Input: Thus, for these polymer architectures, high histidine incorporation may be required for efficient endosomal escape.

histidine


Input: Furthermore, uptake studies indicate that non-acidified caveolae-mediated endocytosis may be the primary route of transfection for these copolymers, suggesting that alternative approaches for increasing endosomal escape may be beneficial for enhancing transfection efficiency with these HPMA-oligolysine copolymers.

HPMA


Input: Surface-sensitive two-dimensional magneto-fingerprint in mesoscopic Bi2Se3 channels.


Input: Periodic Aharonov-Bohm and Altshuler-Aronov-Spivak oscillations have traditionally been observed in lateral transport through patterned mesoscopic loops of diffusive conductors.


Input: However, our studies of perpendicular-to-plane magnetotransport in straight-channel, diffusive devices of epitaxial Bi2Se3 surprisingly reveal signatures of Aharonov-Bohm orbits--periodic conductance fluctuation magneto-fingerprints--even though the devices are not explicitly patterned into loops.


Input: We show that the length scale of these orbits corresponds to the typical perimeter of triangular terraces found on the surface of these thin film devices, strongly suggesting that the periodic magneto-fingerprint arises from coherent scattering of electron waves from the step-edges.


Input: Our interpretation is bolstered by control measurements in devices without such surface morphology which only show a conventional, aperiodic magneto-fingerprint.


Input: These results show that lithographically patterned Bi2Se3 devices provide a novel class of mesoscopic physical systems for systematic studies of coherent surface sensitive transport.


Input: Simulations of droplet coalescence in simple shear flow.


Input: Simulating droplet coalescence is challenging because small-scale (tens of nanometers) phenomena determine the behaviour of much larger (micron-to millimetre-scale) droplets.


Input: In general, liquid droplets colliding in a liquid medium coalesce when the capillary number is less than a critical value.


Input: We present simulations of droplet collisions and coalescence in simple shear flow using the free-energy binary-liquid lattice Boltzmann method.


Input: In previous simulations of low-speed collisions, droplets coalesced at unrealistically high capillary numbers.


Input: Simulations of non-coalescing droplets have not been reported, and therefore the critical capillary number for simulated collisions was unknown.


Input: By simulating droplets with radii up to 100 lattice nodes, we determine the critical capillary number for coalescence and quantify the effects of several numerical and geometric parameters.


Input: The simulations were performed with a well-resolved interface, a Reynolds number of one, and capillary numbers from 0. 01 to 0. 2.


Input: The ratio of the droplet radius and interface thickness has the greatest effect on the critical capillary number.


Input: As in experiments, the critical capillary number decreases with increasing droplet size.


Input: A second numerical parameter, the interface diffusivity (Peclet number) also influences the conditions for coalescence: coalescence occurs at higher capillary numbers with lower Peclet numbers (higher diffusivity).


Input: The effects of the vertical offset between the droplets and the confinement of the droplets were also studied.


Input: Physically reasonable results were obtained and provide insight into the conditions for coalescence.


Input: Simulations that match the conditions of experiments reported in the literature remain computationally impractical.


Input: However, the scale of the simulations is now sufficiently large that a comparison with experiments involving smaller droplets (~ 10 mu m) and lower viscosities (10 (-6) m (2)/s, the viscosity of water) may be possible.


Input: Experiments at these conditions are therefore needed to determine the interface thickness and Peclet number that should be used for predictive simulations of coalescence phenomena.


Input: Carbonic anhydrase inhibitors.


Input: Benzenesulfonamides incorporating cyanoacrylamide moieties strongly inhibit Saccharomyces cerevisiae beta-carbonic anhydrase.

Benzenesulfonamides

cyanoacrylamide


Input: A series of benzenesulfonamides incorporating cyanoacrylamide moieties (tyrphostine analogs) were assayed as inhibitors of the beta-carbonic anhydrase (CA, EC 4. 2. 1. 1) from Saccharomyces cerevisiae, ScCA.

benzenesulfonamides

cyanoacrylamide

tyrphostine


Input: Some of these compounds were low nanomolar or subnanomolar ScCA inhibitors and showed selectivity ratios in the range of 4. 91-69. 86 for inhibiting the yeast enzyme over the offtarget human (h) isoforms hCA I and of 6. 46-13. 52 for inhibiting ScCA over hCA II.


Input: The model organism S. cerevisiae and this particular enzyme may be useful for detecting antifungals with a novel mechanism of action compared to the classical azole drugs to which significant drug resistance emerged.

azole


Input: Indeed, some of these sulfonamides inhibited the growth of the yeast with CC50-s in the range of 0. 73-6. 54 mu M.

sulfonamides


Input: Apoptosis inducing activity of benzophenanthridine-type alkaloids and 2-arylbenzofuran neolignans in HCT116 colon carcinoma cells.

benzophenanthridine-type alkaloids

2-arylbenzofuran neolignans


Input: Thirteen compounds belonging to different classes of alkaloids (1-9) and lignans (10-13), isolated from the methanol extract of roots of the African medicinal plant Zanthoxylum capense, were assayed for their ability as apoptosis inducers in HCT116 colon carcinoma cells.

lignans

methanol


Input: The cytotoxicity of these compounds was evaluated in HCT116 colon carcinoma cells by the MTS assay.

MTS


Input: Out of the tested compounds, three benzophenanthridine alkaloids (1, 4, and 7), a dibenzyl butyrolactone lignan (10), and two 2-arylbenzofuran neolignans (12 and 13) displayed significant cytotoxicity to HCT116 cells, confirmed by the Guava ViaCount viability assay.

benzophenanthridine alkaloids

dibenzyl butyrolactone lignan

2-arylbenzofuran neolignans


Input: The selected compounds (1, 4, 7, 10, 12, and 13) were further tested for apoptosis induction activity in HCT116 cells, by evaluation of nuclear morphology following Hoechst staining, and by caspase-3 like activity assays.


Input: Morphologic evaluation of HCT116 nuclei following Hoechst staining and fluorescence microscopy revealed that compounds 1, 4, 7, 10, 12, and 13 induced apoptosis in HCT116 colon carcinoma cells, producing similar, or higher, apoptosis levels when compared with 5-fluorouracil (5-FU), the cornerstone cytotoxic used in colon cancer treatment for several decades.


Input: In fact, HCT116 cells developed morphological changes characteristic of apoptosis, including chromatin condensation, nuclear fragmentation and formation of apoptotic bodies.


Input: Importantly, compounds 4 and 13 at 20 mu M were the most promising in this study, inducing respectively ~ 11-and 7-fold increases in apoptotic cells as compared to vehicle control, whereas 5-FU increased apoptosis by ~ 2-fold.


Input: Apoptosis induction for compounds 4 and 13 was further confirmed by caspase-3-like activity assays, which showed respectively ~ 2-and 1. 5-fold increases in caspase-3-like activity compared to vehicle control.


Input: These results suggested that specific benzophenanthridine alkaloids and 2-arylbenzofuran neolignans isolated from Zanthoxylum capense show strong anticancer activity in HCT116 colon carcinoma cells.

benzophenanthridine alkaloids

2-arylbenzofuran neolignans


Input: Nordihydroguaiaretic acid induces Nrf2 nuclear translocation in vivo and attenuates renal damage and apoptosis in the ischemia and reperfusion model.

Nordihydroguaiaretic acid


Input: It has been shown that the pretreatment with nordihydroguaiaretic acid (NDGA), a lignan with direct and indirect antioxidant properties, protects against the ischemia-reperfusion (I/R)-induced renal oxidant damage.

nordihydroguaiaretic acid

NDGA


Input: Although it has been shown that NDGA induces Nrf2 nuclear translocation in renal epithelial LLC-PK1 cells in culture, it is unknown if NDGA may induce Nrf2 translocation in vivo.

NDGA

NDGA


Input: In this work was explored if NDGA is able to induce in vivo Nrf2 nuclear translocation in kidneys of rats submitted to uni-nephrectomy (U-NX) or I/R injury.

NDGA


Input: Four groups of male Wistar rats were used: U-NX, NDGA, I/R, and I/R + NDGA.

NDGA

NDGA


Input: NDGA was injected i. p.

NDGA


Input: (10mg/kg/day) starting 48h before I/R.


Input: Kidney samples were obtained at 3h of reperfusion after to measure Nrf2 translocation.


Input: Additional groups of rats were studied at 24h of reperfusion to measure histological damage and apoptosis.


Input: NDGA was able to induce Nrf2 translocation in vivo in kidneys of rats submitted to both U-NX and I/R injury and to protect against renal histological damage and apoptosis.

NDGA


Input: It is concluded that the pretreatment of NDGA is able to induce in vivo nuclear Nrf2 translocation in kidney of rats suggesting that this may be involved in the renoprotection against I/R.

NDGA


Input: Cytokine targets in airway inflammation.


Input: Asthma is an inflammatory disease of the airway wall that leads to bronchial hyper-reactivity and airway obstruction, caused by inflammation, mucus hyper-production and airway wall remodelling.


Input: Central to pathogenesis, Th2 and Th17 lymphocytes of the adaptive immune system control many aspects of the disease by producing cytokines such as IL-4, IL-5, IL-13, and IL-17.


Input: In addition, many cells of the innate immune system such as mast cells, basophils, neutrophils, eosinophils, dendritic cells (DCs), and innate lymphoid cells (ILCs) play an important role in the initiation or maintenance of disease.


Input: Epithelial cells are ever more implicated in disease pathogenesis, as they are able to sense exposure to pathogens via pattern recognition receptors (PRRs) and can activate DCs.


Input: This review article will deal with the role of cytokines that are considered essential controllers of the inflammatory, immune and regenerative response to allergens, viruses and environmental pollutants.


Input: Emerging Th2 cytokines such as thymic stromal lymphopoietin, GM-CSF, IL-1, IL-33, IL-25 mediate the crosstalk between epithelial cells, DCs, and ILCs.


Input: Understanding the crosstalk between structural cells, innate and adaptive immune cells that is mediated by cytokines provides important mechanistic insights into how asthma develops and perpetuates itself.


Input: It could also provide the framework on which we will select new therapeutic strategies that prevent exacerbations and alter the natural course of the disease.


Input: Pharmacokinetic study of four flavones of Glycyrrhiza in rat plasma using HPLC-MS.

flavones


Input: AIM OF THE STUDY: This study aimed to develop a specific HPLC-MS method for simultaneous quantification of four flavones of Glycyrrhiza in rat plasma after oral administration and to describe the pharmacokinetics of four flavones in rat plasma.

flavones

flavones


Input: MATERIALS AND METHODS: A simple, sensitive and selective method for simultaneous determination of four flavones of Glycyrrhiza in rat plasma, i. e., liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, by high performance liquid chromato-graphy-tandem mass spectrometry (HPLC-MS) with negative electrospray ionization mode, was developed and validated.

flavones

liquiritin

isoliquiritin

liquiritigenin

isoliquiritigenin


Input: The method was applied to investigate the pharmacokinetics of four flavones in rat plasma after oral administration of Glycyrrhiza flavones.

flavones

flavones


Input: Chromatographic separation was accomplished on an Agilent TC-C18 column (4. 6mm x 250mm, 5 mu m), with gradient elution by using a mixture of methanoic acid (A) and acetonitrile (B) as the mobile phase at a flow rate of 0. 8mL/min.

methanoic acid

acetonitrile


Input: RESULTS: The calibration curves for four flavones had good linearity in the measured range with higher than 0. 997.

flavones


Input: Relative standard deviations (RSDs) of the intra-and inter-day precision at different levels were all less than 4. 8%.


Input: The pharmacokinetic profile of four flavones in rat plasma was fitted with a two-compartment model detected by a simple, rapid and accurate HPLC-MS method.

flavones


Input: Time (h) to reach peak concentration (mu g/mL) of liquiritin (2. 69 +/- 0. 04), isoliquiritin (10. 16 +/- 0. 02), liquiritigenin (2. 83 +/- 0. 02), isoliquiritigenin (0. 28 +/- 0. 01) were 2. 02 +/- 0. 23, 1. 97 +/- 0. 20, 0. 48 +/- 0. 02, 1. 93 +/- 0. 36, respectively.

liquiritin

isoliquiritin

liquiritigenin

isoliquiritigenin


Input: The distribution and elimination half-life (h) and area under the concentration-time curve (mu g/mL * h) from t = 0 to last time of liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin were 1. 02 +/- 0. 48/2. 27 +/- 0. 53/16. 97 +/- 0. 43, 2. 04 +/- 1. 01/2. 38 +/- 0. 80/69. 20 +/- 5. 24, 0. 35 +/- 0. 10/4. 26 +/- 0. 16/14. 83 +/- 0. 11, 1. 18 +/- 0. 32/3. 04, +/- 0. 22/2. 10 +/- 0. 09, respectively.

liquiritin

isoliquiritin

liquiritigenin

isoliquiritigenin


Input: Isoliquiritin presented the phenomenon of double peaks and the others appeared together in a single and plateau absorption phase.

Isoliquiritin


Input: Isoliquiritigenin had the lowest oral bioavailability because of Cmax and AUC0-infinity.

Isoliquiritigenin


Input: Liquiritigenin had the fastest absorption and distribution rate and the lowest elimination rate according to Tmax, t1/2 alpha, t1/2 beta.

Liquiritigenin


Input: CONCLUSIONS: This paper first reported on identification and determination of four flavones of Glycyrrhiza in rat plasma and their respective pharmacokinetic characteristics.

flavones


Input: The results provided a meaningful basis for better understanding the absorption mechanism of Glycyrrhiza and evaluating the clinical application of this medicine.


Input: Herbalists and wild medicinal plants in M' Sila (North Algeria): An ethnopharmacology survey.


Input: AIM OF THE STUDY: The main aim of this study was to identify, catalogue and document the large number of wild medicinal plants used in the M' Sila region (northern Algeria) for the treatment of several human pathologies.


Input: Another more ambitious aim is to contribute to overcoming the limits of an orally transmitted pharmacopoeia, attempting to exploit the large ethnopharmacology patrimony of the region for further pharmacological purposes.


Input: MATERIALS AND METHODS: Our field study was carried out over a period of three years (2008-2010).


Input: During this period, herbalists were interviewed using semi-structured questionnaires investigating the herbalist as a holder of information (gender, age and educational level) and about wild medicinal plants (local name, uses and part used).


Input: In addition, the relative importance value of the species was determined and informant consensus factor (ICF) was calculated for the medicinal plants included in the study.


Input: RESULTS: A total of 83 herbalists were interviewed, men dominate the practice of traditional medicine in the region.


Input: About 41% of them are between 31-40 years, and about a third (34%) is illiterate.


Input: The traditional herbal knowledge is passed from generation to generation in the verbal form, being almost totally absent a writing tradition.


Input: The interviewed herbalists identified and recorded 58 plants species and 50 genera belonging to 27 plant families.


Input: Lamiaceae and Asteraceae were the most represented plant families.


Input: The aerial parts were the most commonly used plant part, while infusion and decoction were the most common method of traditional drug preparation.


Input: CONCLUSIONS: The survey provides a veritable source of information on the herbalists and wild medicinal plants.


Input: Plants which are used in different parts of the world for the treatment of similar diseases may be deemed to be effective in pharmacological terms.


Input: These medicinal plants may be incorporated into the healthcare delivery system of the country.


Input: Epidemiology of Paget' s disease of Bone: A systematic review and meta-analysis of secular changes.


Input: CONTEXT: Several studies have suggested that the prevalence and severity of PDB have fallen in recent years.


Input: The magnitude of this trend and its globalization have not been well established.


Input: OBJECTIVE: To estimate the pooled magnitude of the changes in the prevalence of PDB.


Input: As a secondary objective, to make up a world atlas of PDB prevalence.


Input: METHODS: Systematic review of English and non-English articles using MEDLINE (1946 to 2013) and EMBASE (1980 to 2013).


Input: Search terms included epidemiology, incidence, prevalence, cohort studies, osteitis deformans or Paget disease of bone.


Input: Studies with incidence and/or prevalence rate for PDB were included.


Input: Two authors independently extracted the data using predefined data fields and quality assessment.


Input: A pooled analyses based on random-effects models was carried out for secular trends.


Input: RESULTS: Twenty-eight articles documented the prevalence of PDB; four articles the incidence and two articles the rate of new referrals.


Input: The prevalence of PDB varied greatly between the different countries, from 0. 00028% in Japan to 5. 4% in UK.


Input: There were available data on changes in prevalence from two different surveys over two different time frames in Europe and New Zealand.


Input: In all but one city (Turin), a drop in the prevalence of PDB was recorded (pooled OR 0. 64: 95% CI: 0. 45-0. 91).


Input: CONCLUSION: The incidence and prevalence rates of PDB vary widely between populations but both have decreased in most regions over recent years.


Input: The changes are heterogeneous however and within countries, the largest changes have been in areas that previously had a high prevalence.


Input: The reasons for these changes remain unclear at present but are likely to be due to an interaction between genetic factors and environmental triggers which may differ in different regions.


Input: Diminished response to in vivo mechanical loading in trabecular and not cortical bone in adulthood of female C57Bl/6 mice coincides with a reduction in deformation to load.


Input: Bone loss occurs during adulthood in both women and men and affects trabecular bone more than cortical bone.


Input: The mechanism responsible for trabecular bone loss during adulthood remains unexplained, but may be due at least in part to a reduced mechanoresponsiveness.


Input: We hypothesized that trabecular and cortical bone would respond anabolically to loading and that the bone response to mechanical loading would be reduced and the onset delayed in adult compared to postpubescent mice.


Input: We evaluated the longitudinal adaptive response of trabecular and cortical bone in postpubescent, young (10 week old) and adult (26 week old) female C57Bl/6J mice to axial tibial compression using in vivo microCT (day 0, 5, 10, and 15) and dynamic histomorphometry (day 15).


Input: Loading elicited an anabolic response in both trabecular and cortical bone in young and adult mice.


Input: As hypothesized, trabecular bone in adult mice exhibited a reduced and delayed response to loading compared to the young mice, apparent in trabecular bone volume fraction and architecture after 10 days.


Input: No difference in mechanoresponsiveness of the cortical bone was observed between young and adult mice.


Input: Finite element analysis showed that load-induced strain was reduced with age.


Input: Our results suggest that trabecular bone loss that occurs in adulthood may in part be due to a reduced mechanoresponsiveness in this tissue and/or a reduction in the induced tissue deformation which occurs during habitual loading.


Input: Therapeutic approaches that address the mechanoresponsiveness of the bone tissue may be a promising and alternate strategy to maintain trabecular bone mass during aging.


Input: Evaluation of genotoxicity of nitrile fragrance ingredients using in vitro and in vivo assays.

nitrile


Input: Genotoxicity studies were conducted on a group of 8 fragrance ingredients that belong to the nitrile family.

nitrile


Input: These nitriles are widely used in consumer products however there is very limited data in the literature regarding the genotoxicity of these nitriles.

nitriles

nitriles


Input: The 8 nitriles were assessed for genotoxicity using an Ames test, in-vitro chromosome aberration test or in-vitro micronucleus test.

nitriles


Input: The positive results observed in the in-vitro tests were further investigated using an in-vivo micronucleus test.


Input: The results from these different tests were compared and these 8 nitriles are not considered to be genotoxic.

nitriles


Input: Dodecanitrile and 2, 2, 3-trimethylcyclopent-3-enylacetonitrile were negative in the in-vitro chromosome aberration test and in-vitro micronucleus test, respectively.

Dodecanitrile

2, 2, 3-trimethylcyclopent-3-enylacetonitrile


Input: While citronellyl nitrile, 3-methyl-5-phenylpentanenitrile, cinnamyl nitrile, and 3-methyl-5-phenylpent-2-enenitrile revealed positive results in the in-vitro tests, but confirmatory in-vivo tests determined these nitriles to be negative in the in-vivo micronucleus assay.

citronellyl nitrile

cinnamyl nitrile

nitriles


Input: The remaining two nitriles (benzonitrile and alpha-cyclohexylidene benzeneacetonitrile) were negative in the in-vivo micronucleus test.

nitriles

benzonitrile

alpha-cyclohexylidene benzeneacetonitrile


Input: This study aims to evaluate the genotoxicity potential of these nitriles as well as enrich the literature with genotoxicity data on fragrance ingredients.

nitriles


Input: Hydroxytyrosyl alkyl ether derivatives inhibit platelet activation after oral administration to rats.

Hydroxytyrosyl alkyl ether


Input: The low lipophilicity of hydroxytyrosol (HT) has motivated efforts to synthesize homologous series with better lipid solubility, such as the ethers, which are more lipophilic than HT.

hydroxytyrosol

ethers


Input: Because HT inhibits platelet aggregation, the aim of the study was to assess the possible anti-platelet effect of five HT ether derivatives (ethyl, butyl, hexyl, octyl and dodecyl) after oral administration to rats.

ether

ethyl

butyl

hexyl

octyl

dodecyl


Input: Whole blood collagen-induced platelet aggregation and calcium-induced thromboxane B2 (TxB2), aortic 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and nitrites + nitrates, plasma concentration of lipid peroxides (TBARS) and red blood cell content of reduced glutathione (GSH) were measured.

calcium

thromboxane B2

6-keto-prostaglandin F1 alpha

6-keto-PGF1 alpha

nitrites

nitrates

peroxides

reduced glutathione

GSH


Input: The administration of 20 mg/kg/day inhibited platelet aggregation, TxB2 and TBARS in a non-linear manner related to the length of the carbon chain, with a cut-off effect in the hexyl derivative.

carbon

hexyl


Input: Aortic nitrite and red blood cell GSH production were also increased.

nitrite

GSH


Input: The aortic production of 6-keto-PGF1 alpha was unaltered except in the group treated with the dodecyl derivative.

6-keto-PGF1 alpha

dodecyl


Input: The administration of 50 mg/kg/day showed a similar pharmacodynamic profile but without the non-linear effect.


Input: In conclusion, HT ethers, especially the hexyl derivative, are a potential alternative to hydroxytyrosol, and their effect merits additional research to determine their role in the prophylaxis of vascular disease.

ethers

hexyl

hydroxytyrosol


Input: Medicines Combinations Options and Regulatory Hurdles.


Input: The number of fixed dose combinations (FDC) on the market is increasing.


Input: However, both regulatory guidelines and the evidence for better effectiveness of fixed dose combinations are not established yet.


Input: These aspects were the topic for a recent EUFEPS workshop in Copenhagen.


Input: The discussion confirms the presence of hurdles and recommendations to further progress and alleviate the problems.


Input: The general conclusion was: Refinement of general systems pharmacology tools for identification of key molecular targets in disease development; Precompetitive methodologies and technologies designed for (co-) development of FDCs; Simulation and modeling algorithms applied on pharmacodynamics (synergy), pharmacokinetics and safety; New formulations of FDCs of solid, liquid or inhalation forms; Prospective clinical studies for measuring the efficacy and effectiveness of use of drug-drug combinations in elderly.


Input: Cyclooxygenase activity contributes to the monoaminergic damage caused by serial exposure to stress and methamphetamine.

methamphetamine


Input: Methamphetamine (Meth) is a widely abused psychostimulant that causes long-term dopamine (DA) and serotonin (5-HT) depletions.

Methamphetamine

Meth

dopamine

serotonin


Input: Stress and Meth abuse are comorbid events in society and stress exacerbates Meth-induced monoaminergic terminal damage.

Meth

Meth


Input: Stress is also known to produce neuroinflammation.


Input: This study examined the role of the neuroinflammatory mediator, cyclooxygenase (COX), in the depletions of monoamines caused by serial exposure to chronic unpredictable stress (CUS) and Meth.

monoamines

Meth


Input: CUS produced an increase in COX-2 protein expression and enhanced Meth-induced monoaminergic depletions in the striatum and hippocampus.

Meth


Input: The enhanced DA and 5-HT depletions in the striatum, but not the hippocampus, were prevented by pretreatment with COX inhibitor, ketoprofen, during stress or during Meth; however, ketoprofen did not attenuate the monoaminergic damage caused by Meth alone.

ketoprofen

Meth

ketoprofen

Meth


Input: The COX-dependent enhancement by stress of Meth-induced monoaminergic depletions was independent of hyperthermia, as ketoprofen did not attenuate Meth-induced hyperthermia.

Meth

ketoprofen

Meth


Input: In addition, the EP1 receptor antagonist, SC-51089, did not attenuate DA or 5-HT depletions caused by stress and Meth.

Meth


Input: These findings illustrate that COX activity, but not activation of the EP1 receptor, is responsible for the potentiation of Meth-induced damage to striatal monoamine terminals by stress and suggests the use of anti-inflammatory drugs for mitigating the neurotoxic effects associated with the combination of stress and Meth.

Meth

monoamine

Meth


Input: Upregulation of the dorsal raphe nucleus-prefrontal cortex serotonin system by chronic treatment with escitalopram in hyposerotonergic Wistar-Kyoto rats.

serotonin

escitalopram


Input: Wistar-Kyoto (WKY) rats are sensitive to chronic stressors and exhibit depression-like behavior.


Input: Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons projecting to the prefrontal cortex (PFC) comprise the important neurocircuitry underlying the pathophysiology of depression.

serotonin


Input: To evaluate the DRN-PFC 5-HT system in WKY rats, we examined the effects of escitalopram (ESCIT) on the extracellular 5-HT level in comparison with Wistar rats using dual-probe microdialysis.

escitalopram

ESCIT


Input: The basal levels of 5-HT in the DRN, but not in the PFC, in WKY rats was reduced as low as 30% of Wistar rats.


Input: Responses of 5-HT in the DRN and PFC to ESCIT administered systemically and locally were attenuated in WKY rats.

ESCIT


Input: Feedback inhibition of DRN 5-HT release induced by ESCIT into the PFC was also attenuated in WKY rats.

ESCIT


Input: Chronic ESCIT induced upregulation of the DRN-PFC 5-HT system in WKY rats, with increases in basal 5-HT in the DRN, responsiveness to ESCIT in the DRN and PFC, and feedback inhibition, whereas downregulation of these effects was induced in Wistar rats.

ESCIT

ESCIT


Input: Thus, the WKY rat is an animal model of depression with low activity of the DRN-PFC 5HT system.


Input: The finding that chronic ESCIT upregulates the 5-HT system in hyposerotonergic WKY rats may contribute to improved understanding of mechanisms of action of antidepressants, especially in depression with 5-HT deficiency.

ESCIT


Input: Bioconcentration of chromium in edible mushrooms: influence of environmental and genetic factors.

chromium


Input: Chromium concentrations were determined in 167 samples of wild edible mushrooms, collected from three different sites (urban, traffic and pastureland areas) in Lugo (NW Spain).

Chromium


Input: The hymenophore (H) and the rest of the fruiting body (RFB) were analysed separately.


Input: The analyses were performed using inductively coupled plasma optical emission spectrometry (ICP-OES).


Input: The highest mean chromium levels (mg/kg dry weight) of 3. 5 and 8. 0, 4. 5 and 6. 2, and 6. 2 and 4. 3 were found in Lycoperdon utriforme, Coprinus comatus and Agaricus campestris in H and RFB, respectively.

chromium


Input: The highest concentrations of chromium were observed in terrestrial saprophytic species in relation to mycorrhizal species.

chromium


Input: With respect to the underlying substrates, chromium concentration was lowest in the pastureland area (24. 6 mg/kg dw).

chromium


Input: All mushroom species were bioexclusors of chromium (BCF < 1) with statistically significant differences (p < 0. 001).

chromium


Input: The consumption of mushrooms harvested from the areas investigated poses no toxicological risk to human health due to chromium.

chromium


Input: Synthetic pathway to 22, 23-dioxocholestanic chain derivatives and their usefulness for obtaining brassinosteroid analogues.

22, 23-dioxocholestanic

brassinosteroid


Input: Recognizing the functionality of the pentacyclic steroidal derivative 7a as important synthon to obtain new brassinosteroid analogs, we have accomplished the derivatization of hecogenin, a sapogenin from the 25R serie containing a carbonyl group at C-12, to a 22, 23-dioxocholestanic chain derivative.

pentacyclic steroidal

brassinosteroid

hecogenin

carbonyl

22, 23-dioxocholestanic


Input: Starting from hecogenin acetate (5a) or hecogenin tosylate (5b), we obtained two pentacyclic derivatives (7a and 7b) which were subjected to an oxidation reaction on the double bond at C-12 (23) to obtain a 22, 23-dioxocholestanic chain, with the regeneration of the carbonyl group at C-12.

hecogenin acetate

hecogenin tosylate

22, 23-dioxocholestanic

carbonyl


Input: Reduction of the carbonyl groups lead to the 20-epi-12, 23-dihydroxy-22-oxo system 11a-b.

carbonyl

20-epi-12, 23-dihydroxy-22-oxo


Input: The absolute configuration of compound 11a was established by X-ray diffraction analysis.


Input: Evolution of Manduca sexta hornworms and relatives: Biogeographical analysis reveals an ancestral center of diversification in Central America.


Input: The hawkmoth genus Manduca is a diverse group of very large, conspicuous moths that has served as an important model across many biological disciplines.


Input: Two species in particular, the tobacco hornworm (Manduca sexta) and the tomato hornworm (Manduca quinquemaculatus) have been researched extensively.


Input: Studies across biological fields have referred to these two species as being closely related or even sister species, but the extent to which these two model organisms are related remains largely unknown.


Input: We conducted a comprehensive multi-gene phylogenetic analysis of Manduca, based on both an ML and Bayesian framework, which resulted in a monophyletic Manduca but only when two other genera, Dolba and Euryglottis are included.


Input: We tentatively conclude that the sister group to Manduca sexta comprises the Caribbean M. afflicta and M. johanni, and the sister lineage to this clade includes M. quinquemaculatus and the Hawaiian M. blackburni.


Input: Thus, M. sexta and M. quinquemaculatus are closely related, but are not sister species.


Input: Biogeographical analyses reveal an ancestral center of diversification in Central America, and Manduca appears to have subsequently colonized North and South America.


Input: Our phylogeny provides an important foundation for comparative studies of two model organisms and their relatives.


Input: Designing, structural elucidation, comparison of DNA binding, cleavage, radical scavenging activity and anticancer activity of copper (I) complex with 5-dimethyl-2-phenyl-4-[(pyridin-2-ylmethylene)-amino]-1, 2-dihydro-pyrazol-3-one Schiff base ligand.

copper (I)

5-dimethyl-2-phenyl-4-[(pyridin-2-ylmethylene)-amino]-1, 2-dihydro-pyrazol-3-one Schiff base


Input: A novel copper (I) Schiff base complex has been synthesized and fully characterized by spectral, analytical and structural modes.

copper (I) Schiff base


Input: Single crystal X-ray diffraction studies revealed that the copper (I) complex [CuCl (PPh3) L] has a distorted tetrahedral geometry around the central copper (I) ion.

copper (I)

[CuCl (PPh3) L]

copper (I)


Input: The interaction of the ligand and the complex with CT-DNA has been explored by absorption titration method which revealed that the compounds could interact with CT-DNA through intercalation.


Input: A gel electrophoresis assay demonstrated the ability of the complex to cleave the pBR322 DNA.


Input: The antioxidative properties showed that the copper (I) complex has a strong radical-scavenging potency than ligands.

copper (I)


Input: Further the cytotoxic effect of the compounds examined on cancerous cell lines showed that the complex exhibited substantial anticancer activity.


Input: Synthesis and biological evaluation of novel phosphatidylinositol 3-kinase inhibitors: Solubilized 4-substituted benzimidazole analogs of 2-(difluoromethyl)-1-[4, 6-di (4-morpholinyl)-1, 3, 5-triazin-2-yl]-1H-benzimidazole (ZSTK474).

phosphatidylinositol

4-substituted benzimidazole

2-(difluoromethyl)-1-[4, 6-di (4-morpholinyl)-1, 3, 5-triazin-2-yl]-1H-benzimidazole


Input: A range of 4-substituted derivatives of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4, 6-di-(4-morpholinyl)-1, 3, 5-triazin-2-yl]-1H-benzimidazole (ZSTK474) were prepared in a search for more soluble analogs.

2-(difluoromethyl)-1-[4, 6-di-(4-morpholinyl)-1, 3, 5-triazin-2-yl]-1H-benzimidazole


Input: 4-Aminoalkoxy substituents provided the most potent derivatives, with the 4-O (CH2) 3NMe2 analog (compound 14) being identified as displaying the best overall activity in combination with good aqueous solubility (25 mg/mL for the hydrochloride salt).

4-O (CH2) 3NMe2

hydrochloride


Input: This compound was tested in a U87MG xenograft model, but displayed less potency than ZSTK474 as a result of an unfavorable pharmacokinetic profile.


Input: Nitroimidazolyl hydrazones are better amoebicides than their cyclized 1, 3, 4-oxadiazoline analogues: In vitro studies and Lipophilic efficiency analysis.

Nitroimidazolyl hydrazones

1, 3, 4-oxadiazoline


Input: Two series of compounds with hydrazone derivatives (HZ1-HZl2, series 1) and oxadiazoline derivatives (OZ1-OZ12, series 2) of the 2-methyl-5-nitro-1H-imidazole scaffold were designed and synthesized.

hydrazone

oxadiazoline


Input: Physicochemical properties and Lipophilic efficiency (LipE) analysis predicted higher intrinsic quality of the acylhydrazone derivatives (series 1) than their corresponding oxadiazoline analogues (series 2).

acylhydrazone

oxadiazoline


Input: In vitro antiamoebic results supported the above findings and validated that the acylhydrazone derivatives (HZ1-HZl2) show better activity than the oxadiazoline derivatives (OZ1-OZ12).

acylhydrazone

oxadiazoline


Input: MTT assay, using HepG2 cell line, revealed noncytotoxic nature of the compounds.

MTT


Input: The most promising results were observed for compounds HZ5 (IC50 = 0. 96 mu M) and HZ9 (IC50 = 0. 81 mu M) both in silico and in vitro.


Input: Analysis of the Lipophilic efficiency (LipE) of the compounds provided new insight for the design of potent and selective amoebicides.


Input: Enmein-type diterpenoid analogs from natural kaurene-type oridonin: Synthesis and their antitumor biological evaluation.

Enmein

diterpenoid

kaurene

oridonin


Input: A series of enmein-type diterpenoid analogs (11-20) derived from natural kaurene-type diterpenoid oridonin were synthesized and biologically evaluated.

enmein

diterpenoid

kaurene

oridonin


Input: All target compounds showed improved anti-proliferative activities against four human cancer cell lines compared with natural oridonin and parent compound 10.

oridonin


Input: Some compounds were more potent than positive control Taxol.

Taxol


Input: Furthermore, mechanistic investigation showed that the representative compound 17 affected cell cycle and induced apoptosis at low micro-molar level in human hepatoma Bel-7402 cells, via an oxidative stress triggered mitochondria-related caspase-dependent pathway.


Input: Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability.


Input: Changes in cell adhesion and polarity are closely associated with epithelial cell transformation and metastatic capacity.


Input: The tumor suppressor protein ASPP (Apoptosis-Stimulating Proteins of p53) 2 has been implicated in control of cell adhesion and polarity through its effect on the PAR complex.


Input: Here we demonstrate that under hypoxic conditions, the ubiquitin ligase Siah (seven in absentia homolog) 2 controls ASPP2 availability, with concomitant effect on epithelial cell polarity.


Input: LC-MS/MS analysis identified ASPP2 and ASPP1 as Siah2-interacting proteins.


Input: Biochemical analysis confirmed this interaction and mapped degron motifs within ASPP2, which are required for Siah2-mediated ubiquitination and proteasomal-dependent degradation.


Input: Inhibition of Siah2 expression increases ASPP2 levels and enhances ASPP2-dependent maintenance of tight junction (TJ) integrity, and polarized architecture in three dimensional (3D) organotypic culture.


Input: Conversely, increase of Siah2 expression under hypoxia decreases ASPP2 levels and the formation of apical polarity in 3D culture.


Input: In all, our studies demonstrate the role of Siah2 in regulation of TJ integrity and cell polarity under hypoxia, through its regulation of ASPP2 stability. Oncogene advance online publication, 6 May 2013; doi: 10. 1038/onc. 2013. 149.


Input: The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample.

oxytocin


Input: RATIONALE: To improve outcomes for patients undergoing extinction-based therapies (e. g., exposure therapy) for anxiety disorders such as post-traumatic stress disorder (PTSD), there has been interest in identifying pharmaceutical compounds that might facilitate fear extinction learning and recall.


Input: Oxytocin (OT) is a mammalian neuropeptide that modulates activation of fear extinction-based neural circuits and fear responses.

Oxytocin


Input: Little is known, however, about the effects of OT treatment on conditioned fear responding and extinction in humans.


Input: OBJECTIVES: The purpose of the present study was to assess the effects of OT in a fear-potentiated startle task of fear conditioning and extinction.


Input: METHODS: A double-blind, placebo-controlled study of 44 healthy human participants was conducted.


Input: Participants underwent a conditioned fear acquisition procedure, after which they were randomized to treatment group and delivered OT (24 IU) or placebo via intranasal (IN) spray.


Input: Forty-five minutes after treatment, participants underwent extinction training.


Input: Twenty-four hours later, subjects were tested for extinction recall.


Input: RESULTS: Relative to placebo, the OT group showed increased fear-potentiated startle responding during the earliest stage of extinction training relative to placebo; however, all treatment groups showed the same level of reduced responding by the end of extinction training.


Input: Twenty-four hours later, the OT group showed significantly higher recall of extinction relative to placebo.


Input: CONCLUSIONS: The current study provides preliminary evidence that OT may facilitate fear extinction recall in humans.


Input: These results support further study of OT as a potential adjunctive treatment for extinction-based therapies in fear-related disorders.


Input: Greater risk sensitivity of dorsolateral prefrontal cortex in young smokers than in nonsmokers.


Input: RATIONALE: Despite a national reduction in the prevalence of cigarette smoking, ~ 19% of the adult US population persists in this behavior, with the highest prevalence among 18-25-year-olds.


Input: Given that the choice to smoke imposes a known health risk, clarification of brain function related to decision-making, particularly involving risk-taking, in smokers may inform prevention and smoking cessation strategies.


Input: OBJECTIVES: This study aimed to compare brain function related to decision-making in young smokers and nonsmokers.


Input: METHODS: The Balloon Analogue Risk Task (BART) is a computerized risky decision-making task in which participants pump virtual balloons, each pump associated with an incremental increase in potential payoff on a given trial but also with greater risk of balloon explosion and loss of payoff.


Input: We used this task to compare brain activation associated with risky decision-making in smokers (n = 18) and nonsmokers (n = 25), while they performed the BART during functional magnetic resonance imaging (fMRI).


Input: The participants were young men and women, 17-21 years of age.


Input: RESULTS: Risk level (number of pumps) modulated brain activation in the right dorsolateral and ventrolateral prefrontal cortices more in smokers than in nonsmokers, and smoking severity (Heaviness of Smoking Index) was positively related to this modulation in an adjacent frontal region.


Input: CONCLUSIONS: Given evidence for involvement of the right dorsolateral and ventrolateral prefrontal cortices in inhibitory control, these findings suggest that young smokers have a different contribution of prefrontal cortical substrates to risky decision-making than nonsmokers.


Input: Future studies are warranted to determine whether the observed neurobiological differences precede or result from smoking.


Input: Measuring nanoparticle flow with the image structure function.


Input: We present a technique to measure the velocity and flow profiles of a nanofluid in a microfluidic channel.


Input: Importantly, we extract the flow velocity from a series of standard brightfield images without employing particle tracking or laser-enhanced methods.


Input: Our analysis retrieves the flow information from the image structure function of sub-diffraction limited nanoparticles in suspension.


Input: We are able to spatially resolve the flow velocity and map out the parabolic flow profile across the width of a microfluidic channel.


Input: Role of quercetin in cadmium-induced oxidative stress, neuronal damage, and apoptosis in rats.

quercetin

cadmium


Input: The present study was carried out to evaluate the neuroprotective effect of quercetin (QE) in protecting the cadmium (Cd)-induced neuronal injury in frontal cortex of rats.

quercetin

cadmium

Cd


Input: A total of 30 adult male Sprague-Dawley rats were randomly divided into three groups of 10 animals each: control, Cd treated and Cd treated with QE.

Cd

Cd


Input: The Cd-treated group was injected subcutaneously with cadmium chloride (CdCl2) dissolved in saline at a dose of 2 ml/kg/day for 30 days, resulting in a dosage of 1 mg/kg Cd.

Cd

cadmium chloride

Cd


Input: The rats in QE-treated groups were given QE (15 mg/kg body weight) once a day intraperitoneally starting 2 days prior to Cd injection, during the study period.

Cd


Input: Rats were sacrificed at the end of the study and the frontal cortex tissues were removed for biochemical and histopathological investigation.


Input: To date, there is no available information on the effect of QE on neuronal injury after Cd exposure.

Cd


Input: Rats intoxicated with Cd for 30 days, significantly increased tissue malondialdehyde (MDA) levels and significantly decreased enzymatic antioxidants superoxide dismutase, glutathione peroxidase and catalase in the frontal cortex tissue.

Cd

malondialdehyde

MDA

superoxide

glutathione


Input: Administration of QE with Cd significantly diminished the levels of MDA and significantly elevated the levels of enzymatic antioxidants in the frontal cortex tissue.

Cd

MDA


Input: The histopathological studies in the brain of rats also supported that QE markedly reduced the Cd-induced histopathological changes and well preserved the normal histological architecture of the frontal cortex tissue.

Cd


Input: The caspase-3 immunopositivity was increased in degenerating neurons of the Cd group.

Cd


Input: Treatment with QE markedly reduced the immunoreactivity of degenerating neurons.


Input: In conclusion, the results of the current study suggest that QE may be beneficial in combating the Cd-induced neurotoxicity in the brain of rats.

Cd


Input: We believe that further preclinical research into the utility of QE may indicate its usefulness as a potential treatment for neurodegeneration after Cd exposure in rats.

Cd


Input: Differential regulation of Arabidopsis plastid gene expression and RNA editing in non-photosynthetic tissues.


Input: RNA editing is one of the post-transcriptional processes that commonly occur in plant plastids and mitochondria.


Input: In Arabidopsis, 34 C-to-U RNA editing events, affecting transcripts of 18 plastid genes, have been identified.


Input: Here, we examined the editing and expression of these transcripts in different organs, and in green and non-green seedlings (etiolated, cia5-2, ispF and ispG albino mutants, lincomycin-, and norflurazon-treated).

lincomycin

norflurazon


Input: The editing efficiency of Arabidopsis plastid transcripts varies from site to site, and may be specifically regulated in different tissues.


Input: Steady state levels of plastid transcripts are low or undetectable in etiolated seedlings, but most editing sites are edited with efficiencies similar to those observed in green seedlings.


Input: By contrast, the editing of some sites is completely lost or significantly reduced in other non-green tissues; for instance, the editing of ndhB-149, ndhB-1255, and ndhD-2 is completely lost in roots and in lincomycin-treated seedlings.

lincomycin


Input: The editing of ndhD-2 is also completely lost in albino mutants and norflurazon-treated seedlings.

norflurazon


Input: However, matK-640 is completely edited, and accD-794, atpF-92, psbE-214, psbF-77, psbZ-50, and rps14-50 are completely or highly edited in both green and non-green tissues.


Input: In addition, the expression of nucleus-encoded RNA polymerase dependent transcripts is specifically induced by lincomycin, and the splicing of ndhB transcripts is significantly reduced in the albino mutants and inhibitor-treated seedlings.

lincomycin


Input: Our results indicate that plastid gene expression, and the splicing and editing of plastid transcripts are specifically and differentially regulated in various types of non-green tissues.


Input: Analysis of the inhibitory activity of Abeliophyllum distichum leaf constituents against aldose reductase by using high-speed counter current chromatography.

aldose


Input: We isolated five phenolic glycosides (acteoside, eutigoside B, isoacteoside, rutin and cornoside) from Abeliophyllum distichum leaves by high-speed counter current chromatography (HSCCC) using a solvent system of ethyl acetate: n-butanol: water (8: 0. 7: 5).

phenolic glycosides

acteoside

eutigoside B

isoacteoside

rutin

cornoside

ethyl acetate

n-butanol


Input: We determined the purity of the 5 compounds by high-performance liquid chromatography, and confirmed their chemical structures by using nuclear magnetic resonance data.


Input: We examined the inhibitory effect of these compounds on rat lens aldose reductase.

aldose


Input: Among these compounds, acteoside (1) showed the most potent inhibitory effect, with an IC50 value of 1. 39 mu M.

acteoside


Input: The inhibitory effect of 1 was 5. 0 times greater than that of quercetin (7. 05 mu M), which was used as a positive control.

quercetin


Input: These results suggest that acteoside may be a promising agent for the prevention or treatment of diabetic complications.

acteoside


Input: Moreover, HSCCC is a promising method for the isolation and purification of biologically active compounds from natural products.


Input: Understanding the Cost-Effectiveness of Influenza Vaccination in Children: Methodological Choices and Seasonal Variability.


Input: BACKGROUND: The universal vaccination of children for influenza has recently been recommended in the UK and is being considered in other developed countries.


Input: OBJECTIVES: The aim of this study was to explore the potential costs and benefits of childhood influenza vaccination to gain a better understanding of the key drivers of cost-effectiveness.


Input: METHODS: As our case study we examined the cost-effectiveness of vaccination in Australian schoolchildren using an age-stratified Susceptible Exposed Infectious Recovered model.


Input: RESULTS: The results of this study highlight the critical role that methodological choices play in determining the cost-effectiveness of influenza vaccination.


Input: These choices include decisions about the structure of the model (including/excluding herd immunity) and what costs and benefits to include in the analysis.


Input: In scenarios where herd protection was included we estimated that the program was likely to be cost-effective.


Input: The study also illustrates the importance of the inherent seasonal variability of influenza, which can produce counter-intuitive results, with low transmission seasons being easier to control by vaccination but resulting in fewer benefits.


Input: CONCLUSIONS: Universal childhood influenza vaccination is likely to be cost-effective if a substantial herd protection effect can be achieved by the program.


Input: However, it is important that decision makers understand the role of seasonal variability and the impact of alternative methodological choices in economic evaluations of influenza vaccination.


Input: The bacterial translocon SecYEG opens upon ribosome binding.


Input: In cotranslational translocation, the ribosome funnel and the channel of the protein translocation complex SecYEG are aligned.


Input: For the nascent chain to enter the channel immediately after synthesis, a yet unidentified signal triggers displacement of the SecYEG sealing plug from the pore.


Input: Here we show that ribosome binding to the resting SecYEG channel triggers this conformational transition.


Input: The purified and reconstituted SecYEG channel opens to form a large ion-conducting channel which has the conductivity of the plug deletion mutant.


Input: The number of ion conducting channels inserted into the planar bilayer per fusion event roughly equals the number of SecYEG channels counted by fluorescence correlation spectroscopy in a single proteoliposome.


Input: Thus, the open probability of the channel must be close to unity.


Input: To prevent the otherwise lethal proton leak, a closed post-translational conformation of the SecYEG complex bound to a ribosome must exist.


Input: Gain-of-function mutations in transient receptor potential C6 (TRPC6) activate extracellular-signal-regulated kinases Erk1/2.


Input: Gain-of-function mutations in the canonical transient receptor potential 6 (TRPC6) gene are a cause of autosomal dominant focal segmental glomerulosclerosis (FSGS4).


Input: The mechanisms whereby abnormal TRPC6 activity results in proteinuria remain unknown.


Input: The Erk1/2 MAP kinases are activated in glomeruli and podocytes in several proteinuric disease models.


Input: We therefore examined whether FSGS-associated mutations in TRPC6 result in activation of these kinases.


Input: In 293T cells and cultured podocytes, overexpression of gain-of-function TRPC6 mutants resulted in increased Erk1/2 phosphorylation, an effect dependent upon channel function.


Input: Pharmacologic inhibitor studies implicated several signaling mediators, including calmodulin and calcineurin, supporting the importance of TRPC6-mediated calcium influx in this process.

calcium


Input: Through media transfer experiments, we uncovered two distinct mechanisms for Erk activation by mutant TRPC6, a cell autonomous, EGFR-independent mechanism and a cell non-autonomous mechanism involving metalloprotease-mediated release of a presumed EGFR ligand.


Input: The inhibitors KN-92 and H89 were able to block both pathways in mutant TRPC6 expressing cells, as well as the prolonged elevation of intracellular calcium levels upon carbachol stimulation seen in these cells.

calcium

carbachol


Input: However, these effects appear independent of their effects on CaMKII and PKA, respectively.


Input: Phosphorylation of T70, S282 and Y31/Y285 were not necessary for Erk activation by mutant TRPC6, though a phosphomimetic TRPC6 S282E mutant was capable of Erk activation.


Input: Taken together, these results identify two pathways downstream of mutant TRPC6 leading to Erk activation that may play a role in the development of FSGS.