Input: The GIPAW method was used to compute the NMR shielding parameters for the different models, which included the alpha-PLLA structure obtained by 2-dimensional wide-angle X-ray diffraction (WAXD) at-150 degrees C (model M1) and at 25 degrees C (model M2), neutron diffraction (WAND) measurements (model M3) and the fully optimized geometry of the PLLA chains in the unit cell with defined size (model M4).

alpha-PLLA


Input: The influence of changes in the chain conformation on the (13) C sigma (ii) NMR shielding parameters is shown.

(13) C


Input: The correlation between the sigma (ii) and delta (ii) values for the M1-M4 models revealed that the M4 model provided the best fit.


Input: Moreover, a comparison of the experimental (13) C NMR spectra with the spectra calculated using the M1-M4 models strongly supports the data for the M4 model.

(13) C


Input: The GIPAW method, via verification using NMR measurements, was shown to be capable of the fine refinement of the crystal structures of polymers when coarse X-ray diffraction data for powdered samples are available.


Input: Photoelectron imaging of small aluminum clusters: quantifying s-p hybridization.

aluminum


Input: Photoelectron imaging experiments and detailed calculations are conducted on Al (n) (-) clusters (n = 3-6) and a calibration method is developed for connecting experimental observations of photoelectron angular distributions to theoretical predictions.

Al (n) (-)


Input: It is shown that this method can be used to quantify the degree to which the molecular orbitals are built from s-or p-like atomic orbitals.


Input: The highest occupied molecular orbitals of these small aluminum clusters are found to contain varying degrees of s-p mixing, with Al (3) (-) containing the " most hybridized " orbital and Al (4) (-) containing the " least hybridized " orbital.

aluminum

Al (3) (-)

Al (4) (-)


Input: It is shown experimentally that s-p hybridization is already present for the trimer species and, similar to other properties of small metal clusters, oscillates with cluster size.


Input: A " clickable " MTX reagent as a practical tool for profiling small-molecule-intracellular target interactions via MASPIT.

MTX


Input: We present a scalable synthesis of a versatile MTX reagent with an azide ligation handle that allows rapid gamma-selective conjugation to yield MTX fusion compounds (MFCs) appropriate for MASPIT, a three-hybrid system that enables the identification of mammalian cytosolic proteins that interact with a small molecule of interest.

MTX

azide

MTX


Input: We selected three structurally diverse pharmacologically active compounds (tamoxifen, reversine, and FK506) as model baits.

tamoxifen

reversine


Input: After acetylene functionalization of these baits, MFCs were synthesized via a CuAAC reaction, demonstrating the general applicability of the MTX reagent.

acetylene

MTX


Input: In analytical mode, MASPIT was able to give concentration-dependent reporter signals for the established target proteins.


Input: Furthermore, we demonstrate that the sensitivity obtained with the new MTX reagent was significantly stronger than that of a previously used non-regiomeric conjugate mixture.

MTX


Input: Finally, the FK506 MFC was explored in a cellular array screen for targets of FK506.


Input: Out of a pilot collection of nearly 2000 full-length human ORF preys, FKBP12, the established target of FK506, emerged as the prey protein that gave the highest increase in luciferase activity.


Input: This indicates that our newly developed synthetic strategy for the straightforward generation of MFCs is a promising asset to uncover new intracellular targets using MASPIT cellular array screening.


Input: The role of silver and vanadium release in the toxicity of silver vanadate nanowires toward Daphnia similis.

silver

vanadium

silver vanadate


Input: Nanomaterials are used in a wide spectrum of applications, including nanowires that are objects with at least one of its dimensions in the range of 1 to 100 nm.


Input: Recently, a new type of silver vanadate nanowire decorated with silver nanoparticles (SVSN-LQES1) with promising antimicrobial activity against different pathogenic bacteria was described.

silver vanadate

silver


Input: The objective of the present study was to evaluate the role of silver and vanadium release in the acute toxicity of this material using Daphnia similis.

silver

vanadium


Input: To verify the effect of the presence of the nanowires in the test solution, tests were performed before and after filtration.


Input: Total silver release to the testing media was determined using the method of inductively coupled plasma atomic emission spectroscopy (ICP-AES).

silver


Input: Silver vanadate nanowires decorated with silver nanoparticles (SVSN-LQES1) are acutely toxic to D. similis.

Silver vanadate

silver


Input: The release of silver from the nanomaterial trapped in the gut along with the silver released to the test media seems to be responsible for the observed toxicity.

silver

silver


Input: Although toxic to Daphnia, vanadium does not contribute to the toxicity of SVSN-LQES1.

vanadium


Input: The observed increase in lipid droplets appears to be related to the exposure of the organisms to the nanomaterials, but the significance of this response needs further investigation.


Input: Central ghrelin signaling mediates the metabolic response of C57BL/6 male mice to chronic social defeat stress.


Input: Chronic stressors promote metabolic disturbances, including obesity and metabolic syndrome.


Input: Ghrelin, a peptide that promotes appetite and the accumulation of adipose tissue, is also secreted in response to stressors to protect the brain and peripheral tissues from the effects of these stressors.


Input: Here we demonstrate that elevated ghrelin levels produced by chronic exposure to social stress are associated with increased caloric intake and body weight gain in male C57BL mice.


Input: In contrast, stressed mice lacking ghrelin receptors (GHSR KO mice) or C57BL mice receiving chronic intracerebroventricular delivery of the ghrelin receptor antagonist [d-Lys (3)]-GHRP-6 show attenuated weight gain and feeding responses under the same social stress paradigm.

Lys


Input: Interestingly, stressed GHSR KO mice showed depleted sc and intrascapular brown fat depots, whereas stressed young wild-type mice did not.


Input: In old wild-type mice, chronic social defeat increased visceral and intrascapular brown fat depots in association with increases in obesity markers like hyperleptinemia and hyperinsulinemia along with increased hypothalamic expression of neuropeptide Y and Agouti related peptide.


Input: Importantly, the elevated expression of these peptides persisted least for 2 weeks after cessation of the stressor regimen.


Input: In contrast, old GHSR KO mice did not show these alterations after chronic social defeat.


Input: These results suggest that ghrelin plays an important role in the metabolic adaptations necessary to meet the energetic demands posed by stressors, but chronic exposure to stress-induced ghrelin elevations ultimately could lead to long lasting metabolic dysfunctions.


Input: Chemical variability of Algerian Myrtus communis L.


Input: The composition of 55 samples of essential oil isolated from the aerial parts of wild growing Myrtus communis L. harvested in 16 locations from East to West Algeria were investigated by GC (determination of retention indices) and (13) C-NMR analyses.

(13) C


Input: The essential oils consisted mainly of monoterpenes, alpha-pinene (27. 4-59. 2%) and 1, 8-cineole (6. 1-34. 3%) being the major components.

monoterpenes

alpha-pinene

1, 8-cineole


Input: They were also characterized by the absence of myrtenyl acetate.

myrtenyl acetate


Input: The compositions of the 55 oils were submitted to k-means partitioning and principal component analysis, which allowed the distinction of two groups within the oil samples, which could be subdivided into two subgroups each.


Input: Groups I (78% of the samples) and II were differentiated on the basis of the contents of alpha-pinene, linalool, and linalyl acetate.

alpha-pinene

linalool

linalyl acetate


Input: Subgroups IA and IB could be distinguished by their contents of alpha-pinene and 1, 8-cineole.

alpha-pinene

1, 8-cineole


Input: Subgroups IIA and IIB differed substantially in their contents of 1, 8-cineole and limonene.

1, 8-cineole

limonene


Input: All the samples contained 3, 3, 5, 5, 8, 8-hexamethyl-7-oxabicyclo [4. 3. 0] non-1 (6)-ene-2, 4-dione (up to 4. 9%).

3, 3, 5, 5, 8, 8-hexamethyl-7-oxabicyclo [4. 3. 0] non-1 (6)-ene-2, 4-dione


Input: Accumulation of dietary methylmercury and effects on growth and survival in two estuarine forage fish: Cyprinodon variegatus and Menidia beryllina.

methylmercury


Input: Dietary methylmercury (MeHg) uptake by fish in relation to life stage, species, and level of exposure is poorly understood in lower trophic levels, particularly in estuarine species.

methylmercury

MeHg


Input: The authors compared accumulation of dietary MeHg as well as sensitivity (survival and growth) to dietary MeHg exposure in two species of estuarine forage fish, Cyprinodon variegatus and Menidia beryllina.

MeHg

MeHg


Input: Fish were fed one of five dietary MeHg concentrations (ranging from 0. 04 to 14 micro g/g dry wt) over a period of 70 d.

MeHg


Input: Growth rate and the level of dietary exposure influenced MeHg tissue concentrations in both species.

MeHg


Input: Mercury in the diet exhibited a strong linear relationship with fish Hg tissue concentrations.

Mercury

Hg


Input: Additionally, the authors found that M. beryllina was more sensitive to dietary MeHg exposure than C. variegatus.

MeHg


Input: Both species showed some decreases in growth related to MeHg exposure, although these patterns were not consistent among treatments.

MeHg


Input: Overall, C. variegatus and M. beryllina were found to have a high tolerance for dietary MeHg exposure.

MeHg


Input: If fish occupying low trophic levels are capable of surviving with high Hg body burdens, this tolerance has important implications for Hg exposure of organisms occupying higher trophic levels.

Hg

Hg


Input: The factor VII-activating protease (FSAP) enhances the activity of bone morphogenetic protein-2 (BMP-2).


Input: Factor VII-activating protease (FSAP) is a circulating protease involved in the pathogenesis of atherosclerosis, calcification, and fibrotic processes.


Input: To understand how FSAP controls the balance of local growth factors, we have investigated its effect on the regulation of bone morphogenetic proteins (BMPs).


Input: BMP-2 is produced as a large pro-form and secreted as a mature heparin-binding growth factor after intracellular processing by pro-protein convertases (PCs).


Input: In this study, we discovered that FSAP enhances the biological activity of mature BMP-2 as well as its pro-form, as shown by osteogenic differentiation of C2C12 myoblasts.


Input: These findings were complemented by knockdown of FSAP in hepatocytes, which revealed BMP-2 processing by endogenous FSAP.


Input: N-terminal sequencing indicated that pro-BMP-2 was cleaved by FSAP at the canonical PC cleavage site, giving rise to mature BMP-2 (Arg (282) v Gln (283)), as well as in the N-terminal heparin binding region of mature BMP-2, generating a truncated mature BMP-2 peptide (Arg (289) v Lys (290)).

N

Arg

Gln

N

Arg

Lys


Input: Similarly, mature BMP-2 was also cleaved to a truncated peptide within its N-terminal region (Arg (289) v Lys (290)).

N

Arg

Lys


Input: Plasmin exhibited a similar activity, but it was weaker compared with FSAP.


Input: Thrombin, Factor VIIa, Factor Xa, and activated protein C were not effective.


Input: These results were further supported by the observation that the mutation of the heparin binding region of BMP-2 inhibited the processing by FSAP but not by PC.


Input: Thus, the proteolysis and activation of pro-BMP-2 and mature BMP-2 by FSAP can regulate cell differentiation and calcification in vasculature and may explain why polymorphisms in the gene encoding for FSAP are related to vascular diseases.


Input: Effect of doping on the magnetostructural ordered phase of iron arsenides: a comparative study of the resistivity anisotropy in doped BaFe2As2 with doping into three different sites.

iron arsenides


Input: To unravel the role of doping in iron-based superconductors, we investigated the in-plane resistivity of BaFe (2) As (2) doped at one of the three different lattice sites, Ba (Fe (1-x) Co (x)) (2) As (2), BaFe (2) (As (1-x) P (x)) (2), and Ba (1-x) K (x) Fe (2) As (2), focusing on the doping effect in the low-temperature antiferromagnetic/orthorhombic (AFO) phase.

iron

BaFe (2) As (2)

Ba (Fe (1-x) Co (x)) (2) As (2)

BaFe (2) (As (1-x) P (x)) (2)

Ba (1-x) K (x) Fe (2) As (2)


Input: A major role of doping in the high-temperature paramagnetic/tetragonal (PT) phase is known to change the Fermi surface by supplying charge carriers or exerting chemical pressure.


Input: In the AFO phase, we found a clear correlation between the magnitude of the residual resistivity and the resistivity anisotropy.


Input: This indicates that the resistivity anisotropy originates from anisotropic impurity scattering due to dopant atoms.


Input: The magnitude of the residual resistivity was also found to be a parameter controlling the suppression rate of the AFO ordering temperature.


Input: Therefore, the dominant role of doping in the AFO phase is to introduce disorder to the system, distinct from that in the PT phase.


Input: SeDeM expert system a new innovator tool to develop pharmaceutical forms.


Input: Abstract Context: The SeDeM expert system is based on the experimental study and quantitative determination of the characterization parameters of powdered substances, the aim being to determine whether a substance is suitable for producing tablets by means of direct compression (DC) technology, thereby reducing the lead time for pre-formulation studies.


Input: Additionally, this expert system also provides formulations with a minimum number of excipients.


Input: Objective: We used this system to analyze suitable formulas for the production of orodispersible ibuprofen tablets.

ibuprofen


Input: Method: Twenty-one disintegrants and ibuprophen were characterized using SeDeM methodology.

ibuprophen


Input: Results: The results indicated that production of ibuprofen tablets by DC would require improvements in the dimension and compressibility factors of the active pharmaceutical ingredient.

ibuprofen


Input: The expert system analysis provided the specific percentage of disintegrant needed to blend with ibuprofen and a standardized formula of lubricants in order to obtain a powder mix that would successfully produce tablets by DC.

ibuprofen


Input: The eight formulas proposed by SeDeM were produced and tested in the laboratory.


Input: Conclusion: All eight formulas successfully produced tablets by DC, but only four of them could be considered suitable for use as an orodispersible tablet and accomplishes all the pharmaceutical quality parameters.


Input: So, in fact, the use of the SeDeM system reduced the time of medicine' s development and therefore the cost of the activity.


Input: Efficient two-electron reduction of dioxygen to hydrogen peroxide with one-electron reductants with a small overpotential catalyzed by a cobalt chlorin complex.

dioxygen

hydrogen peroxide

cobalt chlorin


Input: A cobalt chlorin complex (Co (II) (Ch)) efficiently and selectively catalyzed two-electron reduction of dioxygen (O (2)) by one-electron reductants (ferrocene derivatives) to produce hydrogen peroxide (H (2) O (2)) in the presence of perchloric acid (HClO (4)) in benzonitrile (PhCN) at 298 K.

cobalt chlorin

Co (II) (Ch)

dioxygen

O (2)

ferrocene

hydrogen peroxide

H (2) O (2)

perchloric acid

HClO (4)

benzonitrile

PhCN


Input: The catalytic reactivity of Co (II) (Ch) was much higher than that of a cobalt porphyrin complex (Co (II) (OEP), OEP (2-) = octaethylporphyrin dianion), which is a typical porphyrinoid complex.

Co (II) (Ch)

cobalt porphyrin

Co (II) (OEP)

OEP (2-)

octaethylporphyrin


Input: The two-electron reduction of O (2) by 1, 1'-dibromoferrocene (Br (2) Fc) was catalyzed by Co (II) (Ch), whereas virtually no reduction of O (2) occurred with Co (II) (OEP).

O (2)

1, 1'-dibromoferrocene

Br (2) Fc

Co (II) (Ch)

O (2)

Co (II) (OEP)


Input: In addition, Co (II) (Ch) is more stable than Co (II) (OEP), where the catalytic turnover number (TON) of the two-electron reduction of O (2) catalyzed by Co (II) (Ch) exceeded 30000.

Co (II) (Ch)

Co (II) (OEP)

O (2)

Co (II) (Ch)


Input: The detailed kinetic studies have revealed that the rate-determining step in the catalytic cycle is the proton-coupled electron transfer reduction of O (2) with the protonated Co (II) (Ch) ([Co (II) (ChH)] (+)) that is produced by facile electron-transfer reduction of [Co (III) (ChH)] (2 +) by ferrocene derivative in the presence of HClO (4).

O (2)

Co (II) (Ch)

[Co (II) (ChH)] (+)

[Co (III) (ChH)] (2 +)

ferrocene

HClO (4)


Input: The one-electron-reduction potential of [Co (III) (Ch)] (+) was positively shifted from 0. 37 V (vs SCE) to 0. 48 V by the addition of HClO (4) due to the protonation of [Co (III) (Ch)] (+).

[Co (III) (Ch)] (+)

HClO (4)

[Co (III) (Ch)] (+)


Input: Such a positive shift of [Co (III) (Ch)] (+) by protonation resulted in enhancement of the catalytic reactivity of [Co (III) (ChH)] (2 +) for the two-electron reduction of O (2) with a lower overpotential as compared with that of [Co (III) (OEP)] (+).

[Co (III) (Ch)] (+)

[Co (III) (ChH)] (2 +)

O (2)

[Co (III) (OEP)] (+)


Input: Binary diffusion coefficients for mixtures of ionic liquids [EMIM] [N (CN) 2], [EMIM] [NTf2], and [HMIM] [NTf2] with acetone and ethanol by dynamic light scattering (DLS).

[EMIM] [N (CN) 2]

[EMIM] [NTf2]

[HMIM] [NTf2]

acetone

ethanol


Input: Mutual diffusivities for binary mixtures of the ionic liquids (ILs) [EMIM] [N (CN) 2] (1-ethyl-3-methylimidazolium dicyanimide), [EMIM] [NTf2] (1-ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide), and [HMIM] [NTf2] (1-hexyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide) with acetone and ethanol were studied in dependence on composition in the temperature range from 283. 15 to 323. 15 K, applying dynamic light scattering (DLS).

[EMIM] [N (CN) 2]

1-ethyl-3-methylimidazolium dicyanimide

[EMIM] [NTf2]

1-ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide

[HMIM] [NTf2]

1-hexyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide

acetone

ethanol


Input: The influence of experimental parameters on the achievable uncertainties was analyzed to ensure the acquisition of accurate data in adequate measurement times.


Input: For all probed systems, increasing binary diffusion coefficients were found for increasing temperatures.


Input: The systematic variation of anion and cation of the investigated ILs as well as a comparison with the literature data demonstrates the considerable influence of different ions on the resulting binary diffusion coefficients.


Input: Mutual diffusivities were found to be lower for the mixtures with ethanol than for those with acetone, which could be related to the formation of hydrogen bonds between ethanol and the ions.

ethanol

acetone

hydrogen

ethanol


Input: Most of the investigated IL solvent mixtures show increasing binary diffusion coefficients with increasing solvent concentration.


Input: For the mixtures of [EMIM] [NTf2] with ethanol, however, a minimum of the mutual diffusivities was found in the ethanol mole fraction range from 0. 7 to 0. 8, which may hint at the vicinity of a critical demixing point.

[EMIM] [NTf2]

ethanol

ethanol


Input: The viscosity of the pure ILs turned out to be no reliable indicator for the mutual diffusivity in mixtures with the same solvent.


Input: Generic legislation of new psychoactive drugs.


Input: New psychoactive drugs (NPDs, new psychoactive substances) enter the market all the time.


Input: However, it takes several months to ban these NPDs and immediate action is generally not possible.


Input: Several European countries and drug enforcement officers insist on a faster procedure to ban NPDs.


Input: Introduction of generic legislation, in which clusters of psychotropic drugs are banned in advance, has been mentioned as a possible solution.


Input: Here we discuss the pros and cons of such an approach.


Input: First, generic legislation could unintentionally increase the expenditures of enforcement, black market practices, administrative burden and health risks for users.


Input: Second, it may have a negative impact on research and the development of new treatments.


Input: Third, due to the complexity of generic legislation, problems in the enforcement are anticipated due to lack of knowledge about the chemical nomenclature.


Input: Finally, various legal options are already available to ban the use, sale and trade of NPDs.


Input: We therefore conclude that the currently used scientific benefit-risk evaluation should be continued to limit the adverse health effects of NPDs.


Input: Only in emergency cases, where fatal incidents (may) occur, should this approach be overruled.


Input: Aqueous self-sorting in extended supramolecular aggregates.


Input: Self-organization and self-sorting processes are responsible for the regulation and control of the vast majority of biological processes that eventually sustain life on our planet.


Input: Attempts to unveil the complexity of these systems have been devoted to the investigation of the binding processes between artificial molecules, complexes or aggregates within multicomponent mixtures, which has facilitated the emergence of the field of self-sorting in the last decade.


Input: Since, artificial systems involving discrete supramolecular structures, extended supramolecular aggregates or gel-phase materials in organic solvents or-to a lesser extent-in water have been investigated.


Input: In this review, we have collected diverse strategies employed in recent years to construct extended supramolecular aggregates in water upon self-sorting of small synthetic molecules.


Input: We have made particular emphasis on co-assembly processes in binary mixtures leading to supramolecular structures of remarkable complexity and the influence of different external variables such as solvent and concentration to direct recognition or discrimination processes between these species.


Input: The comprehension of such recognition phenomena will be crucial for the organization and evolution of complex matter.


Input: Beneficial effects of marine algal compounds in cosmeceuticals.


Input: The name " cosmeceuticals " is derived from " cosmetics and pharmaceuticals ", indicating that a specific product contains active ingredients.


Input: Marine algae have gained much importance in cosmeceutical product development due to their rich bioactive compounds.


Input: In the present review, marine algal compounds (phlorotannins, sulfated polysaccharides and tyrosinase inhibitors) have been discussed toward cosmeceutical application.

phlorotannins


Input: In addition, atopic dermatitis and the possible role of matrix metalloproteinase (MMP) in skin-related diseases have been explored extensively for cosmeceutical products.


Input: The proper development of marine algae compounds will be helpful in cosmeceutical product development and in the development of the cosmeceutical industry.


Input: A divergent approach to the synthesis of the yohimbinoid alkaloids venenatine and alstovenine.

yohimbinoid alkaloids venenatine

alstovenine


Input: The yohimbinoid alkaloids continue to receive considerable attention from the synthetic community because of their interesting chemical structures and varied biological activity.

yohimbinoid alkaloids


Input: Although there are several elegant syntheses of certain members of this group of alkaloids, a truly unified approach has yet to be developed.


Input: In short, general approaches to this compound class are hampered by a lack of complete control in setting the C (3) stereocentre at a late stage.


Input: Herein, we report that a functionalized hydrindanone enables a divergent strategy that builds on existing precedent to address this long-standing challenge.

hydrindanone


Input: Utilizing an aminonitrile intermediate, the stereochemistry at C (3) of the yohimbinoid skeleton can be controlled effectively in a Pictet-Spengler reaction.

aminonitrile


Input: We applied this approach to the first total syntheses of the C (3) epimeric natural products venenatine and alstovenine.

venenatine

alstovenine


Input: Organic anion transporter 3 interacts selectively with lipophilic beta-lactam antibiotics.

beta-lactam


Input: Transporters are major determinants of the disposition of xenobiotics and endogenous chemicals in the body.


Input: Organic anion transporter 3 (Oat3) functions in the kidney and brain to remove metabolic waste, toxins, and drugs, and thus transports diverse chemicals.


Input: Some beta-lactam antibiotics interact with Oat3, and penicillin G exhibits a strong dependence on Oat3 for renal elimination.

beta-lactam

penicillin G


Input: However, over 80 beta-lactams exist, and many have not been assessed for an interaction with Oat3.

beta-lactams


Input: Moreover, beta-lactams continue to receive U. S.

beta-lactams


Input: Food and Drug Administration approval.


Input: This study identified new beta-lactam-Oat3 interactions, provided a head-to-head comparison with Oat1, and characterized the physicochemical determinants of affinity for Oat3.

beta-lactam


Input: Cells expressing mouse Oat3 (mOat3) and Oat1 (mOat1), and human OAT3 (hOAT3) were used to test inhibitors, and high-performance liquid chromatography (HPLC) was used to measure transport.


Input: Of 26 beta-lactams tested, 12 were clear inhibitors of Oat3, and 14 exhibited poor interactions.

beta-lactams


Input: Inhibitors exhibited a nearly identical rank-order of potency against mOat3 and hOAT3.


Input: Oat1 demonstrated a poor interaction with most beta-lactams.

beta-lactams


Input: The majority of Oat3 inhibitors were substrates, and there were clear physicochemical differences between inhibitors and noninhibitors.


Input: That is, inhibitors had nearly 40% fewer hydrogen bond donors (P < 0. 001), a lower total polar surface area (P < 0. 05), and greater lipophilicity (LogP of inhibitors, + 1. 41; noninhibitors,-1. 54; P < 0. 001).

hydrogen


Input: Pharmacophore mapping revealed a prohibitive hydrogen bond donor group in noninhibitors adjacent to a hydrophobic moiety that was important for binding to Oat3.

hydrogen


Input: These findings indicate that Oat3 recognizes lipophilic beta-lactams more readily.

beta-lactams


Input: Moreover, this study has potential implications for designing beta-lactams to avoid renal accumulation or brain efflux via Oat3.

beta-lactams


Input: Theoretical design and experimental implementation of Ag/Au electrodes for the electrochemical reduction of nitrate.

Ag

Au

nitrate


Input: The current imbalance in the biogeochemical cycle of nitrogen is as serious as that of carbon.

nitrogen

carbon


Input: One way to mitigate this problem is through the electrochemical reduction of nitrates under mild conditions, which is an appealing though not fully understood process.

nitrates


Input: Therefore, deeper insight into the electrocatalytic reaction mechanism is needed to optimize this process.


Input: Here we thoroughly analyse the adsorption energy of nitrate with DFT calculations on various surface facets of pure Au, Ag, and their near-surface and surface alloys, as the adsorption and subsequent reduction of nitrate are thought to be rate limiting in the electrocatalytic reaction.

nitrate

Au

Ag

nitrate


Input: The observed systematic trends allow prediction of the surface with highest electrocatalytic activity for the reduction of nitrate.

nitrate


Input: This prediction was verified experimentally by depositing sub-monolayer amounts of Ag on polycrystalline Au electrodes.

Ag

Au


Input: We observe a well-defined volcano curve which correlates the amount of Ag deposited on the surface with the current density at a fixed potential, with the peak activity around 2/3 ML Ag surface coverage.

Ag

Ag


Input: The electrocatalytic activity and stability of the bimetallic Ag-Au systems, found through the interplay of theoretical modelling and empirical observations, serve as a clear example for the rational design of novel catalytic materials and confirm the key role that the adsorption of nitrate plays in the overall nitrate reduction rate.

Ag

Au

nitrate

nitrate


Input: Tissue accumulation and species-specific metabolism of technical pentabrominated diphenyl ether (DE-71) in two predator fish.

pentabrominated diphenyl ether


Input: The tissue-specific accumulation and species-specific metabolism of polybrominated diphenyl ethers (PBDEs) in two predator fish species (redtail catfish and oscar fish) feeding on the same prey (tiger barb) that was exposed to technical pentabrominated diphenyl ether (DE-71) in the laboratory were investigated.

polybrominated diphenyl ethers

PBDEs

pentabrominated diphenyl ether


Input: The trends in the wet-weight tissue concentration of PBDEs in two predatory fish species suggested that the tissue distribution of PBDEs occurs through a series of events involving passive diffusion to the lipid compartment.

PBDEs

PBDEs


Input: A comparison of the fugacities of PBDEs in various tissues and in the serum revealed that the liver, gill, and perivisceral adipose tissue readily achieved equilibrium with the serum, but the muscle, kidney, and intestine exhibited the potential to accumulate PBDEs.

PBDEs

PBDEs


Input: The lower fugacities of PBDEs in the intestine may have significance in the transportation of PBDEs from prey to predatory fish.

PBDEs

PBDEs


Input: No tissue-specific differences in PBDE congener profiles were found, while interspecies differences in PBDE profiles were evident.

PBDE

PBDE


Input: The difference in profiles between two species could be attributed to species-specific debromination of PBDE.

PBDE


Input: No metabolic debromination of PBDE was observed in redtail catfish, but extensive debromination of PBDEs occurred in oscar fish.

PBDE

PBDEs


Input: Several hydroxylated PBDEs (OH-PBDEs) were detected in serum samples from the two fish species, but no methoxylated PBDEs were found.

hydroxylated PBDEs

OH-PBDEs

PBDEs


Input: The similarities in the OH-PBDE congener profile and the ratio of OH-PBDEs to total PBDEs between the two fish species indicated that the hydroxylation of PBDEs might not be species-specific.

OH-PBDE

OH-PBDEs

PBDEs

PBDEs


Input: The CXCL12/CXCR4/CXCR7 ligand-receptor system regulates neuro-glio-vascular interactions and vessel growth during human brain development.


Input: This study investigates glio-vascular interactions in human fetal brain at midgestation, specifically examining the expression and immunolocalization of the CXCL12/CXCR4/CXCR7 ligand-receptor axis and its possible role in the vascular patterning of the developing brain.


Input: At midgestation, the telencephalic vesicles are characterized by well developed radial glia cells (RGCs), the first differentiated astrocytes and a basic vascular network mainly built of radial vessels.


Input: RGCs have been recognized to contribute to cerebral cortex neuro-vascular architecture and have also been demonstrated to act as a significant source of neural cells (Rakic, Brain Res 33: 471-476, 1971; Malatesta et al, Development 127: 5253-5263, 2000).


Input: According to our hypothesis CXCL12, a potent migration and differentiation chemokine released by RGCs, may act as a linking factor coordinating neuroblast migration with vessel growth and patterning through the activation of different ligand/receptor axes.


Input: The obtained results support this hypothesis showing that together with CXCR4/CXCR7-reactive neuroblasts, which migrate in close association with CXCL12 RGCs, layer-specific subsets of CXCL12 RGCs and astrocytes specifically contact the microvessel wall.


Input: Moreover, the CXCL12/CXCR4/CXCR7 system appears to be directly involved in microvessel growth, its members being differentially expressed in angiogenically activated microvessels and vascular sprouts.


Input: Using a fragment-based approach to target protein-protein interactions.


Input: The ability to identify inhibitors of protein-protein interactions represents a major challenge in modern drug discovery and in the development of tools for chemical biology.


Input: In recent years, fragment-based approaches have emerged as a new methodology in drug discovery; however, few examples of small molecules that are active against chemotherapeutic targets have been published.


Input: Herein, we describe the fragment-based approach of targeting the interaction between the tumour suppressor BRCA2 and the recombination enzyme RAD51; it makes use of a screening pipeline of biophysical techniques that we expect to be more generally applicable to similar targets.


Input: Disruption of this interaction in vivo is hypothesised to give rise to cellular hypersensitivity to radiation and genotoxic drugs.


Input: We have used protein engineering to create a monomeric form of RAD51 by humanising a thermostable archaeal orthologue, RadA, and used this protein for fragment screening.


Input: The initial fragment hits were thoroughly validated biophysically by isothermal titration calorimetry (ITC) and NMR techniques and observed by X-ray crystallography to bind in a shallow surface pocket that is occupied in the native complex by the side chain of a phenylalanine from the conserved FxxA interaction motif found in BRCA2.

phenylalanine


Input: This represents the first report of fragments or any small molecule binding at this protein-protein interaction site.


Input: Expression of immunoregulatory genes and its relationship to lead exposure and lead-mediated oxidative stress in wild ungulates from an abandoned mining area.


Input: Lead (Pb) is a highly toxic metal that can induce oxidative stress and affect the immune system by modifying the expression of immunomodulator-related genes.

Pb


Input: The aim of the present study was to investigate the association between Pb exposure and the transcriptional profiles of some cytokines, as well as the relationship between Pb exposure and changes in oxidative stress biomarkers observed in the spleen of wild ungulates exposed to mining pollution.

Pb

Pb


Input: Red deer and wild boar from the mining area studied had higher spleen, liver, and bone Pb levels than controls, indicating a chronic exposure to Pb pollution.

Pb

Pb


Input: Such exposure caused a depletion of spleen glutathione levels in both species and disrupted the activity of antioxidant enzymes, suggesting the generation of oxidative stress conditions.

glutathione


Input: Deer from the mining area also showed an induced T-helper (Th)-dependent immune response toward the Th 2 pathway, whereas boar from the mining area showed a cytokine profile suggesting an inclination of the immune response toward the Th 1 pathway.


Input: These results indicate that environmental exposure to Pb may alter immune responses in wild ungulates exposed to mining pollution.

Pb


Input: However, evidence of direct relationships between Pb-mediated oxidative stress and the changes detected in immune responses were not found.

Pb


Input: Further research is needed to evaluate the immunotoxic potential of Pb pollution, also considering the prevalence of chronic infectious diseases in wildlife in environments affected by mining activities.

Pb


Input: Electrocatalytic hydrogenation and deoxygenation of glucose on solid metal electrodes.

glucose


Input: This Full Paper addresses the electrocatalytic hydrogenation of glucose to sorbitol or 2-deoxysorbitol on solid metal electrodes in neutral media.

glucose

sorbitol


Input: Combining voltammetry and online product analysis with high-performance liquid chromatography (HPLC), provides both qualitative and quantitative information regarding the reaction products as a function of potential.


Input: Three groups of catalysts clearly show affinities toward: (1) hydrogen formation [on early transition metals (Ti, V, Cr, Mn, Zr, Nb, Mo, Hf, Ta, We, and Re) and platinum group metals (Ru, Rh, Ir, and Pt)], (2) sorbitol formation [on late transition metals (Fe, Co, Ni, Cu, Pd, Au, and Ag) and Al (sp metal)], and (3) sorbitol and 2-deoxysorbitol formation [on post-transition metals (In, Sn, Sb, Pb, and Bi), as well as Zn and Cd (d metals)].

hydrogen

transition metals

Ti

V

Cr

Mn

Zr

Nb

Mo

Hf

Ta

We

Re

platinum

Ru

Rh

Ir

Pt

sorbitol

transition metals

Fe

Co

Ni

Cu

Pd

Au

Ag

Al

sorbitol

transition metals

In

Sn

Sb

Pb

Bi

Zn

Cd


Input: Ni shows the lowest overpotential for the onset of sorbitol formation (-0. 25 V) whereas Pb generates sorbitol with the highest yield (< 0. 7 mM cm (-2)).

Ni

sorbitol

Pb

sorbitol


Input: Different from a smooth Pt electrode, a large-surface-area Pt/C electrode hydrogenates glucose to sorbitol from-0. 21 V with relatively low current.

Pt

Pt

C

glucose

sorbitol


Input: This emphasizes the importance of the active sites and the surface area of the catalyst.


Input: The mechanism to form 2-deoxysorbitol from glucose and/or fructose is discussed according to the observed reaction products.

glucose

fructose


Input: The yield and selectivity of hydrogenated products are highly sensitive to the chemical nature and state of the catalyst surface.


Input: Characterisation of Nox4 inhibitors from edible plants.


Input: NADPH oxidases transport electrons from cytosolic NADPH through biological membranes to generate reactive oxygen species.

NADPH

NADPH

oxygen


Input: NADPH oxidase 4, broadly expressed in humans, is an interesting pharmacological target, since its activity is deregulated in several diseases, including pulmonary fibrosis, diabetic nephropathy, and cardiac hypertrophy.

NADPH


Input: Whereas several candidate NADPH oxidase 4 inhibitors were recently described, most of these compounds are either unspecific or toxic.

NADPH


Input: Here we set out to identify new NADPH oxidase 4 inhibitors from edible plants, in an attempt to decrease the number of hits with toxic side effects.

NADPH


Input: We screened a compound library prepared from edible plants for new bioactives with the ability to inhibit the activity of NADPH oxidase 4.

NADPH


Input: Using both cell-based and cell-free assays, we identified several compounds with significant inhibitory activity towards NADPH oxidase 4.

NADPH


Input: For selected compounds, the activity profile towards NADPH oxidase 2 and NADPH oxidase 5 was established, and controls were carried out to exclude general reactive oxygen species scavengers.

NADPH

NADPH

oxygen


Input: A number of promising NADPH oxidase 4 inhibitors from edible plants was identified and characterised.

NADPH


Input: Several new chemical entities are disclosed which act as NADPH oxidase 4 inhibitors, and the efficacies of our best hits, in particular several diarylheptanoids and lignans, are comparable to the best available pharmacological NADPH oxidase 4 inhibitors.

NADPH

diarylheptanoids

lignans

NADPH


Input: These findings will provide valuable tools to study mechanisms of NADPH oxidase inhibition.

NADPH


Input: Controlled synthesis of amino acid-based pH-responsive chiral polymers and self-assembly of their block copolymers.

amino acid


Input: Leucine/isoleucine side chain polymers are of interest due to their hydrophobicity and reported role in the formation of alpha-helical structures.

Leucine

isoleucine


Input: The synthesis and reversible addition-fragmentation chain transfer (RAFT) polymerization of amino acid-based chiral monomers, namely Boc-L-leucine methacryloyloxyethyl ester (Boc-L-Leu-HEMA, 1a), Boc-L-leucine acryloyloxyethyl ester (Boc-L-Leu-HEA, 1b), Boc-L-isoleucine methacryloyloxyethyl ester (Boc-L-Ile-HEMA, 1c), and Boc-L-isoleucine acryloyloxyethyl ester (Boc-L-Ile-HEA, 1d), are reported.

amino acid

Boc-L-leucine methacryloyloxyethyl ester

Boc-L-Leu-HEMA

Boc-L-leucine acryloyloxyethyl ester

Boc-L-Leu-HEA

Boc-L-isoleucine methacryloyloxyethyl ester

Boc-L-Ile-HEMA

Boc-L-isoleucine acryloyloxyethyl ester

Boc-L-Ile-HEA


Input: The controlled nature of the polymerization of the said chiral monomers in N, N-dimethylformamide (DMF) at 70 degrees C is evident from the formation of narrow polydisperse polymers, the molecular weight controlled by the monomer/chain transfer agent (CTA) molar ratio and the linear relationship between molecular weight and monomer conversion.

N, N-dimethylformamide

DMF


Input: The resulting well-defined polymers were used as macro-CTAs to prepare corresponding diblock copolymers by RAFT polymerization of methyl (meth) acrylate monomers.

methyl (meth) acrylate


Input: Deprotection of Boc groups in the homopolymers and block copolymers under acidic conditions produced cationic, pH-responsive polymers with primary amine moieties at the side chains.

Boc

primary amine


Input: The optical activity of the homopolymers and block copolymers were studied using circular dichroism (CD) spectroscopy and specific rotation measurements.


Input: The self-assembling nature of the block copolymers to produce highly ordered structures was illustrated through dynamic light scattering (DLS) and atomic force microscopy (AFM) studies.


Input: The side chain amine functionality instills pH-responsive behavior, which makes these cationic polymers attractive candidates for drug delivery applications, as well as for conjugation of biomolecules.

amine


Input: Quantum-dot-sensitized solar cells: understanding linker molecules through theory and experiment.


Input: We have investigated the role of linker molecules in quantum-dot-sensitized solar cells (QDSSCs) using density-functional theory (DFT) and experiments.


Input: Linkers not only govern the number of attached QDs but also influence charge separation, recombination, and transport.


Input: Understanding their behavior is therefore not straightforward.


Input: DFT calculations show that mercaptopropionic acid (MPA) and cysteine (Cys) exhibit characteristic binding configurations on TiO (2) surfaces.

mercaptopropionic acid

MPA

cysteine

Cys

TiO (2)


Input: This information is used to optimize the cell assembly process, yielding Cys-based cells that significantly outperform MPA cells, and reach power conversion efficiencies (PCE) as high as 2. 7% under AM 1. 5 illumination.

Cys

MPA


Input: Importantly, the structural information from theory also helps understand the cause for this improved performance.


Input: Stepwise colonization of the Andes by ruddy ducks and the evolution of novel beta-globin variants.


Input: Andean uplift played a key role in Neotropical bird diversification, yet past dispersal and genetic adaptation to high-altitude environments remain little understood.


Input: Here we use multilocus population genetics to study population history and historical demographic processes in the ruddy duck (Oxyura jamaicensis), a stiff-tailed diving duck comprising three subspecies distributed from Canada to Tierra del Fuego and inhabiting wetlands from sea level to 4500 m in the Andes.


Input: We sequenced the mitochondrial DNA, four autosomal introns and three haemoglobin genes (alpha (A), alpha (D), beta (A)) and used isolation-with-migration (IM) models to study gene flow between North America and South America, and between the tropical and southern Andes.


Input: Our analyses indicated that ruddy ducks dispersed first from North America to the tropical Andes, then from the tropical Andes to the southern Andes.


Input: While no nonsynonymous substitutions were found in either alpha globin gene, three amino acid substitutions were observed in the beta (A) globin.

amino acid


Input: Based on phylogenetic reconstruction and power analysis, the first beta (A) substitution, found in all Andean individuals, was acquired when ruddy ducks dispersed from low altitude in North America to high altitude in the tropical Andes, whereas the two additional substitutions occurred more recently, when ruddy ducks dispersed from high altitude in the tropical Andes to low altitude in the southern Andes.


Input: This stepwise colonization pattern accompanied by polarized beta (A) globin amino acid replacements suggest that ruddy ducks first acclimatized or adapted to the Andean highlands and then again to the lowlands.

amino acid


Input: In addition, ruddy ducks colonized the Andean highlands via a less common route as compared to other waterbird species that colonized the Andes northwards from the southern cone of South America.


Input: Biotransformation and pharmacokinetics of inositol hexanicotinate in rats.

inositol hexanicotinate


Input: Abstract 1.


Input: Inositol hexanicotinate (IHN) is an ester of the anti-hyperlipidemic drug nicotinic acid (NA).

Inositol hexanicotinate

IHN

nicotinic acid


Input: This study assessed the hydrolysis rate of IHN in human and rat plasma, and pharmacokinetics of the drug using a rat animal model.


Input: IHN (10 or 50 micro g/mL) was incubated in plasma at 37 degrees C for 72 h.

IHN


Input: Kinetic parameters were determined based on the disappearance of IHN and the appearance of NA.

IHN


Input: The mean IHN disappearance and NA appearance half-lives were 1. 07 and 3. 93 h in human plasma, and 0. 152 and 2. 68 h in rat plasma.

IHN


Input: Increasing the initial plasma concentration to 50 micro g/mL increased the NA appearance half-life in human and rat plasma to 4. 66 and 6. 47 h, respectively.


Input: After single 50 or 100 mg/kg intravenous dose of IHN to Sprague-Dawley rats, the drug showed statistically significant dose-dependent alterations in systemic clearance, suggesting a non-linear saturable elimination of IHN.

IHN

IHN


Input: Dose-normalized mean plasma levels of NA increased by 30% with increasing IHN dose (p < 0. 02).

IHN


Input: The mean metabolic ratio (i. e. NA/IHN AUC ratio) significantly increased with increasing IHN dose (p < 0. 05).

IHN

IHN


Input: The results provide first indication of saturable elimination and rapid disappearance of IHN, while niacin was slowly formed.

IHN

niacin


Input: Structural and mechanical heterogeneity of the erythrocyte membrane reveals hallmarks of membrane stability.


Input: The erythrocyte membrane, a metabolically regulated active structure that comprises lipid molecules, junctional complexes, and the spectrin network, enables the cell to undergo large passive deformations when passing through the microvascular system.


Input: Here we use atomic force microscopy (AFM) imaging and quantitative mechanical mapping at nanometer resolution to correlate structure and mechanics of key components of the erythrocyte membrane, crucial for cell integrity and function.


Input: Our data reveal structural and mechanical heterogeneity modulated by the metabolic state at unprecedented nanometer resolution.


Input: ATP-depletion, reducing skeletal junction phosphorylation in RBC cells, leads to membrane stiffening.

ATP


Input: Analysis of ghosts and shear-force opened erythrocytes show that, in the absence of cytosolic kinases, spectrin phosphorylation results in membrane stiffening at the extracellular face and a reduced junction remodeling in response to loading forces.


Input: Topography and mechanical mapping of single components at the cytoplasmic face reveal that, surprisingly, spectrin phosphorylation by ATP softens individual filaments.

ATP


Input: Our findings suggest that, besides the mechanical signature of each component, the RBC membrane mechanics is regulated by the metabolic state and the assembly of its structural elements.


Input: The influence of endocrine disruptors in a selected population of infertile women.


Input: Abstract Several studies report that endocrine disrupting chemicals (EDC) able to interfere with endocrine homeostasis may affect women' s reproductive health.


Input: We analyzed EDC serum levels and nuclear receptors (NRs) expression in order to have an indication of the internal dose of biologically active compounds and a measurement of indicators of their effects, as a result of the repeated uptake from environmental source.


Input: The percentage of patients with detectable bisphenol A (BPA) concentrations was significantly higher in the infertile patients compared with fertile subjects.

bisphenol A

BPA


Input: No significant difference was found between the groups with regard to perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), mono-ethylhexyl phthalate (MEHP) and di-(2-ethylhexyl) phthalate (DEHP) concentrations.

perfluorooctane sulfonate

PFOS

perfluorooctanoic acid

PFOA

mono-ethylhexyl phthalate

MEHP

di-(2-ethylhexyl) phthalate

DEHP


Input: Among infertile women, the mean expression of estrogen receptor alpha (ER alpha) and beta (Er beta), androgen receptor (AR) and pregnane X receptor (PXR) was significantly higher than fertile patients.

estrogen

androgen

pregnane


Input: The mean expression of aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor gamma (PPAR gamma) did not show significant differences between two groups.

aryl hydrocarbon


Input: Patients with endometriosis had higher levels of PPAR gamma than all women with other causes of infertility.


Input: This study led further support to EDC exposure as a risk factor for women' s fertility.


Input: Masked mycotoxins are efficiently hydrolyzed by human colonic microbiota releasing their aglycones.


Input: Fusarium mycotoxins are secondary metabolites produced by Fusarium spp. in cereals.


Input: Among them, deoxynivalenol (DON) and zearalenone (ZEN) are widespread worldwide contaminants of cereal commodities and are ranked as the most important chronic dietary risk factors.

deoxynivalenol

DON

zearalenone

ZEN


Input: Their conjugates, known as masked mycotoxins, have been described but are still not accounted for in risk assessment studies.


Input: This study demonstrates for the first time that DON and ZEN are effectively deconjugated by the human colonic microbiota, releasing their toxic aglycones and generating yet unidentified catabolites.

DON

ZEN


Input: For this reason, masked mycotoxins should be considered when evaluating population exposure.


Input: Anti-inflammatory diterpenoids from Croton tonkinensis.

diterpenoids


Input: Phytochemical investigation of the methanolic extract of Croton tonkinensis afforded two known kauranes (1, 2), eight new ent-kauranes (3-10), and 16 known ent-kaurane-type diterpenoids (12-27).

kauranes

ent-kauranes

ent-kaurane

diterpenoids


Input: In addition, 30 known compounds were identified by comparison of their physical and spectroscopic data with reported data.


Input: Among the isolated compounds, ent-18-acetoxykaur-16-en-15-one (20) displayed the most significant inhibition of superoxide anion generation and elastase release.

superoxide


Input: H1152 promotes the degradation of polyglutamine-expanded ataxin-3 or ataxin-7 independently of its ROCK-inhibiting effect and ameliorates mutant ataxin-3-induced neurodegeneration in the SCA3 transgenic mouse.

polyglutamine


Input: Spinocerebellar ataxia type 3 (SCA3) caused by polyglutamine-expanded ataxin-3 is the most prevalent subtype of spinocerebellar ataxias.

polyglutamine


Input: A compound, which decreases protein level of mutant ataxin-3 in SCA3 affected CNS regions, should be a promising therapeutic agent for SCA3.


Input: SCA3 and Huntington' s disease (HD) belong to a family of polyglutamine neurodegenerative diseases.

polyglutamine


Input: Rho-kinase (ROCK) inhibitor Y27632 reduced brain level of polyglutamine-expanded huntingtin in HD transgenic mouse.

polyglutamine


Input: Therefore, we tested the possibility that ROCK inhibitors, Y27632, H1152 and GSK429286, downregulate protein expression of polyglutamine-expanded ataxin-3-Q79.

polyglutamine


Input: Y27632 or H1152 reduced protein level of HA-tagged ataxin-3-Q79 (ATX-3-Q79HA) expressed in HEK 293 cells.


Input: Compared to Y27632, H1152 decreased ATX-3-Q79HA protein level with a significantly more potency and efficacy.


Input: H1152 also reduced protein level of HA-tagged polyglutamine-expanded ataxin-7-Q52 (ATX-7-Q52HA), which causes spinocerebellar ataxia type 7 (SCA7).

polyglutamine


Input: H1152 decreased ATX-3-Q79HA or ATX-7-Q52HA protein level in vitro by augmenting proteasome activity and promoting ATX-3-Q79HA or ATX-7-Q52HA degradation.


Input: GSK429286, which is structurally different from H1152 but equally inhibits ROCK, failed to affect protein level of ATX-3-Q79HA or ATX-7-Q52HA.


Input: Furthermore, shRNA-mediated suppression of ROCK1 or ROCK2 expression in 293 cells did not affect protein level of ATX-3-Q79HA or ATX-7-Q52HA and H1152 reduction of ATX-3-Q79HA.


Input: Daily intraperitoneal administration of H1152 significantly decreased protein level of ATX-3-Q79HA in the cerebellum, pontine nuclei and spinal cord of SCA3 transgenic mice.


Input: H1152 also ameliorated pontine neuronal death and neurological phenotype of SCA3 transgenic mice.


Input: Our results suggest that H1152 might be an effective therapeutic agent for SCA3 or SCA7.


Input: Quercetin ameliorate insulin resistance and up-regulates cellular antioxidants during oleic acid induced hepatic steatosis in HepG2 cells.

Quercetin

oleic acid


Input: Hepatic lipid accumulation and oxidative stress contribute to non-alcoholic fatty liver disease (NAFLD).


Input: Thus, we hypothesized that the hypolipidemic and antioxidant activity of quercetin would attenuate events leading to NAFLD.

quercetin


Input: Addition of 2. 0mM oleic acid (OA) into the culture media induced fatty liver condition in HepG2 cells by 24h.

oleic acid


Input: It was marked by significant accumulation of lipid droplets as determined by Oil-Red-O (ORO) based colorimetric assay, increased triacylglycerol (TAG) and increased lipid peroxidation.

Oil-Red-O

ORO

triacylglycerol

TAG


Input: The inflammatory cytokines TNF-alpha and IL-8 levels were significantly increased with decreased antioxidant molecules.


Input: OA induced insulin resistance which was evident by inhibition of glucose uptake and cell proliferation.

glucose


Input: Quercetin (10 mu M) increased cell proliferation by 3. 05 folds with decreased TAG content (45%) and was effective in increasing insulin mediated glucose uptake by 2. 65 folds.

Quercetin

TAG

glucose


Input: The intracellular glutathione content was increased by 2. 0 folds without substantial increase in GSSG content.

glutathione

GSSG


Input: Quercetin (10 mu M) decreased TNF-alpha and IL-8 by 59. 74% and 41. 11% respectively and inhibited generation of lipid peroxides by 50. 5%.

Quercetin

peroxides


Input: In addition, RT-PCR results confirmed quercetin (10 mu M) inhibited TNF-alpha gene expression.

quercetin


Input: Further, superoxide dismutase, catalase and glutathione peroxidase activities were increased by 1. 68, 2. 19 and 1. 71 folds respectively.

superoxide

glutathione


Input: Albumin and urea content was increased while the alanine aminotransferase (ALAT) activity was significantly decreased by quercetin.

urea

alanine

quercetin


Input: Hence, quercetin effectively reversed NAFLD symptoms by decreased triacyl glycerol accumulation, insulin resistance, inflammatory cytokine secretion and increased cellular antioxidants in OA induced hepatic steatosis in HepG2 cells.

quercetin

triacyl glycerol


Input: The male mammary gland: a target for the xenoestrogen bisphenol A.

bisphenol A


Input: Males of some strains of mice retain their mammary epithelium even in the absence of nipples.


Input: Here, we have characterized the mammary gland in male CD-1 mice both in whole mounts and histological sections.


Input: We also examined the effects of bisphenol A (BPA), an estrogen mimic that alters development of the female mouse mammary gland.

bisphenol A

BPA

estrogen


Input: BPA was administered at a range of environmentally relevant doses (0. 25-250 mu g/kg/day) to pregnant and lactating mice and then the mammary glands of male offspring were examined at several periods in adulthood.

BPA


Input: We observed age-and dose-specific effects on mammary gland morphology, indicating that perinatal BPA exposures alter the male mammary gland in adulthood.

BPA


Input: These results may provide insight into gynecomastia, the most common male breast disease in humans, where proliferation of the mammary epithelium leads to breast enlargement.


Input: A novel coating concept for ileo-colonic drug targeting: Proof of concept in humans using scintigraphy.


Input: The in vivo proof of concept of a novel double-coating system, based on enteric polymers, which accelerated drug release in the ileo-colonic region, was investigated in humans.


Input: Prednisolone tablets were coated with a double-coating formulation by applying an inner layer composed of EUDRAGIT (R) S neutralised to pH 8. 0 and a buffer salt (10% KH (2) PO (4)), which was overcoated with layer of standard EUDRAGIT (R) S organic solution.

Prednisolone

EUDRAGIT

KH (2) PO (4)

EUDRAGIT


Input: For comparison, a single coating system was produced by applying the same amount of EUDRAGIT (R) S organic solution on the tablet cores.

EUDRAGIT


Input: Dissolution tests on the tablets were carried out using USP II apparatus in 0. 1N HCl for 2h and subsequently in pH 7. 4 Krebs bicarbonate buffer.

HCl


Input: For comparison, tablets were also tested under the USP method established for modified release mesalamine formulations.

mesalamine


Input: Ten fasted volunteers received the double-coated and single-coated tablets in a two-way crossover study.


Input: The formulations were radiolabelled and followed by gamma scintigraphy; the disintegration times and positions were recorded.


Input: There was no drug release from the single-coated or double-coated tablets in 0. 1N HCl for 2h.

HCl


Input: The single-coated tablets showed slow release in subsequent Krebs bicarbonate buffer with a lag time of 120min, while in contrast drug release from the double-coated tablets was initiated at 60min.


Input: In contrast, using the USP dissolution method, normally employed for modified release mesalamine products, no discrimination was attained.

mesalamine


Input: The in vivo disintegration of the single-coated EUDRAGIT (R) S tablets in the large intestine was erratic.

EUDRAGIT


Input: Furthermore, in 2 volunteers, the single-coated tablet was voided intact.


Input: Double-coated tablets disintegrated in a more consistent way, mainly in the ileo-caecal junction or terminal ileum.


Input: The accelerated in vivo disintegration of the double-coating EUDRAGIT (R) S system can overcome the limitations of conventional enteric coatings targeting the colon and avoid the pass-through of intact tablets.

EUDRAGIT


Input: Moreover, Krebs bicarbonate buffer has the ability to discriminate between formulations designed to target the ileo-colonic region.

bicarbonate


Input: Dietary relevant mixtures of phytoestrogens inhibit adipocyte differentiation in vitro.


Input: Phytoestrogens (PEs) are naturally occurring plant components, with the ability to induce biological responses in vertebrates by mimicking or modulating the action of endogenous hormones.


Input: Single isoflavones have been shown to affect adipocyte differentiation, but knowledge on the effect of dietary relevant mixtures of PEs, including for instance lignans, is lacking.

isoflavones


Input: In the current study dietary relevant mixtures of isoflavones and their metabolites, lignans and their metabolites, coumestrol, and a mixture containing all of them, were examined for effects on adipogenesis in 3T3-L1 adipocytes, as well as tested for their PPAR gamma activating abilities.

isoflavones

lignans

coumestrol


Input: The results showed that mixtures of isoflavonoid parent compounds and metabolites, respectively, a mixture of lignan metabolites, as well as coumestrol concentration-dependently inhibited adipocyte differentiation.

isoflavonoid

lignan

coumestrol


Input: Furthermore, a mixture of isoflavonoid parent compounds, and a mixture of isoflavonoid metabolites were found to have PPAR gamma activating abilities.

isoflavonoid

isoflavonoid


Input: These results suggest that PEs can affect pathways known to play a role in obesity development, and indicate that the inhibitory effect on adipocyte differentiation does not appear to be strictly associated with PPAR gamma activation/inhibition.


Input: The current study support the hypothesis that compounds with endocrine activity can affect pathways playing a role in the development obesity and obesity related diseases.


Input: A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling.

glutamate


Input: Metabotropic glutamate receptor 5 (mGlu5) is a target for the treatment of central nervous system (CNS) disorders, such as schizophrenia and Alzheimer' s disease.

glutamate


Input: Furthermore, mGlu5 has been shown to play an important role in hippocampal synaptic plasticity, specifically in long-term depression (LTD) and long-term potentiation (LTP), which is thought to be involved in cognition.


Input: Multiple mGlu5-positive allosteric modulators (PAMs) have been developed from a variety of different scaffolds.


Input: Previous work has extensively characterized a common allosteric site on mGlu5, termed the MPEP (2-Methyl-6-(phenylethynyl) pyridine) binding site.

MPEP

2-Methyl-6-(phenylethynyl) pyridine


Input: However, one mGlu5 PAM, CPPHA (N-(4-chloro-2-[(1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl) methyl] phenyl)-2-hydroxybenzamide), interacts with a separate allosteric site on mGlu5.

CPPHA

N-(4-chloro-2-[(1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl) methyl] phenyl)-2-hydroxybenzamide


Input: Using cell-based assays and brain slice preparations, we characterized the interaction of a potent and efficacious mGlu5 PAM from the CPPHA series termed NCFP (N-(4-chloro-2-((4-fluoro-1, 3-dioxoisoindolin-2-yl) methyl) phenyl) picolinamide).

CPPHA

NCFP

N-(4-chloro-2-((4-fluoro-1, 3-dioxoisoindolin-2-yl) methyl) phenyl) picolinamide


Input: NCFP binds to the CPPHA site on mGlu5 and potentiates mGlu5-mediated responses in both recombinant and native systems.

NCFP

CPPHA


Input: However, NCFP provides greater mGlu5 subtype selectivity than does CPPHA, making it more suitable for studies of effects on mGlu5 in CNS preparations.

NCFP

CPPHA


Input: Of interest, NCFP does not potentiate responses involved in hippocampal synaptic plasticity (LTD/LTP), setting it apart from other previously characterized MPEP site PAMs.

NCFP

MPEP


Input: This suggests that although mGlu5 PAMs may have similar responses in some systems, they can induce differential effects on mGlu5-mediated physiologic responses in the CNS.


Input: Such stimulus bias by mGlu5 PAMs may complicate drug discovery efforts but would also allow for specifically tailored therapies, if pharmacological biases can be attributed to different therapeutic outcomes.


Input: Targeting the epithelial cells in fibrosis: a new concept for an old disease.


Input: Fibrosis, which affects millions of individuals worldwide, is a leading cause of organ failure.


Input: For 40 years myofibroblasts have been recognized to be the key cellular players in fibrosis.


Input: Currently, several pharmaceutical targets are under investigation that may contribute to the activation of myofibroblasts.


Input: Recent preclinical and clinical evidence suggests that other components in the fibrotic microenvironment can trigger myofibroblast activation, providing new targets for pharmaceutical intervention.


Input: Epithelial cells may represent the most promising cellular phenotype that could be exploited in the design of new anti-fibrotic medicines through their paracrine action on myofibroblasts.


Input: The present review briefly highlights this hypothesis and discusses some interesting related pharmacological targets.


Input: The stereoisomer (+)-naloxone potentiates G-protein coupling and feeding associated with stimulation of mu opioid receptors in the parabrachial nucleus.

(+)-naloxone


Input: Classically, opioids produce their effects by activating Gi-proteins that inhibit adenylate cyclase activity.


Input: Previous studies proposed that mu-opioid receptors can also stimulate adenylate cyclase due to an initial transient coupling to Gs-proteins.

adenylate


Input: Treatment with ultra-low doses of the nonselective opioid antagonist (-)-naloxone or its inactive enantiomer (+)-naloxone blocks this excitatory effect and enhances Gi-coupling.

(-)-naloxone

(+)-naloxone


Input: Previously we reported that infusion of the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4, Glycinol5]-Enkephalin (DAMGO) into the mu-opioid receptor expressing lateral parabrachial nucleus increases feeding.

[D-Ala2, N-Me-Phe4, Glycinol5]-Enkephalin

DAMGO


Input: Pretreatment with (-)-naloxone blocks this effect.

(-)-naloxone


Input: We used this parabrachial circuit as a model to assess cellular actions of ultra-low doses of (-)-naloxone and (+)-naloxone in modifying the effects of DAMGO.

(-)-naloxone

(+)-naloxone

DAMGO


Input: Our results showed that an ultra-low concentration of (-)-naloxone (0. 001 nM) and several concentrations of (+)-naloxone (0. 01-10 nM) enhanced DAMGO-stimulated guanosine-5'-0-(gamma-thio)-triphosphate incorporation in parabrachial sections in vitro.

(-)-naloxone

(+)-naloxone

DAMGO

guanosine-5'-0-(gamma-thio)-triphosphate


Input: Further, we analyzed the relevance of these effects in vivo.


Input: In the present study, we show that (+)-naloxone can potentiate DAMGO-induced feeding at doses at which (-)-naloxone was an antagonist.

(+)-naloxone

DAMGO

(-)-naloxone


Input: These results implicated (+)-naloxone as a novel tool for studying mu-opioid receptor functions and suggest that (+)-naloxone may have therapeutic value to enhance clinical actions of opiate drugs.

(+)-naloxone

(+)-naloxone


Input: Disruption of the cereblon gene enhances hepatic AMPK activity and prevents high fat diet-induced obesity and insulin resistance in mice.


Input: A nonsense mutation in cereblon (CRBN) causes a mild type of mental retardation in humans.


Input: An earlier study showed that CRBN negatively regulates the functional activity of AMP-activated protein kinase (AMPK) in vitro by binding directly to the alpha 1 subunit of the AMPK complex.

AMP


Input: However, the in vivo role of CRBN was not studied.


Input: To elucidate the physiological functions of Crbn, a mouse strain was generated in which the Crbn gene was deleted throughout the whole body.


Input: In Crbn-deficient mice fed a normal diet, AMPK in the liver showed hyper-phosphorylation, which indicated the constitutive activation of AMPK.


Input: Since Crbn-deficient mice showed significantly less weight gain when fed a high fat diet and their insulin sensitivity was considerably improved, the functions of Crbn in the liver were primarily investigated.


Input: These results provide the first in vivo evidence that Crbn is a negative modulator of AMPK, which suggests that Crbn may be a potential target for metabolic disorders of the liver.


Input: beta-Cells Are Not Generated in Pancreatic Duct Ligation-Induced Injury in Adult Mice.


Input: The existence of adult beta-cell progenitors remains the most controversial developmental biology topic in diabetes research.


Input: It has been reported that beta-cell progenitors can be activated by ductal ligation-induced injury of adult mouse pancreas and apparently act in a cell-autonomous manner to double the functional beta-cell mass within a week by differentiation and proliferation.


Input: Here, we demonstrate that pancreatic duct ligation (PDL) does not activate progenitors to contribute to beta-cell mass expansion.


Input: Rather, PDL stimulates massive pancreatic injury, which alters pancreatic composition and thus complicates accurate measurement of beta-cell content via traditional morphometry methodologies that superficially sample the pancreas.


Input: To overcome this potential bias, we quantified beta-cells from the entire pancreas and observed that beta-cell mass and insulin content are totally unchanged by PDL-induced injury.


Input: Lineage-tracing studies using sequential administration of thymidine analogs, rat insulin 2 promoter-driven cre-lox, and low-frequency ubiquitous cre-lox reveal that PDL does not convert progenitors to the beta-cell lineage.

thymidine


Input: Thus, we conclude that beta-cells are not generated in injured adult mouse pancreas.


Input: Galectin-3 Deficiency Accelerates High-Fat Diet Induced Obesity and Amplifies Inflammation in Adipose Tissue and Pancreatic Islets.


Input: Obesity-induced diabetes is associated with low-grade inflammation in adipose tissue and macrophage infiltration of islets.


Input: We show that ablation of Galectin-3, a galactoside-binding lectin, accelerates high-fat diet-induced obesity and diabetes.


Input: Obese LGALS3 (-/-) mice have increased body weight, amount of total visceral adipose tissue, fasting blood glucose and insulin levels, HOMA-IR and markers of systemic inflammation compared to diet-matched WT animals.

glucose


Input: Obese LGALS3 (-/-) visceral adipose tissue exhibited increased incidence of Type-1 T and NKT lymphocytes and pro-inflammatory CD11c + CD11b macrophages and decreased CD4 + CD25 + FoxP3 + Tregs and M2 macrophages.


Input: Pronounced mononuclear cell infiltrate, increased expression of NLRP3 inflammasome and IL-1 beta in macrophages and increased accumulation of advanced glycation endproducts (AGE) and receptor for AGE (RAGE) expression were present in pancreatic islets of obese LGALS3 (-/-) animals accompanied with elevated phosphorilated NF kappa B p65 and mature Caspase-1 protein expression in pancreatic and visceral adipose tissue.


Input: In vitro stimulation of LGALS3 (-/-) peritoneal macrophages with lypopolysaccharide (LPS) and saturated fatty acid palmitate caused increased Caspase-1 dependent IL-1 beta production and increased phosphorilation of NF kappa B p65 compared to WT cells.

palmitate


Input: Transfection of LGALS3 (-/-) macrophages with NLRP3 siRNA attenuated IL-1 beta production in response to palmitate and LPS plus palmitate.

palmitate

palmitate


Input: Obtained results suggest important protective roles for Gal-3 in obesity-induced inflammation and diabetes.


Input: TSG-6 produced by hMSCs delays the onset of autoimmune diabetes by suppressing Th1 development and enhancing tolerogenicity.


Input: Genetic and immunological screening for type 1 diabetes has led to the possibility of preventing disease in susceptible individuals.


Input: Here, we show that human Mesenchymal Stem/Stromal Cells (hMSCs) and TNF-alpha-stimulated gene 6 (TSG-6), a protein produced by hMSCs in response to signals from injured tissues, delayed the onset of spontaneous autoimmune diabetes in NOD mice by inhibiting insulitis and augmenting regulatory T cells (Tregs) within the pancreas.


Input: Importantly, hMSCs with a knockdown of tsg-6 were ineffective at delaying insulitis and the onset of diabetes in mice.


Input: TSG-6 inhibited the activation of both T cell and antigen presenting cells (APCs) in a CD44-dependent manner.


Input: Moreover, multiple treatments of TSG-6 rendered APCs more tolerogenic, capable of enhancing Treg generation and delaying diabetes in an adoptive transfer model.


Input: Therefore, these results could provide the basis for a novel therapy for the prevention of type 1 diabetes.


Input: The role of GH in adipose tissue: lessons from adipose-specific GH receptor gene-disrupted mice.


Input: GH receptor (GHR) gene-disrupted mice (GHR-/-) have provided countless discoveries as to the numerous actions of GH.


Input: Many of these discoveries highlight the importance of GH in adipose tissue.


Input: For example GHR-/-mice are insulin sensitive yet obese with preferential enlargement of the sc adipose depot.


Input: GHR-/-mice also have elevated levels of leptin, resistin, and adiponectin, compared with controls leading some to suggest that GH may negatively regulate certain adipokines.


Input: To help clarify the role that GH exerts specifically on adipose tissue in vivo, we selectively disrupted GHR in adipose tissue to produce Fat GHR Knockout (FaGHRKO) mice.


Input: Surprisingly, FaGHRKOs shared only a few characteristics with global GHR-/-mice.


Input: Like the GHR-/-mice, FaGHRKO mice are obese with increased total body fat and increased adipocyte size.


Input: However, FaGHRKO mice have increases in all adipose depots with no improvements in measures of glucose homeostasis.

glucose


Input: Furthermore, resistin and adiponectin levels in FaGHRKO mice are similar to controls (or slightly decreased) unlike the increased levels found in GHR-/-mice, suggesting that GH does not regulate these adipokines directly in adipose tissue in vivo.


Input: Other features of FaGHRKO mice include decreased levels of adipsin, a near-normal GH/IGF-1 axis, and minimal changes to a large assortment of circulating factors that were measured such as IGF-binding proteins.


Input: In conclusion, specific removal of GHR in adipose tissue is sufficient to increase adipose tissue and decrease circulating adipsin.


Input: However, removal of GHR in adipose tissue alone is not sufficient to increase levels of resistin or adiponectin and does not alter glucose metabolism.

glucose


Input: Mineralocorticoid receptor-mediated vascular insulin resistance: an early contributor to diabetes-related vascular disease?


Input: Two-thirds of adults in the U. S. are overweight or obese, and another 26 million have type 2 diabetes (T2D).


Input: Patients with diabetes and/or the metabolic syndrome have a significantly increased risk of heart attack and stroke compared with people with normal insulin sensitivity.


Input: Decreased insulin sensitivity in cardiovascular tissues as well as in traditional targets of insulin metabolic signaling, such as skeletal muscle, is an underlying abnormality in obesity, hypertension, and T2D.


Input: In the vasculature, insulin signaling plays a critical role in normal vascular function via endothelial cell nitric oxide production and modulation of Ca (2 +) handling and sensitivity in vascular smooth muscle cells.

nitric oxide

Ca (2 +)


Input: Available evidence suggests that impaired vascular insulin sensitivity may be an early, perhaps principal, defect of vascular function and contributor to the pathogenesis of vascular disease in persons with obesity, hypertension, and T2D.


Input: In the overweight and obese individual, as well as in persons with hypertension, systemic and vascular insulin resistance often occur in concert with elevations in plasma aldosterone.

aldosterone


Input: Indeed, basic and clinical studies have demonstrated that elevated plasma aldosterone levels predict the development of insulin resistance and that aldosterone directly interferes with insulin signaling in vascular tissues.

aldosterone

aldosterone


Input: Furthermore, elevated plasma aldosterone levels are associated with increased heart attack and stroke risk.

aldosterone


Input: Conversely, renin-angiotensin-aldosterone system and mineralocorticoid receptor (MR) antagonism reduces cardiovascular risk in these patient populations.

aldosterone


Input: Recent and accumulating evidence in this area has implicated excessive Ser phosphorylation and proteosomal degradation of the docking protein, insulin receptor substrate, and enhanced signaling through hybrid insulin/IGF-1 receptor as important mechanisms underlying aldosterone-mediated interruption of downstream vascular insulin signaling.

Ser

aldosterone


Input: Prevention or restoration of these changes via blockade of aldosterone action in the vascular wall with MR antagonists (i. e., spironolactone, eplerenone) may therefore account for the clinical benefit of these compounds in obese and diabetic patients with cardiovascular disease.

aldosterone

spironolactone

eplerenone


Input: This review will highlight recent evidence supporting the hypothesis that aldosterone and MR signaling represent an ideal candidate pathway linking early promoters of diabetes, especially overnutrition and obesity, to vascular insulin resistance, dysfunction, and disease.

aldosterone


Input: Photocatalytic properties of graphdiyne and graphene modified TiO 2: from theory to experiment.

graphdiyne

graphene

TiO 2


Input: The chemical structure and electronic properties of two-dimensional (2D) carbon-supported TiO 2, TiO 2-graphdiyne, and TiO 2-graphene composites have been studied by first-principles density functional theory.

carbon

TiO 2

TiO 2-graphdiyne

TiO 2-graphene


Input: Calculation results show that TiO 2 (001)-graphdiyne composites possess superior charge separation and oxidation properties, having the longest lifetimes of photoexcited carriers among all of the 2D composites containing TiO 2 of different facets.

TiO 2

graphdiyne

TiO 2


Input: Our experimental results further proved that TiO 2 (001)-graphdiyne composites could be a promising photocatalyst.

TiO 2

graphdiyne


Input: For photocatalytic degradation of methylene blue, the rate constant of the TiO 2 (001)-graphdiyne composite is 1. 63 +/- 0. 15 times that of the pure TiO 2 (001) and 1. 27 +/- 0. 12 times that of the TiO 2 (001)-graphene composite.

methylene blue

TiO 2

graphdiyne

TiO 2

TiO 2

graphene


Input: In vivo microdialysis for the evaluation of transfersomes as a novel transdermal delivery vehicle for cinnamic acid.

cinnamic acid


Input: Abstract In this study, cinnamic acid-loaded transfersomes were prepared and dermal microdialysis sampling was used in Sprague-Dawley rats to compare the amount of drug released into the skin using transfersomes as transdermal carriers with that released on using conventional liposomes.

cinnamic acid


Input: The formulation of cinnamic acid-loaded transfersomes was optimized by a uniform design through in vitro transdermal permeation studies.

cinnamic acid


Input: Hydration time was confirmed as a significant factor influencing the entrapment efficiency of transfersomes, further affecting their transdermal flux in vitro.


Input: The fluxes of cinnamic acid from transfersomes were all higher than those from conventional liposomes, and the flux from the optimal transfersome formulation was 3. 01-fold higher than that from the conventional liposomes (p < 0. 05).

cinnamic acid


Input: An in vivo microdialysis sampling method revealed that the dermal drug concentrations from transfersomes applied on various skin regions were much lower than those required with conventional liposomes.


Input: After the administration of drug-containing transfersomes and liposomes on abdominal skin regions of rats for a period of 10 h, the C (max) of cinnamic acid from the compared liposomes was 3. 21 +/- 0. 25 mu g/mL and that from the transfersomes was merely 0. 59 +/- 0. 02 mu g/mL.

cinnamic acid


Input: The results suggest that transfersomes can be used as carriers to enhance the transdermal delivery of cinnamic acid, and that these vehicles may penetrate the skin in the complete form, given their significant deformability.

cinnamic acid


Input: Iontophoresis of amoxicillin and cefuroxime: rapid therapeutic concentrations in skin.

amoxicillin

cefuroxime


Input: Abstract Context: Amoxicillin (AMX) and cefuroxime (CFX) are antibiotics used often to treat skin bacterial infections.

Amoxicillin

AMX

cefuroxime

CFX


Input: Typically, high oral doses are required to achieve minimum inhibitory concentration (MIC) at the site of infection that may affect only a very small area of skin.


Input: Objectives: To lower side effects and increase therapeutic effectiveness, the percutaneous absorption and retention of AMX and CFX administered by iontophoresis was investigated in a rabbit model by measuring dermis concentrations via microdialysis.

AMX

CFX


Input: Methods: Iontophoresis was performed using a stainless steel electrode and a non-woven polypropylene pad.

polypropylene


Input: The cartridge pad was soaked with a solution of AMX in glycerin or of CFX in glycerin/water (60: 40).

AMX

CFX


Input: Constant current density of 0, 100, 200 or 300 micro A/cm (2) was applied for 60 min.


Input: Results: For AMX, therapeutically effective skin concentrations were detected immediately after the application of electrical current for any of the current density tested and remained above it for at least 2 h from the end of iontophoresis.

AMX


Input: For CFX, skin concentrations rose above MIC only at the higher current densities and fell below the MIC by the end of the experiment.

CFX


Input: Conclusion: Iontophoresis is a promising method to obtain a fast and sustained concentration of AMX and CFX in skin.

AMX

CFX


Input: Potent elastase inhibitors from cyanobacteria: structural basis and mechanisms mediating cytoprotective and anti-inflammatory effects in bronchial epithelial cells.


Input: We discovered new structural diversity to a prevalent, yet medicinally underappreciated, cyanobacterial protease inhibitor scaffold and undertook comprehensive protease profiling to reveal potent and selective elastase inhibition.


Input: Structure-activity relationship (SAR) studies and X-ray cocrystal structure analysis allowed a detailed assessment of critical and tunable structural elements.


Input: To realize the therapeutic potential of these cyclodepsipeptides, we probed the cellular effects of a novel and representative family member, symplostatin 5 (1), which attenuated the downstream cellular effects of elastase in an epithelial lung airway model system, alleviating clinical hallmarks of chronic pulmonary diseases such as cell death, cell detachment, and inflammation.

symplostatin 5


Input: This compound attenuated the effects of elastase on receptor activation, proteolytic processing of the adhesion protein ICAM-1, NF-kappa B activation, and transcriptomic changes, including the expression of pro-inflammatory cytokines IL1A, IL1B, and IL8.


Input: Compound 1 exhibited activity comparable to the clinically approved elastase inhibitor sivelestat in short-term assays and demonstrated superior sustained activity in longer-term assays.

sivelestat


Input: A novel approach to active compounds identification based on support vector regression model and mean impact value.


Input: Traditionally, active compounds were discovered from natural product extracts by bioassay-guided fractionation, which was with high cost and low efficiency.


Input: A well-trained support vector regression model based on mean impact value was used to identify lead active compounds on inhibiting the proliferation of the HeLa cells in curcuminoids from Curcuma longa L.

curcuminoids


Input: Eight constituents possessing the high absolute mean impact value were identified to have significant cytotoxicity, and the cytotoxic effect of these constituents was partly confirmed by subsequent MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assays and previous reports.

MTT

3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide


Input: In the dosage range of 0. 2-211. 2, 0. 1-140. 2, 0. 2-149. 9 mu m, 50% inhibiting concentrations (IC50) of curcumin, demethoxycurcumin, and bisdemethoxycurcumin were 26. 99 +/- 1. 11, 19. 90 +/- 1. 22, and 35. 51 +/- 7. 29 mu m, respectively.

curcumin

demethoxycurcumin

bisdemethoxycurcumin


Input: It was demonstrated that our method could successfully identify lead active compounds in curcuminoids from Curcuma longa L. prior to bioassay-guided separation.

curcuminoids


Input: The use of a support vector regression model combined with mean impact value analysis could provide an efficient and economical approach for drug discovery from natural products.


Input: Complementary and Alternative Medicine Use Among Patients with Thyroid Cancer.


Input: Background: To report on the incidence and predictors of use of complementary and alternative medicine (CAM) among patients with thyroid cancer.


Input: Methods: Data were collected using a web-based online anonymous survey under IRB approval from Boston University.


Input: This report is based on 1327 responses from subjects with thyroid cancer.


Input: Patient factors were compared by univariate and multivariate analyses.


Input: Results: After excluding multivitamin and prayer use, 74% (n = 941) used CAM.


Input: Respondents were primarily over age 40, White, female and hold a college degree.


Input: The top five modalities were massage therapy, chiropraxy, special diets, herbal tea and yoga.


Input: Few patients reported perceiving a particular modality had a negative effect on treatment.


Input: CAM was more often used for treatment of symptoms (73%) than as part of thyroid cancer treatment (27%).


Input: Multivariable logistic regression demonstrated that patients reporting a poor health status, higher education, cardiovascular disease, pulmonary symptoms, or persistent, recurrent or metastatic disease were more likely to use CAM for treatment of thyroid cancer symptoms.


Input: Nearly 1/3 of respondents reported their CAM use was neither known, prescribed nor asked about by their physicians.


Input: Conclusion: In comparison to national surveys of the general U. S. population, patients with thyroid cancer use CAM therapies twice as often and report their use far less often.


Input: Physicians who treat patients with thyroid cancer should be aware of these data to further assist in their assessment and care.


Input: Cleavage of DNA by proton-coupled electron transfer to a photoexcited, hydrated Ru (II) 1, 10-phenanthroline-5, 6-dione complex.

hydrated Ru (II) 1, 10-phenanthroline-5, 6-dione


Input: Visible light irradiation of a ruthenium (II) quinone-containing complex, [(phen) (2) Ru (phendione)] (2 +) (1 (2 +)), where phendione = 1, 10-phenanthroline-5, 6-dione, leads to DNA cleavage in an oxygen independent manner.

ruthenium (II) quinone

[(phen) (2) Ru (phendione)] (2 +)

phendione

1, 10-phenanthroline-5, 6-dione

oxygen


Input: A combination of NMR analyses, transient absorption spectroscopy, and fluorescence measurements in water and acetonitrile reveal that complex 1 (2 +) must be hydrated at the quinone functionality, giving [(phen) (2) Ru (phenH (2) O)] (2 +) (1H (2) O (2 +), where phenH (2) O = 1, 10-phenanthroline-6-one-5-diol), in order to access a long-lived (3) MLCT (hydrate) state (tau ~ 360 ns in H (2) O) which is responsible for DNA cleavage.

acetonitrile

quinone

[(phen) (2) Ru (phenH (2) O)] (2 +)

1H (2) O (2 +)

phenH (2) O

1, 10-phenanthroline-6-one-5-diol

hydrate

H (2) O


Input: In effect, hydration at one of the carbonyl functions effectively eliminates the low-energy (3) MLCT (SQ) state (Ru (III) phen-semiquinone radical anion) as the predominant nonradiative decay pathway.

carbonyl

Ru (III) phen-semiquinone


Input: This (3) MLCT (SQ) state is very short-lived (< 1 ns) as expected from the energy gap law for nonradiative decay, (1) and too short-lived to be the photoactive species.


Input: The resulting excited state in 1H (2) O (2 +) * has photophysical properties similar to the (3) MLCT state in [Ru (phen) (3)] (2 +) * with the added functionality of basic sites at the ligand periphery.

1H (2) O (2 +)

[Ru (phen) (3)] (2 +)


Input: Whereas [Ru (phen) (3)] (2 +) * does not show direct DNA cleavage, the deprotonated form of 1H (2) O (2 +) * does via a proton-coupled electron transfer (PCET) mechanism where the peripheral basic oxygen sites act as the proton acceptor.

[Ru (phen) (3)] (2 +)

1H (2) O (2 +)

oxygen


Input: Analysis of the small molecule byproducts of DNA scission supports the conclusion that cleavage occurs via H-atom abstraction from the sugar moieties, consistent with a PCET mechanism.

H

sugar


Input: Complex 1 (2 +) is a rare example of a ruthenium complex which' turns on' both reactivity and luminescence upon switching to a hydrated state.

ruthenium


Input: Letter to the Editor: Prescience of a Surgeon in 1980.


Input: A photo copy of a page from an unpublished document written in 1980 by the surgeon Mr. Selwyn Taylor and entitled " The Thyroid and the Thymus ", provides remarkable prescience concerning thyroid lymphocytic infiltrates in Graves' disease and the implications for treating or resolving exophthalmos.


Input: Nano-optomechanical actuator and pull-back instability.


Input: This paper studies the nonlinear behavior of a nano-optomechanical actuator, consisting of a free-standing arc in a ring resonator that is coupled to a bus waveguide through evanescent waves.


Input: The arc deflects when a control light of a fixed wavelength and optical power is pumped into the bus waveguide, while the amount of deflection is monitored by measuring the transmission spectrum of a broadband probe light.


Input: This nanoactuator achieves a maximal deflection of 43. 1 nm, with a resolution of 0. 28 nm.


Input: The optical force is a nonlinear function of the deflection of the arc, leading to pull-back instability when the control light is red-tuned.


Input: This instability is studied by a combination of experiment and modeling.


Input: Potential applications of the nanoactuator include bio-nanomotor, optical switches, and optomechanical memories.


Input: Increased protein sorption in poly (acrylic acid)-containing films through incorporation of comb-like polymers and film adsorption at low pH and high ionic strength.

poly (acrylic acid)


Input: In principle, incorporation of comb-like block copolymers in multilayer polyelectrolyte films can both increase film thickness relative to coatings containing linear polymers and provide more swollen films for increased sorption of proteins.


Input: In the absence of added salt, alternating adsorption of 5 bilayers of protonated poly (allylamine) (PAH) and comb-like poly (2-hydroxyethyl methacrylate)-graft-poly (acrylic acid) (PHEMA-g-PAA) leads to ~ 2-fold thicker coatings than adsorption of PAH and linear PAA, and the difference in the thicknesses of the two coatings increases with the number of bilayers.

poly (allylamine)

PAH

poly (2-hydroxyethyl methacrylate)-graft-poly (acrylic acid)

PHEMA-g-PAA

PAH

PAA


Input: Moreover, the (PAH/PHEMA-g-PAA) n films sorb 2-to 4-fold more protein than corresponding films prepared with linear PAA, and coatings deposited at pH 3. 0 sorb more protein than coatings adsorbed at pH 5. 0, 7. 0, or 9. 0.

PAH

PHEMA-g-PAA

PAA


Input: In fact changes in deposition pH and addition of 0. 5 M NaCl to polyelectrolyte adsorption solutions alter protein sorption more dramatically than variations in the constituent polymer architecture.

NaCl


Input: When deposited from 0. 5 M NaCl at pH 3. 0, both (PAH/PHEMA-g-PAA) 5 and (PAH/PAA) 5 films increase in thickness more than 400% upon adsorption of lysozyme.

NaCl

PAH

PHEMA-g-PAA

PAH

PAA


Input: These films contain a high concentration of free-COOH groups, and subsequent deprotonation of these groups at neutral pH likely contributes to increased protein binding.

COOH


Input: Lysozyme sorption stabilizes these films, as without lysozyme films deposited at pH 3. 0 from 0. 5 M NaCl desorb at neutral pH.

NaCl


Input: Films deposited at pH 9. 0 from 0. 5 M NaCl are more stable and also bind large amounts of lysozyme.

NaCl


Input: The high binding capacities of these films make them attractive for potential applications in protein isolation or immobilization of enzymes.


Input: Denaturation-resistant bifunctional colloidal superstructures assembled via the proteinaceous barnase-barstar interface.


Input: To date, a number of biomolecule-mediated nanoparticle self-assembly systems have been developed that are amenable to controllable disassembly under relatively gentle conditions.


Input: However, for some applications such as design of self-assembled multifunctional theragnostic agents, high stability of the assembled structures can be of primary importance.


Input: Here, we report extraordinarily high durability of protein-assisted nanoparticle self-assembly systems yielding bifunctional colloidal superstructures resistant to extreme denaturing conditions intolerable for most proteins (e. g., high concentrations of chaotropic agents, high temperature).


Input: Among the tested systems (barnase-barstar (BBS), streptavidin-biotin, antibody-antigen, and protein A-immunoglobulin), the BBS is notable due to the combination of its high resistance to severe chemical perturbation and unique advantages offered by genetic engineering of this entirely protein-based system.

streptavidin

biotin


Input: Comparison of the self-assembly systems shows that whereas in all cases the preassembled structures proved essentially resistant to extreme conditions, the ability of the complementary biomolecular pairs to mediate assembly of the initial biomolecule-particle conjugates differs substantially in these conditions.


Input: Cytotoxic constituents of ethyl acetate fraction from Dianthus superbus.

ethyl acetate


Input: The ethyl acetate fraction (EE-DS) from Dianthus superbus was found to possess the cytotoxic activity against cancer cells in previous study.

ethyl acetate


Input: To investigate cytotoxic constituents, the bioassay-guided isolation of compounds from EE-DS was performed.


Input: Two dianthramides (1 and 2), three flavonoids (3-5), two coumarins (6 and 7) and three other compounds (8-10) were obtained.

dianthramides

flavonoids

coumarins


Input: Structures of isolated compounds were identified by spectroscopic analysis.


Input: Cytotoxicity of the compounds against HepG2 cells was evaluated.


Input: Compound 1 showed the strongest cytotoxicity, compounds 10, 4, 3 and 5 had moderate cytotoxicity.


Input: Biosynthesis and characterization of diblock copolymer of p (3-Hydroxypropionate)-block-p (4-hydroxybutyrate) from recombinant Escherichia coli.

p (3-Hydroxypropionate)-block-p (4-hydroxybutyrate)


Input: Poly (4-hydroxybutyrate) (P4HB) is a highly elastic polymer, whereas poly (3-hydroxypropionate) (P3HP) is a polymer with enormous tensile strength.

Poly (4-hydroxybutyrate)

poly (3-hydroxypropionate)


Input: This study aimed to biosynthesize a block copolymer consisting of soft P4HB block with a strong P3HP block to gain unique and excellent material properties.


Input: A recombinant Escherichia coli strain that produces homopolymers of P3HP and P4HB was employed for the block copolymer synthesis.


Input: When the strain was grown in the presence of 1, 4-butanediol (BDO) as a 4HB precursor, P4HB block was formed.

1, 4-butanediol

BDO


Input: Sequential supplementation of 1, 3-propanediol (PDO) as a 3HP precursor allowed the strain to produce P3HP block.

1, 3-propanediol

PDO


Input: Thermal, NMR, fractionation, and mechanical characterizations confirmed the resulting polymer as a block copolymer of P3HP-b-P4HB.


Input: Two block copolymers were formed from this study, including the P3HP-b-29% P4HB and P3HP-b-37% P4HB, they showed superior properties over random copolymers P (3HP-co-4HB).

P (3HP-co-4HB)


Input: The block copolymers had two glass transition temperatures (Tg) and two melting temperatures (Tm).


Input: In comparison to the homopolymers P3HP and P4HB, incorporation of block microstructure resulted in the lowering of Tm, block copolymers were revealed with higher Young' s modulus, yield strengths, and tension strengths much better than the previously reported random copolymers of similar compositions.


Input: Block copolymerization of P3HP and P4HB adds a new vision on PHA polymerization by generation of new polymers with superior properties.

PHA


Input: Neuroprotective effects of inhaled lavender oil on scopolamine-induced dementia via anti-oxidative activities in rats.

scopolamine


Input: Lavender is used in traditional medicines in Asia, Europe, ancient Greece and Rome, and was mentioned in the Bible and in ancient Jewish texts.


Input: Also, lavender is reported to be an effective medical plant in treating inflammation, depression, stress and headache.


Input: The present study was undertaken in order to investigate the antioxidant and antiapoptotic activities of the lavender essential oils from Lavandula angustifolia ssp. angustifolia Mill. and Lavandula hybrida Rev. using superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) specific activities, total content of reduced glutathione (GSH), malondialdehyde (MDA) level (lipid peroxidation) and DNA fragmentation assays in male Wistar rats subjected to scopolamine-induced dementia rat model.

superoxide

glutathione

reduced glutathione

GSH

malondialdehyde

MDA

scopolamine


Input: In scopolamine-treated rats, lavender essential oils showed potent antioxidant and antiapoptotic activities.

scopolamine


Input: Subacute exposures (daily, for 7 continuous days) to lavender oils significantly increased antioxidant enzyme activities (SOD, GPX and CAT), total content of reduced GSH and reduced lipid peroxidation (MDA level) in rat temporal lobe homogenates, suggesting antioxidant potential.

GSH

MDA


Input: Also, DNA cleavage patterns were absent in the lavender groups, suggesting antiapoptotic activity.


Input: Taken together, our results suggest that antioxidant and antiapoptotic activities of the lavender essential oils are the major mechanisms for their potent neuroprotective effects against scopolamine-induced oxidative stress in the rat brain.

scopolamine


Input: Protective effects of oral crocin against intracerebroventricular streptozotocin-induced spatial memory deficit and oxidative stress in rats.

crocin

streptozotocin


Input: Intracerebroventricular (ICV) streptozotocin (STZ) has been shown to cause cognitive impairment, associated with free radical generation.

streptozotocin

STZ


Input: In this study, we evaluated the effects of crocin on cognitive performance in ICV STZ-lesioned rats (3mg/kg bilaterally, on day 1 and 3).

crocin

STZ


Input: Crocin (100mg/kg, p. o.) was administered for 21 consecutive days, starting 1h prior to the first dose of STZ.

Crocin

STZ


Input: Cognitive performance was assessed using Morris water maze task while the parameters of oxidative stress assessed, were malondialdehyde (MDA) and total thiol levels besides glutathione peroxidase (GPx) activity.

malondialdehyde

MDA

thiol

glutathione


Input: STZ-lesioned rats showed a severe deficit in memory associated with elevated MDA levels, reduced GPx activity and total thiol content.

STZ

MDA