Input: We have studied the interactions of three bile acid-tamoxifen conjugates, lithocholic acid-tamoxifen (LA-Tam (1)-Am), deoxycholic acid-tamoxifen (DCA-Tam (2)-Am), and cholic acid-tamoxifen (CA-Tam (3)-Am), possessing 1-3 tamoxifen molecules having an amine headgroup with model DPPC membranes and compared with N-desmethylated tamoxifen (TamNHMe) using DPH based fluorescence anisotropy, Prodan based hydration, and differential scanning calorimetry studies.

bile acid

tamoxifen

lithocholic acid

tamoxifen

LA-Tam

deoxycholic acid

tamoxifen

DCA-Tam

cholic acid

tamoxifen

CA-Tam

tamoxifen

amine

DPPC

N-desmethylated tamoxifen

TamNHMe

DPH

Prodan


Input: DPH based anisotropy studies showed that bile acid-tamoxifen conjugates increase membrane fluidity, which strongly depends on the number of tamoxifen molecules conjugated to bile acid and the percentage of doping of bile acid-tamoxifen conjugates in the DPPC membranes.

DPH

bile acid

tamoxifen

tamoxifen

bile acid

bile acid

tamoxifen

DPPC


Input: The order of membrane fluidity of the coliposomes from bile acid-tamoxifen conjugates and DPPC lipids in gel phase was found to be CA-Tam (3)-Am > DCA-Tam (2)-Am > LA-Tam (1)-Am > TamNHMe.

bile acid

tamoxifen

DPPC

CA-Tam

DCA-Tam

LA-Tam

TamNHMe


Input: Incorporation of bile acid-tamoxifen conjugates showed an unusual complex behavior of membrane hydration, as evident from Prodan based hydration studies.

bile acid

tamoxifen

Prodan


Input: Temperature dependent study showed incorporation of LA-Tam (1)-Am and DCA-Tam (2)-Am conjugates decreases membrane hydration with an increase in temperature up to the phase transition temperature (T (m)).

LA-Tam

DCA-Tam


Input: Differential scanning calorimetry studies showed a decrease in phase transition temperature (T (m)) upon an increase in the percentage of doping of TamNHMe and CA-Tam (3)-Am, whereas LA-Tam (1)-Am and DCA-Tam (2)-Am do not cause a major change in the phase transition temperature (T (m)) of DPPC liposomes.

TamNHMe

CA-Tam

LA-Tam

DCA-Tam

DPPC


Input: These studies showed the differential behavior of bile acid-tamoxifen conjugates regulating the membrane fluidity, hydration, and phase transition of model membranes depending upon the percentage of doping and tamoxifen conjugation to bile acids.

bile acid

tamoxifen

tamoxifen

bile acids


Input: Understanding and Controlling Morphology Formation in Langmuir-Blodgett Block Copolymer Films Using PS-P4VP and PS-P4VP/PDP.

PDP


Input: This contribution offers a comprehensive understanding of the factors that govern the morphologies of Langmuir-Blodgett (LB) monolayers of amphiphilic diblock copolymers (BCs).


Input: This is achieved by a detailed investigation of a wide range of polystyrene-poly (4-vinyl pyridine) (PS-P4VP) block copolymers, in contrast to much more limited ranges in previous studies.

polystyrene-poly (4-vinyl pyridine)


Input: Parameters that are varied include the block ratios (mainly for similar total molecular weights, occasionally other total molecular weights), the presence or not of 3-n-pentadecylphenol (PDP, usually equimolar with VP, with which it hydrogen bonds), the spreading solution concentration (" low " and " high "), and the LB technique (standard vs " solvent-assisted ").

PDP

hydrogen


Input: Our observations are compared with previously published results on other amphiphilic diblock copolymers, which had given rise to contradictory interpretations of morphology formation.


Input: Based on the accumulated results, we re-establish early literature conclusions that three main categories of LB block copolymer morphologies are obtained depending on the block ratio, termed planar, strand, and dot regimes.


Input: The block composition boundaries in terms of mol% block content are shown to be similar for all BCs having alkyl chain substituents on the hydrophilic block (such as PS-P4VP/PDP) and are shifted to higher values for BCs with no alkyl chain substituents (such as PS-P4VP).

PDP


Input: This is attributed to the higher surface area per repeat unit of the hydrophilic block monolayer on the water surface for the former, as supported by the onset and limiting areas of the Langmuir isotherms for the BCs in the dot regime.


Input: 2D phase diagrams are discussed in terms of relative effective surface areas of the two blocks.


Input: We identify and discuss how kinetic effects on morphology formation, which have been highlighted in more recent literature, are superposed on the compositional effects.


Input: The kinetic effects are shown to depend on the morphology regime, most strongly influencing the strand and, especially, planar regimes, where they give rise to a diversity of specific structures.


Input: Besides film dewetting mechanisms, which are different when occurring in structured versus unstructured films (the latter previously discussed in the literature), kinetic influences are discussed in terms of chain association dynamics leading to depletion effects that impact on growing aggregates.


Input: These depletion effects particularly manifest themselves in more dilute spreading solutions, with higher molecular weight polymers, and in composition regimes characterized by equilibrium degrees of aggregation that are effectively infinite.


Input: It is by understanding these various kinetic influences that the diversity of structures can be classified by the three main composition-dependent regimes.


Input: Robust array-based coregulator binding assay predicting ER alpha-agonist potency and generating binding profiles reflecting ligand structure.


Input: Testing chemicals for their endocrine-disrupting potential, including interference with estrogen receptor (ER) signaling, is an important aspect of chemical safety testing.

estrogen


Input: Because of the practical drawbacks of animal testing, the development of in vitro alternatives for the uterotrophic assay and other in vivo (anti) estrogenicity tests has high priority.


Input: It was previously demonstrated that an in vitro assay that profiles ligand-induced binding of ER alpha to a microarray of coregulator-derived peptides might be a valuable candidate for a panel of in vitro assays aiming at an ultimate replacement of the uterotrophic assay.


Input: In the present study, the reproducibility and robustness of this coregulator binding assay was determined by measuring the binding profiles of 14 model compounds that are recommended by the Office of Prevention, Pesticides and Toxic Substances for testing laboratory proficiency in estrogen receptor transactivation assays.

estrogen


Input: With a median coefficient of variation of 5. 0% and excellent correlation (R (2) = 0. 993) between duplicate measurements, the reproducibility of the ER alpha-coregulator binding assay was better than the reproducibility of other commonly used in vitro ER functional assays.


Input: In addition, the coregulator binding assay is correctly predicting the estrogenicity for 13 out of 14 compounds tested.


Input: When the potency of the ER-agonists to induce ER alpha-coregulator binding was compared to their ER binding affinity, their ranking was similar, and the correlation between the EC50 values was excellent (R (2) = 0. 96), as was the correlation with their potency in a transactivation assay (R (2) = 0. 94).


Input: Moreover, when the ER alpha-coregulator binding profiles were hierarchically clustered using Euclidian cluster distance, the structurally related compounds were found to cluster together, whereas the steroid test compounds having an aromatic A-ring were separated from those with a cyclohexene A-ring.

steroid

cyclohexene


Input: We concluded that this assay is capable of distinguishing ER alpha agonists and antagonists and that it even reflects the structural similarity of ER alpha agonists, indicating a potential to achieve identification and classification of ER alpha endocrine disruptors with high fidelity.


Input: Two-photon circular-linear dichroism of perylene in solution: a theoretical-experimental study.

perylene


Input: Herein, we report on the theoretical-experimental analysis of the two-photon absorption (TPA) and two-photon circular-linear dichroism (TPCLD) spectra of a highly conjugated, rigid, and centrosymmetric molecule in solution, that is, perylene/CH2Cl2.

perylene


Input: We show how a three-energy-level diagram, under the sum-over-essential states approach, assists in the determination of the magnitude of transition electric dipole moments and the angle between them for the main TPA transitions.


Input: We demonstrate the potential of TPCLD to reveal the symmetry of excited states and the angles between their transition electric dipole moments and that of the ground state.


Input: By means of TPCLD, we explain how the overwhelming contribution of certain TPA transitions can mask important spectral features in regions where the transition electric dipole moments are perpendicular.


Input: TPCLD is expected to enhance the understanding of the photophysical properties of materials that are not accessible using conventional linear and two-photon spectroscopy.


Input: TPA and TPCLD measurements were performed employing the open-aperture Z-scan technique using an amplified femtosecond system.


Input: Time-dependent density functional theory (TD-DFT) calculations were carried out using response theory at the B3LYP level with the aug-cc-pVDZ basis set.


Input: Solvent effects were included through the polarizable continuum model (PCM).


Input: Molecular imaging by optically detected electron spin resonance of nitrogen-vacancies in nanodiamonds.

nitrogen


Input: We propose a novel biomedical imaging technique, called nanodiamond imaging, that noninvasively records the three-dimensional distribution of biologically tagged nanodiamonds in vivo.


Input: Our technique performs optically detected electron spin resonance of nitrogen-vacancy centers in nanodiamonds, a nontoxic nanomaterial that is easily biologically functionalized.

nitrogen


Input: We demonstrate the feasibility of the technique by imaging multiple nanodiamond targets within pieces of chicken breast; it is the first demonstration of imaging within scattering tissue by optically detected magnetic resonance.


Input: We achieve a sensitivity equivalent to 740 pg of nanodiamond in 100 s of measurement time and a spatial resolution of 800 mu m over a 1 cm (2) field of view, and we show how the technique has the potential to yield images with combined high sensitivity (~ 100 fg nanodiamond) AND high spatial resolution (~ 100 mu m) over organism-scale fields of view, features which are mutually exclusive in existing imaging modalities except at the shallowest imaging depths.


Input: Novel acylethanolamide derivatives that modulate body weight through enhancement of hypothalamic pro-opiomelanocortin (POMC) and/or decreased neuropeptide Y (NPY).

acylethanolamide


Input: Newly synthesized acylethanolamide derivatives oleoyl-L-valinolamide (1), oleoyl-D-valinolamide (2), elaidoyl-L-valinolamide (3), elaidoyl-D-valinolamide (4) stearoyl-L-valinolamide (5), and palmitoyl-L-valinolamide (6) were investigated in mice as antiobesity compounds.

acylethanolamide

oleoyl-L-valinolamide

oleoyl-D-valinolamide

elaidoyl-L-valinolamide

elaidoyl-D-valinolamide

stearoyl-L-valinolamide

palmitoyl-L-valinolamide


Input: Compounds 1, 2, 5, 6 significantly decreased body weight by 6. 57% following eight injections of 1 mg/kg i. p. during 39 days, while 3 and 4 showed no such activity.


Input: Receptor binding indicated that no compound activated CB1, CB2, PPAR alpha, or TRPV1 receptors.


Input: Hypothalamic RT-PCR showed that mRNA expression of the anorexigenic genes POMC and CART was up-regulated by 1, 2, 5 and 1, 2, respectively, while that of the orexigenic genes NPY and CaMKK2 was down-regulated by the respective compounds 1, 5, 6 and 1, 2, 5.


Input: Oleoyl-L-valinolamide enhances anorectic pathways and lead to decreased glucose levels, enhanced locomotor activity, and improved cognition.

Oleoyl-L-valinolamide

glucose


Input: Effects of oleoyl-L-valinolamide on weight were dose-dependent, and it could be given orally.

oleoyl-L-valinolamide


Input: 1, 2, 4, 5 down-regulated FAAH mRNA expression.


Input: The effect of inorganic arsenic on endothelium-dependent relaxation: Role of NADPH oxidase and hydrogen peroxide.

arsenic

NADPH

hydrogen peroxide


Input: Chronic arsenic ingestion predisposes to vascular disease, but underlying mechanisms are poorly understood.

arsenic


Input: In the present study we have analyzed the effects of short-term arsenite exposure on vascular function and endothelium-dependent relaxation.

arsenite


Input: Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the G protein-coupled receptor agonist acetylcholine (ACh) and by cyclopiazonic acid (CPA), which promotes store-operated Ca (2 +) entry by inhibiting the endothelial SERCA pump.

nitric oxide

NO

acetylcholine

ACh

cyclopiazonic acid

CPA

Ca (2 +)


Input: Production of reactive oxygen species (ROS) in the endothelium of rabbit aortic valve leaflets and endothelium-denuded RIA and aortic rings was assessed by imaging of dihydroethidium.

oxygen

dihydroethidium


Input: In the iliac artery, exposure to 100 mu M arsenite for 30min potentiated EDHF-type relaxations evoked by both CPA and ACh.

arsenite

CPA

ACh


Input: Potentiation was prevented by catalase, the catalase/superoxide dismutase mimetic manganese porphyrin and the NADPH oxidase inhibitor apocynin.

superoxide

manganese porphyrin

NADPH

apocynin


Input: By contrast in aortic rings, that exhibited negligible EDHF-type responses, endothelium-dependent NO-mediated relaxations evoked by CPA and ACh were unaffected by arsenite.

NO

CPA

ACh

arsenite


Input: Arsenite induced apocynin-sensitive increases in ROS production in the aortic valve endothelium, but not in the media and adventitia of the iliac artery and aorta.

Arsenite

apocynin


Input: Our results suggest that arsenite can potentiate EDHF-type relaxations via a mechanism that is dependent on hydrogen peroxide, thus demonstrating that dismutation of the superoxide anion generated by NADPH oxidase can potentially offset loss of NO bioavailability under conditions of reduced eNOS activity.

arsenite

hydrogen peroxide

superoxide

NADPH

NO


Input: By contrast, selective increases in endothelial ROS production following exposure to arsenite failed to modify relaxations mediated by endogenous NO.

arsenite

NO


Input: Comparative analysis of human CYP3A4 and rat CYP3A1 induction and relevant gene expression by bisphenol A and diethylstilbestrol: implications for toxicity testing paradigms.

bisphenol A

diethylstilbestrol


Input: Bisphenol A (BPA) and diethylstilbestrol (DES) are endocrine-disrupting chemicals that interact with the human pregnane X receptor (PXR).

Bisphenol A

BPA

diethylstilbestrol

DES


Input: CYP3A4 enzyme is essential in the hydroxylation of steroid hormones and is regulated by PXR.

steroid


Input: In the present study, human and rat hepatoma cell lines were exposed to BPA and DES.


Input: Both BPA and DES (10-50 mu M) caused a significant activation of the CYP3A4 promoter via the PXR in the DPX2 human hepatoma cell line.

BPA

DES


Input: No activation of rat PXR was seen.


Input: BPA and DES treated DPX2 cells demonstrated increased expression of CYP3A4 mRNA, and increased enzyme activity.

BPA

DES


Input: In summary, BPA, in concentrations relevant to current safety levels of human exposure, activates the human PXR and demonstrates an increase in CYP3A4 mRNA expression and enzyme activity.

BPA


Input: BPA actions in this model system occur to a greater extent than DES.

BPA

DES


Input: This study raises concerns regarding our current toxicity testing paradigms and species utilization.


Input: Regulation of amino acid metabolism as a defensive strategy in the brain of three freshwater teleosts in response to high environmental ammonia exposure.

amino acid

ammonia


Input: Many teleosts have evolved mechanisms to cope with ammonia toxicity in the brain when confronted with high environmental ammonia (HEA).

ammonia

ammonia


Input: In the present study, the possible role of conversion of accumulated ammonia to glutamine and other free amino acids in the brain of three freshwater teleosts differing in their sensitivities to ammonia was investigated.

ammonia

glutamine

amino acids

ammonia


Input: The detoxification mode of ammonia in brain is suggested to be through amination of glutamate to glutamine by the coupled activities of glutamate dehydrogenase (GDH), transaminase (aspartate aminotransaminase' AST' and alanine aminotransaminase' ALT') and glutamine synthetase (GSase).

ammonia

glutamate

glutamine

glutamate

aspartate

alanine

glutamine


Input: We investigated the metabolic response of amino acids in the brain of highly sensitive salmonid Oncorhynchus mykiss (rainbow trout), the less sensitive cyprinid Cyprinus carpio (common carp) and the highly resistant cyprinid Carassius auratus (goldfish) when exposed to 1mM ammonia (as NH4HCO3; pH 7. 9) for 0 h (control), 3 h, 12 h, 24 h, 48 h, 84 h and 180 h.

amino acids

ammonia


Input: Results show that HEA exposure increased ammonia accumulation significantly in the brain of all the three species from 12h onwards.

ammonia


Input: Unlike in trout, ammonia accumulation in carp and goldfish was restored to control levels (48-84h); which was accompanied with a significant increase in glutamine content as well as GSase activity.

ammonia

glutamine


Input: In trout, glutamine levels also increased (84-180 h) but GSase was not activated.

glutamine


Input: The elevated glutamine level in trout was accompanied by a significant depletion of the glutamate pool in contrast to the stable glutamate levels seen in carp and goldfish.

glutamine

glutamate

glutamate


Input: This suggests a simultaneous increase in the rate of glutamate formation to match with the demand of glutamine formation in cyprinids.

glutamate

glutamine


Input: The activity of GDH was elevated significantly in carp and goldfish but remained unaltered in trout.


Input: Also, the transaminase enzymes (AST and ALT) were elevated significantly in exposed carp and goldfish while only ALT was up-regulated in trout.


Input: Consequently, in carp and goldfish both aspartate and alanine were utilized under HEA, whereas only alanine was consumed in trout.

aspartate

alanine

alanine


Input: With ammonia treatment, significant changes in concentrations of other amino acids also occurred.

ammonia

amino acids


Input: None of the species could detoxify brain ammonia into urea.

ammonia


Input: This study suggests that protective strategies to combat ammonia toxicity in brain are more pronounced in carp and goldfish than in trout.

ammonia


Input: Basic N-interlinked imipramines show apoptotic activity against malignant cells including Burkitt' s lymphoma.

N

imipramines


Input: We here report the synthesis of ethylene glycol N-interlinked imipramine dimers of various lengths from the tricyclic antidepressant desipramine via an amide coupling reaction followed by reduction with lithium aluminium hydride.

ethylene glycol N

imipramine

desipramine

lithium aluminium hydride


Input: The target molecules were found to be potent inhibitors of cellular viability while inducing cell type specific death mechanisms in three cancer cell lines including a highly chemoresistant Burkitt' s lymphoma cell line.


Input: Basic amine analogues were found to be important for increased potency.

amine


Input: Imipramine and desipramine were also tested for apoptotic activity and were found to be much less active than the novel dimeric compounds.

Imipramine

desipramine


Input: Imipramine dimers were only found to be moderate inhibitors of the human serotonin transporter (hSERT) having IC (50) values in the micromolar region whilst the induction of cell death occurred independently of hSERT expression.

Imipramine

serotonin


Input: These results demonstrate the potential of newly designed and synthesised imipramines derivatives for use against malignant cells, including those resistant to standard chemotherapy.

imipramines


Input: Water ice nanoparticles: size and temperature effects on the mid-infrared spectrum.


Input: Mid-infrared spectra have been measured for cubic ice (I (c)) nanoparticles (3-150 nm diameter) formed by rapid collisional cooling over a wide range of temperatures (5-209 K).


Input: Spectral diagnostics, such as the ratio of surface related dangling OH to interior H-bonded OH stretch bands, reveal the manner in which particle size depends on bath gas temperature and density, and on water molecule concentration.

OH

H

OH


Input: For particles smaller than 5 nm strained intermolecular bonds on the surface and subsurface cause the predominant OH stretch peak position to be dramatically blue shifted by up to 40 cm (-1).

OH


Input: In the size regime of 8-200 nm the position of the OH stretch absorption band maximum is relatively unaffected by particle size and it is possible to measure the temperature dependence of the peak location without influences from the surface or scattering.

OH


Input: The band maximum shifts in a linear fashion from 3218 cm (-1) at 30 K to 3253 cm (-1) at 209 K, which may assist with temperature profiling of ice particles in atmospheric clouds and extraterrestrial systems.


Input: Over the same temperature range the librational mode band shifts very little, from 870 to 860 cm (-1).


Input: In the water stretching and bending regions discrete spectral features associated with the surface or sub-surface layers have been detected in particles as large as 80 nm.


Input: Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options.


Input: Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a genetically and clinically heterogeneous group of autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs.


Input: MDS are due to defects in mtDNA maintenance caused by mutations in nuclear genes that function in either mitochondrial nucleotide synthesis (TK2, SUCLA2, SUCLG1, RRM2B, DGUOK, and TYMP) or mtDNA replication (POLG and C10orf2).


Input: MDS are phenotypically heterogeneous and usually classified as myopathic, encephalomyopathic, hepatocerebral or neurogastrointestinal.


Input: Myopathic MDS, caused by mutations in TK2, usually present before the age of 2 years with hypotonia and muscle weakness.


Input: Encephalomyopathic MDS, caused by mutations in SUCLA2, SUCLG1, or RRM2B, typically present during infancy with hypotonia and pronounced neurological features.


Input: Hepatocerebral MDS, caused by mutations in DGUOK, MPV17, POLG, or C10orf2, commonly have an early-onset liver dysfunction and neurological involvement.


Input: Finally, TYMP mutations have been associated with mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease that typically presents before the age of 20 years with progressive gastrointestinal dysmotility and peripheral neuropathy.


Input: Overall, MDS are severe disorders with poor prognosis in the majority of affected individuals.


Input: No efficacious therapy is available for any of these disorders.


Input: Affected individuals should have a comprehensive evaluation to assess the degree of involvement of different systems.


Input: Treatment is directed mainly toward providing symptomatic management.


Input: Nutritional modulation and cofactor supplementation may be beneficial.


Input: Liver transplantation remains controversial.


Input: Finally, stem cell transplantation in MNGIE disease shows promising results.


Input: Vascular endothelial growth factor induces growth of uterine cervix and immune cell recruitment in mice.


Input: Knowledge of uterine cervical epithelial biology and factors that influence its events may be critical in understanding the process of cervical remodeling (CR).


Input: Here, we examine the impact of exogenous vascular endothelial growth factor (VEGF) on uterine cervical epithelial growth in mice (nonpregnant and pregnant) treated with VEGF agents (recombinant and inhibitor) using a variety of morphological and molecular techniques.


Input: Exogenous VEGF altered various uterine cervical epithelial cellular events, including marked induction of growth, edema, increase in inter-epithelial paracellular space, and recruitment of immune cells to the outer surface of epithelial cells (cervical lumen).


Input: We conclude that VEGF induces multiple alterations in the uterine cervical epithelial tissues that may play a role in local immune surveillance and uterine cervical growth during CR.


Input: Upregulation of nuclear factor of activated T-cells by nerve injury contributes to development of neuropathic pain.


Input: Nerve injury induces long-term changes in gene expression in the nociceptive circuitry and can lead to chronic neuropathic pain.


Input: However, the transcriptional mechanism involved in neuropathic pain is poorly understood.


Input: Nuclear factor of activated T-cells (NFATc) is a transcriptional factor regulated by the Ca (2 +)-dependent protein phosphatase calcineurin.

Ca (2 +)


Input: In this study, we determined nerve injury-induced changes in the expression of NFATc1-c4 in the dorsal root ganglia (DRG) and spinal cords and their role in the development of neuropathic pain.


Input: The mRNA of NFATc1-c4 was detected in the rat DRG and dorsal spinal cord.


Input: Nerve injury transiently elevated NFATc1-c3 mRNA levels and persistently increased NFATc4 and C-C chemokine receptor type 2 (CCR2) mRNA levels in the DRG.


Input: However, NFATc1-c4 mRNA levels in the spinal cord were not altered significantly by nerve injury.


Input: Nerve injury also significantly increased the protein level of dephosphorylated NFATc4 in the DRG.


Input: Intrathecal injection of the specific NFATc inhibitor 11R-VIVIT or the calcineurin inhibitor FK-506 (tacrolimus) early after nerve injury significantly attenuated the development of tactile allodynia.

tacrolimus


Input: In addition, treatment with FK-506 or 11R-VIVIT significantly reduced the mRNA levels of NFATc4 and CCR2 but not large-conductance Ca (2 +)-activated K (+) channels, in the DRG after nerve injury.

Ca (2 +)

K (+)


Input: Our findings suggest that peripheral nerve injury causes a time-dependent change in NFATc1-c4 expression in the DRG.


Input: Calcineurin-NFATc-mediated expression of pronociceptive cytokines contributes to the transition from acute to chronic pain after nerve injury.


Input: Synthesis and biological evaluation of purine 2'-fluoro-2'-deoxyriboside ProTides as anti-influenza virus agents.

purine 2'-fluoro-2'-deoxyriboside


Input: 2'-Fluoro-2'-deoxyguanosine has been reported to have potent anti-influenza virus activity in vitro and in vivo.


Input: Herein we describe the synthesis and biological evaluation of 6-modified 2'-fluoro-2'-deoxyguanosine analogues and their corresponding phosphoramidate ProTides as potential anti-influenza virus agents.

phosphoramidate


Input: Whereas the parent nucleosides were devoid of antiviral activity in two different cellular assays, the 5'-O-naphthyl (methoxy-L-alaninyl) ProTide derivatives of 6-O-methyl-2'-fluoro-2'-deoxyguanosine, 6-O-ethyl-2'-fluoro-2'-deoxyguanosine, and 2'-deoxy-2'-fluoro-6-chloroguanosine, and the 5'-O-naphthyl (ethoxy-L-alaninyl) ProTide of 6-O-ethyl-2'-fluoro-2'-deoxyguanosine displayed antiviral EC (99) values of ~ 12 mu M.

nucleosides

5'-O-naphthyl (methoxy-L-alaninyl)

5'-O-naphthyl (ethoxy-L-alaninyl)


Input: The antiviral results are supported by metabolism studies.


Input: Rapid conversion into the L-alaninyl metabolite and then 6-modified 2'-fluoro-2'-deoxyguanosine 5'-monophosphate was observed in enzymatic assays with yeast carboxypeptidase Y or crude cell lysate.

L-alaninyl

2'-fluoro-2'-deoxyguanosine 5'-monophosphate


Input: Evidence for efficient removal of the 6-substituent on the guanine part was provided by enzymatic studies with adenosine deaminase, and by molecular modeling of the nucleoside 5'-monophosphates in the catalytic site of a model of ADAL1, thus indicating the utility of the double prodrug concept.

guanine

adenosine

nucleoside 5'-monophosphates


Input: Ezogabine: a novel antiepileptic for adjunctive treatment of partial-onset seizures.

Ezogabine


Input: Epilepsy is defined as a tendency toward recurrent seizures unprovoked by any systemic or acute neurologic insults.


Input: It is a disruption of the electrical conductivity or activity in the brain, resulting in a seizure.


Input: In the United States, approximately 120 of every 100, 000 people seek medical attention due to new seizure activity.


Input: Ezogabine, known as retigabine in Europe, is an ethyl N-(2-amino-4-[{fluorophenyl} methlamino] phenylcarbamate).

Ezogabine

retigabine

ethyl N-(2-amino-4-[{fluorophenyl} methlamino] phenylcarbamate)


Input: The drug has been approved by the United States Food and Drug Administration (FDA) and European Medicines Agency for adjunctive treatment of partial-onset seizures in adults.


Input: Ezogabine exerts its therapeutic effect by enhancing transmembrane potassium channels (KCNQ ion channels), which is a novel mechanism in comparison with other antiepileptics.

Ezogabine

potassium


Input: There are no specific documented contraindications to ezogabine.

ezogabine


Input: Warnings target patients that have benign prostatic hyperplasia or are receiving concomitant anticholinergic drugs due to a risk of urinary retention (2%).


Input: The FDA has required that ezogabine be part of a risk evaluation and mitigation strategy program in order to inform health care professionals of the risk of urinary retention.

ezogabine


Input: Prescribers should inform patients that ezogabine can cause urinary retention, including urinary hesitation, and instruct them to seek immediate medical attention if these symptoms occur.

ezogabine


Input: A medication guide has been developed for distribution to patients.


Input: The role of human carboxylesterases in drug metabolism: have we overlooked their importance?


Input: Carboxylesterases are a multigene family of mammalian enzymes widely distributed throughout the body that catalyze the hydrolysis of esters, amides, thioesters, and carbamates.

esters

amides

thioesters

carbamates


Input: In humans, two carboxylesterases, hCE1 and hCE2, are important mediators of drug metabolism.


Input: Both are expressed in the liver, but hCE1 greatly exceeds hCE2.


Input: In the intestine, only hCE2 is present and highly expressed.


Input: The most common drug substrates of these enzymes are ester prodrugs specifically designed to enhance oral bioavailability by hydrolysis to the active carboxylic acid after absorption from the gastrointestinal tract.

ester

carboxylic acid


Input: Carboxylesterases also play an important role in the hydrolysis of some drugs to inactive metabolites.


Input: It has been widely believed that drugs undergoing hydrolysis by hCE1 and hCE2 are not subject to clinically significant alterations in their disposition, but evidence exists that genetic polymorphisms, drug-drug interactions, drug-disease interactions and other factors are important determinants of the variability in the therapeutic response to carboxylesterase-substrate drugs.


Input: The implications for drug therapy are far-reaching, as substrate drugs include numerous examples from widely prescribed therapeutic classes.


Input: Representative drugs include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antiplatelet drugs, statins, antivirals, and central nervous system agents.

statins


Input: As research interest increases in the carboxylesterases, evidence is accumulating of their important role in drug metabolism and, therefore, the outcomes of pharmacotherapy.


Input: Recommendations for meeting the pediatric patient' s need for a clinical pharmacist: a joint opinion of the Pediatrics Practice and Research Network of the American College of Clinical Pharmacy and the Pediatric Pharmacy Advocacy Group.


Input: Children warrant access to care from clinical pharmacists trained in pediatrics.


Input: The American College of Clinical Pharmacy Pediatrics Practice and Research Network (ACCP Pediatrics PRN) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships.


Input: Although progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients.


Input: The purpose of this joint opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by elevating the minimum expectations for pharmacists entering pediatric practice, standardizing pediatric pharmacy education, expanding the current number of pediatric clinical pharmacists, and creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists.


Input: These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, and research initiatives.


Input: Toll-like receptor 2 mediates peripheral nerve injury-induced NADPH oxidase 2 expression in spinal cord microglia.

NADPH


Input: We have previously reported that NADPH oxidase 2 (Nox2) is up-regulated in spinal cord microglia after spinal nerve injury, demonstrating that it is critical for microglia activation and subsequent pain hypersensitivity.

NADPH


Input: However, the mechanisms and molecules involved in Nox2 induction have not been elucidated.


Input: Previous studies have shown that Toll-like receptors (TLRs) are involved in nerve injury-induced spinal cord microglia activation.


Input: In this study, we investigated the role of TLR in Nox2 expression in spinal cord microglia after peripheral nerve injury.


Input: Studies using TLR knock-out mice have shown that nerve injury-induced microglial Nox2 up-regulation is abrogated in TLR2 but not in TLR3 or-4 knock-out mice.


Input: Intrathecal injection of lipoteichoic acid, a TLR2 agonist, induced Nox2 expression in spinal cord microglia both at the mRNA and protein levels.


Input: Similarly, lipoteichoic acid stimulation induced Nox2 expression and reactive oxygen species production in primary spinal cord glial cells in vitro.

oxygen


Input: Studies on intracellular signaling pathways indicate that NF-kappa B and p38 MAP kinase activation is required for TLR2-induced Nox2 expression in glial cells.


Input: Conclusively, our data show that TLR2 mediates nerve injury-induced Nox2 gene expression in spinal cord microglia via NF-kappa B and p38 activation and thereby may contribute to spinal cord microglia activation.


Input: Serum levels of 25-hydroxyvitamin D and the CYP3A biomarker 4 beta-hydroxycholesterol in a high-dose vitamin D supplementation study.

25-hydroxyvitamin D

4 beta-hydroxycholesterol

vitamin D


Input: The primary aim was to study the relationship between individual serum levels of 25-hydroxyvitamin D and 4 beta-hydroxycholesterol, which is an endogenous biomarker of the drug-metabolizing CYP3A enzymes.

25-hydroxyvitamin D

4 beta-hydroxycholesterol


Input: In addition, the relationship between this biomarker and inflammation, measured as C-reactive protein (CRP), was investigated.


Input: Serum samples were used from a recently performed clinical trial in patients with antibody deficiency or increased susceptibility to respiratory tract infections that were randomized to either placebo or high-dose (4000 IU/day) vitamin D for 12 months.

vitamin D


Input: One hundred sixteen patients were included in the final analyses, and serum samples collected 6 months after study start were analyzed.


Input: At this time point, 25-hydroxyvitamin D levels were found to range between 10 and 284 nM.

25-hydroxyvitamin D


Input: Individual levels of 25-hydroxyvitamin D as well as CRP were compared with 4 beta-hydroxycholesterol levels.

25-hydroxyvitamin D

4 beta-hydroxycholesterol


Input: In addition, all participants were genotyped for two polymorphisms (Taq1 and Foq1) in the vitamin D receptor gene.

vitamin D


Input: There was no significant correlation between individual serum levels of 25-hydroxyvitamin D and 4 beta-hydroxycholesterol.

25-hydroxyvitamin D

4 beta-hydroxycholesterol


Input: However, a moderate, but statistically significant, negative correlation between CRP and 4 beta-hydroxycholesterol levels was observed.

4 beta-hydroxycholesterol


Input: This study in patients with highly variable serum levels of 25-hydroxyvitamin D could not reveal any relationship between vitamin D and 4 beta-hydroxycholesterol, an endogenous biomarker of CYP3A activity.

25-hydroxyvitamin D

vitamin D

4 beta-hydroxycholesterol


Input: However, the negative correlation between CRP and 4 beta-hydroxycholesterol supports earlier experimental results that inflammation may suppress hepatic CYP3A activity, a finding of potentially high clinical relevance that warrants further exploration.

4 beta-hydroxycholesterol


Input: Apoptotic cell death in rat epididymis following epichlorohydrin treatment.

epichlorohydrin


Input: Epichlorohydrin (ECH) is an antifertility agent that acts both as an epididymal toxicant and an agent capable of directly affecting sperm motility.

Epichlorohydrin

ECH


Input: This study identified the time course of apoptotic cell death in rat epididymides after ECH treatment.


Input: Rats were administrated with a single oral dose of ECH (50 mg/kg).

ECH


Input: ECH-induced apoptotic changes were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and its related mechanism was confirmed by Western blot analysis and colorimetric assay.

ECH

dUTP


Input: The TUNEL assay showed that the number of apoptotic cells increased at 8 h, reached a maximum level at 12 h, and then decreased progressively.


Input: The Western blot analysis demonstrated no significant changes in proapoptotic Bcl-2-associated X (Bax) and anti-apoptotic Bcl-2 expression during the time course of the study.


Input: However, phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) and phospho-c-Jun amino-terminal kinase (p-JNK) expression increased at 8-24 h.

amino


Input: Caspase-3 and caspase-8 activities also increased at 8-48 h and 12-48 h, respectively, in the same manner as p-p38 MAPK and p-JNK expression.


Input: These results indicate that ECH induced apoptotic changes in rat epididymides and that the apoptotic cell death may be related more to the MAPK pathway than to the mitochondrial pathway.


Input: Isolation and characterization of unusual hydrazides from Streptomyces sp. impact of the cultivation support and extraction procedure.

hydrazides


Input: Three novel hydrazides, geralcins C-E (1-3), were isolated from Streptomyces sp.

hydrazides

geralcins C-E


Input: LMA-545, together with MH-031 and geralcins A and B.

geralcins A and B


Input: This unusual family of compounds was isolated from liquid-state and agar-supported fermentation using Amberlite XAD-16 solid-phase extraction during the cultivation step.

Amberlite XAD-16


Input: The use of such neutral resin during the cultivation step allowed the specific adsorption of microbial secondary metabolites, avoiding any contamination of the crude extracts by the constituents of the culture medium.


Input: The trapped compounds were eluted from the resin with methanol, and their structures elucidated using (1) H, (13) C, and (15) N NMR spectroscopic analysis and high-resolution mass spectrometry.

methanol

(1) H

(13) C

(15) N


Input: Molecular modeling calculations were applied in order to support structural attributions.


Input: No antimicrobial, cytotoxic, or DnaG-inhibition activities were detected for geralcins D and E.

geralcins D and E


Input: Geralcin C has no antimicrobial activity but exhibited an IC (50) of 0. 8 mu M against KB and HCT116 cancer cell lines.

Geralcin C


Input: Furthermore, geralcin C inhibited the E. coli DnaG primase, a Gram-negative antimicrobial target, with an IC (50) of 0. 7 mM.

geralcin C


Input: Sigma receptor modulators: a patent review.


Input: Introduction: Sigma receptors are involved in several central nervous system (CNS) disorders, including mood disorders (depression and anxiety), psychosis, schizophrenia, movement disorders (i. e., Parkinson' s disease) and memory deficits (i. e., Alzheimer' s disease).


Input: Recently, the involvement of sigma receptors in neuropathic pain and cancer has also been observed.


Input: Areas covered: This review aims at highlighting the research advancements published in the patent literature between 1986 and 2012, dividing patents according to both their time frame and applicants.


Input: The review especially focuses on the development of sigma receptor modulators and their application over the years with respect to CNS diseases, neuropathic pain and neurodegenerative pathologies.


Input: The literature was sought through Espacenet, Orbit, ISI Web and PubMed databases.


Input: Expert opinion: In recent years, considerable progress in the knowledge of the biology and pharmacology of sigma receptors has encouraged research on the potential benefits of sigma modulators in a wide range of pathologies.


Input: So far, only few potent agonists and antagonists of sigma receptors are in clinical trial for acute and chronic neurodegenerative diseases (SA4503 and ANAVEX 2-73) or neuropathic pain (E-52862).

ANAVEX 2-73


Input: NMR solution structure study of the representative component hydroxysafflor yellow A and other quinochalcone C-glycosides from Carthamus tinctorius.

hydroxysafflor yellow A

quinochalcone C-glycosides


Input: Hydroxysafflor yellow A (HSYA), a representative component of Carthamus tinctorius, has attracted much attention because of its remarkable cardiovascular activities.

Hydroxysafflor yellow A

HSYA


Input: Its structure was originally reported in 1993 and has been widely cited to date.


Input: In our experiments, its solution structure was studied using NMR techniques in different solvents, including DMSO-d (6), pyridine-d (5), and CD (3) OH.

DMSO-d (6)

pyridine-d (5)

CD (3) OH


Input: The results indicate that the structure of HSYA is different than the previously described 1b, with 3-enol-1, 7-diketo form.

HSYA

3-enol-1, 7-diketo


Input: The structure has two keto-enol tautomers (2a and 2b), and 2a, with the 1-enol-3, 7-diketo form, is the preferred tautomer.

keto-enol

1-enol-3, 7-diketo


Input: On the basis of this finding, other published quinochalcone C-glycoside structures were revised.

quinochalcone C-glycoside


Input: Furthermore, a trend in the (13) C NMR data of the (E)-olefinic carbons of quinochalcone C-glycosides is summarized, and a hypothesis is proposed for the relationship between the features of the molecular structure and the preferred keto-enol tautomer.

(13) C

(E)-olefinic carbons

quinochalcone C-glycosides

keto-enol


Input: Tubulin inhibitors from an endophytic fungus isolated from Cedrus deodara.


Input: From an endophytic fungus, a close relative of Talaromyces sp., found in association with Cedrus deodara, four compounds including two new ones (2 and 4) were isolated and characterized.


Input: The structures of two compounds (1 and 4) were confirmed by X-ray crystallography.


Input: The compounds displayed a range of cytotoxicities against human cancer cell lines (HCT-116, A-549, HEP-1, THP-1, and PC-3).


Input: All the compounds were found to induce apoptosis in HL-60 cells, as evidenced by fluorescence and scanning electron microscopy studies.


Input: Also, the compounds caused significant microtubule inhibition in HL-60 cells.


Input: Differential mRNA expression levels of human histone-modifying enzymes in normal karyotype B cell pediatric acute lymphoblastic leukemia.


Input: Histone modification enzymes regulate gene expression by altering the accessibility of promoters to transcription factors.


Input: We sought to determine whether the genes encoding histone modification enzymes are dysregulated in pediatric acute lymphoblastic leukemia (ALL).


Input: A real-time PCR array was designed, tested and used to profile the expression of 85 genes encoding histone modification enzymes in bone marrow mononuclear cells from 30 pediatric ALL patients and 20 normal controls.


Input: The expression profile of histone-modifying genes was significantly different between normal karyotype B cell pediatric ALL and normal controls.


Input: Eleven genes were upregulated in pediatric ALL, including the histone deacetylases HDAC2 and PAK1, and seven genes were downregulated, including PRMT2 and the putative tumor suppressor EP300.


Input: Future studies will seek to determine whether these genes serve as biomarkers of pediatric ALL.


Input: Ingenuity Pathway Analysis revealed that Gene Expression and Organ Morphology was the highest rated network, with 13 focus molecules (significance score = 35).


Input: Ingenuity Pathway Analysis also indicated that curcumin and miR-34 are upstream regulators of histone-modifying enzymes; future studies will seek to validate these results and examine the role of curcumin and miR-34 in leukemia.

curcumin

curcumin


Input: This study provides new clues into the molecular mechanisms of pediatric ALL.


Input: Self-assembly of pyridine-modified lipoic Acid derivatives on gold and their interaction with thyroxine (t4).

pyridine

lipoic Acid

thyroxine (t4)


Input: Pyridyl derivatives of lipoic acid were prepared as ligands for the study of the interaction with thyroxine (T4).

Pyridyl

thyroxine (T4)


Input: Thin self-assembled films of the ligands were prepared in 70% ethanol on gold and their interaction with T4 was studied by titration experiments in an aqueous buffer solution using Surface Plasmon Resonance (SPR).

ethanol


Input: The thickness and refractive index of the ligand layers were calculated from SPR spectra recorded in two media, also allowing for surface coverage and the density of the layers to be estimated.


Input: Two ligands, a 4-pyridyl and a bis (2-hydroxyethyl) derivative of lipoic acid, were selected to investigate the feasibility for producing molecularly imprinted self-assembled layers on gold for T4.

bis (2-hydroxyethyl)

lipoic acid


Input: The methodology was to co-assemble T4 and the ligand onto the gold surface, elute the T4 from the layer under alkaline conditions, and study the rebinding of T4 to the layer.


Input: Multiple elution/rebinding cycles were conducted in different buffer solutions, and rebinding of T4 could be observed, with a moderate binding affinity that depended greatly on the solvent used.


Input: More optimal binding was observed in HBS buffer, and the affinity of the interaction could be slightly increased when the 4-pyridyl and bis (2-hydroxy-ethyl) derivatives of lipoic acid were combined in the imprinted layer.

bis (2-hydroxy-ethyl)

lipoic acid


Input: Carbon-coated LiFePO4-porous carbon composites as cathode materials for lithium ion batteries.

Carbon

carbon

lithium


Input: This work introduces a facile strategy for the synthesis of carbon-coated LiFePO (4)-porous carbon (C-LiFePO (4)-PC) composites as a cathode material for lithium ion batteries.

carbon

LiFePO (4)

carbon

C

LiFePO (4)

lithium


Input: The LiFePO (4) particles obtained are about 200 nm in size and homogeneously dispersed in porous carbon matrix.

LiFePO (4)

carbon


Input: These particles are further coated with the carbon layers pyrolyzed from sucrose.

carbon

sucrose


Input: The C-LiFePO (4)-PC composites display a high initial discharge capacity of 152. 3 mA h g (-1) at 0. 1 C, good cycling stability, as well as excellent rate capability (112 mA h g (-1) at 5 C).

C

LiFePO (4)


Input: The likely contributing factors to the excellent electrochemical performance of the C-LiFePO (4)-PC composites could be related to the combined effects of enhancement of conductivity by the porous carbon matrix and the carbon coating layers.

C

LiFePO (4)

carbon

carbon


Input: It is believed that further carbon coating is a facile and effective way to improve the electrochemical performance of LiFePO (4)-PC.

carbon

LiFePO (4)


Input: Hepatotumorigenicity of ethyl tertiary-butyl ether with 2-year inhalation exposure in F344 rats.

ethyl tertiary-butyl ether


Input: Carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined with inhalation exposure using F344/DuCrlCrlj rats.

ethyl tertiary-butyl ether

ETBE


Input: Groups of 50 male and 50 female rats, 6 week old at commencement, were exposed to ETBE at 0, 500, 1, 500 or 5, 000 ppm (v/v) in whole-body inhalation chambers for 6 h/day, 5 days/week for 104 weeks.

ETBE


Input: A significant increase in the incidence of hepatocellular adenomas was indicated in males exposed at 5, 000 ppm, but not in females at any concentration.


Input: In addition, significantly increased incidences of eosinophilic and basophilic cell foci were observed in male rats at 5, 000 ppm.


Input: Regarding non-neoplastic lesions, rat-specific changes were observed in kidney, with an increase in the severity of chronic progressive nephropathy in both sexes at 5, 000 ppm.


Input: Increased incidences of urothelial hyperplasia of the pelvis were observed at 1, 500 ppm and above, and mineral deposition was apparent in the renal papilla at 5, 000 ppm in males.


Input: There were no treatment-related histopathological changes observed in any other organs or tissues in either sex.


Input: The present 2-year inhalation study demonstrated hepatotumorigenicity of ETBE in male, but not in female rats.

ETBE


Input: Glucocorticoid programming of the fetal male hippocampal epigenome.


Input: The late-gestation surge in fetal plasma cortisol is critical for maturation of fetal organ systems.

cortisol


Input: As a result, synthetic glucocorticoids (sGCs) are administered to pregnant women at risk of delivering preterm.


Input: However, animal studies have shown that fetal exposure to sGC results in increased risk of behavioral, endocrine, and metabolic abnormalities in offspring.

sGC


Input: Here, we test the hypothesis that prenatal GC exposure resulting from the fetal cortisol surge or after sGC exposure results in promoter-specific epigenetic changes in the hippocampus.

cortisol


Input: Fetal guinea pig hippocampi were collected before (gestational day [GD52]) and after (GD65) the fetal plasma cortisol surge (Term ~ GD67) and 24 hours after (GD52) and 14 days after (GD65) two repeat courses of maternal sGC (betamethasone) treatment (n = 3-4/gp).

cortisol

betamethasone


Input: We identified extensive genome-wide alterations in promoter methylation in late fetal development (coincident with the fetal cortisol surge), whereby the majority of the affected promoters exhibited hypomethylation.

cortisol


Input: Fetuses exposed to sGC in late gestation exhibited substantial differences in DNA methylation and histone h3 lysine 9 (H3K9) acetylation in specific gene promoters; 24 hours after the sGC treatment, the majority of genes affected were hypomethylated or hyperacetylated.


Input: However, 14 days after sGC exposure these differences did not persist, whereas other promoters became hypermethylated or hyperacetylated.


Input: These data support the hypothesis that the fetal GC surge is responsible, in part, for significant variations in genome-wide promoter methylation and that prenatal sGC treatment profoundly changes the epigenetic landscape, affecting both DNA methylation and H3K9 acetylation.


Input: This is important given the widespread use of sGC in the management of women in preterm labor.


Input: Impaired Postural Balance in Turner Syndrome.


Input: An impaired body balance has been found in Turner syndrome (TS) in clinical tests like Rombergs' s test and walking on a balance beam.


Input: The aim of the study was to assess postural balance in TS subjects with specific balance testing using dynamic posturography and relate to body composition.


Input: Nineteen TS subjects (20-57 years) were included.


Input: Balance was measured with dynamic posturography (Equitest) and compared with 19 sex and age-matched controls (22-59 years).


Input: Equitest, visual, vestibular, and somatosensory systems were provoked with increasing difficulty (6 tests, SO1-SO6) and body sway was measured with a dual forceplate.


Input: Body composition was measured with DXA.


Input: No difference was found between the TS subjects and the controls on fixed platform with open eyes (SO1), with closed eyes (SO2), with stable platform and visual disorientation (SO3), or on unstable platform with open eyes (SO4).


Input: In the difficult tests on unstable platform the TS subjects did worse compared with controls both in the test with eyes closed (SO5), p < 0. 01, and in the test with visual disorientation (SO6), p < 0. 05.


Input: Composite (a merge of all six recordings) was significantly lower in the TS-group, p < 0. 05.


Input: In the TS group high total body weight was related to worse outcome on tests SO5, SO6, and composite, while total bone mass, age, height, or waist showed no significant association with balance scores.


Input: Our findings indicate that TS could have an increased risk for falling due to impaired ability to manage complex coordination tasks.


Input: Paclitaxel-conjugated PAMAM dendrimers adversely affect microtubule structure through two independent modes of action.

Paclitaxel

PAMAM


Input: Paclitaxel (Taxol) is an anticancer drug that induces mitotic arrest via microtubule hyperstabilization but causes side effects due to its hydrophobicity and cellular promiscuity.

Paclitaxel

Taxol


Input: The targeted cytotoxicity of hydrophilic paclitaxel-conjugated polyamidoamine (PAMAM) dendrimers has been demonstrated in cultured cancer cells.

paclitaxel

polyamidoamine

PAMAM


Input: Mechanisms of action responsible for this cytotoxicity are unknown, that is, whether the cytotoxicity is due to paclitaxel stabilization of microtubules, as is whether paclitaxel is released intracellularly from the dendrimer.

paclitaxel

paclitaxel


Input: To determine whether the conjugated paclitaxel can bind microtubules, we used a combination of ensemble and single microtubule imaging techniques in vitro.

paclitaxel


Input: We demonstrate that these conjugates adversely affect microtubules by (1) promoting the polymerization and stabilization of microtubules in a paclitaxel-dependent manner, and (2) bundling preformed microtubules in a paclitaxel-independent manner, potentially due to protonation of tertiary amines in the dendrimer interior.

paclitaxel

paclitaxel

tertiary amines


Input: Our results provide mechanistic insights into the cytotoxicity of paclitaxel-conjugated PAMAM dendrimers and uncover unexpected risks of using such conjugates therapeutically.

paclitaxel

PAMAM


Input: Hydrolytic activities of crystalline cellulose nanofibers.


Input: Cellulose is commonly believed to be inactive to organic substances; this inertness is an essential requirement for raw materials in industrial products.


Input: Here we demonstrate the contradictory but promising properties, which are the hydrolytic activities of crystalline cellulose nanofibers for the ester, monophosphate, and even amide bonds of small organic substrates under extremely mild conditions (neutral pH, moderate temperature, and atmospheric pressure).

ester

monophosphate

amide


Input: The hydrolytic activities were significantly extended to decompose the coat proteins of model viruses, followed by a drastic decrease in their infection capabilities to the host cells.


Input: Structure-Relaxivity Relationships of Serum Albumin Targeted MRI Probes Based on a Single Amino Acid Gd Complex.

Amino Acid Gd


Input: The Gd (III) complex of DO3A-N-alpha-aminopropionate, Gd (DOTAla), was used to generate a small library of putative MRI probes targeted to human serum albumin (HSA).

Gd (III)

Gd (DOTAla)


Input: Ten compounds were synthesized via multistep organic synthesis, and the corresponding Gd complexes were investigated for their affinity to HSA, lipophilicity, and relaxivity in the absence and presence of HSA.

Gd


Input: Negative charge and moderate lipophilicity correlate with increased HSA affinity and relaxivity.


Input: Controllable adhesive superhydrophobic surfaces based on PDMS microwell arrays.


Input: This paper presents a one-step method to fabricate superhydrophobic surfaces with extremely controllable adhesion based on PDMS microwell arrays.


Input: The microwell array structures are rapidly produced on PDMS films by a point-by-point femtosecond laser scanning process.


Input: The as-prepared superhydrophobic surfaces show water controllable adhesion that ranges from ultrahigh to ultralow by adjusting the extent of overlap of the adjacent microwells, on which the sliding angle can be controlled from 180 degrees (a water droplet can not slide down even when the as-prepared surface is turned upside down) to 3 degrees.


Input: A " micro-airbag effect " is introduced to explain the adhesion transition phenomenon of the microwell array structures.


Input: This work provides a facile and promising strategy to fabricate superhydrophobic surfaces with controllable adhesion.


Input: A continuous network of lipid nanotubes fabricated from the gliding motility of kinesin powered microtubule filaments.


Input: Synthetic interconnected lipid nanotube networks were fabricated on the millimeter scale based on the simple, cooperative interaction between phospholipid vesicles and kinesin-microtubule (MT) transport systems.


Input: More specifically, taxol-stabilized MTs, in constant 2D motion via surface absorbed kinesin, extracted and extended lipid nanotube networks from large L alpha phase multilamellar liposomes (5-25 mu m).

taxol


Input: Based on the properties of the inverted motility geometry, the total size of these nanofluidic networks was limited by MT surface density, molecular motor energy source (ATP), and total amount and physical properties of lipid source material.

ATP


Input: Interactions between MTs and extended lipid nanotubes resulted in bifurcation of the nanotubes and ultimately the generation of highly branched networks of fluidically connected nanotubes.


Input: The network bifurcation was easily tuned by changing the density of microtubules on the surface to increase or decrease the frequency of branching.


Input: The ability of these networks to capture nanomaterials at the membrane surface with high fidelity was subsequently demonstrated using quantum dots as a model system.


Input: The diffusive transport of quantum dots was also characterized with respect to using these nanotube networks for mass transport applications.


Input: Horizontal gene transfer: linking sex and cell fate.


Input: Integrative conjugative elements (ICEs) enable horizontal gene transfer among bacteria.


Input: In Pseudomonas, only a phenotypically distinct subpopulation of ICE-bearing cells can mobilize ICE DNA to new hosts.


Input: Transfer competence is a terminal state; division is limited, and many cells lyse.


Input: Ultrasound-aided microbubbles facilitate the delivery of drugs to the inner ear via the round window membrane.


Input: The round window membrane (RWM) acts as a barrier between the middle ear and cochlea and can serve as a crucial route for therapeutic medications entering the inner ear via middle ear applications.


Input: In this study, we targeted the practical application of microbubbles (MBs) ultrasound on increasing the RWM permeability for facilitating drug or medication delivery to the inner ear.


Input: Using biotin-fluorescein isothiocyanate conjugates (biotin-FITC) as delivery agents and guinea pig animal models, we showed that MB ultrasound exposure can improve the inner ear system use of biotin-FITC delivery via the RWM by approximately 3. 5 to 38 times that of solely soaking biotin-FITC around the RWM for spontaneous diffusion.

biotin-fluorescein isothiocyanate

biotin

FITC

biotin

FITC

biotin

FITC


Input: We also showed that there was significant enhancement of hair cell uptake of gentamicin in animals whose tympanic bullas were soaked with MB-mixed gentamicin-Texas Red or gentamicin and exposed to ultrasound.

gentamicin

gentamicin

Texas Red

gentamicin


Input: Furthermore, increased permeability of the RWM from acoustic cavitation of MBs could also be visualized immediately following ultrasound exposure by using Alexa Fluor 488-conjugated phalloidin as a tracer.

Alexa Fluor 488

phalloidin


Input: Most importantly, such applications had no resulting damage to the integrity of the RWM or deterioration of the hearing thresholds assessed by auditory brainstem responses.


Input: We herein provide a basis for MB ultrasound-mediated techniques with therapeutic medication delivery to the inner ear for future application in humans.


Input: Protective effects of protein transduction domain-metallothionein fusion proteins against hypoxia-and oxidative stress-induced apoptosis in an ischemia/reperfusion rat model.


Input: Ischemic heart diseases caused by insufficient oxygen supply to the cardiac muscle require pharmaceutical agents for the prevention of the progress and recurrence.

oxygen


Input: Metallothionein (MT) has a potential as a protein therapeutic for the treatment of this disease due to its anti-oxidative effects under stressful conditions.


Input: In spite of its therapeutic potential, efficient delivery systems need to be developed to overcome limitations such as low transduction efficiency, instability and short half-life in the body.


Input: To enhance intra-cellular transduction efficiency, Tat sequence as a protein transduction domain (PTD) was fused with MT in a recombinant method.


Input: Anti-apoptotic and anti-oxidative effects of Tat-MT fusion protein were evaluated under hyperglycemia and hypoxia stress conditions in cultured H9c2 cells.


Input: Recovery of cardiac functions by anti-apoptotic and anti-fibrotic effects of Tat-MT was confirmed in an ischemia/reperfusion (I/R) rat myocardial infarction model.


Input: Tat-MT fusion protein effectively protected H9c2 cells under stressful conditions by reducing intracellular ROS production and inhibiting caspase-3 activation.


Input: Tat-MT fusion protein inhibited apoptosis, reduced fibrosis area and enhanced cardiac functions in I/R.


Input: Tat-MT fusion protein could be a promising therapeutic for the treatment of ischemic heart diseases.


Input: An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis.


Input: Prolonged inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA) and to aspects of osteoarthritis (OA).


Input: The orphan nuclear receptor, NR4A2, is a key regulator and potential biomarker for inflammation and represents a potentially valuable therapeutic target.


Input: Both salmon calcitonin (sCT) and hyaluronic acid (HA) attenuated activated mRNA expression of NR4A1, NR4A2, NR4A3, and matrix metalloproteinases (MMPs) 1, 3 and 13 in three human cell lines: SW1353 chondrocytes, U937 and THP-1 monocytes.


Input: Ad-mixtures of sCT and HA further down-regulated expression of NR4A2 compared to either agent alone at specific concentrations, hence the rationale for their formulation in nanocomplexes (NPs) using chitosan.


Input: The sCT released from NP stimulated cAMP production in human T47D breast cancer cells expressing sCT receptors.

cAMP


Input: When NP were injected by the intra-articular (I. A.) route to the mouse knee during on-going inflammatory arthritis of the K/BxN serum transfer model, joint inflammation was reduced together with NR4A2 expression, and local bone architecture was preserved.


Input: These data highlight remarkable anti-inflammatory effects of sCT and HA at the level of reducing NR4A2 mRNA expression in vitro.


Input: Combining them in NP elicits anti-arthritic effects in vivo following I. A. delivery.


Input: In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths.

perfluorinated carboxylic acids

carbon


Input: Perfluorooctanoic acid (PFOA) is in use for the production of fluoropolymers (PFT).

Perfluorooctanoic acid

PFOA

fluoropolymers

PFT


Input: Due to its toxic properties it was proposed to replace the substance in its industrial applications by homologous compounds with shorter carbon chain length that were supposed to be less toxic compared to PFOA, however, the smaller PFOA homologs are poorly characterized so far.

carbon

PFOA

PFOA


Input: In this study we have conducted a comparative analysis of the toxicity of perfluorinated carboxylic acids (PFCA) with a carbon chain length ranging from four to twelve carbon atoms.

perfluorinated carboxylic acids

PFCA

carbon

carbon


Input: By using the human hepatocarcinoma cell line HepG2 as an in vitro model for human hepatocytes we could show a positive correlation between the carbon chain length of the respective PFCA and its cytotoxicity.

carbon

PFCA


Input: There was, however, no indication of an apoptotic mechanism for cytotoxicity.


Input: All PFCA under investigation were negative in two independent genotoxicity assays.

PFCA


Input: As PFOA, being a well-known peroxisome proliferator, the other PFCA tested in this study were also shown to activate human peroxisome proliferator-activated receptor alpha (PPAR alpha) with PFOA having the highest potential of PPAR alpha activation.

PFOA

PFCA

PFOA


Input: Moreover, the compounds showed weak potential to activate PPAR gamma and hardly activated PPAR delta.


Input: Taken together, the in vitro study revealed that PFCA with a shorter carbon chain length seem to be less toxic than PFOA.

PFCA

carbon

PFOA


Input: Effect of low dose Bisphenol A on the early differentiation of human embryonic stem cells into mammary epithelial cells.

Bisphenol A


Input: It has been previously reported that Bisphenol A (BPA) can disturb the development of mammary structure and increase the risk of breast cancer in experimental animals.

Bisphenol A

BPA


Input: In this study, an in vitro model of human embryonic stem cell (hESC) differentiation into mammary epithelial cells was applied to investigate the effect of low dose BPA on the early stages of mammogenesis.

BPA


Input: A newly established hESC line was directionally differentiated into mammary epithelial cells by a well-established three-dimensional (3D) culture system.


Input: The differentiated mammary epithelial cells were characterized by immunofluorescence and western blotting assay, and were called induced differentiated mammary epithelial cells (iDMECs) based on these data.


Input: The hESCs were treated with low doses of BPA range 10 (-9)-10 (-6) M during the differentiation process, with DMSO as the solvent control and 17-beta-estrodiol (E2) as the estrogen-positive control.

BPA

DMSO


Input: Our results showed that low dose BPA and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of Oct4 and Nanog proteins, while only BPA could downregulate the expression of E-cadherin protein.

BPA

BPA


Input: Taken together, this study provides some insights into the effects of low dose BPA on the early differentiation stage of mammary epithelial cells and suggests an easier canceration status of iDMECs under the effect of low dose BPA during its early differentiation stage.

BPA

BPA


Input: Essential trace and toxic element concentrations in organic and conventional milk in NW Spain.


Input: Dietary composition and husbandry practices largely determine essential trace element status and toxic element exposure of livestock, and consequently their concentrations in animal products.


Input: This study evaluates the main essential trace (Co, Cr, Cu, Fe, I, Mn, Mo, Ni, Se and Zn) and toxic (As, Cd, Hg and Pb) element concentrations in milk from organic and conventional farms in NW Spain (n = 50).

Co

Cr

Cu

Fe

I

Mn

Mo

Ni

Se

Zn

As

Cd

Hg

Pb


Input: Milk samples were acid digested and analyzed by ICP-MS.


Input: Essential trace element concentrations in organic milk were significantly lower compared to conventional milk, this was especially evident for elements that are routinely supplemented at high concentrations in the conventional concentrate feed: Cu (41. 0 and 68. 9 mu g/L in organic and conventional milk, respectively), Zn (3326 and 3933 mu g/L), I (78 and 265 mu g/L) and Se (9. 4 and 19. 2 mu g/L).

Cu

Zn

I

Se


Input: Toxic metal concentrations in milk were in general very low and no statistically significant differences were observed between organic and conventional milk.


Input: In addition, the mineral content of organic milk showed a seasonal pattern, the significantly higher As (65%) and Fe (13%) concentrations found in the winter sampling possibly being related to a higher consumption of concentration feed and soil ingestion when grazing.

As

Fe


Input: The role of aryl hydrocarbon receptor signaling pathway in cardiotoxicity of acute lead intoxication in vivo and in vitro rat model.

aryl hydrocarbon


Input: Lead (Pb (2 +)) is a naturally occurring systemic toxicant heavy metal that affects several organs in the body including the kidneys, liver, and central nervous system.

Pb (2 +)


Input: However, Pb (2 +)-induced cardiotoxicity has never been investigated yet and the exact mechanism of Pb (2 +) associated cardiotoxicity has not been studied.

Pb (2 +)

Pb (2 +)


Input: The current study was designed to investigate the potential effect of Pb (2 +) to induce cardiotoxicity in vivo and in vitro rat model and to explore the molecular mechanisms and the role of aryl hydrocarbon receptor (AhR) and regulated gene, cytochrome P4501A1 (CYP1A1), in Pb (2 +)-mediated cardiotoxicity.

Pb (2 +)

aryl hydrocarbon

Pb (2 +)


Input: For these purposes, Wistar albino rats were treated with Pb (2 +) (25, 50 and 100mg/kg, i. p.) for three days and the effects on physiological and histopathological parameters of cardiotoxicity were determined.

Pb (2 +)


Input: At the in vitro level, rat cardiomyocyte H9c2 cell lines were incubated with increasing concentration of Pb (2 +) (25, 50, and 100 mu M) and the expression of hypertrophic genes, alpha-and beta-myosin heavy chain (alpha-MHC and beta-MHC), brain Natriuretic Peptide (BNP), and CYP1A1 were determined at the mRNA and protein levels using real-time PCR and Western blot analysis, respectively.

Pb (2 +)


Input: The results showed that Pb (2 +) significantly induced cardiotoxicity and heart failure as evidenced by increase cardiac enzymes, lactate dehydrogenase and creatine kinase and changes in histopathology in vivo.

Pb (2 +)

lactate

creatine


Input: In addition, Pb (2 +) treatment induced beta-MHC and BNP whereas inhibited alpha-MHC mRNA and protein levels in vivo in a dose-dependent manner.

Pb (2 +)


Input: In contrast, at the in vitro level, Pb (2 +) treatment induced both beta-MHC and alpha-MHC mRNA levels in time-and dose-dependent manner.

Pb (2 +)


Input: Importantly, these changes were accompanied with a proportional increase in the expression of CYP1A1 mRNA and protein expression levels, suggesting a role for the CYP1A1 in cardiotoxicity.


Input: The direct evidence for the involvement of CYP1A1 in the induction of cardiotoxicity by Pb (2 +) was evidenced by the ability of AhR antagonist, resveratrol, to significantly inhibit the Pb (2 +)-modulated effect on beta-MHC and alpha-MHC mRNAs.

Pb (2 +)

resveratrol

Pb (2 +)


Input: It was concluded that acute lead exposure induced cardiotoxicity through AhR/CYP1A1-mediated mechanism.


Input: The increased number of Leydig cells by di (2-ethylhexyl) phthalate comes from the differentiation of stem cells into Leydig cell lineage in the adult rat testis.

di (2-ethylhexyl) phthalate


Input: The objective of the present study is to determine whether di (2-ethylhexyl) phthalate (DEHP) exposure at adulthood increases rat Leydig cell number and to investigate the possible mechanism.

di (2-ethylhexyl) phthalate

DEHP


Input: 90-day-old Long-Evans rats were randomly divided into 3 groups, and were gavaged with the corn oil (control) or 10 or 750mg/kg DEHP daily for 7 days, and then received an intraperitoneal injection of 75mg/kg ethane dimethanesulfonate (EDS) to eliminate Leydig cells.

DEHP

ethane dimethanesulfonate

EDS


Input: Serum testosterone concentrations were assessed by RIA, and the mRNA levels of Leydig cell genes were measured by qPCR.

testosterone


Input: EDS eliminated all Leydig cells in the control testis on day 4 post-EDS, as judged by undetectable serum testosterone level and no 3 beta-hydroxysteroid dehydrogenase positive (3 beta-HSD (pos)) cells in the interstitium.

EDS

EDS

testosterone

3 beta-hydroxysteroid


Input: However, in DEHP-treated groups, there were detectable serum testosterone concentrations and some oval-shaped 3 beta-HSD (pos) cells in the interstitium.

DEHP

testosterone


Input: These 3 beta-HSD (pos) cells were not stained by the antibody against 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1), a marker for Leydig cells at a more advanced stage.

11 beta-hydroxysteroid


Input: The disappearance of mRNAs of Leydig cell biomarkers including Lhcgr, Cyp11a1, Cyp17a1, Insl3 and Hsd11b1 in the control testis was observed on day 4 post-EDS.

EDS


Input: However, there were detectable concentrations of Lhcgr, Cyp11a1 and Cyp17a1 mRNAs but undetectable concentrations of Insl3, Hsd17b3 and Hsd11b1 in the DEHP-treated testes, indicating that these 3 beta-HSD (pos) cells were newly formed progenitor Leydig cells.

DEHP


Input: The mRNA level for nestin (Nes, biomarker for stem Leydig cells) was significantly increased in the control testis on day 4 post-EDS, but not in the DEHP treated testes, suggesting that these nestin positive stem cells were differentiated into progenitor Leydig cells in the DEHP-treated testes.

EDS

DEHP

DEHP


Input: The present study suggests that DEHP increases the differentiation of stem cells into progenitor Leydig cells.

DEHP


Input: The venom of the fishing spider Dolomedes sulfurous contains various neurotoxins acting on voltage-activated ion channels in rat dorsal root ganglion neurons.


Input: Dolomedes sulfurous is a venomous spider distributed in the south of China and characterized with feeding on fish.


Input: The venom exhibits great diversity and contains hundreds of peptides as revealed by off-line RP-HPLC/MALDI-TOF-MS analysis.


Input: The venom peptides followed a triple-modal distribution, with 40. 7% of peptides falling in the mass range of 1000-3000 Da, 25. 6% peptides in the 7000-9000 Da range and 23. 5% peptides in the 3000-5000 Da range.


Input: This distribution modal is rather different from these of peptides from other spider venoms analyzed.


Input: The venom could inhibit voltage-activated Na (+), K (+) and Ca (2 +) channels in rat DRG neurons as revealed by voltage-clamp analysis.

Na (+)

K (+)

Ca (2 +)


Input: Significantly, the venom exhibited inhibitory effects on TTX-R Na (+) and T-type Ca (2 +) currents, suggesting that there exist both channel antagonists which might be valuable tools for investigation of both channels and drug development.

Na (+)

Ca (2 +)


Input: Additionally, intrathoracically injection of venom could cause serve neurotoxic effects on zebrafish and death at higher concentrations.


Input: The LD50 value was calculated to be 28. 8 mu g/g body weight.


Input: Our results indicated that the venom of D. sulfurous contain diverse neurotoxins which serve to capture prey.


Input: Intensive studies will be necessary to investigate the structures and functions of specific peptides of the venom in the future.


Input: Maternal exposure to mercury chloride during pregnancy and lactation affects the immunity and social behavior of offspring.

mercury chloride


Input: Developmental HgCl2 exposures of F1 offspring (H-2 (q/s)) from unsociable SJL/J (H-2 (s)) dams with high susceptibility to Hg-induced autoimmunity (SFvF1) and from highly sociable FVB/NJ (FVB; H-2 (q)) dams with lower susceptibility to Hg-induced autoimmunity (FvSF1) were investigated.

Hg

Hg


Input: Hg exposure increased the serum IgG levels of all offspring at postnatal day 21 (pnd21) and of SJL/J dams but not of FVB dams.

Hg


Input: Serum IgG anti-brain antibody (Ab) levels of pnd21 SFvF1 offspring and SJL dams were higher than those of the FvSF1 offspring and FVB dams, but Hg only increased the titers of the FVB dams and their offspring.

Hg


Input: Hg significantly elevated the presence of IgG in all brain regions of the pnd21 SFvF1 offspring, and the SFvF1 offspring had greater amounts of IgG in the brain than the FvSF1 offspring, which had Hg-induced increases in only two brain regions.

Hg

Hg


Input: Cytokine levels were elevated in the brain regions of Hg-treated pnd21 SFvF1 but not of FvSF1 offspring, and SFvF1 females had more brain regions expressing cytokines than the males.

Hg


Input: At pnd70, the serum IgG, serum antibrain Abs, amounts of brain IgG, and brain cytokine levels of all of the Hg-treated offspring were equivalent to those of their appropriate controls, suggesting that developmental Hg exposure did not induce chronic immunological effects.

Hg

Hg


Input: However, the social behaviors of Hg-exposed SFvF1 offspring at pnd70 were significantly impaired, and SFvF1 females displayed greater decline in social behaviors than males, suggesting that the higher neuroinflammation of SFvF1 females earlier in life is associated with the altered behavior.

Hg


Input: Thus, developmental Hg exposure induces long-lasting effects on social behavior of offspring, which is dependent on sex and genetics and the induction of neuroinflammation.

Hg


Input: Large-scale and highly efficient synthesis of micro-and nano-fibers with controlled fiber morphology by centrifugal jet spinning for tissue regeneration.


Input: PLLA fibrous tissue scaffolds with controlled fiber nanoscale surface roughness are fabricated with a novel centrifugal jet spinning process.


Input: The centrifugal jet spinning technique is a highly efficient synthesis method for micron-to nano-sized fibers with a production rate up to 0. 5 g min (-1).


Input: During the centrifugal jet spinning process, a polymer solution jet is stretched by the centrifugal force of a rotating chamber.


Input: By engineering the rheological properties of the polymer solution, solvent evaporation rate and centrifugal force that are applied on the solution jet, polyvinylpyrrolidone (PVP) and poly (l-lactic acid) (PLLA) composite fibers with various diameters are fabricated.

polyvinylpyrrolidone

PVP

poly (l-lactic acid)

PLLA


Input: Viscosity measurements of polymer solutions allowed us to determine critical polymer chain entanglement limits that allow the generation of continuous fiber as opposed to beads or beaded fibers.


Input: Above a critical concentration at which polymer chains are partially or fully entangled, lower polymer concentrations and higher centrifugal forces resulted in thinner fibers.


Input: Etching of PVP from the PLLA-PVP composite fibers doped with increasing PVP concentrations yielded PLLA fibers with increasing nano-scale surface roughness and porosity, which increased the fiber hydrophilicity dramatically.

PVP

PLLA

PVP

PVP

PLLA


Input: Scanning electron micrographs of the etched composite fibers suggest that PVP and PLLA were co-contiguously phase separated within the composite fibers during spinning and nano-scale roughness features were created after the partial etching of PVP.

PVP

PLLA

PVP


Input: To study the tissue regeneration efficacy of the engineered PLLA fiber matrix, human dermal fibroblasts are used to simulate partial skin graft.

PLLA


Input: Fibers with increased PLLA surface roughness and porosity demonstrated a trend towards higher cell attachment and proliferation.

PLLA


Input: Vesnarinone Suppresses TNF alpha mRNA Expression by Inhibiting Valosin-Containing Protein.

Vesnarinone


Input: Vesnarinone is a synthetic quinolinone derivative used in the treatment of cardiac failure and cancer.

Vesnarinone

quinolinone


Input: It is also known to cause agranulocytosis as a side effect, which restricts its use, although the mechanism underlying agranulocytosis is not well understood.


Input: Here, we show that vesnarinone binds to valosin-containing protein (VCP), which interacts with polyubiquitinated proteins and is essential for the degradation of I kappa B alpha to activate nuclear factor (NF) kappa B.

vesnarinone


Input: We show that vesnarinone impairs the degradation of I kappa B alpha, and that the impairment of the degradation of I kappa B alpha is the result of the inhibition of the interaction between VCP and the 26S proteasome by vesnarinone.

vesnarinone

vesnarinone


Input: These results suggest that vesnarinone suppresses NF kappa B activation by inhibiting the VCP-dependent degradation of polyubiquitinated I kappa B alpha, resulting in the suppression of tumor necrosis factor-alpha mRNA expression.

vesnarinone


Input: Determinants of Maternal Triglycerides in Women With Gestational Diabetes Mellitus in the Metformin in Gestational Diabetes (MiG) Study.

Triglycerides

Metformin


Input: OBJECTIVEFactors associated with increasing maternal triglyceride concentrations in late pregnancy include gestational age, obesity, preeclampsia, and altered glucose metabolism.

triglyceride

glucose


Input: In a subgroup of women in the Metformin in Gestational Diabetes (MiG) trial, maternal plasma triglycerides increased more between enrollment (30 weeks) and 36 weeks in those treated with metformin compared with insulin.

Metformin

triglycerides

metformin


Input: The aim of this study was to explain this finding by examining factors potentially related to triglycerides in these women. RESEARCH DESIGN AND METHODSOf the 733 women randomized to metformin or insulin in the MiG trial, 432 (219 metformin and 213 insulin) had fasting plasma triglycerides measured at enrollment and at 36 weeks.

triglycerides

metformin

metformin

triglycerides


Input: Factors associated with maternal triglycerides were assessed using general linear modeling. RESULTSMean plasma triglyceride concentrations were 2. 43 (95% CI 2. 35-2. 51) mmol/L at enrollment.

triglycerides

triglyceride


Input: Triglycerides were higher at 36 weeks in women randomized to metformin (2. 94 [2. 80-3. 08] mmol/L; + 23. 13% [18. 72-27. 53%]) than insulin (2. 65 [2. 54-2. 77] mmol/L, P = 0. 002; + 14. 36% [10. 91-17. 82%], P = 0. 002).

Triglycerides

metformin


Input: At 36 weeks, triglycerides were associated with HbA1c (P = 0. 03), ethnicity (P = 0. 001), and treatment allocation (P = 0. 005).

triglycerides


Input: In insulin-treated women, 36-week triglycerides were associated with 36-week HbA1c (P = 0. 02), and in metformin-treated women, they were related to ethnicity. CONCLUSIONSAt 36 weeks, maternal triglycerides were related to glucose control in women treated with insulin and ethnicity in women treated with metformin.

triglycerides

metformin

triglycerides

glucose

metformin


Input: Whether there are ethnicity-related dietary changes or differences in metformin response that alter the relationship between glucose control and triglycerides requires further study.

metformin

glucose

triglycerides


Input: Decreased serum concentrations of 25-hydroxycholecalciferol are associated with increased risk of progression to impaired fasting glucose and diabetes.

glucose


Input: OBJECTIVE To study the association between vitamin D status and the risk of incident impaired fasting glucose (IFG) and diabetes in a population-based cohort of diabetes-free subjects.

vitamin D

glucose


Input: RESEARCH DESIGN AND METHODS In a historical prospective cohort study of subjects from the Clalit Health Services database, which includes information on nearly 4 million people, diabetes-free subjects aged 40-70 years with serum 25-hydroxycholecalciferol (25-OHD) measurements available were followed for 2 years to assess the development of IFG and diabetes in five 25-OHD subgroups: >= 25, 25. 1-37. 5, 37. 6-50, 50. 1-75, and > 75 nmol/L.


Input: RESULTS The baseline cohort included 117, 960 adults: 83, 526 normoglycemic subjects and 34, 434 subjects with IFG.


Input: During follow-up, 8, 629 subjects (10. 3% of the normoglycemic group) developed IFG, and 2, 162 subjects (1. 8% of the total cohort) progressed to diabetes.


Input: A multivariable model adjusted for age, sex, population group, immigrant status, BMI, season of vitamin D measurement, LDL and HDL cholesterol, triglycerides, estimated glomerular filtration rate, history of hypertension or cardiovascular disease, Charlson comorbidity index, smoking, and socioeconomic status revealed an inverse association between 25-OHD and the risk of progression to IFG and diabetes.

vitamin D

cholesterol

triglycerides


Input: The odds of transitioning from normoglycemia to IFG, from normoglycemia to diabetes, and from IFG to diabetes in subjects with a 25-OHD level <= 25 nmol/L were greater than those of subjects with a 25-OHD level > 75 nmol/L [odds ratio 1. 13 (95% CI 1. 03-1. 24), 1. 77 (1. 11-2. 83), and 1. 43 (1. 16-1. 76), respectively].


Input: CONCLUSIONS Vitamin D deficiency appears to be an independent risk factor for the development of IFG and diabetes.

Vitamin D


Input: Nurse-Community Health Worker Team Improves Diabetes Care in American Samoa: Results of a randomized controlled trial.


Input: OBJECTIVETo evaluate the effectiveness of a culturally adapted, primary care-based nurse-community health worker (CHW) team intervention to support diabetes self-management on diabetes control and other biologic measures. RESEARCH DESIGN AND METHODSTwo hundred sixty-eight Samoan participants with type 2 diabetes were recruited from a community health center in American Samoa and were randomly assigned by village clusters to the nurse-CHW team intervention or to a wait-list control group that received usual care. RESULTSParticipants had a mean age of 55 years, 62% were female, mean years of education were 12. 5 years, 41% were employed, and mean HbA (1c) was 9. 8% at baseline.


Input: At 12 months, mean HbA (1c) was significantly lower among CHW participants, compared with usual care, after adjusting for confounders (b =-0. 53; SE = 0. 21; P = 0. 03).


Input: The odds of making a clinically significant improvement in HbA (1c) of at least 0. 5% in the CHW group was twice the odds in the usual care group after controlling for confounders (P = 0. 05).


Input: There were no significant differences in blood pressure, weight, or waist circumference at 12 months between groups. CONCLUSIONSA culturally adapted nurse-CHW team intervention was able to significantly improve diabetes control in the U. S.


Input: Territory of American Samoa.


Input: This represents an important translation of an evidence-based model to a high-risk population and a resource-poor setting.


Input: Quantitative Prediction of Repaglinide-Rifampicin Complex Drug Interactions Using Dynamic and Static Mechanistic Models: Delineating Differential CYP3A4 Induction and OATP1B1 Inhibition Potential of Rifampicin.

Repaglinide

Rifampicin

Rifampicin


Input: Repaglinide is mainly metabolized by cytochrome P450 enzymes CYP2C8 and CYP3A4, and it is also a substrate to a hepatic uptake transporter, organic anion transporting polypeptide (OATP) 1B1.

Repaglinide


Input: The purpose of this study is to predict the dosing time-dependent pharmacokinetic interactions of repaglinide with rifampicin, using mechanistic models.

repaglinide

rifampicin


Input: In vitro hepatic transport of repaglinide, characterized using sandwich-cultured human hepatocytes, and intrinsic metabolic parameters were used to build a dynamic whole-body physiologically-based pharmacokinetic (PBPK) model.

repaglinide


Input: The PBPK model adequately described repaglinide plasma concentration-time profiles and successfully predicted area under the plasma concentration-time curve ratios of repaglinide (within +/- 25% error), dosed (staggered 0-24 hours) after rifampicin treatment when primarily considering induction of CYP3A4 and reversible inhibition of OATP1B1 by rifampicin.

repaglinide

repaglinide

rifampicin

rifampicin


Input: Further, a static mechanistic " extended net-effect " model incorporating transport and metabolic disposition parameters of repaglinide and interaction potency of rifampicin was devised.

repaglinide

rifampicin


Input: Predictions based on the static model are similar to those observed in the clinic (average error ~ 19%) and to those based on the PBPK model.


Input: Both the models suggested that the combined effect of increased gut extraction and decreased hepatic uptake caused minimal repaglinide systemic exposure change when repaglinide is dosed simultaneously or 1 hour after the rifampicin dose.

repaglinide

repaglinide

rifampicin


Input: On the other hand, isolated induction effect as a result of temporal separation of the two drugs translated to an approximate 5-fold reduction in repaglinide systemic exposure.

repaglinide


Input: In conclusion, both dynamic and static mechanistic models are instrumental in delineating the quantitative contribution of transport and metabolism in the dosing time-dependent repaglinide-rifampicin interactions.

repaglinide

rifampicin


Input: Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo [2, 3-d] pyrimidin-4-yl) piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases.

4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo [2, 3-d] pyrimidin-4-yl) piperidine-4-carboxamide


Input: Wide-ranging exploration of analogues of an ATP-competitive pyrrolopyrimidine inhibitor of Akt led to the discovery of clinical candidate AZD5363, which showed increased potency, reduced hERG affinity, and higher selectivity against the closely related AGC kinase ROCK.


Input: This compound demonstrated good preclinical drug metabolism and pharmacokinetics (DMPK) properties and, after oral dosing, showed pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo, and inhibition of tumor growth in a breast cancer xenograft model.


Input: Resolving stable axial trapping points of nanowires in an optical tweezers using photoluminescence mapping.


Input: Axially resolved microphotoluminescence mapping of semiconductor nanowires held in an optical tweezers reveals important new experimental information regarding equilibrium trapping points and trapping stability of high aspect ratio nanostructures.


Input: In this study, holographic optical tweezers are used to scan trapped InP nanowires along the beam direction with respect to a fixed excitation source and the luminescent properties are recorded.


Input: It is observed that nanowires with lengths on the range of 3-15 mu m are stably trapped near the tip of the wire with the long segment positioned below the focus in an inverted trapping configuration.


Input: Through the use of trap multiplexing we investigate the possibility of improving the axial stability of the trapped nanowires.


Input: Our results have important implication for applications of optically assisted nanowire assembly and optical tweezers based scanning probes microscopy.


Input: Parameterization of Reactive Force Field: Dynamics of the [Nb6O19Hx] ((8-x)-) Lindqvist Polyoxoanion in Bulk Water.

[Nb6O19Hx] ((8-x)-)


Input: We present results on parameterization of reactive force field [van Duin, A. C. T.; Dasgupta, S.; Lorant, F.; Goddard, W. A. ReaxFF: A Reactive Force Field for Hydrocarbons. J. Phys. Chem. A2001, 105, 9396-9409] for investigating the properties of the [Nb6O19Hx] ((8-x)-) Lindqvist polyoxoanion, x = 0-8, in water.

Hydrocarbons

[Nb6O19Hx] ((8-x)-)


Input: Force-field parameters were fitted to an extensive data set consisting of structures and energetics obtained at the Perdew-Burke-Ernzerhof density functional level of theory.


Input: These parameters can reasonably describe pure water structure as well as water with an excess of H (+) and OH (-) ions.

H (+)

OH (-)


Input: Molecular dynamics simulations were performed on [Nb6O19Hx] ((8-x)-), x = 0-8, submerged in bulk water at 298 K.

[Nb6O19Hx] ((8-x)-)


Input: Analysis of the MD trajectories showed facile H atom transfer between the protonated polyoxoanion core and bulk water.

H


Input: The number of oxygen sites labeled with an H atom was found to vary depending on the pH of the solution.

oxygen

H


Input: Detailed analysis shows that the total number of protons at bridging (terminal), eta-O (mu 2-O), sites ranges from 3 (1) at pH 7, to 2 (0) at pH 11, to 1 (0) at pH 15.

O

O


Input: These findings closely reflect available experimental measurements.


Input: Antidepressant abietane diterpenoids from Chinese eaglewood.

abietane diterpenoids


Input: Ten new abietane diterpenoids, aquilarabietic acids A-J (1-10), and a new podocarpane diterpenoid, aquilarabietic acid K (11), were isolated from the petroleum ether and ethanol extracts of Chinese eaglewood.

abietane diterpenoids

aquilarabietic acids A-J

podocarpane diterpenoid

aquilarabietic acid K

petroleum ether

ethanol


Input: Among them, 3, 9, and 10 are artifacts.


Input: Their structures were established on the basis of data from extensive spectroscopic and X-ray diffraction analyses.


Input: Bioassay results indicated that 1 at 10 mu M demonstrated remarkable antidepressant activity in vitro by inhibiting norepinephrine reuptake in rat brain synaptosomes by 81. 4% and with an IC (50) value of 9. 1 x 10 (-7) M.

norepinephrine


Input: Institutional profile: Institute of Pharmacogenetics at the University Hospital Essen.


Input: Established in 2005, the Institute of Pharmacogenetics at the University Hospital Essen (Essen, Germany), headed by Winfried Siffert, is devoted to the discovery and validation of genetic variants that may impact upon drug responses especially in the field of cardiovascular disorders and cancer.


Input: Moreover, the institute provides pharmacogenetic testing for those drugs for which pharmacogenetic testing is recommended in order to prevent adverse drug reactions.


Input: Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy.


Input: In the past decade, advances in pharmacogenetics and pharmacogenomics (PGx) have gradually unveiled the genetic basis of interindividual differences in drug responses.


Input: A large portion of these advances have been made in the field of anticancer therapy.


Input: Currently, the US FDA has updated the package inserts of approximately 30 anticancer agents to include PGx information.


Input: Given the complexity of this genetic information (e. g., tumor mutation and gene overexpression, chromosomal translocation and germline variations), as well as the variable level of scientific evidence, the FDA recommendation and potential action needed varies among drugs.


Input: In this review, we have highlighted some of these PGx discoveries for their scientific values and utility in improving therapeutic efficacy and reducing side effects.


Input: Furthermore, examples are also provided for the role of PGx in new anticancer drug development by revealing novel druggable targets.


Input: Uncertain prognosis for high-quality diagnostics: clinical challenges, economic barriers and needed reforms.


Input: Quality healthcare, as measured by outcomes and costs, needs high-quality diagnostics whose use governs the evidence-based flow of patients from screening to treatment to outcomes monitoring.


Input: The current patent, regulatory and reimbursement environment may be inadequate to spur their development, thereby placing in jeopardy the goals of healthcare reform and the aspirations of personalized medicine.


Input: Policy actions to ensure consistent quality standards and to increase development incentives through research support, reimbursement reform, increased intellectual property protection and market-making activities may be required to obtain the well-characterized, clinically proven diagnostics that US healthcare requires.


Input: Tailoring the lasing modes in semiconductor nanowire cavities using intrinsic self-absorption.


Input: Understanding the optical gain and mode-selection mechanisms in semiconductor nanowire (NW) lasers is key to the development of high-performance nanoscale oscillators, amplified semiconductor/plasmon lasers and single photon emitters, and so forth.


Input: Modification of semiconductor band structure/bandgap through electric field modulation, elemental doping, or alloying semiconductors has so far gained limited success in achieving output mode tunability of the NW laser.


Input: One stifling issue is the considerable optical losses induced in the NW cavities by these extrinsic methods that limit their applicability.


Input: Herein we demonstrate a new optical self-feedback mechanism based on the intrinsic self-absorption of the gain media to achieve low-loss, room-temperature NW lasing with a high degree of mode selectivity (over 30 nm).


Input: The cadmium sulfide (CdS) NW lasing wavelength is continuously tunable from 489 to 520 nm as the length of the NWs increases from 4 to 25 mu m.

cadmium sulfide

CdS


Input: Our straightforward approach is widely applicable in most semiconductor or semiconductor/plasmonic NW cavities.


Input: Free energy of adsorption for a peptide at a liquid/solid interface via nonequilibrium molecular dynamics.


Input: Protein adsorption is of wide interest including in many technological applications such as tissue engineering, nanotechnology, biosensors, drug delivery, and vaccine production among others.


Input: Understanding the fundamentals of such technologies and their design would be greatly aided by an ability to efficiently predict the conformation of an adsorbed protein and its free energy of adsorption.


Input: In the study reported here, we show that this is possible when data obtained from nonequilibrium thermodynamic integration (NETI) combined with steered molecular dynamics (SMD) is subject to bootstrapping.