Input: The smooth muscle Ca (2 +) channels and/or Ca (2 +) mobilizing through cells might be involved in the effects of resveratrol on the contractility of RPV.

Ca (2 +)

Ca (2 +)

resveratrol


Input: Our results are important for better understanding the impact of resveratrol on the portal circulation.

resveratrol


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


Input: The antinociceptive effect of milnacipran in the monosodium iodoacetate model of osteoarthritis pain and its relation to changes in descending inhibition.

milnacipran

monosodium iodoacetate


Input: Osteoarthritis (OA) is a chronic joint disorder whose principal symptom is chronic pain.


Input: Current analgesics are inadequate and the mechanisms contributing to this pain are poorly understood but likely to include both local joint changes and central consequences.


Input: These studies used monoamine receptor agents combined with behavioral studies and single-unit dorsal horn recordings to examine whether descending noradrenergic and serotonergic inhibitions are altered in the monosodium iodoacetate model of OA pain, and whether increasing these inhibitions with the serotonin/noradrenaline reuptake inhibitor milnacipran can attenuate the attendant hypersensitivity.

monoamine

monosodium iodoacetate

serotonin

noradrenaline

milnacipran


Input: Early and late in the course of this model, milnacipran (s. c.) reduced behavioral hypersensitivity, and inhibited evoked responses from sensitized dorsal horn neurons.

milnacipran


Input: In na i ve animals and the early, but not late, phase of the model, spinal administration of the alpha (2)-adrenoceptor antagonist atipamezole fully reversed this neuronal inhibition, whereas atipamezole administered alone revealed that endogenous noradrenergic inhibition was reduced in the late phase.

atipamezole

atipamezole


Input: Blocking spinal 5-hydroxytryptamine-7 receptors with (2R)-1-[(3-hydroxyphenyl) sulfonyl]-2-[2-(4-methyl-1-piperidinyl) ethyl] pyrrolidine hydrochloride suggested that the effects of milnacipran in the late phase were partly mediated by these receptors, and that descending serotonergic inhibition was increased in this phase.

(2R)-1-[(3-hydroxyphenyl) sulfonyl]-2-[2-(4-methyl-1-piperidinyl) ethyl] pyrrolidine hydrochloride

milnacipran


Input: An opioidergic mechanism behind the effects of milnacipran was indicated by a partial reversal of these effects with naloxone.

milnacipran

naloxone


Input: These studies demonstrate antinociceptive effects for milnacipran in a model of OA pain, whose effects come via descending serotonergic and noradrenergic, as well as opioidergic, pathways.

milnacipran


Input: Variations in the activity of these pathways over the course of this model may contribute to the presence of behavioral hypersensitivity and determine through which endogenous systems milnacipran exerts its effects.

milnacipran


Input: Sources of mercury in a contaminated stream-implications for the timescale of recovery.

mercury


Input: Mercury contamination in East Fork Poplar Creek in Tennessee arises from dissolved mercury exiting a headwater industrial complex and residual mercury in the streambed and soil throughout the watershed downstream.

Mercury

mercury

mercury


Input: The headwater inputs generate chronic base flow concentrations of total mercury of about 1, 000 ng/L, but most of the annual export of mercury from the system appears to originate farther downstream.

mercury

mercury


Input: Effective targeting of remedial efforts requires determining how long downstream sources might continue to contaminate the system following elimination of the headwater mercury inputs.

mercury


Input: The authors calculations suggest that (1) contaminated soils and sediments account for > 80% of the annual mercury export from the entire watershed, with most export occurring during wet weather events; (2) bank erosion and resuspension of streambed particulates are the major mercury sources maintaining high annual mercury export rates; and (3) the inventory of particle-associated mercury in the streambed was not large enough to sustain the estimated export rates for more than a few years.

mercury

mercury

mercury

mercury


Input: The authors findings imply that to prevent waterborne mercury contamination in this system from continuing for decades, remedial actions will have to control the headwater mercury source that sustains day-to-day base flow mercury concentrations and the riparian stream-bank sources that generate most of the mercury export from the system.

mercury

mercury

mercury

mercury


Input: Effect of major cations (Ca (2 +), Mg (2 +), Na (+), K (+)) and anions (SO 42-, Cl (-), NO 3-) on Ni accumulation and toxicity in aquatic plant (Lemna minor L.): implications For Ni risk assessment.

Ca (2 +)

Mg (2 +)

Na (+)

K (+)

SO 42-

Cl (-)

NO 3-

Ni

Ni


Input: The effect of major cation activity (Ca (2 +), Mg (2 +), Na (+), K (+)) on Ni toxicity, with dose expressed as exposure (total dissolved Ni concentration NiTot) or free Ni ion activity (in solution Ni (2 +)), or as tissue residue (Ni concentration in plant tissue NiTiss) to the aquatic plant Lemna minor L. was examined.

Ca (2 +)

Mg (2 +)

Na (+)

K (+)

Ni

Ni

NiTot

Ni (2 +)

Ni


Input: In addition, Ni accumulation kinetics was explored to provide mechanistic insight into current approaches of toxicity modeling, such as the tissue residue approach and the biotic ligand model (BLM), and the implications for plant Ni risk assessment.

Ni

Ni


Input: Major cations did not inhibit Ni accumulation via competitive inhibition as expected by the BLM framework.

Ni


Input: For example, Ca (2 +) and Mg (2 +) (sulfate as counter-anion) had an anticompetitive effect on Ni accumulation, suggesting that Ca or Mg forms a ternary complex with Ni-biotic ligand.

Ca (2 +)

Mg (2 +)

sulfate

Ni

Ca

Mg

Ni


Input: The counter-anion of the added Ca (sulfate, chloride, or nitrate) affected plant response (percentage of root growth inhibition) to Ni.

Ca

sulfate

chloride

nitrate

Ni


Input: Generally, sulfate and chloride influenced plant response while nitrate did not, even when compared within the same range of Ca (2 +), which suggests that the anion dominated the observed plant response.

sulfate

chloride

nitrate

Ca (2 +)


Input: Overall, although an effect of major cations on Ni toxicity to L. minor L. was observed at a physiological level, Ni (2 +) or NiTot alone modeled plant response, generally within a span of twofold, over a wide range of water chemistry.

Ni

Ni (2 +)


Input: Thus, consideration of major cation competition for improving Ni toxicity predictions in risk assessment for aquatic plants may not be necessary.

Ni


Input: The CMT4B disease-causing phosphatases Mtmr2 and Mtmr13 localize to the Schwann cell cytoplasm and endomembrane compartments, where they depend upon each other to achieve wild-type levels of protein expression.


Input: The demyelinating peripheral neuropathy Charcot-Marie-Tooth type 4B (CMT4B) is characterized by axonal degeneration and myelin outfoldings.


Input: CMT4B results from mutations in either myotubularin-related protein 2 (MTMR2; CMT4B1) or MTMR13 (CMT4B2), phosphoinositide (PI) 3-phosphatases that dephosphorylate phosphatidylinositol 3-phosphate (PtdIns3P) and PtdIns (3, 5) P2, lipids which regulate endo-lysosomal membrane traffic.

phosphatidylinositol 3-phosphate

PtdIns (3, 5) P2


Input: The catalytically active MTMR2 and catalytically inactive MTMR13 physically associate, although the significance of this association is not well understood.


Input: Here we show that Mtmr13 loss leads to axonal degeneration in sciatic nerves of older mice.


Input: In addition, CMT4B2-like myelin outfoldings are present in Mtmr13 (-/-) nerves at postnatal day 3.


Input: Thus, Mtmr13 (-/-) mice show both the initial dysmyelination and later degenerative pathology of CMT4B2.


Input: Given the key role of PI 3-kinase-Akt signaling in myelination, we investigated the state of the pathway in nerves of CMT4B models.


Input: We found that Akt activation is unaltered in Mtmr13 (-/-) and Mtmr2 (-/-) mice.


Input: Mtmr2 and Mtmr13 are found within the Schwann cell cytoplasm, where the proteins are partially localized to punctate compartments, suggesting that Mtmr2-Mtmr13 may dephosphorylate their substrates on specific intracellular compartments.


Input: Mtmr2-Mtmr13 substrates play essential roles in endo-lysosomal membrane traffic.


Input: However, endosomes and lysosomes of Mtmr13 (-/-) and Mtmr2 (-/-) Schwann cells are morphologically indistinguishable from those of controls, indicating that loss of these proteins does not cause wholesale dysregulation of the endo-lysosomal system.


Input: Notably, Mtmr2 and Mtmr13 depend upon each other to achieve wild-type levels of protein expression.


Input: Mtmr2 stabilizes Mtmr13 on membranes, indicating that the Mtmr13 pseudophosphatase is regulated by its catalytically active binding partner.


Input: Polar constituents composition of endemic Sideritis italica (MILL.) GREUTER et BURTER from Central Italy.


Input: Endemic Sideritis italica (MILL.) GREUTER et BURTER (Lamiaceae) occurs mainly in Southern Italy and Sicily and has previously only been studied for the essential oil composition.


Input: In this paper, we complete the phytochemical study of a sample of S. italica, previously analysed for its volatile constituents, occurring in the Appennino Umbro-Marchigiano (Central Italy), which is the northern border of the areal distribution of the species.


Input: The analysis of medium polarity constituents led to the isolation of several glycosides, such as flavonoids, i. e. scutellarein derivatives; phenylethanoids, i. e. verbascoside; and iridoids, i. e. melittoside and 5-allosyloxy-aucubin, besides the diterpene siderol.

flavonoids

scutellarein

phenylethanoids

verbascoside

iridoids

melittoside

siderol


Input: The data reported have chemotaxonomic relevance, since they are in contrast with the hypothesis that in Lamiaceae the species producing iridoids do not usually have relevant essential oil production and vice versa.

iridoids


Input: Effects of garlic fractions consumption on male reproductive functions.


Input: Many researchers have focused on the preventive and curative effects of garlic (Allium sativum), particularly on cardiovascular diseases and cancer.


Input: However, its impacts on the male reproductive system have not been clearly defined.


Input: In this study, the effect of chronic consumption of two garlic fractions was tested: one soluble in water (aqueous solution obtained by grinding and centrifugation) and the other one precipitated by ethanol (alcoholic precipitate obtained by precipitation of the aqueous solution), on different variables of male rats' reproductive functions.

ethanol


Input: These two fractions were targeted to try to identify the nature of the active garlic compounds responsible for the different modifications observed on testicular parameters.


Input: The observation of seminiferous tubules of rats treated with garlic fractions showed an increased number of tubules deprived of spermatozoa.


Input: In addition, garlic fractions induced apoptosis of testicular germ cells (TdT-mediated dUTP-X nick-end labeling [TUNEL] approach) and a decrease of serum testosterone levels and seminiferous tubule DNA concentrations.

dUTP

testosterone


Input: In summary, our histological and molecular results suggest that one or several substances, soluble in water and precipitated by alcohol, impaired spermatogenesis.

alcohol


Input: Essential oils of Thymus leucospermus Hartvig, a Greek endemic rich in phenolic monoterpenes.

phenolic monoterpenes


Input: Thymus leucospermus Hartvig is a Greek endemic species of Section Teucrioides Jalas.


Input: The essential oils obtained from five populations growing wild in the National Park of Northern Pindhos (NW Greece) were studied.


Input: The oil content ranged between 1. 1 and 2. 0 mL per 100 g of dry plant weight.


Input: The oils were particularly rich in phenolic monoterpenes: they had a high thymol (64. 7-92. 0%) or carvacrol (93. 4%) content, whereas in one of the oils considerable amount of both compounds was found (thymol 61. 6% and carvacrol 26. 4%).

phenolic monoterpenes

thymol

carvacrol

thymol

carvacrol


Input: Our results show that T. leucospermus is a high-quality thyme species, with respect to both oil content and composition.


Input: Systematic literature review of the effects of food and drink advertising on food and drink-related behaviour, attitudes and beliefs in adult populations.


Input: A large body of research confirms that food advertising affects the food preferences and behaviour of children.


Input: The impact of food advertising on adults is less clear.


Input: We conducted a systematic review exploring the effects of advertising of food and non-alcoholic drinks (referred to as' food' throughout) on food-related behaviour, attitudes and beliefs in adult populations.


Input: We searched seven electronic databases, grey literature sources, and references and citations of included material for experimental studies written in English investigating the effects of commercial food advertising on the food-related behaviours, attitudes and beliefs of adults aged 16 years and over.


Input: Nine studies, rated moderate to poor quality, were included in the review; all were from developed countries and explored the impact of televised food advertising.


Input: Overall, the results did not show conclusively whether or not food advertising affects food-related behaviour, attitudes or beliefs in adults, but suggest that the impact varies inconsistently within subgroups, including gender, weight and existing food psychology.


Input: The identification of a small number of relevant studies, none of which were high quality, and with substantial heterogeneity, highlights the need for further research.


Input: Future studies investigating longer term outcomes, diverse advertising formats, and in countries with different levels of economic development will be of particular value.


Input: Tunable morphology and mesophase formation by naphthalene-containing poly (aryl ether) dendron-based low-molecular-weight fluorescent gels.

naphthalene

poly (aryl ether)


Input: Novel poly (aryl ether) dendron-based low-molecular-weight organogelaters (LMWG) containing naphthalene units at the core have been synthesized, and the self-assembly of the system has been examined in a variety of solvents and solvent mixtures.

poly (aryl ether)

naphthalene


Input: The compounds readily form gels with attractive critical gel concentration values associated with gelation-induced enhanced emission (GIEE).


Input: In addition to the remarkable properties of the previously reported anthracene and pyrene analogues (Rajamalli, P.; Prasad, E. Org. Lett. 2011, 13, 3714 and Rajamalli, P.; Prasad, E. Soft Matter2012, 8, 8896), the self-assembled systems exhibit distinctly different structure-property relationships.

anthracene

pyrene


Input: Unlike the reported ones, the present system forms sheetlike morphology in nonpolar solvent mixtures, giant vesicles in polar solvent mixtures, and lamellar or hexagonal columnar phases in single solvents.


Input: The unique properties of the self-assembled systems, which were analyzed through electron microscopic (SEM, TEM, AFM) and spectroscopic techniques (POM, fluorescence), are attributed to the replacement of anthracene/pyrene units by naphthalene units.

anthracene

pyrene

naphthalene


Input: The present work unravels the subtle role of minute structural change in altering the properties of LMWGs based on poly (aryl ether) dendrons.

poly (aryl ether)


Input: Mechanism of solid state amorphization of glucose upon milling.

glucose


Input: Crystalline alpha-glucose is known to amorphize upon milling at-15 degrees C while it remains structurally invariant upon milling at room temperature.

alpha-glucose


Input: We have taken advantage of this behavior to compare the microstructural evolutions of the material in both conditions in order to identify the essential microstructural features which drive the amorphization process upon milling.


Input: The investigations have been performed by differential scanning calorimetry and by powder X-ray diffraction.


Input: The results indicate that two different amorphization mechanisms occur upon milling: an amorphization at the surface of crystallites due to the mechanical shocks and a spontaneous amorphization of the crystallites as they reach a critical size, which is close to 200 A in the particular case of alpha-glucose.

alpha-glucose


Input: Luminol as in situ light source in meso-tetraphenylporphyrin-mediated photodynamic therapy.

Luminol

meso-tetraphenylporphyrin


Input: The light sources used in current photodynamic therapy are mainly lasers or light emitting diodes, which are not suitable to treat large-volume tumors and those located in the inner body.


Input: To overcome the limitation, we propose an in situ light source to activate the photosensitizer and kill the cancer cells directly.


Input: In the present work, we use luminol as light source and meso-tetraphenylporphyrin as the photosensitizer.

luminol

meso-tetraphenylporphyrin


Input: According to the results, cells incubated with meso-tetraphenylporphyrin, subsequently triggered by luminol, decreased significantly in assays including cell viability and cytotoxicity, while the other groups showed only minor differences.

meso-tetraphenylporphyrin

luminol


Input: The flow cytometric and fluorescent microscopy analysis showed similar results as well.


Input: In the analysis of cell death pathway, cell shrinkage was noticed after photodynamic therapy treatment, which might refer to apoptosis.


Input: Briefly, we suggest that luminol is a promising light source in meso-tetraphenylporphyrin-mediated photodynamic therapy for its greater penetration depth and well matched emission wavelength.

luminol

meso-tetraphenylporphyrin


Input: Usefulness of ancillary methods for diagnosis, prognosis and targeted therapy in thyroid pathology.


Input: The development of molecular analyses for thyroid pathologies is on going.


Input: These analyses provide new diagnostic tools with the aim of accurately distinguishing malignant and benign thyroid tumors.


Input: They are particularly useful as most of them can be done preoperatively on thyroid fine-needle aspiration biopsy samples.


Input: Furthermore, molecular biomarkers may play a promising role since they are able to predict the prognosis of patients with thyroid tumors.


Input: Moreover, identification of molecular markers as well as a better understanding of thyroid carcinogenesis will help develop innovative targeted therapies, particularly in patients with metastatic iodo-resistant thyroid carcinoma.

iodo


Input: To date, four types of somatic genetic alterations are known to hold potential interest for the diagnosis and/or prognosis of follicular cell-derived thyroid carcinomas: BRAF and RAS mutations, and RET/PTC and PAX8/PPAR gamma rearrangements.


Input: Other recent molecular biomarkers have been investigated in thyroid oncology, in particular different microRNA signatures.


Input: This review describes the different aspects of ancillary methods, including those bassed on molecular biology, that are of current interest for the diagnosis, prognosis and treatment of follicular cell-derived thyroid carcinomas.


Input: Silver nanoparticles in cancer: therapeutic efficacy and toxicity.

Silver


Input: In recent years, there has been escalating interest in the biomedical applications of nanoparticles (NPs).


Input: In particular, silver nanoparticles (AgNPs) are increasingly being investigated as tools for novel cancer therapeutics, capitalizing on their unique properties to enhance potential therapeutic efficacy.

silver


Input: However, questions as to are we able to contain or control the toxicity effects of AgNPs, and how much do we know about the toxicological profile of AgNPs which are commonly used in emerging nanotechnology-based applications, still remain.


Input: Hence, serious considerations have to be given to the hazards and risks of toxicity associated with the use of AgNPs.


Input: This review focuses on the current applications of AgNPs, their known effects and toxicity, as well as the potential of harnessing them for use in cancer therapy.


Input: Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease.

tris-tetrahydrofuran


Input: GRL-0519 (1) is a potent antiviral inhibitor of HIV-1 protease (PR) possessing tris-tetrahydrofuran (tris-THF) at P2.

tris-tetrahydrofuran

tris-THF


Input: The high resolution X-ray crystal structures of inhibitor 1 in complexes with single substitution mutants PR (R8Q), PR (D30N), PR (I50V), PR (I54M), and PR (V82A) were analyzed in relation to kinetic data.


Input: The smaller valine side chain in PR (I50V) eliminated hydrophobic interactions with inhibitor and the other subunit consistent with 60-fold worse inhibition.


Input: Asn30 in PR (D30N) showed altered interactions with neighboring residues and 18-fold worse inhibition.


Input: Mutations V82A and I54M showed compensating structural changes consistent with 6-7-fold lower inhibition.


Input: Gln8 in PR (R8Q) replaced the ionic interactions of wild type Arg8 with hydrogen bond interactions without changing the inhibition significantly.

hydrogen


Input: The carbonyl oxygen of Gly48 showed two alternative conformations in all structures likely due to the snug fit of the large tris-THF group in the S2 subsite in agreement with high antiviral efficacy of 1 on resistant virus.

carbonyl oxygen

tris-THF


Input: A design of experiments to optimize a new manufacturing process for high activity protein-containing submicron particles.


Input: A novel method for the manufacture of protein/peptide-containing submicron particles was developed in an attempt to provide particles with increased activity while using high energy input technologies.


Input: The method consists of antisolvent co-precipitation from an aqueous solution containing both an amino acid core material (e. g. D, L-valine), and either bovine serum albumin (BSA) or lysozyme (Lys) as model proteins.

amino acid

D, L-valine


Input: The aqueous solution was added to the organic phase by means of a nebulizer to increase the total surface area of interaction for the precipitation process.


Input: Sonication proved to be an effective method to produce small particle sizes while maintaining high activity of Lys.


Input: The use of a polysorbate or sorbitan ester derivatives as stabilizers proved to be necessary to yield submicron particles.

polysorbate

sorbitan ester


Input: Particles with very high yields (approximately 100%) and very high activity after manufacture (approximately 100%) could be obtained.


Input: A particle size of 439. 0 nm, with a yield of 48. 8% and with final remaining activity of98. 7% was obtained.


Input: By studying various factors using a design of experiments strategy (DoE) we were able to establish the critical controlling factors for this new method of manufacture.


Input: Synthesis, characterization and targeting potential of zidovudine loaded sialic acid conjugated-mannosylated poly (propyleneimine) dendrimers.

zidovudine

sialic acid

mannosylated poly (propyleneimine)


Input: The present investigation was aimed at exploring dual targeting of anti-HIV drug, zidovudine (ZDV) via sialic acid conjugated-mannosylated poly (propyleneimine) (PPI) dendritic nano-constructs.

zidovudine

ZDV

sialic acid

mannosylated poly (propyleneimine)

PPI


Input: Fourth generation PPI dendrimers, sialic acid conjugated PPI dendrimers (SPPI), mannose conjugated PPI dendrimers (MPPI) and dual ligand system i. e. sialic acid conjugated-mannosylated PPI dendrimers (SMPPI) were synthesized and characterized by FT-IR and (1) H NMR spectroscopies and were further confirmed by size exclusion chromatography and differential scanning calorimetry.

PPI

sialic acid

PPI

mannose

PPI

sialic acid

mannosylated PPI

(1) H


Input: Various parameters like drug loading, pH dependent in vitro release, hemolytic toxicity, macrophage uptake and cytotoxicity concerning PPI, SPPI, MPPI and SMPPI dendrimers were evaluated.

PPI


Input: ZDV loaded SMPPI, SPPI and MPPI have shown reduced hemolytic toxicity, cytotoxicity and in vitro drug release at pH 7. 4.

ZDV


Input: Extremely significant (P < 0. 001) increase in cellular uptake of ZDV by macrophage cells was observed in case of SMPPI as compared to PPI and free drug.

ZDV


Input: The in vivo blood level and tissue distribution studies in albino rats also demonstrated potential of dual targeted system towards sialoadhesin and carbohydrate receptors.

carbohydrate


Input: The drug concentration in lymph nodes was increased to about 28 times in case of SMPPI (1335 +/- 17. 6 ng/g) as compared to free drug (48 +/- 5. 8 ng/g) at 6th hr.


Input: The results suggested that such dual ligand dendritic system (SMPPI) hold potential to enhance biocompatibility and site specific delivery of antiretroviral drug, ZDV.

ZDV


Input: Lamivudine permeability study: a comparison between PAMPA, ex vivo and in situ Single-Pass Intestinal Perfusion (SPIP) in rat jejunum.

Lamivudine


Input: In order to reach the bloodstream and thus the target receptor, an orally-administered drug must first cross the intestinal barrier, which can occur via a paracellular, passive transcellular, or carrier-mediated uptake and/or efflux process (active or concentration gradient-driven).


Input: Our work aimed to explore the transport mechanism of the antiretroviral lamivudine (deoxycytidine nucleoside analogue), using a three-part strategy: in vitro, an ex vivo and an in situ method, represented by PAMPA, rat jejunum patches and rat Single Pass Intestinal Perfusion (SPIP), respectively.

lamivudine

deoxycytidine nucleoside


Input: The determined permeability coefficients were compared with those from a published Caco-2 and MDCK study.


Input: Computational prediction of human jejunal permeability was explored, using various non-human permeability coefficients as descriptors.


Input: The ex vivo technique was performed in Franz-type diffusion cells, mounted with male Wistar rat jejunum segment patches.


Input: PAMPA was performed with an acceptor solution simulating the binding of serum proteins, an artificial membrane impregnated with egg lecithin/cholesterol and a gradient of pH between donor and acceptor solutions.

cholesterol


Input: The SPIP was conducted by proximal jejunum cannulation and drug perfusion in a constant flow rate of 0. 2 mL/min.


Input: The outcomes of our studies showed the following predicted pattern for lamivudine effective jejunal permeability: P (eff) (exvivoA > B) > P (eff) (SPIP) > P (eff) (exvivo B > A) > P (eff) (Caco-2) =~ P (eff) (MDCK) =~ P (eff) (PAMPA), strongly suggesting that this compound has carrier-mediated uptake as its dominant transport mechanism.

lamivudine


Input: Notwithstanding, Caco-2 cells may indicate an under-expression of uptake transporters and possibly an over-expression efflux transporters, compared to that found in the rat jejunum.


Input: Biodegradable core-shell nanoassemblies for the delivery of docetaxel and Zn (II)-phthalocyanine inspired by combination therapy for cancer.

docetaxel

Zn (II)

phthalocyanine


Input: Combination therapies for cancer aim to exploit either additive or synergistic effects arising from the action of two species with the final goal to maximize the therapeutic efficacy.


Input: In this work, we develop multifunctional nanoparticles (NPs) for co-delivery of the conventional anticancer drug docetaxel (DTX) and the second generation photosensitizer zinc-phthalocyanine (ZnPc) as potential dual carrier system for the combination of chemotherapy and photodynamic therapy (PDT).

docetaxel

DTX

zinc

phthalocyanine

ZnPc


Input: Biodegradable and amphiphilic block copolymers based on poly (epsilon-caprolactone) (PCL = B) and poly (ethylene oxide) (PEO = A), with AB and ABA architectures, were assembled in " core-shell " NPs and loaded with both DTX and ZnPc employing the melting/sonication method.

poly (epsilon-caprolactone)

PCL

poly (ethylene oxide)

PEO

DTX

ZnPc


Input: Hydrodynamic diameters within the range 60-100nm and low polydispersity indexes were obtained.


Input: Zeta potential was negative for all the formulations and unaffected by drug encapsulation.


Input: Concerning drug loading ability of NPs, the entrapment efficiency was related to initial ZnPc/DTX ratio.

ZnPc

DTX


Input: Steady-stationary and time-resolved emission fluorescence measurements pointed out the embedding of monomeric ZnPc in the NPs, excluding the presence of ZnPc self-supramolecular oligomers.

ZnPc

ZnPc


Input: The release of DTX was biphasic whereas ZnPc remained mainly associated with NPs.

DTX

ZnPc


Input: Singlet oxygen generation was observed when ZnPc-loaded NPs were irradiated at 610nm within a 45min time range, despite that ZnPc was not released in the medium.

oxygen

ZnPc

ZnPc


Input: Stability of NPs in the presence of serum proteins and plasma was excellent and no toxicity toward red blood cells was found.


Input: NPs cytotoxicity was evaluated in HeLa cells irradiated for 30min with a halogen lamp.


Input: After 72h, viability of cells treated with ZnPc/DTX-loaded NPs strongly decreased as compared to NPs loaded only with DTX, thus showing a combined effect of both DTX and ZnPc.

ZnPc

DTX

DTX

DTX

ZnPc


Input: Superior antitumor activity of ZnPc/DTX-loaded NPs as compared to DTX-loaded NPs was confirmed in an animal model of orthotopic amelanotic melanoma, thus pointing to the application of PEO-PCL NPs in the combined chemo-photodynamic therapy of cancer.

ZnPc

DTX

DTX

PEO

PCL


Input: Polyethylenimine combined with liposomes and with decreased numbers of primary amine residues strongly enhanced therapeutic antiviral efficiency against herpes simplex virus type 2 in a mouse model.

Polyethylenimine

primary amine


Input: The development of antiviral agents that have novel mechanisms of action is urgently required in the topical therapy of herpes simplex virus type 2 (HSV-2) infections.


Input: We reported previously that topical application of branched 3610-Da polyethylenimine (PEI) exhibited preventative antiviral activity.

polyethylenimine

PEI


Input: In this study, to develop therapeutic anti-HSV-2 agents, the most potent PEI combined with ~ 200 nm-sized liposomes with or without oleic acid (liposomes/PEI) was selected in vitro and further evaluated using in vivo studies.

PEI

oleic acid

PEI


Input: The mechanism of action in vivo was elucidated using PEIs with decreased numbers of primary amine residues, resulting from ethylene carbonate treatment, and polyallylamine, a linear polyamine consisting of primary amines.

PEIs

primary amine

ethylene carbonate

polyallylamine

polyamine

primary amines


Input: Cytotoxicity and antiviral activity in vitro, and the appearance of acute herpetic disease and virus yields in mice intravaginally administered with liposomes/PEI were evaluated in cell culture assays and a mouse genital herpes model, respectively.

PEI


Input: In addition, the cellular association of liposome/PEI was examined by flow cytometry and confocal microscopy.

PEI


Input: PEI showed higher antiviral activity postinfection than preinfection in vivo.

PEI


Input: Liposome/PEI and PEI with decreased numbers of primary amine residues at a dose of 0. 2 mg PEI/mouse exhibited more potent therapeutic antiviral activity than acyclovir and PEI alone without acute lesion appearance or toxicity pre-or postinfection, but polyallylamine was moderately effective only preinfection.

PEI

PEI

primary amine

PEI

acyclovir

PEI

polyallylamine


Input: Liposome concentrations were important for the effectiveness of liposome/PEI.

PEI


Input: This finding suggests that PEI combined with liposomes and with slightly decreased numbers of primary amines may be an effective vaginally administrated antiviral drug, and secondary and tertiary amine residues of PEI may contribute to the inhibitory efficiency against viral infection.

PEI

primary amines

secondary and tertiary amine

PEI


Input: In situ forming nimodipine depot system based on microparticles for the treatment of posthemorrhagic cerebral vasospasm.

nimodipine


Input: The present study was conducted to examine the feasibility of nimodipine-loaded PLGA microparticles suspended in Tisseel (TM) fibrin sealant as an in situ forming depot system.

nimodipine

PLGA


Input: This device locally placed can be used for the treatment of vasospasm after a subarachnoid hemorrhage.


Input: Microparticles were prepared via spray-drying by using the vibration mesh spray technology of Nano Spray Dryer B-90.


Input: Spherically shaped microparticles with different loadings and high encapsulation efficiencies of 93. 3-97. 8% were obtained.


Input: Depending on nimodipine loading (10-40%), the particle diameter ranged from 1. 9 +/- 1. 2 mu m to 2. 4 +/- 1. 3 mu m.

nimodipine


Input: Thermal analyses using DSC revealed that nimodipine is dissolved in the PLGA matrix.

nimodipine


Input: Also, fluorescent dye loaded microparticles were encapsulated in Tisseel (TM) to examine the homogeneity of particles.


Input: 3D-pictures of the in situ forming devices displayed uniform particle homogeneity in the sealant matrix.


Input: Drug release was examined by fluorescence spectrophotometry which demonstrated a drug release proportional to the square root of time.


Input: A prolonged drug release of 19. 5h was demonstrated under in vitro conditions.


Input: Overall, the nimodipine in situ forming device could be a promising candidate for the local treatment of vasospasm after a subarachnoid hemorrhage.

nimodipine


Input: Induction of HO-1 through p38 MAPK/Nrf2 signaling pathway by ethanol extract of Inula helenium L. reduces inflammation in LPS-activated RAW 264. 7 cells and CLP-induced septic mice.

ethanol


Input: High mobility group box 1 (HMGB1) plays a crucial mediator in the pathogenesis of many inflammatory diseases.


Input: We recently proposed that heme oxygenase-1 (HO-1) negatively regulates HMGB1 in inflammatory conditions.

heme


Input: We investigated whether ethanol extract of Inula helenium L.

ethanol


Input: (EIH) activates p38 MAPK/Nrf2/HO-1 pathways in RAW264. 7 cells and reduces inflammation in CLP-induced septic mice.


Input: EIH induced expression of HO-1 protein in a time-and concentration-dependent manner.


Input: EIH significantly diminished HO-1 expression in siNrf2 RNA-transfected cells.


Input: As expected, the inhibited expression of iNOS/NO, COX-2/PGE2, HMGB1 release by EIH in LPS-activated RAW264. 7 cells was significantly reversed by siHO-1RNA transfection.


Input: Furthermore, EIH not only inhibited NF-kappa B luciferase activity, phosphorylation of I kappa B alpha in LPS-activated cells but also significantly suppressed expression of adhesion molecules (ICAM-1 and VCAM-1) in TNF-alpha activated human umbilical vein endothelial cells.


Input: The induction of HO-1 by EIH was inhibited by SB203580 but not by SP600125, PD98059, nor LY294002.


Input: Most importantly, administration of EIH significantly reduced not only increase in blood HMGB1, ALT, AST, BUN, creatinine levels but also decrease macrophage infiltrate in the liver of septic mice, which were reversed by ZnPPIX, a HO-1 inhibitor.

creatinine


Input: We concluded that EIH has anti-inflammatory effect via the induction of p38 MAPK-dependent HO-1 signaling pathway.


Input: Evaluation of insulin-like growth factor acid-labile subunit as a potential biomarker of effect for deoxynivalenol-induced proinflammatory cytokine expression.

deoxynivalenol


Input: Consumption of the trichothecene deoxynivalenol (DON) suppresses growth in experimental animals-an adverse effect that was used to establish the tolerable daily intake for this toxin.

deoxynivalenol

DON


Input: DON ingestion has been recently found to suppress plasma insulin-like growth factor acid-labile subunit (IGFALS), a protein essential for growth.

DON


Input: Studies were conducted to explore the feasibility of using plasma IGFALS as a biomarker of effect for DON.

DON


Input: In the first study, weanling mice were fed 0, 1, 2. 5, 5 and 10 ppm DON and weight and plasma IGFALS determined at intervals over 9 wk.

DON


Input: Reduced body weight gains were detectable beginning at wk 5 in the 10 ppm dose and wk 7 at the 5 ppm dose.


Input: Plasma IGFALS was significantly depressed at wk 5 in the 5 and 10 ppm groups at wk 9 in the 10 ppm group.


Input: Depressed IGFALS significantly correlated with reduced body weight at wk 5 and 9.


Input: Benchmark dose modeling revealed the BMDL and BMD for plasma IGFALS reduction were 1. 1 and 3. 0 ppm DON and for weight reduction were 2. 1 and 4. 5 ppm DON.

DON

DON


Input: In the second study, it was demonstrated that mice fed 15 ppm DON diet had significantly less plasma IGFALS than mice fed identical amounts of control diet.

DON


Input: Thus DON' s influence on IGFALS likely reflects the combined effects of reduced food intake as well as its physiological action involving suppressors of cytokine signaling.

DON


Input: Taken together, these findings suggest that plasma IGFALS might be a useful biomarker for DON' s adverse effects on growth.

DON


Input: Locally administered prostaglandin E2 prevents aeroallergen-induced airway sensitization in mice through immunomodulatory mechanisms.

prostaglandin E2


Input: Prostaglandin E2 attenuates airway pathology in asthmatic patients and exerts a protective effect in antigen-sensitized mice when administered systemically.

Prostaglandin E2


Input: We aimed to establish the consequences of intranasal PGE2 administration on airway reactivity to aeroallergens in mice and reveal the underlying immunoinflammatory mechanisms.


Input: PGE2 was administered either daily during a 10-day exposure to house dust mite (HDM) extracts or for limited intervals.


Input: Airway hyperreactivity was measured by whole-body and invasive plethysmography.


Input: The phenotypes of lung immune cells and cytokine production were analysed by flow cytometry and ELISA, respectively.


Input: Airway hyperreactivity was sustainably reduced only when PGE2 administration was restricted to the initial 5 days of exposure to HDM.


Input: Lung inflammation, IL-4 production, and airway mast cell activity were also prevented under this early short-term treatment with PGE2.


Input: Interestingly, a Th2 response was already committed on day 5 of exposure to HDM.


Input: This was paralleled by GM-CSF and osteopontin upregulation and a decreased number of plasmacytoid dendritic and T regulatory cells, as well as a trend towards reduced IL-10 expression.


Input: Local PGE2 administration prevented the increase of airway IL-13 and osteopontin and kept lung plasmacytoid dendritic cell counts close to baseline.


Input: GM-CSF and Tregs were unaffected by the treatment.


Input: These findings suggest that the protection provided by PGE2 is a result of the modulation of early lung immunomodulatory mechanisms, and possibly a shift in the balance of dendritic cells towards a tolerogenic profile.


Input: Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency.

benzyloxazoles

nucleoside


Input: Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved activity towards Tyr181Cys containing variants was pursued with the assistance of free energy perturbation (FEP) calculations.

nucleoside


Input: Optimization of the 4-R substituent in 1 led to ethyl and isopropyl analogs 1e and 1f with 1-7 nM potency towards both the wild-type virus and a Tyr181C variant.

ethyl

isopropyl


Input: Methadone N-demethylation by the common CYP2B6 allelic variant CYP2B6. 6.

Methadone N


Input: The long-acting opioid methadone displays considerable unexplained interindividual pharmacokinetic variability.

methadone


Input: Methadone metabolism clinically occurs primarily by N-demethylation to 2-ethyl-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP), catalyzed predominantly by CYP2B6.

Methadone

N

2-ethyl-1, 5-dimethyl-3, 3-diphenylpyrrolidine

EDDP


Input: Retrospective studies suggest that the common allele variant CYP2B6 * 6 may influence methadone plasma concentrations.

methadone


Input: The catalytic activity of CYP2B6. 6, encoded by CYP2B6 * 6, is highly substrate-dependent.


Input: This investigation compared methadone N-demethylation by CYP2B6. 6 with that by wild-type CYP2B6. 1.

methadone N


Input: Methadone enantiomer and racemate N-demethylation by recombinant-expressed CYP2B6. 6 and CYP2B6. 1 was determined.

Methadone

N


Input: At substrate concentrations (0. 25-2 micro M) approximating plasma concentrations occurring clinically, rates of methadone enantiomer N-demethylation by CYP2B6. 6, incubated individually or as the racemate, were one-third to one-fourth those by CYP2B6. 1.

methadone

N


Input: For methadone individual enantiomers and metabolism by CYP2B6. 6 compared with CYP2B6. 1, Vmax was diminished, Ks was greater and the in vitro intrinsic clearance was diminished 5-to 6-fold.

methadone


Input: The intrinsic clearance for R-and S-EDDP formation from racemic methadone was diminished approximately 6-fold and 3-fold for R-and S-methadone, respectively.

R-and S-EDDP

racemic methadone

R-and S-methadone


Input: Both CYP2B6. 6 and CYP2B6. 1 showed similar stereoselectivity (S > R-methadone).

S > R-methadone


Input: Human liver microsomes with diminished CYP2B6 content due to a CYP2B6 * 6 allele had lower rates of methadone N-demethylation.

methadone N


Input: Results show that methadone N-demethylation catalyzed by CYP2B6. 6, the CYP2B6 variant encoded by the CYP2B6 * 6 polymorphism, is catalytically deficient compared with wild-type CYP2B6. 1.

methadone N


Input: Diminished methadone N-demethylation by CYP2B6. 6 may provide a mechanistic explanation for clinical observations of altered methadone disposition in individuals carrying the CYP2B6 * 6 polymorphism.

methadone N

methadone


Input: 3D structures and ligand specificities of nuclear xenobiotic receptors CAR, PXR and VDR.


Input: The nuclear receptors constitutive androstane receptor (CAR), pregnane X receptor (PXR) and vitamin D receptor (VDR) control a large array of genes that code for important proteins in humans including metabolic enzymes and transporters.

androstane

pregnane

vitamin D


Input: 3D structures for the ligand-binding domain (LBD) of these receptors are abundantly available, providing valuable insights into the ligand-binding specificity as well as the activation mechanisms.


Input: The ligand-binding site of PXR is large and flexible, whereas those of CAR and VDR are compact and rigid, respectively.


Input: In general, the ligand profiles of the receptors are in agreement with the LBD structures.


Input: The crystal structures have greatly helped us to understand the promiscuity and/or specificity of CAR, PXR and VDR.


Input: A 5-year retrospective evaluation of snakebite cases in Hatay, Turkey.


Input: Snakebites are relatively rare medical emergency cases that might lead to serious consequences.


Input: This study aims to evaluate snakebite cases in terms of medical follow-up, antivenom therapy and antivenom reactions.


Input: Medical records of patients admitted to emergency department between January 1, 2006 and December 31, 2010 were retrospectively investigated.


Input: Snakebite-related cases of a total of 125 patients were included in the scope of the study.


Input: Of the total 125 cases, 54. 4% were male and 45. 6% were female.


Input: Most of cases (n: 65, 52%) were aged over 30 years, while the mean age was 34. 87 +/- 19. 29 years.


Input: Snakebite-related applications to the emergency department were mostly seen in June with 27 cases.


Input: Upon admitting, all patients were recorded to be conscious and showing good general conditions; however, they suffered from pain and edema at the site of bite.


Input: Of all, 25 patients only suffered from bite injury and ecchymosis due to snakebite.


Input: The site of bite was upper extremities in 66 patients (52. 8%), whereas it was lower extremities in 58 (46. 4%).


Input: Of all, antivenom was unnecessary in 25 (20%) patients, while four antivenoms were administered to each of the 23 (18. 4%) patients.


Input: Furthermore, six (4. 8%) patients needed nine antivenom administrations for each.


Input: Anaphylaxis (n: 2, 1. 6%), compartment syndrome (n: 2, 1. 6%) and serum sickness (n: 1, 0. 8%) encountered in remaining cases.


Input: Of all, 86 (68. 8%) patients were hospitalized in the emergency department, while 25 (20. 0%) patients were followed up by observation in emergency service.


Input: Only one patient was treated and followed up in intensive care unit.


Input: Implementation of antivenom therapy is considered unnecessary for the treatment of all snakebite cases.


Input: Antivenom reactions and number of related cases might be reduced by continuous close monitoring, appropriate prophylaxis and controlled slow infusion administration of medications.


Input: Subacute oral toxicity of combinations of selected synthetic pyrethroids, piperonyl butoxide, and tetramethrin in rats.

pyrethroids

piperonyl butoxide

tetramethrin


Input: In this study, 70 Wistar rats were randomly divided into seven equal groups (six experimental and one control), which consisted of animals belonging to both sexes.


Input: Different combinations of insecticides were administered daily to the experimental groups (group 1: cypermethrin + piperonyl butoxide (PBO); group 2: alphacypermethrin + PBO; group 3: deltamethrin + PBO; group 4: cypermethrin + PBO + tetramethrin; group 5: alphacypermethrin + PBO + tetramethrin; and group 6: deltamethrin + PBO + tetramethrin) for 28 days.

cypermethrin

piperonyl butoxide

PBO

alphacypermethrin

PBO

deltamethrin

PBO

cypermethrin

PBO

tetramethrin

alphacypermethrin

PBO

tetramethrin

deltamethrin

PBO


Input: During the study period, mortality and serious clinical findings were not observed in any animal.


Input: However, feed consumptions decreased in groups 1 and 3 (p < 0. 05).


Input: Red blood cells, white blood cells, and hemoglobin levels, especially in cypermethrin and alphacypermethrin groups (groups 1, 2, and 4), were found to be higher than the control group (p < 0. 05).

cypermethrin

alphacypermethrin


Input: Furthermore, biochemical changes related to liver, kidney functions, and protein metabolism occurred in males of almost all the groups.


Input: Relative liver and kidney weights of the male animals increased in the cypermethrin and alphacypermethrin groups (p < 0. 05).

cypermethrin

alphacypermethrin


Input: The most common finding observed during the histopathological examination of all the experimental groups was centrilobular degeneration in the liver.


Input: It was concluded that although clinical symptoms were not observed, synthetic pyrethroid, synergist, and knockdown agent combinations might cause serious abnormalities when administered in certain doses in mammalians.

pyrethroid


Input: A Serum-Tolerant Hydroxyl-Modified Polyethylenimine as Versatile Carriers of pDNA/siRNA.

Hydroxyl

Polyethylenimine


Input: The polyethylenimine (PEI) derivatives (PTn) are prepared by treating PEI25k with Tris (hydroxymethyl) acrylamidomethane via the Michael addition.

polyethylenimine

PEI

Tris (hydroxymethyl) acrylamidomethane


Input: These PTns can effectively condense nucleic acids into nanosized particles with positive surface charges.


Input: The PTns show lower cytotoxicity and better serum-resistant capacity than PEI25k.


Input: Specially, the transfection efficiency of PT26/DNA is 29-fold higher than that of PEI25k in HeLa cells in serum-containing medium.


Input: The PTn/siRNA complexes show superior knockdown effect in CT26 cells in serum-containing medium.


Input: In addition, flow cytometry analysis shows that the PTns can efficiently mediate the entry of nucleic acids into the cell.


Input: Thus, PTns are potentially applicable as non-viral carriers of nucleic acids and warrant further development for use in gene therapy.


Input: Sociocultural behavior, sex-biased admixture, and effective population sizes in Central African Pygmies and non-Pygmies.


Input: Sociocultural phenomena, such as exogamy or phylopatry, can largely determine human sex-specific demography.


Input: In Central Africa, diverging patterns of sex-specific genetic variation have been observed between mobile hunter-gatherer Pygmies and sedentary agricultural non-Pygmies.


Input: However, their sex-specific demography remains largely unknown.


Input: Using population genetics and approximate Bayesian computation approaches, we inferred male and female effective population sizes, sex-specific migration, and admixture rates in 23 Central African Pygmy and non-Pygmy populations, genotyped for autosomal, X-linked, Y-linked, and mitochondrial markers.


Input: We found much larger effective population sizes and migration rates among non-Pygmy populations than among Pygmies, in agreement with the recent expansions and migrations of non-Pygmies and, conversely, the isolation and stationary demography of Pygmy groups.


Input: We found larger effective sizes and migration rates for males than for females for Pygmies, and vice versa for non-Pygmies.


Input: Thus, although most Pygmy populations have patrilocal customs, their sex-specific genetic patterns resemble those of matrilocal populations.


Input: In fact, our results are consistent with a lower prevalence of polygyny and patrilocality in Pygmies compared with non-Pygmies and a potential female transmission of reproductive success in Pygmies.


Input: Finally, Pygmy populations showed variable admixture levels with the non-Pygmies, with often much larger introgression from male than from female lineages.


Input: Social discrimination against Pygmies triggering complex movements of spouses in intermarriages can explain these male-biased admixture patterns in a patrilocal context.


Input: We show how gender-related sociocultural phenomena can determine highly variable sex-specific demography among populations, and how population genetic approaches contrasting chromosomal types allow inferring detailed human sex-specific demographic history.


Input: Lower Adiponectin Levels at First Trimester of Pregnancy Are Associated With Increased Insulin Resistance and Higher Risk of Developing Gestational Diabetes Mellitus.


Input: OBJECTIVETo evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, beta-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women. RESEARCH DESIGN AND METHODSWe performed anthropometric measurements and collected blood samples at 1st (6-13 weeks) and 2nd (24-28 weeks) trimesters.


Input: Diagnosis of GDM was made at 2nd trimester, based on a 75-g oral glucose tolerance test (International Association of Diabetes and Pregnancy Study Group criteria).

glucose


Input: Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), beta-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUC (insulin/glucose)), and beta-cell compensation (insulin secretion sensitivity index-2).

glucose


Input: Adiponectin was measured by radioimmunoassay. RESULTSAmong the 445 participants included in this study, 38 women developed GDM.


Input: Women who developed GDM had lower 1st-trimester adiponectin levels (9. 67 +/- 3. 84 vs. 11. 92 +/- 4. 59 micro g/mL in women with normal glucose tolerance).

glucose


Input: Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1. 12 per 1 micro g/mL decrease of adiponectin levels; P = 0. 02, adjusted for BMI and HbA (1c) at 1st trimester).


Input: Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r =-0. 22, P < 0. 0001) and Matsuda index (r = 0. 28, P < 0. 0001, and r = 0. 29, P < 0. 0001).


Input: After adjustment for confounding factors, we found no significant association with HOMA-B and AUC (insulin/glucose). CONCLUSIONSPregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements.

glucose


Input: Nanoparticle adhesion to the cell membrane and its effect on nanoparticle uptake efficiency.


Input: The interactions between nanosized particles and living systems are commonly mediated by what adsorbs to the nanoparticle in the biological environment, its biomolecular corona, rather than the pristine surface.


Input: Here, we characterize the adhesion toward the cell membrane of nanoparticles of different material and size and study how this is modulated by the presence or absence of a corona on the nanoparticle surface.


Input: The results are corroborated with adsorption to simple model supported lipid bilayers using a quartz crystal microbalance.

quartz


Input: We conclude that the adsorption of proteins on the nanoparticle surface strongly reduces nanoparticle adhesion in comparison to what is observed for the bare material.


Input: Nanoparticle uptake is described as a two-step process, where the nanoparticles initially adhere to the cell membrane and subsequently are internalized by the cells via energy-dependent pathways.


Input: The lowered adhesion in the presence of proteins thereby causes a concomitant decrease in nanoparticle uptake efficiency.


Input: The presence of a biomolecular corona may confer specific interactions between the nanoparticle-corona complex and the cell surface including triggering of regulated cell uptake.


Input: An important effect of the corona is, however, a reduction in the purely unspecific interactions between the bare material and the cell membrane, which in itself disregarding specific interactions, causes a decrease in cellular uptake.


Input: We suggest that future nanoparticle-cell studies include, together with characterization of size, charge, and dispersion stability, an evaluation of the adhesion properties of the material to relevant membranes.


Input: Aminoalkyl derivatives of guanidine diaromatic minor groove binders with antiprotozoal activity.

Aminoalkyl

guanidine


Input: Considering the strong DNA minor groove binding observed for our previous series of diaromatic symmetric and asymmetric guanidinium and 2-aminoimidazolinium derivatives, we report now the synthesis of new aminoalkyl derivatives of diaromatic guanidines with potential as DNA minor groove binders and antiprotozoal activity.

guanidinium

aminoalkyl


Input: The preparation of these aminoalkyl derivatives (12a-e, 13a-e, 14a-c, e, 15a-e, 16a-e) is presented as well as their affinity for DNA which was evaluated by means of DNA thermal denaturation experiments.

aminoalkyl


Input: Finally, the antiprotozoal activity of most of these aminoalkyl minor groove binders was evaluated in vitro against Trypanosoma brucei rhodesiense (8 compounds) and Plasmodium falciparum (18 compounds).

aminoalkyl


Input: The O-linked derivatives 13c and 14c showed 100 nM activities against P. falciparum, whereas for T.

O


Input: b. rhodesiense all compounds tested showed micromolar activity.


Input: Some of the derivatives prepared seem to exert the antimalarial activity by binding to the DNA minor groove whereas other sets of compounds could exert this antimalarial activity by inhibiting the parasite dihydrofolate reductase, for example.

dihydrofolate


Input: Phenyl linker-induced dense PEG conformation improves the efficacy of C-terminally monoPEGylated staphylokinase.

Phenyl

PEG

C


Input: PEGylation can improve the protein efficacy by prolonging serum half-life and reducing proteolytic sensitivity and immunogenicity.


Input: However, PEGylation may decrease the bioactivity of a protein by interfering with binding of its substrate or receptors.


Input: Here, staphylokinase (SAK), a thrombolysis agent for therapy of myocardial infarction, was mono-PEGylated at the C-terminus of SAK far from its bioactive domain.

C


Input: Phenyl, propyl, and amyl moieties were used as linkers between SAK and polyethylene glycol (PEG), respectively.

Phenyl

propyl

amyl

polyethylene glycol

PEG


Input: Flexible propyl and amyl linkers lead to loose conformation.

propyl

amyl


Input: In contrast, rigid and hydrophobic phenyl linker induces dense PEG conformation that can extensively shield most domains adjacent to C-terminus (e. g., the antigen epitopes and proteolytic sites) of SAK and inefficiently shield its bioactive domain.

phenyl

PEG

C


Input: As compared with loose PEG conformation, dense PEG conformation is more efficient to maintain the bioactivity, increase the plasma half-life, and decrease the proteolytic sensitivity and immunogenicity of the PEGylated SAK.

PEG

PEG


Input: Optical probing of the electronic interaction between graphene and hexagonal boron nitride.

graphene

boron nitride


Input: Even weak van der Waals (vdW) adhesion between two-dimensional solids may perturb their various materials properties owing to their low dimensionality.


Input: Although the electronic structure of graphene has been predicted to be modified by the vdW interaction with other materials, its optical characterization has not been successful.

graphene


Input: In this report, we demonstrate that Raman spectroscopy can be utilized to detect a few percent decrease in the Fermi velocity (v (F)) of graphene caused by the vdW interaction with underlying hexagonal boron nitride (hBN).

graphene

boron nitride


Input: Our study also establishes Raman spectroscopic analysis which enables separation of the effects by the vdW interaction from those by mechanical strain or extra charge carriers.


Input: The analysis reveals that spectral features of graphene on hBN are mainly affected by change in v (F) and mechanical strain but not by charge doping, unlike graphene supported on SiO 2 substrates.

graphene

graphene

SiO 2


Input: Graphene on hBN was also found to be less susceptible to thermally induced hole doping.

Graphene


Input: Bioactive flavaglines and other constituents isolated from Aglaia perviridis.

flavaglines


Input: Eight new compounds, including two cyclopenta [b] benzopyran derivatives (1, 2), two cyclopenta [b] benzofuran derivatives (3, 4), three cycloartane triterpenoids (5-7), and an apocarotenoid (8), together with 16 known compounds, were isolated from the chloroform-soluble partitions of separate methanol extracts of a combination of the fruits, leaves, and twigs and of the roots of Aglaia perviridis collected in Vietnam.

cyclopenta [b] benzopyran

cyclopenta [b] benzofuran

cycloartane triterpenoids

chloroform

methanol


Input: Isolation work was monitored using human colon cancer cells (HT-29) and facilitated with an LC/MS dereplication procedure.


Input: The structures of the new compounds (1-8) were determined on the basis of spectroscopic data interpretation.


Input: The Mosher ester method was employed to determine the absolute configurations of 5-7, and the absolute configuration of the 9, 10-diol unit of compound 8 was established by a dimolybdenum tetraacetate [Mo2 (AcO) 4] induced circular dichroism procedure.

diol

dimolybdenum tetraacetate

Mo2 (AcO) 4


Input: Seven known rocaglate derivatives (9-15) exhibited significant cytotoxicity against the HT-29 cell line, with rocaglaol (9) being the most potent (ED50 0. 0007 mu M).

rocaglate

rocaglaol


Input: The new compounds 2-4 were also active against this cell line, with ED50 values ranging from 0. 46 to 4. 7 mu M.


Input: The cytotoxic compounds were evaluated against a normal colon cell line, CCD-112CoN.


Input: In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), and a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant NF-kappa B (p65) inhibitory activity in an ELISA assay.

perviridicin B

rocaglate

sesquiterpene


Input: Increasing the order parameter of quasi-hexagonal micellar nanostructures by ultrasound annealing.


Input: Nanopatterning with block copolymers finds many applications ranging from optics to bioscience.


Input: Many of these uses demand highly ordered patterns that are difficult to obtain because of environmental influences during fabrication.


Input: Here we demonstrate that ultrasonication improves the hexagonal order of artificially disturbed micellar nanopatterns.


Input: A powerful aluminum catalyst for the synthesis of highly functional organic carbonates.

aluminum

organic carbonates


Input: An aluminum complex based on an amino triphenolate ligand scaffold shows unprecedented high activity (initial TOFs up to 36, 000 h (-1)), broad substrate scope, and functional group tolerance in the formation of highly functional organic carbonates prepared from epoxides and CO (2).

aluminum

amino triphenolate

organic carbonates

epoxides

CO (2)


Input: The developed catalytic protocol is further characterized by low catalyst loadings and relative mild reaction conditions using a cheap, abundant, and nontoxic metal.


Input: A chemical approach to searching for bioactive ingredients in cigarette smoke.


Input: Cigarette smoke, a collection of many toxic chemicals, contributes to the pathogenesis of smoking-related diseases such as chronic obstructive pulmonary disease and cancer.


Input: Much work has been done on the chemical analysis of ingredients in cigarette smoke, but there are few reports on the active ingredients that can modify biomolecules.


Input: We used a sensitive liquid chromatography-mass spectrometry (LC/MS) and LC/MS/MS method to show that L-tyrosine (Tyr), an amino acid with a highly reactive hydroxyl group, readily reacts with cigarette smoke extract (CSE) at body temperature (37 degrees C) to form various Tyr derivatives.

L-tyrosine

Tyr

amino acid

hydroxyl

Tyr


Input: Among these derivatives were N-(3-oxobutyl)-Tyr and two acetylated compounds, N-acetyl-Tyr and O-acetyl-Tyr, which were synthesized by reaction of Tyr with methyl vinyl ketone and acetic anhydride, respectively, at 37 degrees C.

N-acetyl-Tyr

O-acetyl-Tyr

Tyr

methyl vinyl ketone

acetic anhydride


Input: The presence of methyl vinyl ketone and acetic anhydride in CSE was confirmed by gas chromatography-mass spectrometry (GC/MS).

methyl vinyl ketone

acetic anhydride


Input: These results indicate that Tyr can easily react with active ingredients in CSE.

Tyr


Input: The present analytical methods should aid the search for active ingredients in cigarette smoke.


Input: Schisphenlignans A-E: five new dibenzocyclooctadiene lignans from Schisandra sphenanthera.

Schisphenlignans A-E

dibenzocyclooctadiene lignans


Input: Five new dibenzocyclooctadiene lignans, schisphenlignans A-E (1-5), together with eight known ones, were isolated from the stems of Schisandra sphenanthera.

dibenzocyclooctadiene lignans

schisphenlignans A-E


Input: The structures of 1-5 were elucidated based on the analysis of their NMR, MS and circular dichroism (CD) spectra.


Input: Some isolates were tested for their acute activities on insulin sensitivity in 3T3-L1 differentiated adipocytes, but none of them showed significant bioactivity with 10 micro M administration of the tested compounds.


Input: EPR spin Hamiltonian parameters of encapsulated spin-labels: impact of the hydrogen bonding topology.

hydrogen


Input: Encapsulation of spin-labels into " host " compounds, like cucurbit [n] urils or cyclodextrins, in solutions has profound effects on the EPR spin Hamiltonian parameters of the spin-labels.


Input: In this work we study the microscopic origin of the EPR spin Hamiltonian parameters of spin-labels enclosed in hydrophobic cavities.


Input: We focus on the dependence of the EPR properties of encapsulated spin-labels on the hydrogen bonding topologies that occur upon encapsulation, and quantize various contributions to these parameters according to specific hydrogen bonding patterns.

hydrogen

hydrogen


Input: The obtained results provide refined insight into the role of the hydrogen bonding induced encapsulation shifts of EPR spin Hamiltonian parameters in solvated " spin-label @host compound " complexes.

hydrogen


Input: Lactobacillus johnsonii inhibits indoleamine 2, 3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats.

indoleamine

tryptophan


Input: In our previous work, we found that feeding Lactobacillus johnsonii to BioBreeding diabetes-prone (BBDP) rats decreased the incidence of diabetes development.


Input: The aim of this study was to investigate host pathways affected by L. johnsonii, with specific focus on the rate-limiting enzyme of tryptophan catabolism, indoleamine 2, 3-dioxygenase (IDO).

tryptophan

indoleamine


Input: Suspensions of L. johnsonii or an equal volume of vehicle were orally administered to BBDP rats.


Input: Tissue IDO was investigated using quantitative RT-PCR and Western blot, whereas tryptophan, kynurenine, and 5-hydroxytryptamine (5-HT) concentrations were quantified by HPLC and ELISA.

tryptophan

kynurenine


Input: IDO activity was also investigated using L. johnsonii culture cell-free supernatant (CFS) with affinity-purified IDO and HT-29 intestinal epithelial cells.


Input: L. johnsonii feeding resulted in a 17% reduction in serum kynurenine compared with that in vehicle-fed controls, correlating with a 1. 4-fold elevation in 5-HT levels.

kynurenine


Input: H2O2 produced by L. johnsonii abolished IDO activity in vitro, and L. johnsonii feeding resulted in a 3. 9-fold increase in ileum lumen H2O2.


Input: L. johnsonii CFS significantly reduced IDO activity in HT-29 intestinal epithelial cells (47% reduction) compared with that in vehicle-treated controls, an effect abolished by catalase treatment.


Input: These data support the role of H2O2 in commensal bacteria-host interactions and highlight the influence of commensal bacteria-derived H2O2 on host physiology.-Valladares, R., Bojilova, L., Potts, A.


Input: H., Cameron, E., Gardner, C., Lorca, G., Gonzalez, C.


Input: F.


Input: Lactobacillus johnsonii inhibits indoleamine 2, 3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats.

indoleamine

tryptophan


Input: Roughening of Pt nanoparticles induced by surface-oxide formation.

Pt

oxide


Input: Using density functional theory (DFT) and thermodynamic considerations we studied the equilibrium shape of Pt nanoparticles (NPs) under electrochemical conditions.

Pt


Input: We found that at very high oxygen coverage, obtained at high electrode potentials, the experimentally-observed tetrahexahedral (THH) NPs consist of high-index (520) faces.

oxygen


Input: Since high-index surfaces often show higher (electro-) chemical activity in comparison to their close-packed counterparts, the THH NPs can be promising candidates for various (electro-) catalytic applications.


Input: Sample solution constraints on motor-driven diagnostic nanodevices.


Input: The last decade has seen appreciable advancements in efforts towards increased portability of lab-on-a-chip devices by substituting microfluidics with molecular motor-based transportation.


Input: As of now, first proof-of-principle devices have analyzed protein mixtures of low complexity, such as target protein molecules in buffer solutions optimized for molecular motor performance.


Input: However, in a diagnostic work-up, lab-on-a-chip devices need to be compatible with complex biological samples.


Input: While it has been shown that such samples do not interfere with crucial steps in molecular diagnostics (for example antibody-antigen recognition), their effect on molecular motors is unknown.


Input: This critical and long overlooked issue is addressed here.


Input: In particular, we studied the effects of blood, cell lysates and solutions containing genomic DNA extracts on actomyosin and kinesin-microtubule-based transport, the two biomolecular motor systems that are most promising for lab-on-a-chip applications.


Input: We found that motor function is well preserved at defined dilutions of most of the investigated biological samples and demonstrated a molecular motor-driven label-free blood type test.


Input: Our results support the feasibility of molecular-motor driven nanodevices for diagnostic point-of-care applications and also demonstrate important constraints imposed by sample composition and device design that apply both to kinesin-microtubule and actomyosin driven applications.


Input: Enhancing catalytic selectivity of supported metal nanoparticles with capping ligands.


Input: Enhancing catalytic selectivity of supported metal nanoparticles with capping ligands is demonstrated using an Au/SiO (2) catalyst in liquid phase aerobic oxidation of benzyl alcohol.

Au

SiO (2)

benzyl alcohol


Input: Chemisorption of an appropriate amount of polyvinylpyrrolidone on the Au/SiO (2) catalyst greatly enhances the benzaldehyde selectivity from 43% to ~ 100% and its yield from 4. 9% to 7. 2%.

polyvinylpyrrolidone

Au

SiO (2)

benzaldehyde


Input: Voltage tuning of ferromagnetic resonance with bistable magnetization switching in energy-efficient magnetoelectric composites.


Input: Dual E-and H-field control of microwave performance with enhanced ferromagnetic resonance (FMR) tunability has been demonstrated in microwave composites FeGaB/PZN-PT (011).

FeGaB

PZN-PT


Input: A voltage-impulse-induced non-volatile magnetization switching was also realized in this work, resulting from the hysteretic type of phase transition in PZN-PT (011) at high electric fields.

PZN-PT


Input: The results provide a framework for developing lightweight, energy efficient, voltage-tunable RF/microwave devices.


Input: Halogen bonding: an interim discussion.

Halogen


Input: Halogen bonding is a noncovalent interaction that is receiving rapidly increasing attention because of its significance in biological systems and its importance in the design of new materials in a variety of areas, for example, electronics, nonlinear optical activity, and pharmaceuticals.

Halogen


Input: The interactions can be understood in terms of electrostatics/polarization and dispersion; they involve a region of positive electrostatic potential on a covalently bonded halogen and a negative site, such as the lone pair of a Lewis base.

halogen


Input: The positive potential, labeled a sigma hole, is on the extension of the covalent bond to the halogen, which accounts for the characteristic near-linearity of halogen bonding.

halogen

halogen


Input: In many instances, the lateral sides of the halogen have negative electrostatic potentials, allowing it to also interact favorably with positive sites.

halogen


Input: In this discussion, after looking at some of the experimental observations of halogen bonding, we address the origins of sigma holes, the factors that govern the magnitudes of their electrostatic potentials, and the properties of the resulting complexes with negative sites.

halogen


Input: The relationship of halogen and hydrogen bonding is examined.

halogen

hydrogen


Input: We also point out that sigma-hole interactions are not limited to halogens, but can also involve covalently bonded atoms of Groups IV-VI.

halogens


Input: Examples of applications in biological/medicinal chemistry and in crystal engineering are mentioned, taking note that halogen bonding can be " tuned " to fit various requirements, that is, strength of interaction, steric factors, and so forth.

halogen


Input: STEPS: a grid search methodology for optimized peptide identification filtering of MS/MS database search results.


Input: For bottom-up proteomics, there are wide variety of database-searching algorithms in use for matching peptide sequences to tandem MS spectra.


Input: Likewise, there are numerous strategies being employed to produce a confident list of peptide identifications from the different search algorithm outputs.


Input: Here we introduce a grid-search approach for determining optimal database filtering criteria in shotgun proteomics data analyses that is easily adaptable to any search.


Input: Systematic Trial and Error Parameter Selection--referred to as STEPS--utilizes user-defined parameter ranges to test a wide array of parameter combinations to arrive at an optimal " parameter set " for data filtering, thus maximizing confident identifications.


Input: The benefits of this approach in terms of numbers of true-positive identifications are demonstrated using datasets derived from immunoaffinity-depleted blood serum and a bacterial cell lysate, two common proteomics sample types.


Input: Proteomic methods reveal cyclophilin a function as a host restriction factor against rotavirus infection.


Input: Rotavirus (RV) infection is the main cause of acute dehydrating diarrhea in infants and young children below 5 years old worldwide.


Input: RV infection causes a global shutoff of host proteins as many other viruses do.


Input: However, previous studies revealed that RV could selectively upregulated the expression of some host proteins that then played important roles in RV infection.


Input: To globally explor such host proteins that were upregulated in early human rotavirus (HRV) infection, proteomic methods were used and a total of ten upregulated host proteins were unambiguously identified.


Input: Cyclophilin A (CYPA), a peptidyl-prolyl cis-trans isomerase, was among these upregulated host proteins.

prolyl


Input: Following infection, CYPA was recruited to the viroplasm and interacted with HRV structural protein VP2; CYPA reduced host susceptibility to HRV infection and inhibited replication of HRV by repressing the expression of viral proteins.


Input: Furthermore, we found that the increased expression of CYPA in enterocytes of small intestine correlated to the period when BALB/c mice became resistant to RV diarrhea.


Input: Together, we identified CYPA as a novel host restriction factor that confered protection against RV infection and might contribute to host susceptibility to RV diarrhea.


Input: A fluorescent " allosteric scorpionand " complex visualizes a biological recognition event.


Input: We describe a new class of fluorescent reporter and its employment to visualize the biotin/avidin binding interaction.

biotin


Input: Derivatives of the azamacrocycle cyclam that contain a pendant naphthalimide dye are inherently fluorescent when zinc (II) is coordinated.

cyclam

naphthalimide

zinc (II)


Input: Introducing a second pendant group--biotin--affords an unsymmetrical bis-triazole-scorpionand ligand that interacts specifically with avidin.

biotin

bis-triazole


Input: This ligand has been assembled by using a one-pot " double-click " strategy and complexed with copper (II) and zinc (II).

copper (II)

zinc (II)


Input: The zinc (II) complex is fluorescent, and its fluorescence output changes in the presence of avidin.

zinc (II)


Input: Upon avidin binding, the fluorescence output is diminished by interaction with the protein, at [complex]/[avidin] ratios of up to 4: 1.


Input: The observed change might arise from a specific quenching effect in the biotin binding pocket or from a binding-induced change in the coordination geometry of the complex.

biotin


Input: Promiscuous catalysis of asymmetric Michael-type additions of linear aldehydes to beta-nitrostyrene by the proline-based enzyme 4-oxalocrotonate tautomerase.

aldehydes

beta-nitrostyrene

proline


Input: Exploiting catalytic promiscuity: The proline-based enzyme 4-oxalocrotonate tautomerase (4-OT) promiscuously catalyzes asymmetric Michael-type additions of linear aldehydes--ranging from acetaldehyde to octanal--to trans-beta-nitrostyrene in aqueous solvent.

proline

aldehydes

acetaldehyde

octanal

trans-beta-nitrostyrene


Input: The presence of 1. 4 mol% of 4-OT effected formation of the anticipated gamma-nitroaldehydes in fair to good yields with dr values of up to 93: 7 and ee values of up to 81%.

gamma-nitroaldehydes


Input: Successful application of an ionic liquid carrying the fluoride counter-ion in biomacromolecular chemistry: microwave-assisted acylation of cellulose in the presence of 1-allyl-3-methylimidazolium fluoride/DMSO mixtures.

fluoride

1-allyl-3-methylimidazolium fluoride

DMSO


Input: The use of ionic liquids with fluoride anion (IL-F) is challenging because of side reactions.

fluoride


Input: Neat 1-allyl-3-methylimidazolium fluoride (AlMeImF) is used as a solvent in microwave-assisted acylation of cellulose.

1-allyl-3-methylimidazolium fluoride

AlMeImF


Input: The results are disappointing due to side reactions in the IL proper, and F (-)-mediated hydrolysis of the produced ester.

F (-)

ester


Input: A dramatic improvement is observed, when AlMeImF/DMSO mixture is employed.

AlMeImF

DMSO


Input: The results are comparable to those obtained when pure 1-allyl-3-methylimidazolium chloride is employed.

1-allyl-3-methylimidazolium chloride


Input: FTIR spectroscopy shows that dissolving a carboxylic acid anhydride in IL-F leads to the formation of acyl fluoride.

carboxylic acid anhydride

acyl fluoride


Input: Thus ILs are far from being " spectator " solvents.


Input: The new approach (use of IL-F/DMSO) is attractive because of its efficiency, low cost, and applicability to the derivatization of any polymer.

DMSO


Input: Semisynthesis and myocardial activity of thaliporphine N-homologues.

thaliporphine N


Input: The N-homologues and optical isomers of thaliporphine (5a), a potent antiarrhythmic agent, were prepared starting from laurolitsine (1), an abundant aporphine present in Phoebe formosana.

N

thaliporphine

laurolitsine

aporphine


Input: Treating N-propylnorglaucine with 90% H2SO4 yielded one additional product, an 11-sulfonyl-1, 11-anhydroaporphine.

N-propylnorglaucine

11-sulfonyl-1, 11-anhydroaporphine


Input: Reaction of N-formylnorglaucine (3a) with 90% H2SO4, however, yielded the 9-sulfonyl-seco product as a major product.

N-formylnorglaucine


Input: Treatment of 3a with 98% H2SO4 yielded pancordine (10), which, upon catalytic hydrogenation, yielded (+/-)-wilsonirine.

(+/-)-wilsonirine


Input: (1) H NMR spectroscopic analysis was applied successfully to monitor the optical purity of the crystalline salt while undertaking optical resolution.

(1) H


Input: Thaliporphine (5a) was demonstrated to possess better positive inotropic and less negative chronotropic effects than the left-hand optical isomer and showed the best activity on rat cardiac tissue among the N-homologues prepared.

Thaliporphine

N


Input: Surface transformations of Bioglass 45S5 during scaffold synthesis for bone tissue engineering.

Bioglass 45S5


Input: In physiological fluid, a layer of hydroxycarbonate apatite, similar to bone mineral, develops on the surface of Bioglass 45S5.

hydroxycarbonate apatite

Bioglass 45S5


Input: Collagen from the surrounding tissue is adsorbed on this layer that attracts osteoblasts, and favors bone regrowth.


Input: Bioglass is therefore an osteoinductive material.


Input: Still, due to its brittleness, the glass alone cannot be used to heal large bone defects.


Input: To overcome this issue, Bioglass is used to form a composite scaffold with poly (D, L-lactide) (PDLLA), a biodegradable polymer.

poly (D, L-lactide)

PDLLA


Input: The goal of this work is to understand Bioglass reactivity throughout scaffold fabrication via a low-temperature route, the solvent casting and particulate leaching technique.


Input: Changes in Bioglass (especially its surface) are susceptible to occur both while in contact with the processing fluids and potentially through a reaction with the surrounding polymeric matrix.


Input: Here we analyzed the surface changes of three different Bioglass samples: (i) as-received, (ii) treated in solutions that parallel those used in scaffold fabrication, and (iii) extracted from the scaffolds.


Input: We showed that extracted, just like treated, Bioglass deviates from the as-received, but to a larger extent.


Input: X-ray photoelectron and infrared spectroscopy support the theory that Bioglass surface was modified not just through contact with the solutions in scaffold fabrication, but upon an interaction with the polymeric matrix.


Input: The polymer network slows down the Na (+)/H (+) exchange between Bioglass and water used to leach salt particles to create pores within the scaffold.

Na (+)

H (+)


Input: Changes in surface properties affect the bioactivity of Bioglass and thus of the composite scaffolds, and are therefore critical to identify.


Input: Plasmonic coupling and long-range transfer of an excitation along a DNA nanowire.


Input: We demonstrate an excitation transfer along a fluorescently labeled dsDNA nanowire over a length of several micrometers.


Input: Launching of the excitation is done by exciting a localized surface plasmon mode of a 40 nm silver nanoparticle by 800 nm femtosecond laser pulses via two-photon absorption.

silver


Input: The plasmonic mode is subsequently coupled or transformed to excitation in the nanowire in contact with the particle and propagated along it, inducing bleaching of the dyes on its way.


Input: In situ as well as ex situ fluorescence microscopy is utilized to observe the phenomenon.


Input: In addition, transfer of the excitation along the nanowire to another nanoparticle over a separation of 5. 7 mu m was clearly observed.


Input: The nature of the excitation coupling and transfer could not be fully resolved here, but injection of an electron into the DNA from the excited nanoparticle and subsequent coupled transfer of charge (Dexter) and delocalized exciton (Frenkel) is the most probable mechanism.


Input: However, a direct plasmonic or optical coupling and energy transfer along the nanowire cannot be totally ruled out either.


Input: By further studies the observed phenomenon could be utilized in novel molecular systems, providing a long-needed communication method between molecular devices.


Input: Pharmacokinetics, metabolism, and excretion of the glycogen synthase kinase-3 inhibitor LY2090314 in rats, dogs, and humans: a case study in rapid clearance by extensive metabolism with low circulating metabolite exposure.


Input: LY2090314 (3-[9-fluoro-2-(piperidin-1-ylcarbonyl)-1, 2, 3, 4-tetrahydro [1, 4] diazepino [6, 7, 1-hi] indol-7-yl]-4-imidazo [1, 2-a] pyridin-3-yl-1H-pyrrole-2, 5-dione) is an intravenous glycogen synthase kinase-3 inhibitor in oncology trials.

3-[9-fluoro-2-(piperidin-1-ylcarbonyl)-1, 2, 3, 4-tetrahydro [1, 4] diazepino [6, 7, 1-hi] indol-7-yl]-4-imidazo [1, 2-a] pyridin-3-yl-1H-pyrrole-2, 5-dione


Input: Drug disposition was characterized after intravenous infusion of [(14) C] LY2090314 to rats and dogs, and was related to available clinical data.

[(14) C] LY2090314


Input: LY2090314 exhibited high clearance (approximating hepatic blood flow) and a moderate volume of distribution (~ 1-2 l/kg) resulting in rapid elimination (half-life ~ 0. 4, 0. 7, and 1. 8-3. 4 hours in rats, dogs, and humans, respectively).


Input: Scaled clearance from liver microsomes accurately predicted perfusion-limited clearance across species.


Input: LY2090314 was cleared by extensive metabolism, and the numerous metabolites were rapidly excreted into feces via bile (69-97% of dose; 62-93% within 0-24 hours); urinary recovery of drug-related material was low (<= 3% of dose).


Input: Despite extensive metabolism, in rats and humans the parent compound was the sole identifiable drug-related moiety in plasma.


Input: Even in Mdr1a-, Bcrp-, and Mrp2-knockout rats, LY2090314 metabolites did not appear in circulation, and their urinary excretion was not enhanced, because the hypothesized impaired biliary excretion of metabolites in the absence of these canalicular transporters was not observed.


Input: Canine metabolite disposition was generally similar, with the notable exception of dog-unique LY2090314 glucuronide.

LY2090314 glucuronide


Input: This conjugate was formed in the dog liver and was preferentially excreted into the blood, where it accounted for the majority of circulating radioactivity at later times, and was predominantly recovered in urine (16% of dose).


Input: In conclusion, LY2090314 was rapidly cleared by extensive metabolism with negligible circulating metabolite exposures due to biliary excretion of metabolites into feces with no apparent intestinal reabsorption.


Input: Three new phenolic compounds from the roots of Glycyrrhiza yunnanensis.

phenolic


Input: Three new phenolic compounds (1-3), together with 16 known compounds (4-19), were isolated from the roots of Glycyrrhiza yunnanensis Cheng f.

phenolic


Input: et L.


Input: K.


Input: Dai.


Input: On the basis of 1D and 2D NMR, HR-ESI-MS, and circular dichroism (CD) spectroscopic analysis, structures of the new compounds were elucidated as 2-(2'-methoxy-4'-hydroxy)-aryl-3-methy-6-hydroxy-benzofuran (1), (2S)-6, 7-(2, 2-dimethyldihydropyrano)-8-prenyl-4'-hydroxyflavanone (2), and 6-prenyl-7, 3', 4'-trihydroxyflavone (3).

2-(2'-methoxy-4'-hydroxy)-aryl-3-methy-6-hydroxy-benzofuran

(2S)-6, 7-(2, 2-dimethyldihydropyrano)-8-prenyl-4'-hydroxyflavanone

6-prenyl-7, 3', 4'-trihydroxyflavone


Input: Compounds 1, 3, 5, 12, 14, 15 and 16 showed antioxidant activity by an ABTS-based assay.

ABTS


Input: Identification of aldo-keto reductases as NRF2-target marker genes in human cells.


Input: Transcription factor NF-E2-related factor 2 (NRF2) plays a crucial role in the cellular defense against oxidative/electrophilic stress by up-regulating multiple antioxidant genes.


Input: Numerous studies with genetically modified animals have demonstrated that Nrf2 is a sensitivity determining factor upon the exposure to environmental chemicals including carcinogens.


Input: Moreover, recent studies have demonstrated that polymorphism in the human NRF2 promoter is associated with higher risks for developing acute lung injury, gastric mucosal inflammation, and nephritis.


Input: Therefore, the identification of reliable and effective human target genes of NRF2 may allow the monitoring of NRF2 activity and to predict individual sensitivity to environmental stress-induced damage.


Input: For this purpose, we investigated genes that are tightly controlled by NRF2 to establish markers for NRF2 activity in human cells.


Input: Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.

sulforaphane

tert-butylhydroquinone

cinnamic aldehyde

hydrogen peroxide


Input: Accordantly, the basal and inducible expressions of AKRs were significantly attenuated in NRF2-silenced HK-2 cells.


Input: Whereas, cells with stable KEAP1 knockdown, which causes a modest NRF2 activation, demonstrated substantially increased levels of AKR1A1, 1B1, 1B10, 1C1, 1C2, and 1C3.


Input: Secondly, the linkage between NRF2 and the AKRs was confirmed in human monocytic leukemia cell line U937, which can be a model of peripherally available blood cells.


Input: The treatment of U937 cells with NRF2 inducers including sulforaphane effectively elevated the expression of AKR1B1, 1B10, 1C1, 1C2, and 1C3.

sulforaphane


Input: Whereas, the levels of both the basal and sulforaphane-inducible expression of AKR1C1 were significantly reduced in NRF2-silenced stable U937 cells compared to the control cells.

sulforaphane


Input: Similarly, the inducible expression of AKR1C1 was observed in another human monocytic leukemia cell line THP-1 as well as in human primary blood CD14 (+) monocytes.


Input: In conclusion, together with the high inducibility and NRF2 dependency shown in renal epithelial cells as well as in peripherally available blood cells, current findings suggest that AKRs can be utilized as a marker of NRF2 activity in human cells.


Input: Mitochondrial dysfunction contributes to the cytotoxicity of some 3, 5-bis (benzylidene)-4-piperidone derivatives in colon HCT-116 cells.

3, 5-bis (benzylidene)-4-piperidone


Input: The objectives of this study are to investigate the possible ways by which the curcumin analogs 2a and 2b exert their antiproliferative properties.


Input: The analogs 2a and 2b have submicromolar IC (50) values towards human HCT-116 colon cancer cells but are far less toxic to human non-malignant CRL-1790 colon cells.


Input: Both compounds affected a number of mitochondrial functions in HCT-116 cells namely increasing the intracellular concentrations of reactive oxygen species, inhibiting oxygen consumption and decreasing the mitochondrial membrane potential.

oxygen

oxygen


Input: These molecules also produced swelling of isolated rat liver mitochondria, supporting a mitochondrial mechanism of cytotoxicity.


Input: Both compounds reacted with glutathione in the presence of glutathione S-transferase pi and hence they may be classified as thiol alkylators.

glutathione

glutathione S

thiol


Input: Preparation of apigenin nanocrystals using supercritical antisolvent process for dissolution and bioavailability enhancement.

apigenin


Input: The aim of the study was to investigate the potential of nanocrystals to enhance the oral bioavailability of apigenin (AP), a bioactive flavonoid with various pharmacological activities but poor aqueous solubility.

apigenin

flavonoid


Input: In the present investigation, the AP nanocrystals were prepared by the supercritical antisolvent process.


Input: In vitro characterization was performed by scanning electron microscopy, FT-IR, differential scanning calorimetry, X-ray powder diffractometry.


Input: In vitro dissolution of prepared nanocrystals was studied and compared with untreated coarse powder.


Input: In addition, the pharmacokinetic study of AP nanocrystals, in comparison to coarse powder, was also performed in rats after a single oral dose.


Input: The prepared AP nanocrystals, without change in crystalline structure, appeared in spherical shape with particle size of about 400-800 nm.


Input: The reduction of particle size resulted in a more rapid dissolution of AP from nanocrystals than from coarse powder.


Input: In comparison to coarse powder, AP nanocrystals exhibited a significantly decreased t (max), a 3. 6-fold higher peak plasma concentration (C (max)) and 3. 4-fold higher area under the curve (AUC).


Input: Effects of tris (1, 3-dichloro-2-propyl) phosphate and triphenyl phosphate on receptor-associated mRNA expression in zebrafish embryos/larvae.

tris (1, 3-dichloro-2-propyl) phosphate

triphenyl phosphate


Input: Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP) are frequently detected in biota, including fish.

Tris (1, 3-dichloro-2-propyl) phosphate

TDCPP

triphenyl phosphate

TPP


Input: However, knowledge of the toxicological and molecular effects of these currently used flame retardants is limited.


Input: In the present study, an in vivo screening approach was developed to evaluate effects of TDCPP and TPP on developmental endpoints and receptor-associated expression of mRNA in zebrafish embryos/larvae.

TDCPP

TPP


Input: Exposure to TDCPP or TPP resulted in significantly smaller rates of hatching and survival, in dose-and time-dependent manners.

TDCPP

TPP


Input: The median lethal concentration (LC (50)) was 7. 0 mg/L for TDCPP and 29. 6 mg/L for TPP at 120 hour post-fertilization (hpf).

TDCPP

TPP


Input: Real-time PCR revealed alterations in expression of mRNAs involved in aryl hydrocarbon receptors (AhRs)-, peroxisome proliferator-activated receptor alpha (PPAR alpha)-, estrogenic receptors (ERs)-, thyroid hormone receptor alpha (TR alpha)-, glucocorticoid receptor (GR)-, and mineralocorticoid receptor (MR)-centered gene networks.

aryl hydrocarbon

thyroid hormone


Input: Exposure to positive control chemicals significantly altered abundances of mRNA in corresponding receptor-centered gene networks, a result that suggests that it is feasible to use zebrafish embryos/larvae to evaluate effects of chemicals on mRNA expression in these gene networks.


Input: Exposure to TDCPP altered transcriptional profiles in all six receptor-centered gene networks, thus exerting multiple toxic effects.

TDCPP


Input: TPP was easily metabolized and its potency to change expression of mRNA involved in receptor-centered gene networks was weaker than that of TDCPP.

TPP

TDCPP


Input: The PPAR alpha-and TR alpha-centered gene networks might be the primary pathways affected by TPP.

TPP


Input: Taken together, these results demonstrated that TDCPP and TPP could alter mRNA expression of genes involved in the six receptor-centered gene networks in zebrafish embryos/larvae, and TDCPP seemed to have higher potency in changing the mRNA expression of these genes.

TDCPP

TPP

TDCPP


Input: Lipid composition of Chlorella vulgaris (Trebouxiophyceae) as a function of different cadmium and phosphate concentrations.

cadmium

phosphate


Input: Fatty acids are the fundamental structural components of membrane lipids, and the degree of saturation of the long hydrocarbon chains in microalgae contributes to regulation of growth, biomass production and reproduction of aquatic consumers.

Fatty acids

hydrocarbon


Input: This research aimed at evaluating the effects of cadmium (2 x 10 (-8); 10 (-7) mol L (-1) Cd) on lipid class and fatty acid composition of the microalga Chlorella vulgaris under varying phosphate (PO (4) (3-)) concentrations (6. 0 x 10 (-7) to 2. 3 x 10 (-4) mol L (-1)).

cadmium

Cd

fatty acid

phosphate

PO (4) (3-)


Input: Under PO (4) (3-) limitation and Cd stress, the storage lipid class triacylglycerol (TAG) was the most accumulated among the lipid classes.

PO (4) (3-)

Cd

triacylglycerol

TAG


Input: Fatty acid composition revealed that the degree of saturation increased with increasing Cd stress and PO (4) (3-) limitation.

Fatty acid

Cd

PO (4) (3-)


Input: Decreasing PO (4) (3-) and increasing Cd concentrations resulted in higher saturated fatty acid (SAFA) and monounsaturated FA (MUFA) concentrations.

PO (4) (3-)

Cd

saturated fatty acid

SAFA

monounsaturated FA

MUFA


Input: Total polyunsaturated FA (PUFA) and omega 3 PUFA, and PUFA: SAFA ratios were higher in the control (2. 3 x 10 (-4) mol L (-1) PO (4) (3-)) cells than in either PO (4) (3-) limitation or Cd stress, or in the combination of both stresses.

polyunsaturated FA

PUFA

omega 3 PUFA

PUFA

SAFA

PO (4) (3-)

PO (4) (3-)

Cd


Input: Contrasting with all the other PUFAs, 18: 2n-6 increased as PO (4) (3-) limitation increased.

PUFAs

PO (4) (3-)


Input: A significant positive relationship of PUFAs, acetone mobile polar lipids (AMPL) and phospholipids (PL) with phosphate concentration in the culture media was obtained, while TAG concentrations had a positive association with total MUFA and SAFA.

PUFAs

acetone

phosphate

TAG

MUFA

SAFA


Input: Total SAFA, 14: 0, 18: 1n-9 and 18: 2n-6 were positively correlated with Cd and negatively with PO (4) (3-) concentrations.

SAFA

Cd

PO (4) (3-)


Input: The microalga responded to combined PO (4) (3-) limitation and Cd exposure by increasing its total lipid production and significantly altering its lipid composition.

PO (4) (3-)

Cd


Input: The FA 18: 2n-6 may be considered a stress biomarker for PO (4) (3-) limitation and Cd stress in C. vulgaris.

PO (4) (3-)

Cd


Input: Mammalian complex I pumps 4 protons per 2 electrons at high and physiological proton motive force in living cells.


Input: Mitochondrial complex I couples electron transfer between matrix NADH and inner-membrane ubiquinone to the pumping of protons against a proton motive force.

NADH

ubiquinone


Input: The accepted proton pumping stoichiometry was 4 protons per 2 electrons transferred (4H (+)/2e (-)) but it has been suggested that stoichiometry may be 3H (+)/2e (-) based on the identification of only 3 proton pumping units in the crystal structure and a revision of the previous experimental data.

4H (+)

3H (+)


Input: Measurement of proton pumping stoichiometry is challenging because, even in isolated mitochondria, it is difficult to measure the proton motive force while simultaneously measuring the redox potentials of the NADH/NAD (+) and ubiquinol/ubiquinone pools.

NADH

NAD (+)

ubiquinol

ubiquinone


Input: Here we employ a new method to quantify the proton motive force in living cells from the redox poise of the bc (1) complex measured using multiwavelength cell spectroscopy and show that the correct stoichiometry for complex I is 4H (+)/2e (-) in mouse and human cells at high and physiological proton motive force.

4H (+)


Input: Probing circulating tumor cells in microfluidics.


Input: Circulating tumor cells (CTCs) are important targets for study as we strive to better understand, diagnose, and treat cancers.


Input: However, CTCs are found in blood at extremely low concentrations; this makes isolation, enrichment, and characterization of CTCs technically challenging.


Input: Recently, the development of CTC separation devices has grown rapidly in both academia and industry.


Input: Part of this development effort centered on microfluidic platforms, exploiting the advantages of microfluidics to improve CTC separation performance and device integration.


Input: In this Focus article, we highlight some of the recent work in microfluidic CTC separation and detection systems and discuss our appraisal of what the field should do next.


Input: The hepatoprotection of caffeic acid and rosmarinic acid, major compounds of Perilla frutescens, against t-BHP-induced oxidative liver damage.

caffeic acid

rosmarinic acid

t-BHP


Input: Perilla frutescens leaves are often used in East Asian gourmet food.


Input: In this study, we investigated the hepatoprotective effects of caffeic acid (CA), rosmarinic acid (RA), and their combination.

caffeic acid

rosmarinic acid


Input: P. frutescens contains 1. 32 mu g CA/mg dry material (DM) and 26. 84 mu g RA/mg DM analyzed by HPLC-DAD and HPLC-MS.


Input: CA remarkably reduced the oxidative damage than rosmarinic acid in an in vitro study.

rosmarinic acid