenine

cytidine


Input: Pro-drugs of the parent nucleoside phosphonates improved the cell-based activity.

nucleoside phosphonates


Input: Synthesis and ionophoric activities of functionalized bis (choloyl) conjugates with a rigid core.

bis (choloyl)


Input: Three bis (choloyl) conjugates bearing a rigid p-phenylenediamine/p-bis (aminomethyl) benzene linker and amino/acetamido groups were synthesized, and fully characterized on the basis of (1) H NMR, ESI-MS and HRMS.

bis (choloyl)

p-phenylenediamine

p-bis (aminomethyl) benzene

amino

acetamido

(1) H


Input: Their ionophoric activities were investigated by means of pH discharge assay.


Input: The results indicate that these conjugates exhibit potent ionophoric activities across egg-yolk l-alpha-phosphatidylcholine (EYPC)-based liposomal membranes, via a cation/proton antiport mechanism.

l-alpha-phosphatidylcholine


Input: They show moderate ion selectivity among alkali metal ions.


Input: Of the three conjugates, the ones having amino groups transport alkali metal ions in the order of Na (+) > Li (+) > K (+) =~ Rb (+) =~ Cs (+), whereas the one having acetamido groups functions in the order of Li (+) > Na (+) > K (+) =~ Rb (+) =~ Cs (+).

amino

Na (+)

Li (+)

K (+)

Rb (+)

Cs (+)

acetamido

Li (+)

Na (+)

K (+)

Rb (+)

Cs (+)


Input: Doxorubicin induces protein ubiquitination and inhibits proteasome activity during cardiotoxicity.

Doxorubicin


Input: Anthracycline-induced cardiotoxicity is a clinically complex syndrome that leads to substantial morbidity and mortality for cancer survivors.

Anthracycline


Input: Despite several years of research, the underlying molecular mechanisms remain largely undefined and thus effective therapies to manage this condition are currently non-existent.


Input: This study therefore aimed to determine the contribution of the ubiquitin-proteasome pathway (UPP) and endoplasmic reticulum (ER)-stress within this context.


Input: Cardiotoxicity was induced with the use of doxorubicin (DXR) in H9C2 rat cardiomyoblasts (3 mu M) for 24hrs, whereas the tumour-bearing GFP-LC3 mouse model was treated with a cumulative dose of 20mg/kg.

doxorubicin

DXR


Input: Markers for proteasome-specific protein degradation were significantly upregulated in both models following DXR treatment, however proteasome activity was lost.

DXR


Input: Moreover, ER-stress as assessed by increased ER load was considerably augmented (in vitro) with modest binding of DXR with ER.

DXR


Input: These results suggest that DXR induces intrinsic activation of the UPP and ER stress which ultimately contributes to dysfunction of the myocardium during this phenomenon.

DXR


Input: Synthetic chalcones and sulfonamides as new classes of Yersinia enterocolitica YopH tyrosine phosphatase inhibitors.

chalcones

sulfonamides

tyrosine


Input: YopH plays a relevant role in three pathogenic species of Yersinia.


Input: Due to its importance in the prevention of the inflammatory response of the host, this enzyme has become a valid target for the identification and development of new inhibitors.


Input: In this work, an in-house library of 283 synthetic compounds was assayed against recombinant YopH from Yersinia enterocolitica.


Input: From these, four chalcone derivatives and one sulfonamide were identified for the first time as competitive inhibitors of YopH with binding affinity in the low micromolar range.

chalcone

sulfonamide


Input: Molecular modeling investigations indicated that the new inhibitors showed similar binding modes, establishing polar and hydrophobic contacts with key residues of the YopH binding site.


Input: Application of COSMO-RS as an Excipient Ranking Tool in Early Formulation Development.


Input: The low amounts of drug available in early discovery often results in limited information on the physico-chemical (solubility etc.) properties of a compound being obtained.


Input: As a result, predictive tools and miniaturised screens have been investigated to aid formulation development in early discovery.


Input: This study looks at the potential application of the quantum chemistry program, Conductor Screening Model for Real Solvents (COSMO-RS) to help with the selection of excipients for formulation development in early discovery.


Input: The excipient solubility predictions obtained from COSMO-RS were compared to experimentally obtained solubilities.


Input: The results showed that in general, COSMO-RS was able to help formulators with the selection of the most appropriate excipients to solubilise the model compound.


Input: Enzyme-responsive surface erosion of poly (ethylene carbonate) for controlled drug release.

poly (ethylene carbonate)


Input: Cholesterol esterase (CE) induced surface erosion of poly (ethylene carbonate) (PEC) and drug release from PEC under mild physiological environment was investigated.

Cholesterol

poly (ethylene carbonate)

PEC

PEC


Input: The degradation process was monitored by changes of mass and molecular weight (MW) and surface morphology of polymer films.


Input: During the whole period of degradation, MW of PEC was unchanged.

PEC


Input: Water uptake of the polymer was only 2. 8 and 0. 2% for PEC with the MW of 200 kDa (PEC200) and PEC with the MW of 41 kDa (PEC41), respectively.

PEC

PEC


Input: Degradation of less hydrophilic PEC41 with higher density was slower than that of PEC200.


Input: By this mechanism, CE-responsive drug in vitro release from PEC in situ forming depots (ISFD) was conducted successfully.

PEC


Input: As expected, less bovine serum albumin (BSA) was released from PEC41 compared with that of PEC200 in the same time period.


Input: In conclusion, this work enabled the in vitro drug release evaluation of existing PEC devices and implied a new candidate for the development of enzyme-responsive systems.

PEC


Input: In vivo administration of VEGF-and GDNF-releasing biodegradable polymeric microspheres in a severe lesion model of Parkinson' s disease.


Input: In this work, the neuroregenerative potentials of microencapsulated VEGF, GDNF and their combination on a severely lesioned rat model were compared with the aim of developing a new strategy to treat advanced stages of Parkinson' s disease.


Input: Both neurotrophic factors were separately encapsulated into polymeric microspheres (MS) to obtain a continuous drug release over time.


Input: The regenerative effects of these growth factors were evaluated using a rotation behaviour test and quantified by the number of surviving TH + cells.


Input: The biological activities of encapsulated vascular endothelial growth factor (VEGF) and glial cell line derived neurotrophic factor (GDNF) were investigated in HUVEC and PC12 cells, respectively.


Input: The treatment of 6-OHDA-lesioned rats with GDNF microspheres and with both VEGF and GDNF microspheres resulted in improved results in the rotation behaviour test.


Input: Both groups also showed higher levels of neuroregeneration/neuroreparation in the substantia nigra than the control group did.


Input: These results were confirmed by the pronounced TH + neuron recovery in the group receiving VEGF + GDNF-MS, demonstrating regenerative effects.


Input: Ultrasound-assisted extraction of Na and K from swine feed and its application in a digestibility assay: A green analytical procedure.

K


Input: The study is aimed to evaluate the efficiency of ultrasound-assisted extraction (UAE) as a simple strategy focused on sample preparation for metal determination in biological samples.


Input: The extraction of sodium and potassium extraction was carried out from swine feed followed by determination of the concentration of these metals by flame atomic emission spectrometry (FAES).

sodium

potassium


Input: The experiment was performed to cover the study of the variables influencing the extraction process and its optimal conditions (sample mass, particle size, acid concentration, sonication time and ultrasound power); the determination of these analytical characteristics and method validation using certified reference material; and the analysis of pre-starter diets.


Input: The optimal conditions established conditions were as follows: mass: 100mg, particle size: < 60 mu m, acid concentration: 0. 10molL (-1) HCl, sonication time: 50s and ultrasound power: 102W.

HCl


Input: The proposed method (UAE) was applied in digestibility assays of those nutrients present in different piglet pre-starter feeds and their results proved to be compatible with those obtained from mineralized samples (P < 0. 05).


Input: The ultrasound extraction method was demonstrated to be an excellent alternative for handless sampling and operational costs and the method also has the advantage of does not generating toxic residues that may negatively affect human health and contaminate the environment.


Input: Microfluidics on liquid handling stations (mu F-on-LHS): an industry compatible chip interface between microfluidics and automated liquid handling stations.


Input: We describe a generic microfluidic interface design that allows the connection of microfluidic chips to established industrial liquid handling stations (LHS).


Input: A molding tool has been designed that allows fabrication of low-cost disposable polydimethylsiloxane (PDMS) chips with interfaces that provide convenient and reversible connection of the microfluidic chip to industrial LHS.

polydimethylsiloxane

PDMS


Input: The concept allows complete freedom of design for the microfluidic chip itself.


Input: In this setup all peripheral fluidic components (such as valves and pumps) usually required for microfluidic experiments are provided by the LHS.


Input: Experiments (including readout) can be carried out fully automated using the hardware and software provided by LHS manufacturer.


Input: Our approach uses a chip interface that is compatible with widely used and industrially established LHS which is a significant advancement towards near-industrial experimental design in microfluidics and will greatly facilitate the acceptance and translation of microfluidics technology in industry.


Input: Characterization of surface ligands on functionalized magnetic nanoparticles using laser desorption/ionization mass spectrometry (LDI-MS).


Input: Functionalized magnetic nanoparticles (MNPs) have been characterized by laser desorption/ionization mass spectrometry (LDI-MS).


Input: Quantitative information about surface ligand composition and structure for monolayer and mixed monolayer protected Fe3O4 and FePt NPs can be obtained rapidly with very little sample consumption.

FePt


Input: Free volume in ionic liquids: a connection of experimentally accessible observables from PALS and PVT experiments with the molecular structure from XRD data.


Input: In the current work, free volume concepts, primarily applied to glass formers in the literature, were transferred to ionic liquids (ILs).


Input: A series of 1-butyl-3-methylimidazolium ([C4MIM] (+)) based ILs was investigated by Positron Annihilation Lifetime Spectroscopy (PALS).

[C4MIM] (+)


Input: The phase transition and dynamic properties of the ILs [C4MIM] [X] with [X] (-) = [Cl] (-), [BF4] (-), [PF6] (-), [OTf] (-), [NTf2] (-) and [B (hfip) 4] (-) were reported recently (Yu et al., Phys. Chem. Chem. Phys., 2012, 14, 6856-6868).

[Cl] (-)

[BF4] (-)

[PF6] (-)

[OTf] (-)

[NTf2] (-)

[B (hfip) 4] (-)


Input: In this subsequent work, attention was paid to the connection of the free volume from PALS (here the mean hole volume, < vh >) with the molecular structure, represented by volumes derived from X-ray diffraction (XRD) data.


Input: These were the scaled molecular volume Vm, scaled and the van der Waals volume Vvdw.


Input: Linear correlations of < vh > at the " knee " temperature (< vh > (Tk)) with Vm, scaled and Vvdw gave good results for the [C4MIM] (+) series.

[C4MIM] (+)


Input: Further relationships between volumes from XRD data with the occupied volume Vocc determined from PALS/PVT (Pressure Volume Temperature) measurements and from Sanchez-Lacombe Equation of State (SL-EOS) fits were elaborated (Vocc (SL-EOS) =~ 1. 63 Vvdw, R (2) = 0. 981 and Vocc (SL-EOS) =~ 1. 12 Vm, scaled, R (2) = 0. 980).


Input: Finally, the usability of Vm, scaled was justified in terms of the Cohen-Turnbull (CT) free volume theory.


Input: Empirical CT type plots of viscosity and electrical conductivity showed a systematic increase in the critical free volume with molecular size.


Input: Such correlations allow descriptions of IL properties with the easily accessible quantity Vm, scaled within the context of the free volume.


Input: Structure-Activity Relationships of Quinoxaline-Based 5-HT3 A and 5-HT3 AB Receptor-Selective Ligands.

Quinoxaline


Input: Until recently, discriminating between homomeric 5-HT3 A and heteromeric 5-HT3 AB receptors was only possible with ligands that bind in the receptor pore.


Input: This study describes the first series of ligands that can discriminate between these receptor types at the level of the orthosteric binding site.


Input: During a recent fragment screen, 2-chloro-3-(4-methylpiperazin-1-yl) quinoxaline (VUF10166) was identified as a ligand that displays an 83-fold difference in [(3) H] granisetron binding affinity between 5-HT3 A and 5-HT3 AB receptors.

2-chloro-3-(4-methylpiperazin-1-yl) quinoxaline

[(3) H] granisetron


Input: Fragment hit exploration, initiated from VUF10166 and 3-(4-methylpiperazin-1-yl) quinoxalin-2-ol, resulted in a series of compounds with higher affinity at either 5-HT3 A or 5-HT3 AB receptors.

3-(4-methylpiperazin-1-yl) quinoxalin-2-ol


Input: These ligands reveal that a single atom is sufficient to change the selectivity profile of a compound.


Input: At the extremes of the new compounds were 2-amino-3-(4-methylpiperazin-1-yl) quinoxaline, which showed 11-fold selectivity for the 5-HT3 A receptor, and 2-(4-methylpiperazin-1-yl) quinoxaline, which showed an 8. 3-fold selectivity for the 5-HT3 AB receptor.

2-amino-3-(4-methylpiperazin-1-yl) quinoxaline

2-(4-methylpiperazin-1-yl) quinoxaline


Input: These compounds represent novel molecular tools for studying 5-HT3 receptor subtypes and could help elucidate their physiological roles.


Input: Facile Fluorescence-Based Detection of PAD4-Mediated Citrullination.


Input: The post-translational modifications of histone proteins are highly diverse and dynamic processes.


Input: It is becoming increasingly evident that modifying histone proteins can have a direct influence on both cellular homeostasis and disease states.


Input: Protein arginine deiminase 4 (PAD4) is an enzyme that converts peptidyl-arginine to citrulline.

arginine

arginine


Input: The overexpression of PAD4 has been found in numerous types of human cancer and autoimmune diseases.


Input: We report a new, facile, fluorescence-based assay for the detection of PAD4 activity that exploits the substrate specificity of trypsin to monitor the citrullination reaction carried out by PAD4 based on the fact that, upon citrullination, the positively charged arginine side chain is converted to the neutral citrulline.

trypsin

citrulline


Input: We show that the assay can be performed rapidly with readily available reagents and that it responds accordingly to a known PAD4 inhibitor.


Input: The Distorted Tropane of Scopoline.

Tropane

Scopoline


Input: The structural isomerization of scopine into scopoline (oscine) has been observed in a supersonic jet expansion using microwave spectroscopy.

scopine

scopoline

oscine


Input: The rotational spectrum evidences a single structure in the gas phase, providing a first description of the (three-ring) structurally distorted tropane in scopoline.

tropane

scopoline


Input: The absence of rotational signatures of any scopine conformation suggests a practically quantitative isomerization at the vaporization temperatures of the experiment (ca. 90 degrees C).

scopine


Input: The determined rotational parameters of scopoline reveal the structural consequences of the intramolecular cyclation of scopine, which breaks the original epoxy group and creates a new ether bridge and a 7 beta-hydroxytropane configuration.

scopoline

scopine

epoxy

7 beta-hydroxytropane


Input: The hydroxy group further stabilizes the molecule by an O <F8FF> H... N intramolecular hydrogen bond, which, in turn, forces the N-methyl group to the less stable axial form.

hydroxy

O <F8FF> H

N

hydrogen

N-methyl


Input: Supporting ab initio (MP2) and DFT (B3LYP, M06-2X) calculations are included.


Input: Anti-inflammatory Activities of an Active Fraction Isolated from the root of Astragalus membranaceus in RAW 264. 7 Macrophages.


Input: The root of Astragalus membranaceus (AR), which has been widely used in Traditional Chinese herbal formulae for treating foot ulcer, was found to exhibit anti-inflammatory property, but its molecular mechanism still remains unknown.


Input: We previously identified the anti-inflammatory sub-fraction using bioassay-guided fractionation.


Input: The objective of the present study was to investigate the anti-inflammatory mechanism of the major active fraction (MAF) (0. 039 to 0. 156 mg/mL) using lipopolysaccharide (LPS)-stimulated mouse macrophage RAW 264. 7 cells.


Input: MAF was shown to inhibit LPS-induced mRNA and protein expression of inducible nitric oxide synthase by 54. 7% and 65. 1%, respectively.

nitric oxide


Input: Additionally, MAF down-regulated the protein expression of cyclooxygenase-2 and MAPK regulator by 45. 0% to 74. 6%, as well as the reduction of DNA binding activity of nuclear factor kappa B (NF kappa B) by 66. 5%.


Input: It also attenuated the production of prostaglandin E2, interleukin-1 beta (IL-1 beta), IL-6 and tumor necrosis factor alpha by 21. 2% to 86. 2%.

prostaglandin E2


Input: Furthermore, the chemical constituents of MAF were identified.


Input: A total of 13 known chemical compounds were found in MAF, including five isoflavonoids and eight saponins.

isoflavonoids

saponins


Input: In conclusion, a bioactive fraction of AR was identified which possessed anti-inflammatory property by reducing the release of inflammatory mediators and inactivation of NF kappa B through MAPK signalling pathway.


Input: Copyright (c) 2013 John Wiley & Sons, Ltd.


Input: Associations of TSH within the reference range with future blood pressure and lipid concentrations.


Input: 11-year follow-up of the HUNT Study.


Input: Objective In cross-sectional studies, TSH levels within the reference range have been positively associated with blood pressure and adverse serum lipid levels.


Input: In a prospective study, we aimed to find out if differences in TSH within the reference range are associated with future levels of blood pressure and lipids. Design Prospective population-based study. Methods Among 9709 women and 4644 men without previous thyroid disease who had a baseline TSH of 0. 45-4. 5 mU/l, we studied the associations of baseline TSH with blood pressure and lipid levels at follow-up 11 years later. Results Higher TSH at baseline was associated with higher systolic (P = 0. 002 in women) and diastolic (P = 0. 03 in women) blood pressure, non-HDL cholesterol (P = 0. 01 in men), and triglycerides (P = 0. 008 in men), and lower HDL cholesterol (P < 0. 001 in women and men) at follow-up, but the associations were very modest and not consistent between sexes.

cholesterol

triglycerides

cholesterol


Input: Among people who remained free of thyroid disease, changes in TSH during follow-up were associated with concomitant changes in systolic and diastolic blood pressure, non-HDL cholesterol, and triglyceride levels (all P < 0. 001), with similar results for women and men.

cholesterol

triglyceride


Input: Thus, blood pressure and lipid levels increased among people with increase in TSH, and decreased among people with a decrease in TSH, compared to people with no change in TSH. Conclusions High TSH levels within the reference range may be associated with modestly higher future levels of blood pressure and adverse serum lipids.


Input: TSH may co-vary with blood pressure and lipid levels among people with apparently normal thyroid function.


Input: Cavity Ringdown Spectroscopy of the Hydroxy-Methyl-Peroxy Radical.

Hydroxy-Methyl-Peroxy


Input: We report vibrational and electronic spectra of the hydroxyl-methyl-peroxy radical (HOCH2OO, or HMP), the primary product of the reaction of the hydroperoxy radical, HO2, and formaldehyde, HCHO.

hydroxyl-methyl-peroxy

HMP

hydroperoxy

formaldehyde

HCHO


Input: The nu 1 vibrational (OH stretch) spectrum and the A-X electronic spectrum of HMP were detected by Infrared Cavity Ringdown Spectroscopy (IR-CRDS), and assignments were verified with density functional calculations.

OH

HMP


Input: The HMP radical was generated in reactions of HCHO with HO2.

HMP

HCHO


Input: Free radical reactions were initiated by pulsed laser photolysis (PLP) of Cl2 in the presence of HCHO and O2 in a flow reactor at 300-330 Torr and 295K.

HCHO


Input: IR-CRDS spectra were measured in mid-IR and near-IR regions over the ranges 3525-3700 cm (-1) (nu 1) and 7250-7800 cm (-1) (A-X) (respectively, at a delay time 100 micro s after photolysis.


Input: The nu 1 spectrum had an origin at 3622 cm (-1) and exhibited partially resolved P-and R-branch contours and a small Q branch.


Input: At these short delay times, spectral interference from HOOH and HCOOH was minimal, and could be subtracted.

HOOH

HCOOH


Input: From B3LYP/6-31G + (d, p) calculations, we found that the anharmonic vibrational frequency and band contour predicted for the lowest energy conformer, HMP-A, The calculated anharmonic vibrational frequency and band contour computed using B3LYP/63-1G (d, p) level were in good agreement with the observed spectrum.

HMP


Input: In the near-IR, we observed four well spaced vibronic bands, each with partially resolved rotational contours.


Input: We assigned the apparent origin of the electronic spectrum of HMP at 7392 cm (-1) and two bands to the blue to a progression in nu 15', the lowest torsional mode of the state (nu 15' = 171 cm (-1)).

HMP


Input: The band furthest to the red was assigned as a hot band in nu 15 ", leading to a ground state torsional frequency of (nu 15 " = 122 cm (-1)).


Input: We simulated the spectrum using second order vibrational perturbation theory (VPT2) with B3LYP/6-31 + G (d, p) calculations at the minimum energy geometries of the HMP-A conformer on the X and A states.

HMP


Input: The predictions of the electronic origin frequency, torsional frequencies, anharmonicities and rotational band contours matched the observed spectrum.


Input: We investigated the torsional modes more explicitly by computing potential energy surfaces of HMP as a function of the two dihedral angles tau OCOH and tau OOCO.

HMP

OCOH

OOCO


Input: Wave functions and energy levels were calculated based on this potential surface; these results were used to calculate the Franck-Condon factors, which reproduced the vibronic band intensities in the observed electronic spectrum.


Input: The transitions that we observed all involved states with wave functions localized on the minimum energy conformer, HMP-A.

HMP


Input: Our calculations indicated that the observed near-IR spectrum was that of the minimum energy conformer HMP-A, but that this conformer is not the lowest energy conformer in the state, which remains unobserved.

HMP


Input: We estimated that the energy of this lowest conformer (HMP-B) of the A state to be T0 (A) =~ 7200 cm (-1), based on the energy difference E0 (HMP-B)-E0 (HMP-A) on the A state computed at the B3LYP/6-31 + G (d, p) level.

HMP

HMP

HMP


Input: Using human recombinant UDP-glucuronosyltransferase isoforms and a relative activity factor approach to model total body clearance of laropiprant (MK-0524) in humans.

UDP

laropiprant


Input: Abstract 1. A major pathway of elimination of the prostaglandin D2 receptor 1 antagonist laropiprant in humans is by uridine diphosphate-glucuronosyltransferase (UGT)-mediated biotransformation.

prostaglandin D2

laropiprant

uridine diphosphate


Input: In this study, liver and kidney relative activity factors were developed for UGT1A1, 1A9 and 2B7 to allow for in vitro-in vivo extrapolation of intrinsic clearance data to whole organ clearance using recombinant human UGT isoforms applying this to laropiprant as a model substrate.

laropiprant


Input: 2. The total body metabolic clearance of laropiprant determined using this approach (5. 0 L/hr) agreed well with the value determined in vivo following intravenous administration to healthy human volunteers (5. 1 L/hr).

laropiprant


Input: 3. The results suggest that approximately 36%, 36% and 28% of the hepatic metabolic clearance of laropiprant was mediated by UGT1A1, 1A9 and 2B7, respectively.

laropiprant


Input: Likewise, 80% and 20% of the renal metabolic clearance was mediated by UGT1A9 and 2B7, respectively.


Input: Furthermore, the data suggested that the contribution of the kidney to the overall total metabolic clearance was minor relative to the liver (~ 12%).


Input: Semi-synthesis of radiolabeled amino acid and lipid brevetoxin metabolites and their blood elimination kinetics in C57BL/6 mice.

amino acid

brevetoxin


Input: Brevetoxin B (BTX-B), produced by dinoflagellates of the species Karenia, is a highly reactive molecule, due in part to an alpha, beta-unsaturated aldehyde group at the terminal side chain, leading to the production of metabolites by reduction, oxidation, and conjugation.

Brevetoxin B

BTX-B

alpha, beta-unsaturated aldehyde


Input: We have investigated in mice the blood elimination of three common bioactive brevetoxin metabolites found in shellfish, which have been semi-synthesized from BTX-B in radioactive forms.

brevetoxin

BTX-B


Input: BTX-B was reduced at C42 to yield [3H] dihydro-BTX-B.

BTX-B

[3H] dihydro-BTX-B


Input: [3H] S-desoxy-BTX-B2 (cysteine brevetoxin B) was semi-synthesized from BTX-B by conjugation of cysteine at the C50 olefinic group, then [3H] radiolabeled by C42 aldehyde reduction.

[3H] S-desoxy-BTX-B2

cysteine brevetoxin B

BTX-B

cysteine

olefinic

aldehyde


Input: [14C] N-palmitoyl-S-desoxy-BTX-B2 was prepared using S-desoxy-BTX-B2 as the starting material with addition of the [14C] radiolabeled fatty acid via the cysteine-amide linkage.

[14C] N-palmitoyl-S-desoxy-BTX-B2

fatty acid

cysteine

amide


Input: The elimination of intravenously administered [3H] S-desoxy-BTX-B2, [14C] N-palmitoyl-S-desoxy-BTX-B2, or [3H] dihydro-BTX-B was measured in blood collected from C57BL/6 mice over a 48 hour period.

[3H] S-desoxy-BTX-B2

[14C] N-palmitoyl-S-desoxy-BTX-B2

[3H] dihydro-BTX-B


Input: Each brevetoxin metabolite tested exhibited biexponential elimination kinetics and fit a two-compartment model of elimination that was applied to generate toxicokinetic parameters.

brevetoxin


Input: The rate of transfer between the central compartment (i. e., blood) and the peripheral compartment (e. g., tissue) for each brevetoxin differed substantially, with dihydro-BTX-B exchanging rapidly with the peripheral compartment, and S-desoxy-BTX-B2 eliminating rapidly from the central compartment and N-palmitoyl-S-desoxy-BTX-B2 eliminating slowly from the central compartment.

brevetoxin

dihydro-BTX-B


Input: Toxicokinetic parameters were analyzed in the context of the unique structure of each brevetoxin metabolite resulting from a reduction, amino acid conjugation, or fatty acid addition to BTX-B.

brevetoxin

amino acid

fatty acid

BTX-B


Input: Synthesis of 7-oxabicyclo [2. 2. 1] hept-5-en-2-yl derivatives and their screening for antimicrobial and antioxidant properties.

7-oxabicyclo [2. 2. 1] hept-5-en-2-yl


Input: Novel 7-oxabicyclo [2. 2. 1] hept-5-en-2-yl derivatives have been synthesized using boron trifluoride diethyl etherate catalyzed Diels-Alder reaction.

7-oxabicyclo [2. 2. 1] hept-5-en-2-yl

boron trifluoride diethyl etherate


Input: This method presents considerable synthetic advantages in terms of high atom economy, mild reaction condition and good yields.


Input: The synthesized compounds have been screened for their antibacterial and antioxidant activities.


Input: Cross-protection by co-immunization with influenza hemagglutinin DNA and inactivated virus vaccine using coated microneedles.


Input: The need for annual revaccination against influenza is a burden on the healthcare system, leads to low vaccination rates and makes timely vaccination difficult against pandemic strains, such as during the 2009 H1N1 influenza pandemic.


Input: In an effort toward achieving a broadly protective vaccine that provides cross-protection against multiple strains of influenza, this study developed a microneedle patch to co-immunize with A/PR8 influenza hemagglutinin DNA and A/PR8 inactivated virus vaccine.


Input: We hypothesize that this dual component vaccination strategy administered to the skin using microneedles will provide cross-protection against other strains of influenza.


Input: To test this hypothesis, we developed a novel coating formulation that did not require additional excipients to increase coating solution viscosity by using the DNA vaccine itself to increase viscosity and thereby enable thick coatings of DNA vaccine and inactivated virus vaccine on metal microneedles.


Input: Co-immunization in this way not only generated robust antibody responses against A/PR8 influenza but also generated robust heterologous antibody responses against pandemic 2009 H1N1 influenza in mice.


Input: Challenge studies showed complete cross-protection against lethal challenge with live pandemic 2009 H1N1 virus.


Input: Control experiments using A/PR8 inactivated influenza virus vaccine with placebo DNA coated onto microneedles produced lower antibody titers and provided incomplete protection against challenge.


Input: Overall, this is the first study showing DNA solution as a microneedle coating agent and demonstrating cross-protection by co-immunization with inactivated virus and DNA vaccine using coated microneedles.


Input: Water extract of licorice had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Licorice (Glycyrrhiza uralensis Fisch., Leguminosae) has been used in herbal medicine and food supplement worldwide for centuries.


Input: Licorice is a common ingredient of several prescriptions of traditional Chinese medicine which have been proved to inhibit infection of human respiratory syncytial virus (HRSV).


Input: There are two preparations of licorice, Radix Glycyrrhizae and Radix Glycyrrhizae Preparata.


Input: However, it is unknown whether licorice or which preparation of licorice is effective against HRSV, nor is its active constituent.


Input: AIM OF THE STUDY: We tested the hypothesis that Radix Glycyrrhizae can effectively decrease HRSV-induced plaque formation in respiratory mucosal cell lines.


Input: We also tried to find out the active constituent.


Input: MATERIALS AND METHODS: Anti-HRSV activities of hot water extracts of preparations of licorice, glycyrrhizin and 18 beta-glycyrrhetinic acid (18 beta-GA), the active constituents of licorice, were examined by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines.

glycyrrhizin

18 beta-glycyrrhetinic acid

18 beta-GA


Input: Abilities of crude licorice to inhibit viral replication and to stimulate IFN-beta were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively.


Input: RESULTS: Radix Glycyrrhizae and Radix Glycyrrhizae Preparata dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cell lines (p < 0. 0001).


Input: The effect of Radix Glycyrrhizae was better than that of Radix Glycyrrhizae Preparata on HEp-2 cells.


Input: However, there was no difference of their anti-HRSV effects on A549 cells.


Input: Besides, glycyrrhizin was ineffective at all.

glycyrrhizin


Input: Nevertheless, 18 beta-GA showed a potent anti-HRSV activity.

18 beta-GA


Input: Radix Glycyrrhizae was more effective when given before viral inoculation (p < 0. 0001) which may be due to its inhibition of viral attachment on (p < 0. 0001) and penetration (p < 0. 0001) into the host cells.


Input: The anti-HRSV activity of Radix Glycyrrhizae was further confirmed by RT-PCR and qRT-PCR.


Input: 300 mu g/ml Radix Glycyrrhizae markedly decreased the viral amounts within the cells and in the suspension.


Input: Radix Glycyrrhizae might further stimulate mucosal cells to secrete IFN-beta to counteract viral infection.


Input: CONCLUSIONS: Both Radix Glycyrrhizae and Radix Glycyrrhizae Preparata are effective against HRSV infection on airway epithelial cells.


Input: Radix Glycyrrhizae inhibited HRSV mainly by preventing viral attachment, internalization, and by stimulating IFN secretion.


Input: 18 beta-GA may be one of its active constituents.

18 beta-GA


Input: Sustained resistance to acute MPTP toxicity by hypothalamic dopamine neurons following chronic neurotoxicant exposure is associated with sustained up-regulation of parkin protein.

MPTP

dopamine


Input: Hypothalamic tuberoinfundibular dopamine (TIDA) neurons remain unaffected in Parkinson disease (PD) while there is significant degeneration of midbrain nigrostriatal dopamine (NSDA) neurons.

dopamine

dopamine


Input: A similar pattern of susceptibility is observed following acute exposure to the neurotoxicant 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), and the resistance of TIDA neurons to MPTP is associated with increased expression of parkin and ubiquitin carboxy-terminal hydrolase L-1 (UCHL-1).

1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine

MPTP

MPTP

carboxy


Input: In the present study, the response of TIDA and NSDA neurons to acute MPTP administration following chronic MPTP exposure was examined.

MPTP

MPTP


Input: Mice were treated with ten injections of either MPTP (20 mg/kg; s. c.; every 3. 5 days) or saline vehicle (10 ml/kg; s. c.; every 3. 5 days).

MPTP


Input: Following a 21 day recovery period, chronic saline-and MPTP-treated mice received an additional injection of either saline (10 ml/kg; s. c.) or MPTP (20 mg/kg; s. c.) and were sacrificed 24 h later.

MPTP

MPTP


Input: NSDA neurons displayed significant axon terminal degeneration (as indexed by decreases in DA, tyrosine hydroxylase (TH) and DA transporter concentrations in the striatum) as well as loss of TH-immunoreactive (IR) neurons in the substantia nigra (SN) following MPTP, whereas TIDA neurons revealed no overt axon terminal pathology or loss of TH-IR cell bodies.

tyrosine

MPTP


Input: NSDA neuronal pathology was associated with transient decreases in concentrations of parkin and UCHL-1 protein in the SN, which returned to normal levels by 21 days following cessation of chronic neurotoxicant exposure.


Input: Resistance of TIDA neurons to MPTP toxicity was correlated with a transient increase in UCHL-1 and a sustained elevation in parkin in the arcuate nucleus.

MPTP


Input: TIDA neurons represent a DA neuron population with a unique and inherent ability to adapt to acute and chronic toxicant administration with a sustained elevation of the neuroprotective protein parkin.


Input: The correlation between the ability to increase parkin and UCHL-1 expression and the resistance of DA neurons to neurotoxicant exposure is consistent with a functional link between these features and an underlying differential susceptibility to toxicant-associated neurodegeneration.


Input: Vitamin C and Lifespan in Model Organisms.

Vitamin C


Input: The process of ageing has been repeatedly associated with increasing oxidative damage which has led to the hypothesis that reducing oxidative stress through antioxidant dietary factors may prolong lifespan.


Input: Ascorbic acid is an essential antioxidant in human diets and is widely used for supplementation.

Ascorbic acid


Input: However, it is rather unclear if and to what extent ascorbic acid may affect lifespan in humans and model organisms.

ascorbic acid


Input: In our review of literature on vitamin C supplementation and its effect on lifespan in different model organisms we found that some studies suggest an increase in lifespan, other studies failed to observe any beneficial effect of vitamin C on longevity and some studies even reported a decrease in lifespan following vitamin C supplementation.

vitamin C

vitamin C

vitamin C


Input: Of the 14 studies included in our analysis, 3 were carried out in worms, 4 in flies and 7 in rodents.


Input: The discrepancies between the studies may be related to species-specific differences, the concentration of vitamin C administered, the duration of supplementation and whether vitamin C was used alone or as part of a combined antioxidant diet.

vitamin C

vitamin C


Input: Potential underlying mechanisms through which vitamin C may influence lifespan and differences amongst species regarding the capacity to produce vitamin C endogenously are discussed.

vitamin C

vitamin C


Input: The use of antioxidant enzymes in freshwater biofilms: Temporal variability vs. toxicological responses.


Input: This study aims to investigate the potential of antioxidant enzyme activities (AEA) as biomarkers of oxidative stress in freshwater biofilms.


Input: Therefore, biofilms were grown in channels for 38 days and then exposed to different concentrations (0-150 mu gL (-1)) of the herbicide oxyfluorfen for 5 more weeks.

oxyfluorfen


Input: Under control conditions, the AEA of biofilms were found to change throughout time with a significant increase in ascorbate peroxidase (APX) activity during the exponential growth and a more important role of catalase (CAT) and glutathione reductase (GR) activities during the slow growth phase.

ascorbate

glutathione


Input: Chronic exposure to oxyfluorfen led to slight variations in AEA, however, the ranges of variability of AEA in controls and exposed communities were similar, highlighting the difficulty of a direct interpretation of AEA values.

oxyfluorfen


Input: After 5 weeks of exposure to oxyfluorfen, no clear effects were observed on chl-a concentration or on the composition of other pigments suggesting that algal group composition was not affected.

oxyfluorfen

chl-a


Input: Eukaryotic communities were structured clearly by toxicant concentration and both eukaryotic and bacterial richness were reduced in communities exposed to the highest concentration.


Input: In addition, during acute exposure tests performed at the end of the chronic exposure, biofilms chronically exposed to 75 and 150 mu gL (-1) oxyfluorfen showed a higher CAT activity than controls.

oxyfluorfen


Input: Chronic exposure to oxyfluorfen provoked then structural changes but also functional changes in the capacity of biofilm CAT activity to respond to a sudden increase in concentration, suggesting a selection of species with higher antioxidant capacity.

oxyfluorfen


Input: This study highlighted the difficulty of interpretation of AEA values due to their temporal variation and to the absence of absolute threshold value indicative of oxidative stress induced by contaminants.


Input: Nevertheless, the determination of AEA pattern throughout acute exposure test is of high interest to compare oxidative stress levels undergone by different biofilm communities and thus determine their antioxidant capacity.


Input: Juglone, isolated from Juglans mandshurica Maxim, induces apoptosis via down-regulation of AR expression in human prostate cancer LNCaP cells.

Juglone


Input: Juglone is a natural compound which has been isolated from Juglans mandshurica Maxim.

Juglone


Input: Recent studies have shown that juglone had various pharmacological effects such as anti-viral, anti-bacterial and anti-cancer.

juglone


Input: However, its anti-cancer activity on human prostate cancer LNCaP cell has not been examined.


Input: Thus, the current study was designed to elucidate the molecular mechanism of apoptosis induced by juglone in androgen-sensitive prostate cancer LNCaP cells.

juglone

androgen


Input: MTT assay was performed to examine the anti-proliferative effect of juglone.

MTT

juglone


Input: Occurrence of apoptosis was detected by Hoechst 33342 staining and flow cytometry in LNCaP cells treated with juglone for 24h.

Hoechst 33342

juglone


Input: The result shown that juglone inhibited the growth of LNCaP cells in a dose-dependent manner.

juglone


Input: Morphological changes of apoptotic body formation after juglone treatment were observed by Hoechst 33342 staining.

juglone

Hoechst 33342


Input: This apoptotic induction was associated with loss of mitochondrial membrane potential, and caspase-3,-9 activation.


Input: Moreover, we found that juglone significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT).

juglone

androgen

dihydrotestosterone

DHT


Input: Take together, our results demonstrated that juglone might induce the apoptosis in LNCaP cell via down-regulation of AR expression.

juglone


Input: Therefore, our results indicated that juglone may be a potential candidate of drug for androgen-sensitive prostate cancer.

juglone

androgen


Input: 1, 4-Substituted 4-(1H)-pyridylene-hydrazone-type inhibitors of AChE, BuChE, and amyloid-beta aggregation crossing the blood-brain barrier.

1, 4-Substituted 4-(1H)-pyridylene-hydrazone


Input: Given the fundamentally multifactorial character of Alzheimer' s disease (AD), addressing more than one target for disease modification or therapy is expected to be highly advantageous.


Input: Here, following the cholinergic hypothesis, we aimed to inhibit both acetyl-and butyrylcholinesterase (AChE and BuChE) in order to increase the concentration of acetylcholine in the synaptic cleft.

acetyl

acetylcholine


Input: In addition, the formation of the amyloid fibrils should be inhibited and already preformed fibrils should be destroyed.


Input: Based on a recently identified AChE inhibitor with a 1, 4-substituted 4-(1H)-pyridylene-hydrazone skeleton, a substance library has been generated and tested for inhibition of AChE, BuChE, and fibril formation.

1, 4-substituted 4-(1H)-pyridylene-hydrazone


Input: Blood-brain barrier mobility was ensured by a transwell assay.


Input: Whereas the p-nitrosubstituted compound 18C shows an anti-AChE activity in the nanomolar range of concentration (IC50 = 90 nM), the bisnaphthyl substituted compound 20L was found to be the best overall inhibitor of AChE/BuChE and enhances the fibril destruction.