Input: Glycerol and urea can be used to increase skin permeability in reduced hydration conditions.

Glycerol

urea


Input: The natural moisturizing factor (NMF) is a group of hygroscopic molecules that is naturally present in skin and protects from severe drying.


Input: Glycerol and urea are two examples of NMF components that are also used in skin care applications.

Glycerol

urea


Input: In the present study, we investigate the influence of glycerol and urea on the permeability of a model drug (metronidazole, Mz) across excised pig skin membranes at different hydrating conditions.

glycerol

urea

metronidazole


Input: The degree of skin hydration is regulated by the gradient in water activity across the membrane, which in turn depends on the water activity of the formulation in contact with the skin membrane.


Input: Here, we determine the water activity of all formulations employed using an isothermal calorimetric method.


Input: Thus, the gradient in water activity is controlled by a novel experimental set-up with well-defined boundary conditions on both sides of the skin membrane.


Input: The results demonstrate that glycerol and urea can retain high steady state flux of Mz across skin membranes at dehydrating conditions, which otherwise would decrease the permeability due to dehydration.

glycerol

urea


Input: X-ray diffraction measurements are performed to give insight into the effects of glycerol and urea on SC molecular organization.

glycerol

urea


Input: The novel steady state flux results can be related to the observation that water, glycerol, and urea all affect the structural features of the SC molecular components in a similar manner.

glycerol

urea


Input: Repeated potentiation of the metabotropic glutamate receptor 5 and the alpha 7 nicotinic acetylcholine receptor modulates behavioural and GABAergic deficits induced by early postnatal phencyclidine (PCP) treatment.

glutamate

acetylcholine

phencyclidine

PCP


Input: The underlying mechanism of the GABAergic deficits observed in schizophrenia has been proposed to involve NMDA receptor hypofunction.

NMDA


Input: An emerging treatment strategy therefore aims at enhancing GABAergic signalling by increasing the excitatory transmission onto interneurons.


Input: We wanted to determine whether behavioural and GABAergic functional deficits induced by the NMDA receptor channel blocker, phencyclidine (PCP), could be reversed by repeated administration of two drugs known to enhance GABAergic transmission: the positive allosteric modulator (PAM) of the metabotropic glutamate receptor 5 (mGluR5), ADX47273, and the partial agonist of the alpha 7 nicotinic acetylcholine receptor (alpha 7 nAChR), SSR180711.

NMDA

phencyclidine

PCP

glutamate

acetylcholine


Input: Adolescent rats (4-5 weeks) subjected to PCP treatment during the second postnatal week displayed a consistent deficit in prepulse inhibition (PPI), which was reversed by a one week treatment with ADX47273 or SSR180711.

PCP


Input: We examined GABAergic transmission by whole cell patch-clamp recordings of miniature inhibitory postsynaptic currents (mIPSC) in pyramidal neurons in layer II/III of prefrontal cortex (PFC) and by activation of extrasynaptic delta-containing GABAA receptors by THIP.

THIP


Input: Following PCP treatment, pyramidal neurons displayed a reduced mIPSC frequency and up-regulation of extrasynaptic THIP-induced current.

PCP

THIP


Input: ADX47273 treatment restored this up-regulation of THIP-induced current.

THIP


Input: Finally, we showed that repeated treatment with ADX47273 and SSR180711 decreased the induction of spontaneous inhibitory current caused by acute and direct agonism of mGluR5s and alpha 7 nAChRs in slices.


Input: These results show that repeated administration of ADX47273 or SSR180711 reverses certain behavioural and functional deficits induced by PCP, likely through down-regulation or desensitisation of mGluR5s and alpha 7 nAChRs, respectively.

PCP


Input: Pharmacological and genetic evidence for pre-and postsynaptic D2 receptor involvement in motor responses to nociceptin/orphanin FQ receptor ligands.


Input: A combined pharmacological and genetic approach was undertaken to investigate the contribution of endogenous dopamine to the motor actions of nociceptin/orphanin FQ (N/OFQ) receptor (NOP receptor) ligands.

dopamine


Input: Motor activity was evaluated by a battery of behavioural tests in mice.


Input: The involvement of the various DA receptor subtypes in the motor effects of N/OFQ and NOP receptor antagonists was evaluated pharmacologically, using D1/D5 (SCH23390), D2/D3 (raclopride, amisulpride) and D3 (S33084) receptor antagonists, and by using D2 receptor knockout mice.

raclopride

amisulpride


Input: Low doses of N/OFQ and NOP receptor antagonists promoted movement whereas higher doses inhibited it.


Input: Motor facilitation was selectively prevented by raclopride while motor inhibition was prevented by amisulpride.

raclopride

amisulpride


Input: Amisulpride also attenuated the hypolocomotion induced by the D2/D3 receptor agonist pramipexole and dopamine precursor L-3, 4-dihydroxyphenylalanine, whereas raclopride (and S33084) worsened it.

Amisulpride

pramipexole

dopamine

L-3, 4-dihydroxyphenylalanine

raclopride


Input: To dissect out the contribution of pre-and postsynaptic D2 receptors, mice lacking the D2 receptor (D2R (-/-)) or its long isoform (D2L (-/-)) were used.


Input: Motor facilitation induced by N/OFQ and NOP receptor antagonists was lost in D2R (-/-) and D2L (-/-) mice whereas motor inhibition induced by NOP receptor antagonists (and pramipexole) was lost in D2R (-/-) but preserved in D2L (-/-) mice.

pramipexole


Input: N/OFQ-induced hypolocomotion was observed in both genotypes.


Input: We demonstrate that motor actions of NOP receptor ligands rely on the modulation of endogenous dopamine.

dopamine


Input: Motor facilitation induced by NOP receptor antagonists as well as low dose N/OFQ is mediated through D2L postsynaptic receptors whereas motor inhibition observed with higher doses of N/OFQ occurs by direct inhibition of mesencephalic DA neurons.


Input: Motor inhibition seen with high doses of NOP receptor antagonists appears to be mediated through the D2 presynaptic autoreceptors.


Input: These data confirm that endogenous N/OFQ is a powerful modulator of dopamine transmission in vivo and that the effects of NOP receptor antagonists on motor function reflect the blockade of this endogenous N/OFQ tone.


Input: Prosocial effects of oxytocin in two mouse models of autism spectrum disorders.

oxytocin


Input: Clinical evidence suggests that oxytocin treatment improves social deficits and repetitive behavior in autism spectrum disorders (ASDs).

oxytocin


Input: However, the neuropeptide has a short plasma half-life and poor ability to penetrate the blood-brain barrier.


Input: In order to facilitate the development of more bioavailable oxytocinergic compounds as therapeutics to treat core ASD symptoms, small animal models must be validated for preclinical screens.


Input: This study examined the preclinical utility of two inbred mouse strains, BALB/cByJ and C58/J, that exhibit phenotypes relevant to core ASD symptoms.


Input: Mice from both strains were intraperitoneally administered oxytocin, using either acute or sub-chronic regimens.

oxytocin


Input: Acute oxytocin did not increase sociability in BALB/cByJ; however, sub-chronic oxytocin had significant prosocial effects in both BALB/cByJ and C58/J.

oxytocin

oxytocin


Input: Increased sociability was observed 24 hours following the final oxytocin dose in BALB/cByJ, while prosocial effects of oxytocin emerged 1-2 weeks post-treatment in C58/J.

oxytocin

oxytocin


Input: Furthermore, acute oxytocin decreased motor stereotypy in C58/J and did not induce hypoactivity or anxiolytic-like effects in an open field test.

oxytocin


Input: This study demonstrates that oxytocin administration can attenuate social deficits and repetitive behavior in mouse models of ASD, dependent on dose regimen and genotype.

oxytocin


Input: These findings provide validation of the BALB/cByJ and C58/J models as useful platforms for screening novel drugs for intervention in ASDs and for elucidating the mechanisms contributing to the prosocial effects of oxytocin.

oxytocin


Input: In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration.


Input: Polymeric nanocarriers have shown great promise as delivery systems.


Input: An alternative strategy has been to explore new delivery routes, such as intradermal (i. d.) that can be used for vaccines and patch-based drug delivery.


Input: Despite their many advantages, there are few toxicity studies, especially in vivo.


Input: We report a safety assessment of biodegradable poly (-caprolactone) lipid-core nanocapsules (LNC) with a mean size of 245 +/- 10 nm following single and repeated intradermal injections to Wistar rats.

poly (-caprolactone)


Input: Suspensions were prepared by interfacial deposition of polymer.


Input: The animals (n = 6/group) received a single dose of saline solution (1. 2 ml/kg) or LNC (7. 2 x 10 (12) LNC/kg), or repeated doses of two controls, saline solution or Tween 80 (0. 9 ml/kg), or three different concentrations of LNC (1. 8, 3. 6, and 5. 4 x 10 (12) LNC/kg) for 28 consecutive days.

Tween 80


Input: Clinical and physiological signs and mortality were observed.


Input: Samples of urine, blood, and tissue were used to perform toxicological evaluation.


Input: There were no clinical signs of toxicity or mortality, but there was a slight decrease in the relative body weights in the Tween 80-treated group (p < 0. 01) after repeated administration.

Tween 80


Input: No histopathological alterations were observed in tissues or significant changes in blood and urinary biomarkers for tissue damage.


Input: Mild alterations in white blood cells count with increases in granulocytes in the Tween-80 group (p < 0. 05) were found.


Input: Genotoxicity was evaluated through the comet assay and no statistical difference was observed among the groups.


Input: Therefore, we conclude that, under the conditions of these experiments, biodegradable LNC did not present appreciable toxicity after 28 consecutive days of intradermal administration and is promising for its future application in vaccines and patch-based devices for enhancing the delivery of drugs.


Input: Therapeutic cell encapsulation: Ten steps towards clinical translation.


Input: Since the conception of cell microencapsulation, many scientists bet on this biotechnology as they saw in it a promising alternative to protect transplanted cells from host immunoresponse.


Input: Some decades later, this initial enthusiasm is giving rise to a phase of certain conformism and lack of novel advances in the field.


Input: This perspective critically discusses current challenges needed to help this approach become a realistic clinical proposal.


Input: Alginate seems to be well established as the biomaterial of choice, but additional efforts are needed regarding current cross-linkers and coatings.


Input: Biofunctionalization of the matrices may provide the necessary biomimetic microenvironment to control cell behavior.


Input: Different alginate degradation rates would allow widening the applications of this biotechnology from drug delivery to cell delivery.


Input: In this sense, stem cells from stromal tissues could be the most suitable cell source due to their intrinsic hypoimmunogenicity, their immunomodulatory effets and their capacity to cell homing.


Input: The incorporation of suicide and reporter genes in the genome of enclosed cells may overcome some of the existing biosafety concerns.


Input: Administration and extraction by means of less invasive procedures also need to be developed to succeed in clinical translation.


Input: Finally, improving cost-effectiveness for the scale-up, together with establishing and fulfilling a series of strict regulatory aspects will be indispensable to make the final step to the clinic.


Input: Activator or Inhibitor?


Input: GSK-3 as a new drug target.


Input: Glycogen synthase kinase-3 (GSK-3) is a cytoplasmic serine/threonine protein kinase that phosphorylates and inhibits glycogen synthase, thereby inhibiting glycogen synthesis from glucose.

serine

threonine

glucose


Input: However, this serine/threonine kinase is now known to regulate numerous cellular processes through a number of signaling pathways important for cell proliferation, stem cell renewal, apoptosis and development.

serine

threonine


Input: Because of these diverse roles, malfunction of this kinase is also known to be involved in the pathogenesis of human diseases, such as nervous system disorders, diabetes, bone formation, inflammation, cancer and heart failure.


Input: Therefore, GSK-3 is recognized as an attractive target for the development of new drugs.


Input: The present review summarizes the roles of GSK-3 in the insulin, Wnt/beta-catenin and hedgehog signaling pathways including the regulation of their activities.


Input: The roles of GSK-3 in the development of human diseases within the context of its participation in various signaling pathways are also summarized.


Input: Finally, the possibility of new drug development targeting this kinase is discussed with recent information about inhibitors and activators of GSK-3.


Input: Methods for Detection and Analysis of Apoptosis Signalling in the C. elegans Germline.


Input: This review assesses current and emerging methods for the detection, and analysis of apoptosis in the C. elegans germline.


Input: The nematode worm C. elegans is highly tractable to genetic manipulation, making it an excellent model for elucidating mechanisms of apoptosis signalling in a multicellular setting.


Input: Here we profile the most efficacious fluorescent tools to visualize and quantify germline apoptosis.


Input: We focus specifically on the application of fluorescent markers to screen by RNAi for genes and pathways that regulate germline apoptosis under normal conditions or in response to genotoxic stress.


Input: We also present the limitations of these methods, and suggest complimentary techniques in order that researchers new to the field can comprehensively assess apoptosis phenotypes in the C. elegans germline.


Input: Induction of the liver cancer-down-regulated long noncoding RNA uc002mbe. 2 mediates trichostatin-induced apoptosis of liver cancer cells.

trichostatin


Input: Differential expression of long non-coding RNAs (lncRNAs) plays critical roles in hepatocarcinogenesis.


Input: Considerable attention has focused on the antitumor effect of histone deacetylase inhibitor (Trichostatin A, TSA) as well as the coding gene expression-induced apoptosis of cancer cells.

Trichostatin A

TSA


Input: However, it is not known whether lncRNA has a role in TSA-induced apoptosis of human hepatocellular carcinoma (HCC) cells.

TSA


Input: The global expression of lncRNAs and coding genes was analyzed with the Human LncRNA Array V2. 0 after 24h treatment.


Input: Expression was verified in cell lines and tissues by quantitative real-time PCR.


Input: The data showed that 4. 8% (959) of lncRNA and 6. 1% (1849) of protein coding gene were significantly differentially expressed.


Input: The differential expressions of lncRNA and protein coding genes had distinguishable hierarchical clustering expression profiling pattern.


Input: Among these differentially expressed lncRNAs, the greatest change was noted for uc002mbe. 2, which had more than 300 folds induction upon TSA treatment.

TSA


Input: TSA selectively induced uc002mbe. 2 in four studied HCC cell lines.

TSA


Input: Compared with normal human hepatocytes and adjacent noncancerous tissues, uc002mbe. 2 expression level was significantly lower in the HCC cell lines and liver cancer tissues.


Input: The TSA-induced uc002mbe. 2 expression was positively correlated with the apoptotic effect of TSA in HCC cells.

TSA

TSA


Input: In addition, knockdown the expression of uc002mbe. 2 significantly reduced TSA-induced apoptosis of Huh7cells.

TSA


Input: Therefore, TSA-induced apoptosis of HCC cells is uc002mbe. 2 dependent and reduced expression of uc002mbe. 2 may be associated with liver carcinogenesis.

TSA


Input: (99m) Tc-labeled dibenzylideneacetone derivatives as potential SPECT probes for in vivo imaging of beta-amyloid plaque.

(99m) Tc-labeled dibenzylideneacetone


Input: Four (99m) Tc-labeled dibenzylideneacetone derivatives and corresponding rhenium complexes were successfully synthesized and biologically evaluated as potential imaging probes for A beta plaques using SPECT.

(99m) Tc-labeled dibenzylideneacetone

rhenium


Input: All rhenium complexes (5a-d) showed affinity for A beta (1-42) aggregates (Ki = 13. 6-120. 9 nM), and selectively stained the A beta plaques on brain sections of transgenic mice.

rhenium


Input: Biodistribution in normal mice revealed that [(99m) Tc] 5a-d exhibited moderate initial uptake (0. 31%-0. 49% ID/g at 2 min) and reasonable brain washout at 60 min post-injection.

(99m) Tc


Input: Although additional optimizations are still needed to facilitate it' s penetration through BBB, the present results indicate that [(99m) Tc] 5a may be a potential SPECT probe for imaging A beta plaques in Alzheimer' s brains.

(99m) Tc


Input: In vitro biosynthesis, isolation, and identification of predominant metabolites of 2-(4-(2-hydroxyethoxy)-3, 5-dimethylphenyl)-5, 7-dimethoxyquinazolin-4 (3H)-one (RVX-208).

2-(4-(2-hydroxyethoxy)-3, 5-dimethylphenyl)-5, 7-dimethoxyquinazolin-4 (3H)-one


Input: The structures of the two predominant metabolites (M4 and M5) of RVX-208, observed both in in vitro human and animal liver microsomal incubations, as well as in plasma from animal in vivo studies, were determined.


Input: A panel of biocatalytic systems was tested to identify biocatalysts suitable for milligram scale production of metabolite M4 from RVX-208.


Input: Rabbit liver S9 fraction was selected as the most suitable system, primarily based on pragmatic metrics such as catalyst cost and estimated yield of M4 (~ 55%).


Input: Glucuronidation of RVX-208 catalyzed by rabbit liver S9 fraction was optimized to produce M4 in amounts sufficient for structural characterization.


Input: Structural studies using LC/MS/MS analysis and (1) H NMR spectroscopy showed the formation of a glycosidic bond between the primary hydroxyl group of RVX-208 and glucuronic acid.

(1) H

primary hydroxyl

glucuronic acid


Input: NMR results suggested that the glycosidic bond has the beta-anomeric configuration.


Input: A synthetic sample of M4 confirmed the proposed structure.


Input: Metabolite M5, hypothesized to be the carboxylate of RVX-208, was prepared using human liver microsomes, purified by HPLC, and characterized by LC/MS/MS and (1) H NMR.

carboxylate

(1) H


Input: The structure was confirmed by comparison to a synthetic sample.


Input: Both samples confirmed M5 as a product of oxidation of primary hydroxyl group of RVX-208 to carboxylic acid.

primary hydroxyl

carboxylic acid


Input: Glycosylation enhances the anti-migratory activities of isomalyngamide A analogs.

isomalyngamide A


Input: Three, new, fully synthetic glycosylated isomalyngamide A analogs 4-6 were prepared and evaluated for their anti-migratory activities in human breast cancer cells.

glycosylated isomalyngamide A


Input: The results of the study show that two glycosylated derivatives 4 and 5, containing mannose and galactose appendages, suppress metastatic events (e. g., migration, invasion and adhesion) in human breast adenocarcinoma MDA-MB-231 cells at " nontoxic " concentration levels.

mannose

galactose


Input: In contrast, derivative 6 that contains a lactose moiety, displays a less potent activity.

lactose


Input: The findings show that monosaccharide rather than disaccharide appendages to the isomalyngamide A backbone more greatly influence cell migration and invasive ability.

monosaccharide

disaccharide

isomalyngamide A


Input: Evidence has been gained for a mechanism for inhibition of metastatic activities in MDA-MB-231 cells by 4 and 5, involving inactivation of the expression of p-FAK and paxillin through the integrin-mediated antimetastatic pathway.


Input: Synthesis, characterization and in vitro pharmacological evaluation of new water soluble Ni (II) complexes of 4N-substituted thiosemicarbazones of 2-oxo-1, 2-dihydroquinoline-3-carbaldehyde.

Ni (II)

4N-substituted thiosemicarbazones

2-oxo-1, 2-dihydroquinoline-3-carbaldehyde


Input: Four new Ni (II) complexes of general formula [Ni (H2-Qtsc-R) 2] (NO3) 2 (H2-Qtsc-R = 4N-substituted thiosemicarbazones of 2-oxo-1, 2-dihydroquinoline-3-carbaldehyde, where R = H (1), Me (2), Et (3), or Ph (4)) have been synthesized and characterized.

Ni (II)

[Ni (H2-Qtsc-R) 2] (NO3) 2

4N-substituted thiosemicarbazones

2-oxo-1, 2-dihydroquinoline-3-carbaldehyde

H

Me

Et

Ph


Input: The geometry of the complexes was confirmed by single crystal X-ray crystallography for one of the complexes (3).


Input: The binding affinity of the complexes with DNA and protein have been studied which indicate that they could interact with calf thymus DNA and bovine serum albumin protein.


Input: Investigations of antioxidative properties showed that all the complexes have strong radical scavenging properties.


Input: Cytotoxic studies showed that the complexes exhibited effective cytotoxic activity against a panel of human cancer cells without affecting the normal cells much.


Input: Synthetic tactics of new class of 4-aminothieno [2, 3-d] pyrimidine-6-carbonitrile derivatives acting as antimicrobial agents.

4-aminothieno [2, 3-d] pyrimidine-6-carbonitrile


Input: Thermal selective reactions were studied on oxothieno [2, 3-d] pyrimidine-6-carboxamide 3 with POCl3 and PCl5.

oxothieno [2, 3-d] pyrimidine-6-carboxamide


Input: At 25-50 degrees C, the C7-amide rearranges to nitrile furnished compound 4 in 85-90% yield, while at 80-110 degrees C furnished mixture of products 4 and 5 in 28-68% yields.

nitrile


Input: The chloro displacement with amines in compound 5 yielded 4-aminothieno [2, 3-d] pyrimidine-6-carbonitrile derivatives 8 (a-h) and 9 (a-e).

chloro

amines

4-aminothieno [2, 3-d] pyrimidine-6-carbonitrile


Input: Antimicrobial activity of new compounds was studied against several bacteria such as Staphylococcus aureus MTCC-96, Escherichia coli MTCC-443, Pseudomonas aeruginosa MTCC-4 41, Streptococcus pyogenes MTCC-442 and fungi Aspergillus niger MTCC-282, Aspergillus clavatus MTCC-1323, Candida albicans MTCC-227 using broth microdilution method.


Input: Compounds 4, 8b, 8d, 8e, 8h and 9a showed promising antibacterial activity compared to ampicillin and compounds 8b, 8h showed better antifungal activity compared to greseofulvin.

ampicillin

greseofulvin


Input: Ibuprofen plus Isosorbide Dinitrate treatment in the mdx mice ameliorates dystrophic heart structure.

Ibuprofen

Isosorbide Dinitrate


Input: BACKGROUND: Co-administration of ibuprofen (IBU) and isosorbide dinitrate (ISDN) provides synergistic beneficial effects on dystrophic skeletal muscle.

ibuprofen

IBU

isosorbide dinitrate

ISDN


Input: Whether this treatment has also cardioprotective effects in this disease was still unknown.


Input: Aims: to evaluate the effects of co-administration of IBU and ISDN (a) on left ventricular (LV) structure and function, and (b) on cardiac inflammatory response and fibrosis in mdx mice.

IBU

ISDN


Input: METHODS: three groups of mice were studied: mdx mice treated with IBU (50mgkg (-1)) + ISDN (30mgkg (-1)) administered daily in the diet, mdx mice that received standard diet without drugs and wild type aged-matched mice.

IBU

ISDN


Input: Animals were analysed after 10-11 months of treatment.


Input: Structural and functional parameters were evaluated by echocardiography while histological analyses were performed to evaluate inflammatory response, collagen deposition, cardiomyocyte number and area.


Input: RESULTS: treatment for 10-11 months with IBU + ISDN preserved LV wall thickness and LV mass.

IBU

ISDN


Input: Drug treatment also preserved the total number of cardiomyocytes in the LV and attenuated the increase in cardiomyocyte size, when compared to untreated mdx mice.


Input: Moreover, a trend towards a decreased number of inflammatory cells, a reduced LV myocardial interstitial fibrosis and an enhanced global LV function response to stress was observed in treated mdx mice.


Input: CONCLUSIONS: treatment for 10-11 months with IBU + ISDN is effective in preventing the alterations in LV morphology of mdx mice while not reaching statistical significance on LV function and cardiac inflammation.

IBU

ISDN


Input: Solution-processed organic spin-charge converter.


Input: Conjugated polymers and small organic molecules are enabling new, flexible, large-area, low-cost optoelectronic devices, such as organic light-emitting diodes, transistors and solar cells.


Input: Owing to their exceptionally long spin lifetimes, these carbon-based materials could also have an important impact on spintronics, where carrier spins play a key role in transmitting, processing and storing information.

carbon


Input: However, to exploit this potential, a method for direct conversion of spin information into an electric signal is indispensable.


Input: Here we show that a pure spin current can be produced in a solution-processed conducting polymer by pumping spins through a ferromagnetic resonance in an adjacent magnetic insulator, and that this generates an electric voltage across the polymer film.


Input: We demonstrate that the experimental characteristics of the generated voltage are consistent with it being generated through an inverse spin Hall effect in the conducting polymer.


Input: In contrast with inorganic materials, the conducting polymer exhibits coexistence of high spin-current to charge-current conversion efficiency and long spin lifetimes.


Input: Our discovery opens a route for a new generation of molecular-structure-engineered spintronic devices, which could lead to important advances in plastic spintronics.


Input: An associative capacitive network based on nanoscale complementary resistive switches for memory-intensive computing.


Input: We report on the implementation of an Associative Capacitive Network (ACN) based on the nondestructive capacitive readout of two Complementary Resistive Switches (2-CRSs).


Input: ACNs are capable of performing a fully parallel search for Hamming distances (i. e. similarity) between input and stored templates.


Input: Unlike conventional associative memories where charge retention is a key function and hence, they require frequent refresh cycles, in ACNs, information is retained in a nonvolatile resistive state and normal tasks are carried out through capacitive coupling between input and output nodes.


Input: Each device consists of two CRS cells and no selective element is needed, therefore, CMOS circuitry is only required in the periphery, for addressing and read-out.


Input: Highly parallel processing, nonvolatility, wide interconnectivity and low-energy consumption are significant advantages of ACNs over conventional and emerging associative memories.


Input: These characteristics make ACNs one of the promising candidates for applications in memory-intensive and cognitive computing, switches and routers as binary and ternary Content Addressable Memories (CAMs) and intelligent data processing.


Input: HDAC6 and Ovarian Cancer.


Input: The special class IIb histone deacetylase, HDAC6, plays a prominent role in many cellular processes related to cancer, including oncogenesis, the cell stress response, motility, and myriad signaling pathways.


Input: Many of the lessons learned from other cancers can be applied to ovarian cancer as well.


Input: HDAC6 interacts with diverse proteins such as HSP90, cortactin, tubulin, dynein, p300, Bax, and GRK2 in both the nucleus and cytoplasm to carry out these cancerous functions.


Input: Not all pro-cancer interactions of HDAC6 involve deacetylation.


Input: The idea of using HDAC6 as a target for cancer treatment continues to expand in recent years, and more potent and specific HDAC6 inhibitors are required to effectively down-regulate the tumor-prone cell signaling pathways responsible for ovarian cancer.


Input: Oestrogen action on thyroid progenitor cells: relevant for the pathogenesis of thyroid nodules?

Oestrogen


Input: Benign and malignant thyroid nodules are more prevalent in females than in men.


Input: Experimental data suggest that the proliferative effect of oestrogen rather than polymorphisms is responsible for this gender difference.

oestrogen


Input: This study analysed whether both differentiated thyroid cells and thyroid stem and progenitor cells are a target of oestrogen action.

oestrogen


Input: In thyroid stem/progenitor cells derived from nodular goitres the ability of 17beta-oestradiol to induce thyrosphere formation, the expression of oestrogen receptors and the effect of 17beta-oestradiol on growth, expression of marker of stem cells and thyroid differentiation (TSH receptor, thyroperoxidase, thyroglobulin, sodium iodide symporter expression) were analysed.

oestrogen

sodium iodide


Input: 17beta-oestradiol induced thyrosphere formation, albeit to lower extent than other growth factors.


Input: Thyroid stem and progenitor cells expressed oestrogen receptor alpha and beta with an 8 time higher expression level of oestrogen receptor alpha mRNA compared to differentiated thyrocytes.

oestrogen

oestrogen


Input: 17beta-oestradiol was a potent stimulator of thyroid stem/progenitor cell growth.


Input: In contrast, TSH-induced differentiation of progenitor cells, in particular the expression of the sodium iodide symporter, was significantly inhibited by 17beta-oestradiol. In conclusion, oestrogen stimulated growth and simultaneously inhibited differentiation of thyroid nodules derived stem/progenitor cells.

sodium iodide

oestrogen


Input: From these data and based on the concept of cellular heterogeneity, we hypothesize a supportive role of oestrogen in the propagation of thyroid stem/progenitor cells leading to a selection of a progeny of growth-prone cells with a decreased differentiation.

oestrogen


Input: These cells may be the origin of hypo-or non-functioning thyroid nodules in females.


Input: Repression of mammary adipogenesis by genistein limits mammosphere formationof human MCF-7 cells.

genistein


Input: Mammary adipose tissue may contribute to breast cancer development and progression by altering neighboring epithelial cell behavior and phenotype through paracrine signaling.


Input: Dietary exposure to soy foods is associated with lower mammary tumor risk and reduced body weight and adiposity in humans and in rodent breast cancer models.


Input: Despite the suggested linkage between obesity and breast cancer, the local influence of bioactive dietary components on mammary adiposity for anti-tumor effects remains unknown.


Input: Herein, we report that post-weaning dietary exposure to soy protein isolate and its bioactive isoflavone genistein lowered mammary adiposity and increased mammary tumor suppressor PTEN and E-cadherin expression in female mice, relative to control casein diet.

isoflavone genistein


Input: To ascertain genistein' s role in mammary adipose deposition that may affect underlying epithelial cell phenotype, we evaluated genistein' s effects on SV40-immortalized mouse mammary stromal fibroblast-like (MSF) cells during differentiation to adipocytes.

genistein

genistein


Input: MSF cultured in differentiation medium with 40 nM genistein showed reductions in mature adipocyte numbers, triglyceride accumulation, and PPAR gamma and fatty acid synthase transcript levels.

genistein

triglyceride

fatty acid


Input: Genistein inhibition of adipose differentiation was accompanied by increased estrogen receptor (ER)-beta gene expression and was modestly recapitulated by ER beta selective agonist 2, 3-bis (4-hydroxyphenyl)-propionitrile (DPN).

Genistein

estrogen

2, 3-bis (4-hydroxyphenyl)-propionitrile

DPN


Input: Reduction of ER beta expression by siRNA targeting increased PPAR gamma transcript levels and stromal fibroblast differentiation into mature adipocytes; the latter was reversed by genistein but not DPN.

genistein

DPN


Input: Conditioned medium from genistein-treated adipocytes diminished anchorage-independent mammosphere formation of human MCF-7 breast cancer cells.

genistein


Input: Our results suggest a mechanistic pathway to support direct regulation by genistein of mammary adiposity for breast cancer prevention.

genistein