Input: The substantial influence of the solvent (water) polarization on the energetics, geometries, and bonding of the molecular complexes was also investigated by the conductor-like screening solvation model (COSMO).


Input: In an attempt to simulate the complexes in an aqueous environment, water molecules were added explicitly to complete the coordination sphere of the metal cations, and the corresponding metal-ion affinities were calculated to study the effect of microhydration.


Input: Planar to 3D transition in the B6H (y) anions.

B6H (y)


Input: Potential energy surfaces of anionic B (6) H (y) clusters were sampled using the coalescence kick method.

B (6) H (y)


Input: We found that the planar to three-dimensional transition occurs in this system when y = 4.


Input: This is an important discovery because this transition suggests a major structural change as a function of dehydrogenation for the stoichiometric B (n) H (n) (-) polyhedral boranes.

B (n) H (n) (-) polyhedral boranes


Input: We also found that the B (6) H (3) (-) global minimum structure has an optical isomer.

B (6) H (3) (-)


Input: The chemical bonding patterns revealed by the adaptive natural density partitioning (AdNDP) analysis explain the geometric structure of all clusters presented here.


Input: From our chemical bonding analysis, we concluded that the 2D-3D transition occurs at B (6) H (4) (-) because the addition of one extra hydrogen atom further destroys the network of the peripheral 2c-2e B-B sigma-bonding, making planar structures less stable, and because the distorted octahedral structure provides some occupation of all s-and p-AOs of boron, avoiding the presence of any empty atomic orbitals.

B (6) H (4) (-)

hydrogen

B-B

boron


Input: Theoretical vertical electron detachment energies (VDEs) were calculated for comparison with future experimental work.


Input: The transcription factor Pitx3 is expressed selectively in midbrain dopaminergic neurons susceptible to neurodegenerative stress.


Input: The homeodomain transcription factor Pitx3 is critical for the survival of midbrain dopaminergic (mDA) neurons.


Input: Pitx3-deficient mice exhibit severe but selective developmental loss of mDA neurons, with accompanying locomotor deficits resembling those seen in Parkinson' s disease (PD) models.


Input: Here, we identify specific mDA cell subpopulations that are consistently spared in adult Pitx3-hypomorphic (aphakia) mice, demonstrating that Pitx3 is not indiscriminately required by all mDA neurons for their survival.


Input: In aphakia mice, virtually all surviving mDA neurons in the substantia nigra (SN) and the majority of neurons in the adjacent ventral tegmental area (VTA) also express calbindin-D28k, a calcium-binding protein previously associated with resistance to injury in PD and in animal models.

calcium


Input: Cell-mapping studies in wild-type mice revealed that Pitx3 is primarily expressed in the ventral SN, a region particularly susceptible to MPTP and other dopaminergic neurotoxins.

MPTP


Input: Furthermore, Pitx3-expressing SN cells are preferentially lost following MPTP treatment.

MPTP


Input: Finally, SN mDA neurons in Pitx3 hemizygous mice show increased sensitivity when exposed to MPTP.

MPTP


Input: Thus, SN mDA neurons are represented by at least two distinct subpopulations including MPTP-resistant Pitx3-autonomous, calbindin-positive neurons, and calbindin-negative Pitx-3-dependent cells that display elevated vulnerability to toxic injury, and probably correspond to the subpopulation that degenerates in PD.

MPTP


Input: Impairment of Pitx3-dependent pathways therefore increases vulnerability of mDA neurons to toxic injury.


Input: Together, these data suggest a novel link between Pitx3 function and the selective pattern of mDA cell loss observed in PD.


Input: Fundamental studies of electrochemically controlled surface oxidation and hydrophobicity of natural enargite.

enargite


Input: The surface oxidation and hydrophobicity of natural enargite (Cu (3) AsS (4)) and the formation of oxidation species at the mineral surface have been examined by a novel experimental approach that combines electrochemical techniques and atomic force microscopy (AFM).

enargite

Cu (3) AsS (4)


Input: This approach allows for in-situ, synchronized electrochemical control and examination of the oxidative surface morphology of enargite.

enargite


Input: Combined with ex-situ cryo X-ray photoelectron spectroscopy surface analysis, the surface speciation of enargite surface oxidation has been obtained, comparing the newly fractured natural enargite surface with those that have been electrochemically oxidized at pHs 4 and 10.

enargite

enargite


Input: At pH 4, surface layer formations consisting of metal-deficient sulfide and elemental sulfur were identified, associated with a limited increase in root-mean-square (rms) roughness (1. 228 to 3. 143 nm) and apparent heterogeneous distribution of surface products as demonstrated by AFM imaging.

sulfide

sulfur


Input: A mechanism of initial rapid dissolution of Cu followed by diffusion-limited surface layer deposition was identified.

Cu


Input: At pH 10, a similar mechanism was identified although the differences between the initial and diffusion-limited phases were less definitive.


Input: Surface species were identified as copper sulfate and copper hydroxide.

copper sulfate

copper hydroxide


Input: A significant increase in surface roughness was found as rms roughness increased from 0. 795 to 9. 723 nm.


Input: Dynamic (receding) contact angle measurements were obtained by a droplet evaporation method.


Input: No significant difference in the contact angle on a surface oxidized at pH 10 and the freshly polished surface was found.


Input: A significant difference was found between the polished surface and that oxidized at pH 4, with an increase in contact angle of about 13 degrees (46 degrees to 59 degrees) after oxidation.


Input: Competing effects of hydrophilic (copper oxides and hydroxides) and hydrophobic (elemental sulfur) species on the mineral surface under oxidizing conditions at pH 4 and the change in surface roughness at pH 10 may contribute to the observed effects of electrochemically controlled oxidation on enargite hydrophobicity.

copper oxides and hydroxides

sulfur

enargite


Input: Crystal and magnetic structures and physical properties of a new pyroxene NaMnGe2O6 synthesized under high pressure.

pyroxene NaMnGe2O6


Input: A new pyroxene compound, NaMnGe (2) O (6), has been synthesized at 3 GPa and 800 degrees C and fully characterized by X-ray single-crystal diffraction, neutron powder diffraction, and measurements of magnetization and specific heat.

pyroxene

NaMnGe (2) O (6)


Input: NaMnGe (2) O (6) crystallizes into a monoclinic C2/c structure with unit-cell parameters a = 9. 859 (2) A, b = 8. 7507 (18) A, c = 5. 5724 (11) A, and beta = 105. 64 (3) degrees at 153 K.

NaMnGe (2) O (6)


Input: A cooperative Jahn-Teller distortion is formed by an ordering of the longest Mn-O bonds between two neighboring octahedra along the chain direction.

Mn-O


Input: This feature distinguishes NaMnGe (2) O (6) from other pyroxene compounds without Jahn-Teller active cations and suggests that the Jahn-Teller distortion competes with the intrinsic local distortion in the pyroxene structure.

NaMnGe (2) O (6)

pyroxene

pyroxene


Input: No orbital order-disorder transition has been found up to 750 K.


Input: Like other alkali-metal pyroxenes with S > (1)/(2), NaMnGe (2) O (6) (S = 2) was found to undergo a long-range antiferromagnetic (AF) ordering at T (N) = 7 K due to intrachain and interchain exchange interactions.

pyroxenes

NaMnGe (2) O (6)


Input: Due to the peculiar structural features and the corresponding magnetic coupling, the weak AF spin ordering gives way to a ferromagnetic-like state at a sufficiently high magnetic field.


Input: Specific-heat measurements demonstrated that a large portion of the magnetic entropy, > 60%, has been removed above T (N) as a result of strong spin correlations within the quasi-one-dimensional Mn (3 +)-spin chains.

Mn (3 +)


Input: The Reitveld refinement of neutron powder diffraction data gives a commensurate magnetic structure defined by k = [0 0 0. 5] with Mn moments aligned mainly along the c-axis with a small component along both a-and b-axes.

Mn


Input: Sequence-specific transcription factor NF-Y displays histone-like DNA binding and H2B-like ubiquitination.


Input: The sequence-specific transcription factor NF-Y binds the CCAAT box, one of the sequence elements most frequently found in eukaryotic promoters.


Input: NF-Y is composed of the NF-YA and NF-YB/NF-YC subunits, the latter two hosting histone-fold domains (HFDs).


Input: The crystal structure of NF-Y bound to a 25 bp CCAAT oligonucleotide shows that the HFD dimer binds to the DNA sugar-phosphate backbone, mimicking the nucleosome H2A/H2B-DNA assembly.

sugar

phosphate


Input: NF-YA both binds to NF-YB/NF-YC and inserts an alpha helix deeply into the DNA minor groove, providing sequence-specific contacts to the CCAAT box.


Input: Structural considerations and mutational data indicate that NF-YB ubiquitination at Lys138 precedes and is equivalent to H2B Lys120 monoubiquitination, important in transcriptional activation.


Input: Thus, NF-Y is a sequence-specific transcription factor with nucleosome-like properties of nonspecific DNA binding and helps establish permissive chromatin modifications at CCAAT promoters.


Input: Our findings suggest that other HFD-containing proteins may function in similar ways.


Input: Physical exercise and its effects on coronary artery disease.


Input: The beneficial effects of physical exercise on stable coronary artery disease (CAD) have been shown by an increasing number of studies.


Input: Exercise training leads to an improved bioavailability of the endothelial nitric oxide and partially attenuates endothelial dysfunction.

nitric oxide


Input: Further effects are an economization of ventricular function and a reduction of cardiovascular risk factors.


Input: In clinical studies exercise training was associated with a decreased total and cardiovascular mortality and a reduced angina pectoris threshold.


Input: Thus exercise training has developed to an evidence-based therapeutic option of stable CAD with a Class Ia recommendation in the guidelines.


Input: Composition and anti-oxidant, anti-cancer and anti-inflammatory activities of Artemisia herba-alba, Ruta chalpensis L. and Peganum harmala L.


Input: In this study, biological activities of methanolic extracts from Artemisia herba-alba, Ruta chalpensis L. and Peganum harmala L. plants, collected in Centre of Tunisia, were investigated.


Input: Results showed an important phenolic composition of Artemisia herba-alba (123. 95 +/- 4. 3g GAE/kg of dry mass).


Input: The extract of this plant showed, using different antioxidant assays (DPPH, ABTS and AAPH/linoleic acid methods) and an IFN-gamma/LPS induced RAW 264. 7 murine macrophages' assay, the highest antioxidant (IC50 (DPPH assay) 20. 64 +/- 0. 84mg/L) and anti-inflammatory (72% inhibition at 150mg/L) activities, respectively.

DPPH

ABTS

AAPH

linoleic acid

DPPH


Input: Excepting Peganum harmala L. extract, the two other extracts showed a high anticancer activity against several cell lines (human bladder carcinoma RT112, human laryngeal carcinoma Hep2 and human myelogenous leukemia K562), for A. herba-laba IC50 = 81. 59 +/- 4. 4, 59. 05 +/- 3. 66 and 90. 96mg/L respectively, but not on normal peripheral blood mononuclear cells.


Input: All these biological activities are well correlated with the phenolic contents of these extracts.


Input: These findings demonstrate the remarkable potential of these plants as valuable source of antioxidants with exhibit original and interesting anti-inflammatory and anticancer capacities.


Input: Areca nut procyanidins ameliorate streptozocin-induced hyperglycemia by regulating gluconeogenesis.

procyanidins

streptozocin


Input: Hepatic gluconeogenesis is a major contributor to blood glucose in diabetes mellitus.

glucose


Input: Our previous study indicated that areca nut extract enriched with catechin-based procyanidins from oligomers to polymers gave rise to anti-inflammatory effects in vitro and in vivo.

catechin

procyanidins


Input: Here we have surveyed the molecular features of areca nut procyanidins (ANPs) using quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS) and the resulting mass spectrum accurately described ANP from monomer to hexadecamer.

procyanidins


Input: Furthermore, the potential of ANP in terms of blood glucose homeostasis was explored using cyclic adenosine monophosphate (cAMP)/dexamethasone stimulated primary mouse hepatocytes and multiple low dose streptozocin (MLD-STZ) treated mice.

glucose

cyclic adenosine monophosphate

cAMP

dexamethasone

streptozocin

STZ


Input: With the primary hepatocytes, ANP dose-dependently inhibited gluconeogenesis and reduced the mRNA expression of two gluconeogenic key enzymes, phosphoenol-pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase).

phosphoenol-pyruvate

glucose


Input: Intragastrically feeding of 10mg/kg ANP for 4weeks reduced the levels of fasting blood glucose, PEPCK and G6Pase in MLD-STZ mice.

glucose

STZ


Input: In additional, the level of 5'-AMP-activated protein kinase (AMPK) expression showed a trend towards being restored in the ANP treated MLD-STZ-mice.

STZ


Input: This study indicated that ANP has the potential to improve hyperglycemia by regulating gluconeogenic related kinases in MLD-STZ-mice.

STZ


Input: Suppression of Src/ERK and GSK-3/beta-catenin signaling by pinosylvin inhibits the growth of human colorectal cancer cells.

pinosylvin


Input: Pinosylvin, a naturally occurring trans-stilbenoid mainly found in Pinus species, has exhibited a potential cancer chemopreventive activity.

Pinosylvin

trans-stilbenoid


Input: However, the growth inhibitory activity against cancer cells and the underlying molecular mechanisms remain to be elucidated.


Input: Therefore, the anti-proliferative activity of pinosylvin was investigated in human colorectal HCT 116 cancer cells.

pinosylvin


Input: Pinosylvin inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21 (WAF1/CIP1) and p53.

Pinosylvin


Input: Pinosylvin was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase 3 beta (GSK-3 beta) signaling pathway.

Pinosylvin

phosphoinositide


Input: Subsequently, pinosylvin suppressed the nuclear translocation of beta-catenin, one of downstream molecules of PI3K/Akt/GSK-3 beta signaling, and these events led to the sequential downregulation of beta-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc.

pinosylvin


Input: These findings demonstrate that the anti-proliferative activity of pinosylvin might be associated with the cell cycle arrest and downregulation of cell proliferation regulating signaling pathways in human colorectal cancer cells.

pinosylvin


Input: Comparative pharmacokinetic profiles of picrosides I and II from kutkin, Picrorhiza kurroa extract and its formulation in rats.

picrosides I and II


Input: Picrosides I and II are the active chemical constituents, present in the roots and rhizomes of Picrorhiza kurroa Royle (family: Scrophulariaceae).

Picrosides I and II


Input: The plant is ethnomedically claimed for the treatment of liver and upper respiratory tract infection, fever, dyspepsia and scorpion sting.


Input: This study attempts to determine the in vivo pharmacokinetic profile of picrosides I and II in rats after oral administration of three different preparations namely, kutkin (a mixture of picrosides I and II), P. kurroa extract and Picrolax (R) capsule (marketed formulation).

picrosides I and II

kutkin

picrosides I and II


Input: A simple, precise, specific and sensitive method was developed for simultaneous quantification of picrosides I and II in rat plasma and was applied for the pharmacokinetic study.

picrosides I and II


Input: Pharmacokinetic parameters were calculated from the observed plasma concentration of picrosides I and II.

picrosides I and II


Input: The results showed a significant difference (p <= 0. 05) in oral bioavailability of picrosides I and II from different preparations.

picrosides I and II


Input: Both the compounds were found to be more bioavailable from P. kurroa extract followed by Picrolax (R) capsule and kutkin.

kutkin


Input: Moreover, we also developed a novel method for isolation of kutkin from roots of P. kurroa with a high yield of 2. 4% w/w.

kutkin


Input: The information gained from this study provides a meaningful basis for clinical application and mechanistic study of such phytochemicals.


Input: Correlation between the antibacterial activity and the composition of extracts derived from various Spanish Cistus species.


Input: Cistaceae is a large family of shrubs commonly distributed in the Mediterranean ecosystem.


Input: The aim of this study was to explore the potential antimicrobial properties against Escherichia coli and/or Staphylococcus aureus of different extracts obtained from four Cistaceae species that are especially abundant in Spanish semi-arid regions.


Input: MIC50 values of the extracts of C. salviifolius exhibited potent bacteriostatic effects against S. aureus compared with the other Cistus species tested.


Input: Spray-drying had less impact on the antimicrobial activities and polyphenolic contents than did evaporation followed by freeze-drying.

polyphenolic


Input: When C. salviifolius extract was concentrated and the polar fraction was removed, its bacteriostatic and bactericidal activities against both strains were significantly enhanced.


Input: Seasonal influences on the composition have also been found.


Input: Up to 48 compounds were found in the aqueous extract of C. salviifolius using RRLC-ESI-TOF-MS.


Input: The analysis of the composition of the extracts revealed that the inhibitory activity against E. coli may be related to the presence of galloylated flavanols and specific flavonols, whereas the inhibitory capacity against S. aureus may be related primarily to polar compounds and to other flavonols.

galloylated flavanols

flavonols

flavonols


Input: Potential synergistic effects among polyphenols may deserve further studies.

polyphenols


Input: These extracts may serve as an alternative source of antimicrobial ingredients focused on medical devices or cosmetics.


Input: I kappa B kinase epsilon (IKK epsilon): a therapeutic target in inflammation and cancer.


Input: The innate immune system forms our first line of defense against invading pathogens and relies for a major part on the activation of two transcription factors, NF-kappa B and IRF3.


Input: Signaling pathways that activate these transcription factors are intertwined at the level of the canonical I kappa B kinases (IKK alpha, IKK beta) and non-canonical IKK-related kinases (IKK epsilon, TBK1).


Input: Recently, significant progress has been made in understanding the function and mechanism of action of IKK epsilon in immune signaling.


Input: In addition, IKK epsilon impacts on cell proliferation and transformation, and is thereby also classified as an oncogene.


Input: Studies with IKK epsilon knockout mice have illustrated a key role for IKK epsilon in inflammatory and metabolic diseases.


Input: In this review we will highlight the mechanisms by which IKK epsilon impacts on signaling pathways involved in disease development and discuss its potential as a novel therapeutic target.


Input: Genotoxic and inflammatory effects of organic extracts from traffic-related particulate matter in human lung epithelial A549 cells: the role of quinones.

quinones


Input: Traffic-related particulate matter (PM) is associated with adverse health effects.


Input: Quinones present in the traffic-related PM are hypothesized to contribute to these harmful effects through reactive oxygen species (ROS) generation.

Quinones

oxygen


Input: However, the impacts of the traffic-related PM and quinones on inflammatory processes and genotoxic damages are less well known.

quinones


Input: In present study we aimed to examine the genotoxic and inflammatory impacts of organic extracts from traffic-related PM (oTRP) in human lung epithelial A549 cells, and reveal the contributions from quinones.

quinones


Input: Significant cytotoxicity and DNA damage were caused by oTRP.


Input: The pro-inflammatory genes, interleukin-6 (Il-6), interleukin-8 (Il-8) and tumor necrosis factor (Tnf), and two aromatic hydrocarbon receptor-regulated genes, Cyp1a1 and 1b1, were significantly up-regulated by oTRP.

aromatic hydrocarbon


Input: A concomitant increase in ROS was observed, suggesting that oTRP may mediate genotoxic and inflammatory effects through oxidative stress pathway.


Input: Second, the effects from two typical airborne quinones, 9, 10-anthraquinone (AQ) and 1, 4-naphthroquinone (NQ) were compared.

quinones

9, 10-anthraquinone

1, 4-naphthroquinone


Input: NQ, but not AQ, induced significant DNA damage in A549 cells.


Input: NQ up-regulated Il-8, Tnf, and Mcp-1 genes, while AQ induced the expression of Rantes gene.


Input: These results suggest that the NQ and AQ may participate in the pro-inflammatory responses through releasing different types of cytokines/chemokines.


Input: Activation of Rac1 GTPase by nanoparticulate structures in human macrophages.


Input: Inflammatory activation of alveolar macrophages by ambient particles can be facilitated via Toll-like receptors (TLR).


Input: The action of TLR agonists and antagonists has been reported to depend on the formation of nanoparticulate structures.


Input: Aim of the present study was to identify the signaling pathways induced by nanoparticulate structures in human macrophages, which might be critical for inflammatory cell activation.


Input: METHODS: Studies were performed in primary human alveolar macrophages or in differentiated THP-1 macrophages.


Input: Silica nanoparticles were prepared by St o ber synthesis and characterized by dynamic light scattering and scanning electron microscopy.

Silica


Input: Mycobacterial DNA was isolated from Mycobacterium bovis BCG, and nanoparticle formation was assessed by atomic force microscopy and dynamic light scattering.


Input: Actin polymerization was measured by phalloidin-TRITC staining, and cell activation was determined by reverse transcription quantitative PCR analysis, L929 cytotoxicity assay (cytokine induction), and pull-down assays (Rho GTPases).

phalloidin

TRITC


Input: RESULTS: In contrast to immune stimulatory sequence ISS 1018, BCG DNA spontaneously formed nanoparticulate structures and induced actin polymerization as did synthetic silica nanoparticles.

silica


Input: Co-incubation with silica nanoparticles amplified the responsiveness of macrophages toward the TLR9 ligand ISS 1018.

silica


Input: The activation of Rac1 was induced by silica nanoparticles as well as BCG DNA and is suggested as the critical signaling event inducing both cytoskeleton changes as well as inflammatory cell activation.

silica


Input: CONCLUSION: Nanoparticles can induce signaling pathways, which amplify an inflammatory response in macrophages.


Input: Administration of the optimized beta-Lapachone-poloxamer-cyclodextrin ternary system induces apoptosis, DNA damage and reduces tumor growth in a human breast adenocarcinoma xenograft mouse model.

beta-Lapachone

poloxamer


Input: beta-Lapachone (beta-Lap) is a 1, 2-orthonaphthoquinone that selectively induces cell death in human cancer cells through NAD (P) H: quinone oxidoreductase-1 (NQO1).

beta-Lapachone

beta-Lap

1, 2-orthonaphthoquinone

NAD (P) H

quinone


Input: NQO1 is overexpressed in a variety of tumors, as compared to normal adjacent tissue.


Input: However, the low solubility and non-specific distribution of beta-Lap limit its suitability for clinical assays.

beta-Lap


Input: We formulated beta-Lap in an optimal random methylated-beta-cyclodextrin/poloxamer 407 mixture (i. e., beta-Lap ternary system) and, using human breast adenocarcinoma MCF-7 cells and immunodeficient mice, performed in vitro and in vivo evaluation of its anti-tumor effects on proliferation, cell cycle, apoptosis, DNA damage, and tumor growth.

beta-Lap

methylated-beta-cyclodextrin

poloxamer 407

beta-Lap


Input: This ternary system is fluid at room temperature, gels over 29 degrees C, and provides a significant amount of drug, thus facilitating intratumoral delivery, in situ gelation, and the formation of a depot for time-release.


Input: Administration of beta-Lap ternary system to MCF-7 cells induces an increase in apoptosis and DNA damage, while producing no changes in cell cycle.

beta-Lap


Input: Moreover, in a mouse xenograft tumor model, intratumoral injection of the system significantly reduces tumor volume, while increasing apoptosis and DNA damage without visible toxicity to liver or kidney.


Input: These anti-tumoral effects and lack of visible toxicity make this system a promising new therapeutic agent for breast cancer treatment.


Input: Hydrophobicity of rare-earth oxide ceramics.

oxide


Input: Hydrophobic materials that are robust to harsh environments are needed in a broad range of applications.


Input: Although durable materials such as metals and ceramics, which are generally hydrophilic, can be rendered hydrophobic by polymeric modifiers, these deteriorate in harsh environments.


Input: Here we show that a class of ceramics comprising the entire lanthanide oxide series, ranging from ceria to lutecia, is intrinsically hydrophobic.

lanthanide oxide


Input: We attribute their hydrophobicity to their unique electronic structure, which inhibits hydrogen bonding with interfacial water molecules.

hydrogen


Input: We also show with surface-energy measurements that polar interactions are minimized at these surfaces and with Fourier transform infrared/grazing-angle attenuated total reflection that interfacial water molecules are oriented in the hydrophobic hydration structure.


Input: Moreover, we demonstrate that these ceramic materials promote dropwise condensation, repel impinging water droplets, and sustain hydrophobicity even after exposure to harsh environments.


Input: Rare-earth oxide ceramics should find widespread applicability as robust hydrophobic surfaces.

oxide


Input: Microcalcifications in breast cancer: Lessons from physiological mineralization.


Input: Mammographic mammary microcalcifications are routinely used for the early detection of breast cancer, however the mechanisms by which they form remain unclear.


Input: Two species of mammary microcalcifications have been identified; calcium oxalate and hydroxyapatite.

calcium oxalate

hydroxyapatite


Input: Calcium oxalate is mostly associated with benign lesions of the breast, whereas hydroxyapatite is associated with both benign and malignant tumors.

Calcium oxalate

hydroxyapatite


Input: The way in which hydroxyapatite forms within mammary tissue remains largely unexplored, however lessons can be learned from the process of physiological mineralization.

hydroxyapatite


Input: Normal physiological mineralization by osteoblasts results in hydroxyapatite deposition in bone.

hydroxyapatite


Input: This review brings together existing knowledge from the field of physiological mineralization and juxtaposes it with our current understanding of the genesis of mammary microcalcifications.


Input: As an increasing number of breast cancers are being detected in their non-palpable stage through mammographic microcalcifications, it is important that future studies investigate the underlying mechanisms of their formation in order to fully understand the significance of this unique early marker of breast cancer.


Input: Self-assembly of double helical nanostructures inside carbon nanotubes.

carbon


Input: We use molecular dynamics (MD) simulations to show that a DNA-like double helix of two poly (acetylene) (PA) chains can form inside single-walled carbon nanotubes (SWNTs).

poly (acetylene)

carbon


Input: The computational results indicate that SWNTs can activate and guide the self-assembly of polymer chains, allowing them to adopt a helical configuration in a SWNT through the combined action of the van der Waals potential well and the pi-pi stacking interaction between the polymer and the inner surface of SWNTs.


Input: Meanwhile both the SWNT size and polymer chain stiffness determine the outcome of the nanostructure.


Input: Furthermore, we also found that water clusters encourage the self-assembly of PA helical structures in the tube.


Input: This molecular model may lead to a better understanding of the formation of a double helix biological molecule inside SWNTs.


Input: Alternatively, it could form the basis of a novel nanoscale material by utilizing the' empty' spaces of SWNTs.


Input: Human skin neural crest progenitor cells are susceptible to BRAF (V600E)-induced transformation.


Input: Adult stem cells are multipotent and persist in small numbers in adult tissues throughout the lifespan of an organism.


Input: Unlike differentiated cells, adult stem cells are intrinsically resistant to senescence.


Input: It is unclear how adult stem cells in solid organs respond to oncogenic stimulation and whether these cells have a role in tumor initiation.


Input: We report here that expression of BRAF (V600E) in human neural crest progenitor cells (hNCPCs) did not induce growth arrest as seen in human melanocytes, but instead, increased their cell proliferation capacity.


Input: These cells (hNCPCs (V600E)) acquired anchorage-independent growth ability and were weakly tumorigenic in vivo.


Input: Unlike in human melanocytes, BRAF (V600E) expression in hNCPCs did not induce p16 (INK4a) expression.


Input: BRAF (V600E) induced elevated expression of CDK2, CDK4, MITF and EST1/2 protein in hNCPCs, and also induced melanocytic differentiation of these cells.


Input: Furthermore, overexpression of MITF in hNCPCs (V600E) dramatically increased their tumorigenicity and resulted in fully transformed tumor cells.


Input: These findings indicate that hNCPCs are susceptible to BRAF (V600E)-induced transformation, and MITF potentiates the oncogenic effect of BRAF (V600E) in these progenitor cells.


Input: These results suggest that the hNCPCs are potential targets for BRAF (V600E)-induced melanocytic tumor formation. Oncogene advance online publication, 21 January 2013; doi: 10. 1038/onc. 2012. 642.


Input: Almorexant effects on CYP3A4 activity studied by its simultaneous and time-separated administration with simvastatin and atorvastatin.

Almorexant

simvastatin

atorvastatin


Input: PURPOSE: To characterise further the previously observed cytochrome P450 3A4 (CYP3A4) interaction of the dual orexin receptor antagonist almorexant.

almorexant


Input: METHODS: Pharmacokinetic interactions were investigated (n = 14 healthy male subjects in two treatment groups) between almorexant at steady-state when administered either concomitantly or 2 h after administration of single doses of simvastatin (40 mg) or atorvastatin (40 mg).

almorexant

simvastatin

atorvastatin


Input: RESULTS: Almorexant dose-dependently increased simvastatin exposure (AUC (0-infinity)) when administered concomitantly [geometric mean ratios (90% CI): 2. 5 (2. 1, 2. 9) (100 mg), 3. 9 (3. 3, 4. 6) (200 mg)], but not C (max) [3. 7 (3. 0, 4. 5) for both doses].

Almorexant

simvastatin


Input: Time-separated administration resulted in relevant reductions of the interaction [AUC (0-infinity): 1. 4 (1. 2, 1. 7) (100 mg), 1. 7 (1. 5, 2. 0) (200 mg); C (max): 1. 5 (1. 3, 1. 9) (100 mg), 1. 9 (1. 6, 2. 4) (200 mg)].


Input: Similar results were obtained for hydroxyacid simvastatin.

hydroxyacid simvastatin


Input: Independent of almorexant dose and relative time of administration, AUC (0-infinity) and C (max) of atorvastatin increased (ratios ranged from 1. 1 to 1. 5).

almorexant

atorvastatin


Input: AUC (0-infinity) and C (max) of o-hydroxy atorvastatin decreased dose-independently [AUC (0-infinity): 0. 8 (0. 8, 0. 9) (100 mg), 0. 6 (0. 5, 0. 6) (200 mg); C (max): 0. 3 (0. 3, 0. 4) (100 mg), 0. 2 (0. 2, 0. 3) (200 mg)] when atorvastatin was concomitantly administered.

o-hydroxy atorvastatin

atorvastatin


Input: C (max) of o-hydroxy atorvastatin slightly decreased (0. 8 for both doses) following time-separated administration; AUC (0-infinity) was unchanged.

o-hydroxy atorvastatin


Input: CONCLUSIONS: Whereas almorexant increased simvastatin exposure dose-and relative time of administration-dependently, atorvastatin exposure increased to a smaller extent and irrespective of dose and time.

almorexant

simvastatin

atorvastatin


Input: This suggests that the observed interaction of almorexant with simvastatin is mainly caused by intestinal CYP3A4 inhibition, whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition.

almorexant

simvastatin

atorvastatin


Input: Designing high-performance electrochemical energy-storage nanoarchitectures to balance rate and capacity.


Input: The impressive specific capacitance and high-rate performance reported for many nanometric charge-storing films on planar substrates cannot impact a technology space beyond microdevices unless such performance translates into a macroscale form factor.


Input: In this report, we explore how the nanoscale-to-macroscale properties of the electrode architecture (pore size/distribution, void volume, thickness) define energy and power performance when scaled to technologically relevant dimensions.


Input: Our test bed is a device-ready electrode architecture in which scalable, manufacturable carbon nanofoam papers with tunable pore sizes (5-200 nm) and thickness (100-300 mu m) are painted with ~ 10 nm coatings of manganese oxide (MnOx).

carbon

manganese oxide

MnOx


Input: The quantity of capacitance and the rate at which it is delivered for four different MnOx-C variants was assessed by fabricating symmetric electrochemical capacitors using a concentrated aqueous electrolyte.

MnOx

C


Input: Carbon nanofoam papers containing primarily 10-20 nm mesopores support high MnOx loadings (60 wt%) and device-level capacitance (30 F g (-1)), but the small mesoporous network hinders electrolyte transport and the low void volume restricts the quantity of charge-compensating ions within the electrode, making the full capacitance only accessible at slow rates (5 mV s (-1)).

Carbon

MnOx


Input: Carbon nanofoam papers with macropores (100-200 nm) facilitate high rate operation (50 mV s (-1)), but deliver significantly lower device capacitance (13 F g (-1)) as a result of lower MnOx loadings (41 wt%).

Carbon

MnOx


Input: Devices comprising MnOx-carbon nanofoams with interconnecting networks of meso-and macropores balance capacitance and rate performance, delivering 33 F g (-1) at 5 mV s (-1) and 23 F g (-1) at 50 mV s (-1).

MnOx

carbon


Input: The use of carbon nanofoam papers with size-tunable pore structures and thickness provides the opportunity to engineer the electrode architecture to deliver scalable quantities of capacitance (F cm (-2)) in tens of seconds with a single device.

carbon


Input: Microfluidic chemostat for measuring single cell dynamics in bacteria.


Input: We designed a microfluidic chemostat consisting of 600 sub-micron trapping/growth channels connected to two feeding channels.


Input: The microchemostat traps E. coli cells and forces them to grow in lines for over 50 generations.


Input: Excess cells, including the mother cells captured at the start of the process, are removed from both ends of the growth channels by the media flow.


Input: With the aid of time-lapse microscopy, we have monitored dynamic properties such as growth rate and GFP expression at the single-cell level for many generations while maintaining a population of bacteria of similar age.


Input: We also use the microchemostat to show how the population responds to dynamic changes in the environment.


Input: Since more than 100 individual bacterial cells are aligned and immobilized in a single field of view, the microchemostat is an ideal platform for high-throughput intracellular measurements.


Input: We demonstrate this capability by tracking with sub-diffraction resolution the movements of fluorescently tagged loci in more than one thousand cells on a single device.


Input: The device yields results comparable to conventional agar microscopy experiments with substantial increases in throughput and ease of analysis.


Input: High-grade prostate cancer and biochemical recurrence after radical prostatectomy among men using 5 alpha-reductase inhibitors and alpha-blockers.


Input: BACKGROUND: Two clinical trials have shown that users of 5 alpha-reductase inhibitors finasteride and dutasteride (5-ARIs) have reduced overall prostate cancer risk, while the proportion of high-grade tumors is increased.

finasteride

dutasteride


Input: We studied tumor characteristics, risk of biochemical recurrence and mortality after radical prostatectomy in 5-ARI and alpha-blocker users.


Input: METHODS: The study cohort consisted of 1, 315 men who underwent radical prostatectomy at the Tampere University Hospital during 1995-2009.


Input: Biochemical relapse was defined as serum PSA >= 0. 2 ng/ml after the operation.


Input: Information on mortality and medication purchases was obtained from national registries.


Input: Cox proportional regression was used to analyze hazard ratios (HRs) and 95% confidence intervals (95% CI) of biochemical relapse and death.


Input: RESULTS: The proportion of high-grade (Gleason 7-10) tumors was significantly elevated among men who had used 5-ARIs for 4 years or longer compared to the non-users (83. 3% vs. 53. 3%, respectively).


Input: Survival curves for biochemical relapse-free survival differed between long-term and short-term 5-ARI users, but the hazard ratio remained statistically non-significant.


Input: Risk of biochemical recurrence was elevated among alpha-blocker users (HR 1. 68, 95% CI 1. 37-2. 06), but in sensitivity analyses this was evident only in men using alpha-blockers after prostatectomy.


Input: Mortality was not associated with medication usage.


Input: CONCLUSIONS: Long-term users of finasteride or dutasteride had more often high-grade prostate cancer.

finasteride

dutasteride


Input: Our results suggest also worse progression-free survival.


Input: The association between risk of biochemical recurrence and post-operative alpha-blocker usage suggests that voiding or storage symptoms after prostatectomy may predict biochemical relapse.


Input: Prostate (c) 2013 Wiley Periodicals, Inc.


Input: Fluocinolone acetonide intravitreal implant (Iluvien (R)): in diabetic macular oedema.

Fluocinolone acetonide

Iluvien


Input: Fluocinolone acetonide intravitreal implant (Iluvien (R)) is an injectable, non-erodible, corticosteroid implant that is approved in several European countries for the treatment of chronic diabetic macular oedema (DMO).

Fluocinolone acetonide

Iluvien

corticosteroid


Input: In analyses of two multinational trials in patients with DMO previously treated with macular laser photocoagulation, fluocinolone acetonide intravitreal implant 0. 2 mu g/day was significantly more efficacious than sham injection in improving visual acuity.

fluocinolone acetonide


Input: At 24 months post injection, 29% of fluocinolone acetonide intravitreal implant 0. 2 mu g/day recipients had an improvement in the best-corrected visual acuity (BCVA) letter score of >= 15 compared with 16% in the sham injection group (p = 0. 002) [primary endpoint].

fluocinolone acetonide


Input: Treatment benefit was most evident in the subgroup of patients whose duration of DMO was >= 3 years.


Input: In this subgroup at 36 months, 34% of fluocinolone acetonide intravitreal implant 0. 2 mu g/day recipients had an increase in the BCVA score of >= 15, compared with 13% of sham injection recipients (p < 0. 001).

fluocinolone acetonide


Input: Fluocinolone acetonide intravitreal implant recipients also had generally greater benefits than sham injection recipients on secondary endpoints.

Fluocinolone acetonide


Input: In patients who were phakic in the study eye at baseline, cataracts occurred in 82% of fluocinolone acetonide intravitreal implant 0. 2 mu g/day recipients and 51% of sham injection recipients.

fluocinolone acetonide


Input: Overall, 37% and 12% of patients in the fluocinolone acetonide intravitreal implant and sham injection groups developed raised intraocular pressure (IOP), which was generally controlled with IOP-lowering drugs.

fluocinolone acetonide


Input: Group I mGluRs evoke K-ATP current by intracellular Ca2 + mobilization in rat subthalamus neurons.

K

ATP

Ca2 +


Input: We reported previously that Ca (2 +) influx through N-methly-d-aspartate-gated channels evokes ATP-sensitive K (+) (K-ATP) currents in rat subthalamic nucleus (STN) neurons.

Ca (2 +)

N-methly-d-aspartate

ATP

K (+)

K

ATP


Input: By using whole-cell patch clamp recordings in brain slices, we investigated the ability of (RS)-3, 5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR) agonist, to evoke K-ATP currents.

(RS)-3, 5-dihydroxyphenylglycine

DHPG

glutamate

K

ATP


Input: DHPG (20 micro M) evoked outward current at-70 mV and was associated with a positive slope conductance of 2. 7 nS.

DHPG


Input: The sulfonylurea agent tolbutamide (100 micro M) converted the positive slope to negative slope conductance, indicating mediation by K-ATP channels (ATP-sensitive K + channels).

sulfonylurea

tolbutamide

K

ATP

ATP

K +


Input: Currents evoked by DHPG were significantly reduced by a combination of mGluR1 and mGluR5 negative allosteric modulators.

DHPG


Input: DHPG-evoked outward current was blocked by cyclopiazonic acid and thapsigargin and mimicked by caffeine, suggesting mediation by release of intracellular Ca (2 +).

DHPG

cyclopiazonic acid

thapsigargin

caffeine

Ca (2 +)


Input: DHPG outward current was also blocked by ryanodine and 2-aminoethoxydiphenylborane, suggesting mediation by ryanodine-and inositol 1, 4, 5-triphosphate-sensitive Ca (2 +) release.

DHPG

ryanodine

ryanodine

inositol 1, 4, 5-triphosphate

Ca (2 +)


Input: The nitric oxide synthase inhibitor N (G)-nitro-l-arginine methyl ester and inhibitors of protein kinase G activity also suppressed DHPG-induced outward current.

nitric oxide

N (G)-nitro-l-arginine methyl ester

DHPG


Input: Voltage recordings showed that tolbutamide prolonged depolarizing plateau potentials and increased the spontaneous firing rate of STN neurons recorded in the presence of DHPG.

tolbutamide

DHPG


Input: These results show that group I mGluR stimulation generates K-ATP current by a nitric oxide-and protein kinase G-dependent process that is mediated by release of Ca (2 +) from intracellular stores.

K

ATP

nitric oxide

Ca (2 +)


Input: Because burst firing is linked to symptoms of Parkinson' s disease, we suggest that K-ATP channels might provide a physiologically important inhibitory influence on STN neuronal activity.

K

ATP


Input: Internalization Pathways of Anisotropic Disc-Shaped Zeolite L Nanocrystals with Different Surface Properties in HeLa Cancer Cells.

Zeolite L


Input: Information about the mechanisms underlying the interactions of nanoparticles with living cells is crucial for their medical application and also provides indications of the putative toxicity of such materials.


Input: Here the uptake and intracellular delivery of disc-shaped zeolite L nanocrystals as porous aminosilicates with well-defined crystal structure, uncoated as well as with COOH-, NH (2)-, polyethyleneglycol (PEG)-and polyallylamine hydrochloride (PAH) surface coatings are reported.

zeolite L

aminosilicates

COOH-

NH (2)-

polyethyleneglycol

PEG

polyallylamine hydrochloride

PAH


Input: HeLa cells are used as a model system to demonstrate the relation between these particles and cancer cells.


Input: Interactions are studied in terms of their fates under diverse in vitro cell culture conditions.


Input: Differently charged coatings demonstrated dissimilar behavior in terms of agglomeration in media, serum protein adsorption, nanoparticle cytotoxicity and cell internalization.


Input: It is also found that functionalized disc-shaped zeolite L particles enter the cancer cells via different, partly not yet characterized, pathways.


Input: These in vitro results provide additional insight about low-aspect ratio anisotropic nanoparticle interactions with cancer cells and demonstrate the possibility to manipulate the interactions of nanoparticles and cells by surface coating for the use of nanoparticles in medical applications.


Input: Nanostructural anisotropy underlies anisotropic electrical bistability.


Input: Regular arrays of nanorods having asymmetric cross-sections are fabricated by a combination of electrodeposition and glancing-angle deposition (GLAD).


Input: When these nanorods are embedded in a polymer matrix, they give rise to composite materials in which the structural anisotropy at the nanoscale translates into functional anisotropy in the form of direction-dependent electrical bistability.


Input: The degree of this directional bistability depends on and can be controlled by the spacing between the nearby nanorods.


Input: Comparative toxicological study of the novel protein phosphatase inhibitor 19-Epi-okadaic acid in primary cultures of rat cerebellar cells.

19-Epi-okadaic acid


Input: Okadaic acid (OKA) and analogues are frequent contaminants of coastal waters and seafood.

Okadaic acid

OKA


Input: Structure analysis of the isolated OKA analogue 19-epi-OKA showed important conformation differences expected to result in lower protein phosphatase (PP) inhibitory potencies than OKA.

OKA

OKA


Input: However, 19-epi-OKA and OKA inhibitory activities versus PP2A were unexpectedly found to be virtually equipotent.

OKA


Input: To investigate the toxicological relevance of these findings, we tested the effects of 19-epi-OKA on cultured cerebellar cells and compared them with those of OKA and its isomer dinophysistoxin-2.

OKA


Input: 19-epi-OKA caused degeneration of neurites and neuronal death with much lower potency than its congeners.


Input: The concentration of 19-epi-OKA that reduced after 24h the maximum neuronal survival (EC5024) by 50% was ~ 300nM compared with ~ 2nM and ~ 8nM for OKA and dinophysistoxin-2, respectively.

OKA


Input: Exposure to 19-epi-OKA resulted also in less toxicity for cultured glial cells (EC5024, 19-epi-OKA ~ 600nM; EC5024, OKA ~ 20nM).

OKA


Input: 19-epi-OKA induced apoptotic condensation and fragmentation of chromatin, activation of caspases, and activation of ERK1/2 MAP kinases, features previously reported for OKA and dinophysistoxin-2.

OKA


Input: Also, differential sensitivity to 19-epi-OKA was observed between neuronal and glial cells, a specific characteristic shared by OKA and dinophysistoxin-2 but not by other toxins.

OKA


Input: Our results are consistent with 19-epi-OKA being included among the group of toxins of OKA and derivatives and support the suitability of cellular bioassays for the detection of these compounds.

OKA


Input: Hypoxia stress test reveals exaggerated cardiovascular effects in hypertensive rats after exposure to the air pollutant acrolein.

acrolein


Input: Exposure to air pollution increases the risk of cardiovascular morbidity and mortality, especially in susceptible populations.


Input: Despite increased risk, adverse responses are often delayed and require additional stress tests to reveal latent effects of exposure.


Input: The goal of this study was to use an episode of " transient hypoxia " as an extrinsic stressor to uncover latent susceptibility to environmental pollutants in a rodent model of hypertension.


Input: We hypothesized that exposure to acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke, diesel exhaust, and power plant emissions, would increase cardiopulmonary sensitivity to hypoxia, particularly in hypertensive rats.

acrolein

aldehyde


Input: Spontaneously hypertensive and Wistar Kyoto (normotensive) rats, implanted with radiotelemeters, were exposed once for 3h to 3 ppm acrolein gas or filtered air in whole-body plethysmograph chambers and challenged with a 10% oxygen atmosphere (10min) 24h later.

acrolein

oxygen


Input: Acrolein exposure increased heart rate, blood pressure, breathing frequency, and minute volume in hypertensive rats and also increased the heart rate variability parameter LF, suggesting a potential role for increased sympathetic tone.

Acrolein


Input: Normotensive rats only had increased blood pressure during acrolein exposure.

acrolein


Input: The hypoxia stress test after acrolein exposure revealed increased diastolic blood pressure only in hypertensive rats and increased minute volume and expiratory time only in normotensive rats.

acrolein


Input: These results suggest that hypertension confers exaggerated sensitivity to air pollution and that the hypoxia stress test is a novel tool to reveal the potential latent effects of air pollution exposure.


Input: Gobichelin A and B: Mixed-Ligand Siderophores Discovered Using Proteomics.

Gobichelin A and B


Input: " Omic " strategies have been increasingly applied to natural product discovery processes, with (meta-) genome sequencing and mining implemented in many laboratories to date.


Input: Using the proteomics-based discovery platform called PrISM (Proteomic Investigation of Secondary Metabolism), we discovered two new siderophores gobichelin A and B from Streptomyces sp.

gobichelin A and B


Input: NRRL F-4415, a strain without a sequenced genome.


Input: Using the proteomics information as a guide, the 37 kb gene cluster responsible for production of gobichelins was sequenced and its 20 open reading frames interpreted into a biosynthetic scheme.

gobichelins


Input: This led to the targeted detection and structure elucidation of the new compounds produced by nonribosomal peptide (NRP) synthesis.


Input: Mechanistic insight into inhibition of two-component system signaling.


Input: Two-component signal transduction systems (TCSs) are commonly used by bacteria to couple environmental stimuli to adaptive responses.


Input: Targeting the highly conserved kinase domain in these systems represents a promising strategy for the design of a broad-spectrum antibiotic; however, development of such compounds has been marred by an incomplete understanding of the conserved binding features within the active site that could be exploited in molecule design.


Input: Consequently, a large percentage of the available TCS inhibitors demonstrate poor target specificity and act via multiple mechanisms, with aggregation of the kinase being the most notable.


Input: In order to elucidate the mode of action of some of these compounds, molecular modeling was employed to dock a suite of molecules into the ATP-binding domain of several histidine kinases.

ATP

histidine


Input: This effort revealed a key structural feature of the domain that is likely interacting with several known inhibitors and is also highly conserved.


Input: Furthermore, generation of several simplified scaffolds derived from a reported inhibitor and characterization of these compounds using activity assays, protein aggregation studies and saturation transfer differential (STD) NMR suggests that targeting of this protein feature may provide a basis for the design of ATP-competitive compounds.

ATP


Input: 5-Hydroxytryptamine type 7 receptor neuroprotection against NMDA-induced excitotoxicity is PDGF beta receptor dependent.

NMDA


Input: The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the hippocampus.

serotonin


Input: Long-term (2-24 h) activation of 5-HT7 receptors regulates growth factor receptor expression, including the expression of platelet-derived growth factor (PDGF) beta receptors.


Input: Direct activation of PDGF beta receptors in primary hippocampal and cortical neurons inhibits NMDA receptor activity and attenuates NMDA receptor-induced neurotoxicity.

NMDA

NMDA


Input: Our objective was to investigate whether the 5-HT7 receptor-induced increase in PDGF beta receptor expression would be similarly neuroprotective.


Input: We demonstrate that 5-HT7 receptor agonist treatment in primary hippocampal neurons also increases the expression of phospholipase C (PLC) gamma, a downstream effector of PDGF beta receptors associated with the inhibition of NMDA receptor activity.

NMDA


Input: To determine if the up-regulation of PDGF beta receptors is neuroprotective, primary hippocampal neurons were incubated with the 5-HT7 receptor agonist, LP 12, for 24 h.

LP 12


Input: Indeed, LP 12 treatment prevented NMDA-induced neurotoxicity and this effect was dependent on PDGF beta receptor kinase activity.

LP 12

NMDA


Input: Treatment of primary neurons with LP 12 also differentially altered NMDA receptor subunit expression, reducing the expression of NR1 and NR2B, but not NR2A.

LP 12

NMDA


Input: These findings demonstrate the potential for providing growth factor receptor-dependent neuroprotective effects using small-molecule ligands of G protein-coupled receptors.


Input: Mixed valency in hydrogen bonded' dimers of dimers'.

hydrogen


Input: Dimolybdenum quadruply bonded compounds containing a pendant lactam functional group form self-complementary hydrogen bonded' dimers of dimers' in the solid-state and CH (2) Cl (2) solutions.

Dimolybdenum

lactam

hydrogen

CH (2) Cl (2)


Input: Electrochemical studies in CH (2) Cl (2) show two consecutive one-electron redox processes corresponding to oxidation of the Mo (2) (4 +) cores.

CH (2) Cl (2)

Mo (2) (4 +)


Input: Spectroelectrochemical studies on the' dimers of dimers' show no evidence of intervalence charge transfer bands in the mixed valence radical cations formed by one-electron oxidation, indicating that they are examples of proton-coupled mixed valency.


Input: Lower physical activity is a risk factor for a clustering of metabolic risk factors in non-obese and obese Japanese subjects: The Takahata study.


Input: In several countries including Japan, people without obesity but with a clustering of metabolic risk factors (MetRFs) were not considered to have the metabolic syndrome (MetS).


Input: Here, we examined whether lifestyle characteristics differed between non-obese and obese subjects with or without a clustering of MetRFs.


Input: From a population-based cross-sectional study of Japanese subjects aged >= 40 years, 1, 601 subjects (age: 61. 9 +/- 10. 3 years; 710/891 men/women) were recruited.


Input: Physical activity status and daily nutritional intake were estimated using questionnaires.


Input: A clustering of MetRFs was defined based on the presence of at least two non-essential risk factors for the diagnosis of the MetS in Japan.


Input: Energy intake was not higher in subjects with a clustering of MetRFs compared with those without.


Input: Among men, energy expenditure at work was significantly lower in non-obese (9. 0 +/- 8. 2 vs. 11. 3 +/- 9. 3 METs (metabolic equivalents), P =. 025) and obese (9. 0 +/- 7. 9 vs. 11. 6 +/- 9. 4 METs, P =. 017) subjects with a clustering of MetRFs than in those without.


Input: Multiple logistic regression analysis showed that energy expenditure at work was significantly associated with a clustering of MetRFs after adjusting for possible confounding factors including total energy intake.


Input: The ORs (per 1 MET (metabolic equivalent)) were 0. 970 (95% CI, 0. 944-0. 997; P =. 032) in non-obese men and 0. 962 (0. 926-0. 999; P =. 043) in obese men.


Input: Similar associations were not observed in women.


Input: In Japanese males, lower physical activity, but not excessive energy intake, is a risk factor for a clustering of MetRFs independent of their obesity status.


Input: Drug shortages in the United States: a critical evaluation of root causes and the need for action.


Input: Every day it is easy to find news articles detailing the impact of drug shortages on patients.


Input: Where this was once only a concern of patients with rare, orphan diseases, it is now the concern of patients receiving even the most common chemotherapeutic regimens, the most efficacious antimicrobial therapy, or even the most rapid-acting analgesics, largely as a result of manufacturing quality problems.


Input: Unfortunately for many of these patients, there are no efficacious alternatives.


Input: Call to action: finding solutions for the drug shortage crisis in the United States.


Input: In their article in this issue of CPT, Woodcock and Wosinska are the first to clearly outline the quality and manufacturing problems causing drug shortages of generic injectables.


Input: These authors have focused on the main issue, namely, that manufacturing problems and the lack of incentives for quality products are the primary reasons for most recent shortages of generic injectable drugs.


Input: Anagliptin, a DPP-4 inhibitor, suppresses proliferation of vascular smooth muscles and monocyte inflammatory reaction and attenuates atherosclerosis in male apo E-deficient mice.

Anagliptin


Input: Dipeptyl peptidase-4 (DPP-4) inhibitors modulate the progression of atherosclerosis.

Dipeptyl


Input: To gain insights into their mechanism of action, 9-wk-old male apolipoprotein E (apoE)-deficient mice were fed a DPP-4 inhibitor, anagliptin-containing diet.

anagliptin


Input: The effects of anagliptin were investigated in, a monocyte cell line, human THP-1 cells, and rat smooth muscle cells (SMCs).

anagliptin


Input: Treatment with anagliptin for 16 wk significantly reduced accumulation of monocytes and macrophages in the vascular wall, SMC content in plaque areas, and oil red O-stained area around the aortic valve without affecting glucose tolerance or body weight.

anagliptin

oil red O

glucose


Input: Serum DPP-4 concentrations were significantly higher in apoE-deficient mice than control mice, and the levels increased with aging, suggesting the involvement of DPP-4 in the progression of atherosclerosis.


Input: Indeed, soluble DPP-4 augmented cultured SMC proliferation, and anagliptin suppressed the proliferation by inhibiting ERK phosphorylation.

anagliptin


Input: In THP-1 cells, anagliptin reduced lipopolysaccharide-induced TNF-alpha production with inhibiting ERK phosphorylation and nuclear translocation of nuclear factor-kappa B.

anagliptin


Input: Quantitative analysis also showed that anagliptin reduced the area of atherosclerotic lesion in apoE-deficient mice.

anagliptin


Input: These results indicated that the anti-atherosclerotic effect of anagliptin is mediated, at least in part, through its direct inhibition of SMC proliferation and inflammatory reaction of monocytes.

anagliptin


Input: Prenatal exposure to bisphenol A impacts midbrain dopamine neurons and hippocampal spine synapses in non-human primates.

bisphenol A

dopamine


Input: Prevalent use of bisphenol-A (BPA) in the manufacture of resins, plastics and paper products has led to frequent exposure of most people to this endocrine disruptor.

bisphenol-A

BPA


Input: Some rodent studies have suggested that BPA can exert detrimental effects on brain development.

BPA


Input: However as rodent models cannot be relied on to predict consequences of human exposure to BPA during development, it is important to investigate the effects of BPA on non-human primate brain development.

BPA

BPA


Input: Previous research suggests that BPA preferentially targets dopamine neurons in ventral mesencephalon and glutamatergic neurons in hippocampus, so the present work examined the susceptibility of these systems to low dose BPA exposure at the fetal and juvenile stages of development in non-human primates.

BPA

dopamine

BPA


Input: Exposure of pregnant rhesus monkeys to relatively low levels of BPA during the final 2 months of gestation, induced abnormalities in fetal ventral mesencephalon and hippocampus.

BPA


Input: Specifically, light microscopy revealed a decrease in tyrosine hydroxylase-expressing (dopamine) neurons in the midbrain of BPA-exposed fetuses and electron microscopy identified a reduction in spine synapses in the CA1 region of hippocampus.

tyrosine

dopamine

BPA


Input: In contrast, administration of BPA to juvenile vervet monkeys (14-18 months of age) was without effect on these indices, or on dopamine and serotonin concentrations in striatum and prefrontal cortex, or on performance of a cognitive task that tests working memory capacity.

BPA

dopamine

serotonin


Input: These data indicate that BPA exerts an age-dependent detrimental impact on primate brain development, at blood levels within the range measured in humans having only environmental contact with BPA.

BPA

BPA


Input: Assessment of emerging biomarkers of liver injury in human subjects.


Input: Hepatotoxicity remains a major challenge in drug development.


Input: Although alanine aminotransferase (ALT) remains the gold standard biomarker of liver injury, alternative biomarker strategies to better predict the potential for severe drug-induced liver injury (DILI) are essential.

alanine


Input: In this study, we evaluated the utility of glutamate dehydrogenase (GLDH), purine nucleoside phosphorylase (PNP), malate dehydrogenase (MDH), and paraxonase 1 (PON1) as indicators of liver injury in cohorts of human subjects, including healthy subjects across age and gender, subjects with a variety of liver impairments, and several cases of acetaminophen poisoning.

glutamate

purine nucleoside

malate

acetaminophen


Input: In the healthy subjects, levels of GLDH and MDH were not affected by age or gender.


Input: Reference ranges for GLDH and MDH in healthy subjects were 1-10 and 79-176U/L, respectively.


Input: In contrast, the levels of PON1 and PNP were not consistent across cohorts of healthy subjects.


Input: Furthermore, GLDH and MDH had a strong correlation with elevated ALT levels and possessed a high predictive power for liver injury, as determined by ROC analysis.


Input: In contrast, PON1 and PNP did not detect liver injury in our study.


Input: Finally, evaluation of patients with acetaminophen-induced liver injury provided evidence that both GLDH and MDH might have utility as biomarkers of DILI in humans.

acetaminophen


Input: This study is the first to evaluate GLDH, MDH, PON1, and PNP in a large number of human subjects and, and it provides an impetus for prospective clinical studies to fully evaluate the diagnostic value of GLDH and MDH for detection of liver injury.


Input: Graphene nanoribbons as an advanced precursor for making carbon fiber.

Graphene

carbon


Input: Graphene oxide nanoribbons (GONRs) and chemically reduced graphene nanoribbons (crGNRs) were dispersed at high concentrations in chlorosulfonic acid to form anisotropic liquid crystal phases.

Graphene oxide

reduced graphene

chlorosulfonic acid


Input: The liquid crystal solutions were spun directly into hundreds of meters of continuous macroscopic fibers.


Input: The relationship of fiber morphology to coagulation bath conditions was studied.


Input: The effects of colloid concentration, annealing temperature, spinning air gap, and pretension during annealing on the fibers' performance were also investigated.


Input: Heat treatment of the as-spun GONR fibers at 1500 degrees C produced thermally reduced graphene nanoribbon (trGNR) fibers with a tensile strength of 378 MPa, Young' s modulus of 36. 2 GPa, and electrical conductivity of 285 S/cm, which is considerably higher than that in other reported graphene-derived fibers.

reduced graphene

graphene


Input: This better trGNR fiber performance was due to the air gap spinning and annealing with pretension that produced higher molecular alignment within the fibers, as determined by X-ray diffraction and scanning electron microscopy.


Input: The specific modulus of trGNR fibers is higher than that of the commercial general purpose carbon fibers and commonly used metals such as Al, Cu, and steel.

carbon

Al

Cu

steel


Input: The properties of trGNR fibers can be further improved by optimizing the spinning conditions with higher draw ratio, annealing conditions with higher pretensions, and using longer flake GONRs.


Input: This technique is a new high-carbon-yield approach to make the next generation carbon fibers based on solution-based liquid crystal phase spinning.

carbon

carbon


Input: Time-dependent changes in hepatic and intestinal induction of cytochrome P450 3A after administration of dexamethasone to rats.

dexamethasone


Input: Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively.

dexamethasone 21-phosphate

DEX-P

midazolam

MDZ


Input: 2. The number of times DEX-P was administered was not a significant factor in the induction of either hepatic or intestinal CYP3A; however, administration of DEX-P multiple times markedly decreased the bioavailability of DEX-P by self-induction of CYP3A.

DEX-P

DEX-P

DEX-P


Input: 3. CYP3A induction in the liver increased depending on the dose of DEX-P, whereas that in intestine showed a mild increase, but the induction level was almost constant regardless of the dose of DEX-P.

DEX-P

DEX-P


Input: 4. Administration of a single dose of DEX-P showed a temporal increase in CYP3A activity in both tissues and the induction ratios reached maximum values at 12 h after DEX-P administration.

DEX-P

DEX-P


Input: On the other hand, a mild increase of CYP3A activity, which lasted for at least 48 h, was observed in both tissues after administration of multiple doses.


Input: 5. Some physiological compounds such as cytokines might be involved in decreasing the CYP3A activity to maintain homeostasis of the body.


Input: Photoinduced formation mechanism of the thymine-thymine (6-4) adduct.

thymine-thymine (6-4)


Input: The photoinduced mechanism leading to the formation of the thymine-thymine (6-4) photolesion has been studied by using the CASPT2//CASSCF approach over a dinucleotide model in vacuo.

thymine-thymine (6-4)

dinucleotide


Input: Following light absorption, localization of the excitation on a single thymine leads to fast singlet-triplet crossing that populates the triplet (3) (n pi *) state of thymine.

thymine

thymine


Input: This state, displaying an elongated C (4) = O bond, triggers (6-4) dimer formation by reaction with the C (5) = C (6) double bond of the adjacent thymine, followed by a second intersystem crossing, which acts as a gate between the excited state of the reactant and the ground state of the photoproduct.

thymine


Input: The requirement of localized excitation on just one thymine, whose main decay channel (by radiationless repopulation of its ground state) is nonphotochemical, can rationalize the experimentally observed low quantum yield of formation for the thymine-thymine (6-4) adduct.

thymine

thymine-thymine (6-4)


Input: Assessment of effects of IR and IPC on activities of cytochrome P450 isozymes in rats by a five-drug cocktail approach.


Input: Abstract Background and objective: To evaluate the effects of ischemia and reperfusion (IR) and ischemic preconditioning (IPC) on the metabolic activities of cytochrome P450 (CYP) isozymes in rats by a five-drug cocktail approach.


Input: Methods: Cocktail approach was used to evaluate the influence of IR and IPC on the activities of CYP1A2, CYP2C9, CYP2E1, CYP2D6 and CYP3A4, which were reflected by the changes of pharmacokinetic parameters of five specific probe drugs: caffeine, chlorzoxazone, tolbutamide, metoprolol and midazolam, respectively.

caffeine

chlorzoxazone

tolbutamide

metoprolol

midazolam


Input: Rats were randomly divided into IR, IPC and sham groups, and then injected the mixture of five probe drugs.


Input: Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by a HPLC method with UV detection.


Input: The pharmacokinetic parameters were calculated by the software of DAS 2. 0.


Input: Results: The parameters including t (1/2 beta), CLs, AUC, MRT and K (10) exhibited a similar tendency for both IR and IPC groups.


Input: Compared with sham group, CLs and K (10) of five probe drugs were significantly lower (p < 0. 05), AUC and t (1/2 beta) of five or some probe drugs were significantly increased in IR and IPC groups (p < 0. 05).


Input: Compared with IPC group, CLs of five probe drugs were decreased and AUC were significantly increased in the IR group (p < 0. 05).


Input: Conclusion: IR can variably decrease the activities of CYP isozymes in rats and this decrease can be attenuated by IPC.


Input: In vitro toxicity of camalexin derivatives in human cancer and non-cancer cells.

camalexin


Input: The aim of the study was to investigate the cytotoxic activity of camalexin and its five synthetic derivatives in cancer and non-cancer cells.

camalexin


Input: In cancer cells the benzocamalexin (BC) displayed the most potent activity with an IC value of 23. 3-30. 1 mu mol/L.

benzocamalexin


Input: On the other hand, minimal toxicity (IC > 100. 0 mu mol/L) in non-cancer cells was observed.


Input: Based on these results, BC was selected for further studies.


Input: Flow cytometric analysis revealed a BC-induced arrest of the cell cycle in the G2 phase associated with downregulation of alpha-tubulin, alpha 1-tubulin, beta 5-tubulin expression.


Input: These findings suggest that the inhibitory effect of BC is mediated via inhibition of microtubule formation.


Input: Moreover, BC downregulated the expression of microtubule-related protein indicating the effect of this compound on microtubule assembly.


Input: After treatment with BC increase of the sub-G DNA content fraction was noted which is considered to be a marker of apoptotic cell death.


Input: Apoptosis was also confirmed by DNA fragmentation assay.


Input: Moreover, quantitative real-time PCR showed that BC downregulated the expression of antiapoptotic genes Bcl-2 and Bcl-xL and upregulated the expression of proapoptotic Bax.


Input: Taken together, our study suggests that the blockade of cell cycle progression and initiation of apoptosis may play an important role in the antiproliferative activity of BC in human cancer cells.


Input: Antivenom therapy of carpet viper (Echis ocellatus) envenoming: Effectiveness and strategies for delivery in West Africa.


Input: In West Africa, response to specific, geographically appropriate, antivenom is often dramatic following carpet viper (Echis ocellatus) envenoming with rapid restoration of blood coagulability and resolution of spontaneous haemorrhage.


Input: Envenoming from Australasian snakes causing similar coagulopathies may respond less dramatically and the effectiveness of antivenom is being questioned.


Input: Here we have reviewed and re-analysed all published preclinical and clinical studies on envenoming and antivenom therapy conducted in West Africa to determine the effectiveness of antivenom.


Input: 22 studies provided relevant information: 12 observational studies, 4 RCTs and 6 preclinical studies.


Input: Four comparative studies confirmed statistically significant protection against mortality ranging from 57 to 87% using specific antivenoms compared to non-specific or no antivenoms.


Input: Meta-analysis estimated combined Odds Ratio (95% CI) of 0. 25 (0. 14-0. 45) of dying among those treated with specific antivenom or 75% (95% CI: 55-86%) protection against death.


Input: Mortality more than doubled during times when stocks of reliable antivenoms ran out, with Relative Risk (95% CI)] of 2. 33 (1. 26-4. 06).


Input: Serum kinetics of venom antigen/antivenom levels also confirmed that decline of venom antigen levels coincided with resolution of coagulopathy while decline of antivenom levels was associated with venom antigen reappearance and recurrence of coagulopathy.


Input: Preclinical and antivenomics analysis confirmed efficacy of regionally appropriate antivenoms against E. ocellatus and related species' venoms in Sub-Saharan Africa but not against Asian Echis carinatus venom.


Input: Antivenoms raised against E. carinatus were ineffective in human studies.


Input: In West Africa, specific antivenom is effective in managing carpet viper envenoming.


Input: A centralized hub-and-spoke strategy is suggested for broadening antivenom access to endemic rural areas together with instituting quality assurance, standardization and manpower training.


Input: Benefits, risks, cost-effectiveness and feasibility of the approach should be formally assessed.


Input: Medical aspects of bio-terrorism.


Input: INTRODUCTION: Bioterrorism is a terrorist action involving the intentional release or dissemination of a biological warfare agent (BWA), which includes some bacteria, viruses, rickettsiae, fungi or biological toxins.


Input: BWA is a naturally occurring or human-modified form that may kill or incapacitate humans, animals or plants as an act of war or terrorism.


Input: BWA is a weapon of choice for mass destruction and terrorism, because of the incubation period, less effective amount than chemical warfare agents, easily distribution, odorless, colorless, difficult to detect, no need of specialized equipment for production and naturally distribution which can easily be obtained.


Input: BWA may be disseminating as an aerosol, spray, explosive device, and by food or water.


Input: CLASSIFICATION: Based on the risk for human health, BWAs have been prioritized into three categories of A, B and C.


Input: Category A includes microorganisms or toxins that easily spread, leading to intoxication with high death rates such as Anthrax, Botulism, Plague, Smallpox, Tularemia and Viral hemorrhagic fevers.


Input: Category B has lower toxicity with wider range, including Staphylococcal Entrotoxin type B (SEB), Epsilon toxin of Clostridium perfringens, Ricin, Saxotoxins, Abrin and Trichothecene mycotoxins.

Saxotoxins

Trichothecene


Input: The C category includes emerging pathogens that could also be engineered for mass spread such as Hanta viruses, multidrug-resistant tuberculosis, Nipah virus, the tick-borne encephalitis viruses, hemorrhagic fever viruses and yellow fever.


Input: CLINICAL MANIFESTATIONS OF BIOTOXINS IN HUMAN: Clinical features and severity of intoxication depend on the agent and exposed dose, route of entry, individual variation and environmental factors.


Input: Onset of symptoms varies from 2-24 h in Ricin to 24-96 h in Botulism.


Input: Clinical manifestations also vary from irritation of the eyes, skin and mucus membranes in T (2) toxin to an acute flaccid paralysis of bilateral cranial nerve impairment of descending manner in botulism.

T (2) toxin


Input: Most of the pyrogenic toxins such as SEB produce the same signs and symptoms as toxic shock syndrome including a rapid drop in blood pressure, elevated temperature, and multiple organ failure.


Input: MANAGEMENT: There is no specific antidote or effective treatment for most of the biotoxins.


Input: The clinical management is thus more supportive and symptomatic.


Input: Fortunately vaccines are now available for most of BWA.


Input: Therefore, immunization of personnel at risk of exposure is recommended.


Input: CONCLUSION: Biotoxins are very wide and bioterrorism is a heath and security threat that may induce national and international problems.


Input: Therefore, the security authorities, health professional and even public should be aware of bioterrorism.


Input: Sonochemical effects on free phenolic acids under ultrasound treatment in a model system.

phenolic acids


Input: Sonochemical effects on seven free phenolic acids under ultrasound treatment in a model system have been investigated.

phenolic acids


Input: The degradation products have also been tentatively identified by FTIR and HPLC-UV-ESIMS.


Input: Five phenolic acids (protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, p-coumaric acid, and ferulic acid) proved to be stable, while two others (caffeic acid and sinapic acid) were degraded under ultrasound treatment.

phenolic acids

protocatechuic acid

p-hydroxybenzoic acid

vanillic acid

p-coumaric acid

ferulic acid

caffeic acid

sinapic acid


Input: The nature of the solvent and the temperature has been identified as important factors in determining the degradation reaction.


Input: Liquid height, ultrasonic intensity, and duty cycle of the ultrasound exposure affected only the degradation rate and did not change the nature of the degradation.


Input: The degradation rates of caffeic acid and sinapic acid decreased with increasing temperature.

caffeic acid

sinapic acid


Input: The degradation kinetics of these two acids under ultrasound conformed to zeroth-order reactions at-5 to 25 degrees C.


Input: Both decomposition and polymerization reactions occurred when caffeic acid and sinapic acid were subjected to ultrasound.

caffeic acid

sinapic acid


Input: Degradation products, such as the corresponding decarboxylation products and their dimers, have been tentatively identified.


Input: Characterization of a key aminoglycoside phosphotransferase in gentamicin biosynthesis.

aminoglycoside

gentamicin


Input: Gentamicin is an aminoglycoside antibiotic obtained from cultures of Micromonospora as the important anti-infective agents.

Gentamicin

aminoglycoside


Input: Gentamicin which lacks 3'-hydroxyl group can avoid the attack from the modification enzymes of antibiotic-resistant bacteria in clinic.

Gentamicin


Input: Consequently, C-3' dehydroxylation is the key step in gentamicins biosynthesis.

gentamicins


Input: We suppose that there are some enzymes responsible for converting intermediate JI-20A to 3', 4'-bisdehydroxylated final product gentamicin C (1a), while phosphorylation of 3'-OH is possibly the first step for C-3' dehydroxylation.

gentamicin C


Input: The gentamicin biosynthetic gene gntI, encoding an aminoglycoside phosphotransferase, was cloned from Micromonospora echinospora ATCC15835 and overexpressed in Escherichia coli.

gentamicin

aminoglycoside


Input: The resulting phosphotransferase was purified, and the kinetic parameters for Kanamycin A, Kanamycin B, Neomycin B and Amikacin were determined.

Kanamycin A

Kanamycin B

Neomycin B

Amikacin


Input: Elucidation of NMR data of phosphorylated kanamycin B has unambiguously demonstrated a regiospecific phosphorylation of 3'-hydroxyl of the 6-aminohexose ring.

phosphorylated kanamycin B


Input: The results described here partly confirm that the 3'-dehydroxylation step is preceded by a 3' phosphorylation step.


Input: It is predicted that GntI belongs to a new aminoglycoside phosphotransferase group involved with aminoglycoside antibiotics biosynthesis pathway.

aminoglycoside

aminoglycoside


Input: Relationship of cellular topoisomerase II alpha inhibition to cytotoxicity and published genotoxicity of fluoroquinolone antibiotics in V79 cells.

fluoroquinolone


Input: Fluoroquinolone (FQ) antibiotics are bacteriocidal through inhibition of the bacterial gyrase and at sufficient concentrations in vitro, they can inhibit the homologous eukaryotic topoisomerase (TOPO) II enzyme.

Fluoroquinolone


Input: FQ exert a variety of genotoxic effects in mammalian systems through mechanisms not yet established, but which are postulated to involve inhibition of TOPO II enzymes.


Input: To assess the relationship of inhibition of cell nuclear TOPO II to cytotoxicity and reported genotoxicity, two FQ, clinafloxacin (CLFX) and lomefloxacin (LOFX), having available genotoxicity data showing substantial differences with CLFX being more potent than LOFX, were selected for study.

clinafloxacin

CLFX

lomefloxacin

LOFX

CLFX

LOFX


Input: The relative inhibitory activities of these FQ on nuclear TOPO II alpha in cultured Chinese hamster lung fibroblasts (V79 cells) over dose ranges and at equimolar concentrations were assessed by measuring nuclear stabilized cleavage complexes of TOPO II alpha-DNA.


Input: Cytotoxicity was measured by relative cell counts.


Input: Both FQ inhibited V79 cell nuclear TOPO II alpha.


Input: The lowest-observed-adverse-effect levels for TOPO II alpha inhibition were 55 mu M for CLFX, and 516 mu M for LOFX.

CLFX

LOFX


Input: The no-observed-adverse-effect-levels were 41 mu M for CLFX, and 258 mu M for LOFX.

CLFX

LOFX


Input: At equimolar concentrations (175 mu M), CLFX was more potent than LOFX.

CLFX

LOFX


Input: Likewise, CLFX was more cytotoxic than LOFX.

CLFX

LOFX


Input: Thus, the two FQ, inhibited TOPO II alpha in intact V79 cells, differed in their potencies and exhibited no-observed-adverse-effect levels.


Input: These findings are in concordance with published genotoxicity data and observed cytotoxicity.


Input: IGF-I signaling is essential for FSH stimulation of AKT and steroidogenic genes in granulosa cells.


Input: FSH and IGF-I synergistically stimulate gonadal steroid production; conversely, silencing the FSH or the IGF-I genes leads to infertility and hypogonadism.

steroid


Input: To determine the molecular link between these hormones, we examined the signaling cross talk downstream of their receptors.


Input: In human and rodent granulosa cells (GCs), IGF-I potentiated the stimulatory effects of FSH and cAMP on the expression of steroidogenic genes.

cAMP


Input: In contrast, inhibition of IGF-I receptor (IGF-IR) activity or expression using pharmacological, genetic, or biochemical approaches prevented the FSH-and cAMP-induced expression of steroidogenic genes and estradiol production.

cAMP

estradiol


Input: In vivo experiments demonstrated that IGF-IR inactivation reduces the stimulation of steroidogenic genes and follicle growth by gonadotropins.


Input: FSH or IGF-I alone stimulated protein kinase B (PKB), which is also known as AKT and in combination synergistically increased AKT phosphorylation.


Input: Remarkably, blocking IGF-IR expression or activity decreased AKT basal activity and abolished AKT activation by FSH.


Input: In GCs lacking IGF-IR activity, FSH stimulation of Cyp19 expression was rescued by overexpression of constitutively active AKT.


Input: Our findings demonstrate, for the first time, that in human, mouse, and rat GCs, the well-known stimulatory effect of FSH on Cyp19 and AKT depends on IGF-I and on the expression and activation of the IGF-IR.


Input: Palladium nanoparticles supported on nitrogen-doped HOPG: a surface science and electrochemical study.

Palladium

nitrogen


Input: We have investigated by photoemission spectroscopy and scanning tunnelling microscopy what are the chemical and structural changes induced by nitrogen ion implantation (500 eV) on highly oriented pyrolytic graphite and how the defects induced by this process modify the growth and thermal stability of palladium nanoparticles, deposited in situ by physical vapour deposition.

nitrogen

graphite

palladium


Input: Since nitrogen derived defects are mostly buried below the surface, they are not accessible for a chemical interaction with metal nanoparticles; however, the amorphization induced by the ion beam in the outermost layers of the substrate beneficially affects the metal morphology, limiting the size of the nanoparticles and improving their thermal stability.

nitrogen


Input: The supported nanoparticles have been tested towards the oxygen reduction reaction indicating that the electrochemical activity does not depend significantly on the ion implantation, but mostly on the amount of palladium.

oxygen

palladium


Input: Metabolic profiles of brain metastases.


Input: Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis.


Input: A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases.


Input: The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) to correlate the metabolic profiles to clinical and pathological information.


Input: Biopsy samples of human brain metastases (n = 49) were investigated.


Input: A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0. 01), irrespective of their primary origin.


Input: The principal component analysis (PCA) showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes.


Input: Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases.

glycerophosphocholine


Input: A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0. 01), indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets.

Nile Red


Input: MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.


Input: Low oxygen tension maintains multipotency, whereas normoxia increases differentiation of mouse bone marrow stromal cells.

oxygen


Input: Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine.


Input: O (2) regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O (2) concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds.

O (2)

O (2)


Input: In our present work, we isolated mouse bone marrow stromal cells (BMSC) and showed that they contained a population meeting requirements for MSC definition.


Input: In order to establish the effect of low O (2) on cellular properties, we examined BSMC cultured under hypoxic (3% O (2)) conditions.

O (2)

O (2)


Input: Our results demonstrate that 3% O (2) augmented proliferation of BMSC, as well as the formation of colonies in the colony-forming unit assay (CFU-A), the percentage of quiescent cells, and the expression of stemness markers Rex-1 and Oct-4, thereby suggesting an increase in the stemness of culture when exposed to hypoxia.

O (2)


Input: In contrast, intrinsic differentiation processes were inhibited by 3% O (2).

O (2)


Input: Overall yield of differentiation was dependent on the adjustment of O (2) tension to the specific stage of BMSC culture.

O (2)


Input: Thus, we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3% O (2), followed by differentiation stage at 21% O (2).

O (2)

O (2)


Input: We also demonstrated that 3% O (2) affected BMSC differentiation in p53 and reactive oxygen species (ROS) independent pathways.

O (2)

oxygen


Input: Our findings can significantly contribute to the obtaining of high-quality MSC for effective cell therapy.


Input: The first dehydration and the competing reaction pathways of glucose homogeneously and heterogeneously catalyzed by acids.

glucose


Input: The dehydration mechanisms for glucose in beta-pyranose (BP) and in open-chain (OC) forms, catalyzed by acids homogeneously and heterogeneously, were investigated using density functional and two-layer ONIOM calculations.

glucose

beta-pyranose


Input: The first dehydration reaction and competing reaction pathways are the main focus of the present study.


Input: The energetics of five dehydration and two isomerization pathways were examined for the protonated form of BP in acidic aqueous solutions and the most favorable pathway of these was found to be the dehydration at the anomeric site.


Input: No dehydration pathway of OC glucose is favored over its isomerization to BP or to fructose.

glucose

fructose


Input: The relative ease of dehydration over isomerization depends on the selection of the reaction media for the protonated form of BP.


Input: These two reaction pathways catalyzed by a surface Br o nsted acid site were then examined and the isomerization pathway was found to be more favorable than dehydration at the anomeric site on a surface acid site.


Input: These mechanistic insights provide an important guide for the catalyst design/selection of the reaction media for glucose dehydration.

glucose


Input: Early-Adulthood Cardiovascular Disease Risk Factor Profiles Among Individuals With and Without Diabetes in the Framingham Heart Study.


Input: OBJECTIVEMany studies of diabetes have examined risk factors at the time of diabetes diagnosis instead of considering the lifetime burden of adverse risk factor levels.


Input: We examined the 30-year cardiovascular disease (CVD) risk factor burden that participants have up to the time of diabetes diagnosis. RESEARCH DESIGN AND METHODSAmong participants free of CVD, incident diabetes cases (fasting plasma glucose >= 126 mg/dL or treatment) occurring at examinations 2 through 8 (1979-2008) of the Framingham Heart Study Offspring cohort were age-and sex-matched 1: 2 to controls.

glucose


Input: CVD risk factors (hypertension, high LDL cholesterol, low HDL cholesterol, high triglycerides, obesity) were measured at the time of diabetes diagnosis and at time points 10, 20, and 30 years prior.

cholesterol

cholesterol

triglycerides


Input: Conditional logistic regression was used to compare risk factor levels at each time point between diabetes cases and controls. RESULTSWe identified 525 participants with new-onset diabetes who were matched to 1, 049 controls (mean age, 60 years; 40% women).


Input: Compared with those without diabetes, individuals who eventually developed diabetes had higher levels of hypertension (odds ratio [OR], 2. 2; P = 0. 003), high LDL (OR, 1. 5; P = 0. 04), low HDL (OR, 2. 1; P = 0. 0001), high triglycerides (OR, 1. 7; P = 0. 04), and obesity (OR, 3. 3; P < 0. 0001) at time points 30 years before diabetes diagnosis.

triglycerides


Input: After further adjustment for BMI, the ORs for hypertension (OR, 1. 9; P = 0. 02) and low HDL (OR, 1. 7; P = 0. 01) remained statistically significant. CONCLUSIONSCVD risk factors are increased up to 30 years before diagnosis of diabetes.


Input: These findings highlight the importance of a life course approach to CVD risk factor identification among individuals at risk for diabetes.


Input: Television Viewing and Low Leisure-Time Physical Activity in Adolescence Independently Predict the Metabolic Syndrome in Mid-Adulthood.


Input: OBJECTIVEWe investigated whether television (TV) viewing and low leisure-time physical activity in adolescence predict the metabolic syndrome in mid-adulthood. RESEARCH DESIGN AND METHODSTV viewing habits and participation in leisure-time physical activity at age 16 years were assessed by self-administered questionnaires in a population-based cohort in Northern Sweden.


Input: The presence of the metabolic syndrome at age 43 years was ascertained in 888 participants (82% of the baseline sample) using the International Diabetes Federation criteria.


Input: Odds ratios (ORs) and CIs were calculated using logistic regression. RESULTSThe overall prevalence of the metabolic syndrome at age 43 years was 26. 9%.


Input: Adjusted OR for the metabolic syndrome at age 43 years was 2. 14 (95% CI 1. 24-3. 71) for those who reported " watching several shows a day " versus " one show/week " or less and 2. 31 (1. 13-4. 69) for leisure-time physical activity " several times/month " or less compared with " daily " leisure-time physical activity at age 16 years.


Input: TV viewing at age 16 years was associated with central obesity, low HDL cholesterol, and hypertension at age 43 years, whereas low leisure-time physical activity at age 16 years was associated with central obesity and triglycerides at age 43 years. CONCLUSIONSBoth TV viewing and low leisure-time physical activity in adolescence independently predicted the metabolic syndrome and several of the metabolic syndrome components in mid-adulthood.

cholesterol

triglycerides


Input: These findings suggest that reduced TV viewing in adolescence, in addition to regular physical activity, may contribute to cardiometabolic health later in life.


Input: 25-Hydroxyvitamin D in Obese Youth Across the Spectrum of Glucose Tolerance From Normal to Prediabetes to Type 2 Diabetes.

25-Hydroxyvitamin D

Glucose


Input: OBJECTIVETo 1) determine if plasma 25-hydroxyvitamin D (25 [OH] D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes, and 2) assess the relationships between 25 (OH) D and in vivo insulin sensitivity and beta-cell function in this cohort. RESEARCH DESIGN AND METHODSPlasma 25 (OH) D concentrations were examined in banked specimens in 9-to 20-year-old obese youth (n = 175; male 42. 3%, black 46. 3%) (NGT, n = 105; impaired glucose tolerance [IGT], n = 43; type 2 diabetes, n = 27) who had in vivo insulin sensitivity and secretion measured by hyperinsulinemic-euglycemic and hyperglycemic clamp techniques and had an assessment of total body composition and abdominal adiposity. RESULTSThe mean age and BMI of the subjects were 14. 3 +/- 2. 1 years and 35. 7 +/- 5. 6 kg/m (2), respectively.

25-hydroxyvitamin D

25 [OH] D

glucose

25 (OH) D

25 (OH) D

glucose


Input: BMI, plasma 25 (OH) D, and the proportion of vitamin D-deficient and-insufficient children did not differ across the three groups.

25 (OH) D

vitamin D


Input: Furthermore, there was no association between 25 (OH) D and in vivo insulin sensitivity or beta-cell function relative to insulin sensitivity (disposition index) in all groups combined or in each group separately. CONCLUSIONSOur data in obese youth show 1) no differences in plasma 25 (OH) D concentrations across the glucose tolerance groups, and 2) no relationship between 25 (OH) D and in vivo insulin sensitivity and beta-cell function relative to insulin sensitivity in any of the groups.

25 (OH) D

25 (OH) D

glucose

25 (OH) D


Input: It remains uncertain if enhancement of the vitamin D status could improve pathophysiological mechanisms of prediabetes and type 2 diabetes in obese youth.

vitamin D


Input: Serum 25-hydroxyvitamin D, parathyroid hormone, and their association with metabolic syndrome in Chinese.

25-hydroxyvitamin D


Input: Increasing evidence suggests that 25-hydroxyvitamin D [25 (OH) D] and parathyroid hormone (PTH) levels are associated with metabolic syndrome (MetS).

25-hydroxyvitamin D

25 (OH) D


Input: In 2010, we explored the association of serum 25 (OH) D and PTH levels with MetS in 1, 390 Chinese participants, aged 20-83 years.

25 (OH) D


Input: Anthropometric phenotypes, blood pressure, and the incidence of MetS were evaluated.


Input: In addition, serum lipids, 25 (OH) D, and PTH were measured.

25 (OH) D


Input: The median concentration of 25 (OH) D and PTH were 55. 3 nmol/l and 2. 8 pmol/l, respectively.

25 (OH) D


Input: The prevalence of vitamin D deficiency (< 50 nmol/l) was 39. 9%, with 34. 5% in men and 47. 8% in women.

vitamin D


Input: After accounting for confounding factors and serum PTH, a 10 nmol/l higher serum 25 (OH) D level was associated with a 10% lower risk of MetS (OR = 0. 90, 95% CI 0. 84-0. 96, P = 0. 0007).

25 (OH) D


Input: Furthermore, participants with vitamin D sufficiency had a 35% lower risk of MetS than those with vitamin D deficiency (OR = 0. 65, 95% CI 0. 51-0. 84, P = 0. 0009).

vitamin D

vitamin D


Input: PTH was not associated with the risk of MetS after adjustment for confounding factors.


Input: These results were confirmed in both men and women.


Input: Thus in this cohort of Chinese individuals, vitamin D deficiency is common and optimal vitamin D level is inversely associated with MetS, independent of several confounders and PTH level.

vitamin D

vitamin D


Input: The clinical significance of these findings warrants further study.


Input: Novel type II fatty acid biosynthesis (FAS II) inhibitors as multistage antimalarial agents.

fatty acid


Input: Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world.


Input: The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics.


Input: In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood.


Input: At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito.


Input: These insects act as a vector, subsequently spreading the disease to other humans.


Input: In order to cure not only malaria but prevent transmission as well, a drug must target both the blood-and pre-erythrocytic liver stages of the parasite.


Input: P. falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial type II fatty acid biosynthesis (FAS II).

enoyl acyl

fatty acid


Input: It has been shown to be essential for liver-stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis.


Input: Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors.


Input: Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite.


Input: These two most promising derivatives were found to inhibit blood-stage parasite growth with IC (50) values of 1. 7 and 3. 0 mu M and lead to a more prominent developmental attenuation of liver-stage parasites than the gold-standard drug, primaquine.

primaquine


Input: A Robust Route to Enzymatically Functional, Hierarchically Self-Assembled Peptide Frameworks.


Input: The addition of enzyme biofunctionality to self-assembling peptide nanofibers is challenging since such additions can inhibit functionality or self-assembly.


Input: We introduce a method for peptide nanofiber enzyme functionalization, demonstrated by the attachment of a polymerization synthase to peptide nanofibers.