Input: This binding is observed in the livers of male mice, but not in the livers of female mice and requires the pituitary gland, because hypophysectomy abrogates it.


Input: Hyperplasia further progressed in the livers of Kcnk1 (-/-) male mice compared with those of Kcnk1 (+/+) males after phenobarbital treatment.

phenobarbital


Input: Thus, KCNK1 suppresses phenobarbital-induced hyperplasia.

phenobarbital


Input: These results indicate that phenobarbital treatment induces KCNK1 to elicit a male-specific and growth-suppressing signal.

phenobarbital


Input: Thus, KCNK1 and Kcnk1 (-/-) mice provide an experimental tool for further investigation into the molecular mechanism of CAR-mediated promotion of the development of hepatocellular carcinoma in mice.


Input: Postweaning exposure to dietary zearalenone, a mycotoxin, promotes premature onset of puberty and disrupts early pregnancy events in female mice.

zearalenone


Input: Zearalenone (ZEA) is a mycotoxin commonly found in contaminated livestock feed and human food with levels in the range of ppb and low ppm.

Zearalenone

ZEA


Input: It was hypothesized that ZEA, an endocrine disruptor, could affect puberty and early pregnancy.

ZEA


Input: To test this hypothesis, newly weaned (3 weeks old) C57BL/6J female mice were exposed to 0, 0. 002, 4, 10, and 40 ppm ZEA and 0. 05 ppm diethylstilbestrol (positive control) in phytoestrogen-free AIN-93G diet.

ZEA

diethylstilbestrol


Input: Females exposed to 10 and 40 ppm ZEA diets showed earlier onset of vaginal opening.

ZEA


Input: Those treated with 40 ppm ZEA diet also had earlier first copulation plug and irregular estrous cyclicity.

ZEA


Input: At 8 weeks old, all females were mated with untreated stud males on AIN-93G diet during mating.


Input: Treatment resumed upon identification of a vaginal plug on gestation day 0. 5 (D0. 5).


Input: Embryo implantation was assessed on D4. 5.


Input: Exposure to 40 ppm ZEA diet resulted in reduced percentage of plugged mice with implantation sites, distended uterine appearance, and retained expression of progesterone receptor in D4. 5 uterine epithelium.

ZEA

progesterone


Input: To determine the exposure timing and mechanisms of disrupted embryo implantation, four groups of females were fed with 0 or 40 ppm ZEA diets during premating (weaning to mating) and postmating (D0. 5-D4. 5), respectively.

ZEA


Input: Premating exposure to 40 ppm ZEA diet reduced fertilization rate, whereas postmating exposure to 40 ppm ZEA diet delayed embryo transport and preimplantation embryo development, which subsequently affected embryo implantation.

ZEA

ZEA


Input: These data demonstrate that postweaning exposure to dietary ZEA can promote premature onset of puberty and disrupt early pregnancy events.

ZEA


Input: Autophagy inhibition for chemosensitization and radiosensitization in cancer: do the preclinical data support this therapeutic strategy?


Input: Recognition of the cytoprotective functions of autophagy that occur in tumor cells exposed to various forms of chemotherapy or radiation has generated intense interest in the possibility that pharmacological interference with autophagy could provide a clinical strategy for overcoming therapeutic resistance.


Input: Multiple clinical trials are currently in progress to evaluate the antimalarial agent chloroquine (generally in its clinical formulation as hydroxychloroquine) and its impact on various forms of cancer therapy.

chloroquine

hydroxychloroquine


Input: In this commentary/review, we focus on the relatively limited number of studies in the literature where chloroquine has been tested in combination with chemotherapy or radiation in experimental tumor-bearing animal models.

chloroquine


Input: We also present recent data from our own laboratories, in cell culture experiments as well as in vivo studies, which demonstrate that neither chloroquine nor silencing of an autophagy regulatory gene was effective in conferring radiation sensitivity in an experimental model of breast cancer.

chloroquine


Input: The capacity for sensitization by chloroquine appears to be quite wide-ranging, with dramatic effects for some drugs/tumor models and modest or minimal effects in others.

chloroquine


Input: One possible caveat is that, with only a few exceptions, experiments have generally been performed in xenograft models, thereby eliminating the involvement of the immune system, which might ultimately be proven to play a central role in determining the effectiveness of autophagy inhibition in chemosensitization or radiosensitization.


Input: Nevertheless, a careful review of the current literature suggests that caution is likely to be warranted in translating preclinical findings relating to autophagy inhibition as an adjunctive therapeutic strategy.


Input: Synthesis of selenolate-protected Au18 (SeC6H5) 14 nanoclusters.

selenolate

Au18 (SeC6H5) 14


Input: This work reports the first synthesis of selenophenolate-protected Au (18) (SePh) (14) nanoclusters.

selenophenolate

Au (18) (SePh) (14)


Input: This cluster exhibits distinct differences from its thiolate analogue in terms of optical absorption properties.


Input: The Au (18) (SePh) (14) nanoclusters were obtained via a controlled reaction of Au (25) (SCH (2) CH (2) Ph) (18) with selenophenol.

Au (18) (SePh) (14)

Au (25) (SCH (2) CH (2) Ph) (18)

selenophenol


Input: Electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) revealed the crude product to contain predominantly Au (18) (SePh) (14) nanoclusters, and side products include Au (15) (SePh) (13), Au (19) (SePh) (15) and Au (20) (SePh) (16).

Au (18) (SePh) (14)

Au (15) (SePh) (13)

Au (19) (SePh) (15)

Au (20) (SePh) (16)


Input: High-performance liquid chromatography (HPLC) was employed to isolate Au (18) (SePh) (14) nanoclusters.

Au (18) (SePh) (14)


Input: The results of thermogravimetric analysis (TGA), elemental analysis (EA), and (1) H/(13) C NMR spectroscopy confirmed the cluster composition.

(1) H

(13) C


Input: To the best of our knowledge, this is the first report of selenolate-protected Au (18) nanoclusters.

selenolate

Au (18)


Input: Future theoretical and X-ray crystallographic work will reveal the geometric structure and the nature of selenolate-gold bonding in the nanocluster.

selenolate


Input: The physico-chemical " anatomy " of the tautomerization through the DPT of the biologically important pairs of hypoxanthine with DNA bases: QM and QTAIM perspectives.

hypoxanthine


Input: The biologically important tautomerization of the Hyp. Cyt, Hyp *. Thy and Hyp. Hyp base pairs to the Hyp *. Cyt *, Hyp. Thy * and Hyp *. Hyp * base pairs, respectively, by the double proton transfer (DPT) was comprehensively studied in vacuo and in the continuum with a low dielectric constant (epsilon = 4) corresponding to hydrophobic interfaces of protein-nucleic acid interactions by combining theoretical investigations at the B3LYP/6-311 + + G (d, p) level of QM theory with QTAIM topological analysis.

Hyp

Cyt

Hyp

Thy

Hyp

Hyp

Hyp

Cyt

Hyp

Thy

Hyp

Hyp


Input: Based on the sweeps of the energetic, electron-topological, geometric and polar parameters, which describe the course of the tautomerization along the intrinsic reaction coordinate (IRC), it was proved that the tautomerization through the DPT is concerted and asynchronous process for the Hyp. Cyt and Hyp *. Thy base pairs, while concerted and synchronous for the Hyp. Hyp homodimer.

Hyp

Cyt

Hyp

Thy

Hyp

Hyp


Input: The continuum with epsilon = 4 does not affect qualitatively the course of the tautomerization reaction for all studied complexes.


Input: The nine key points along the IRC of the Hyp. Cyt <--> Hyp *. Cyt * and Hyp *. Thy <--> Hyp. Thy * tautomerizations and the six key points of the Hyp. Hyp <--> Hyp *. Hyp * tautomerization have been identified and fully characterized.

Hyp

Cyt

Hyp

Cyt

Hyp

Thy

Hyp

Thy

Hyp

Hyp

Hyp

Hyp


Input: These key points could be considered as electron-topological " fingerprints " of concerted asynchronous (for Hyp. Cyt and Hyp *. Thy) or synchronous (for Hyp. Hyp) tautomerization process via the DPT.

Hyp

Cyt

Hyp

Thy

Hyp

Hyp


Input: It was found, that in the Hyp *. Cyt *, Hyp. Thy *, Hyp. Hyp and Hyp *. Hyp * base pairs all H-bonds are significantly cooperative and mutually reinforce each other, while the C2H ... O2 H-bond in the Hyp. Cyt base pair and the O6H ... O4 H-bond in the Hyp *. Thy base pair behave anti-cooperatively, i. e., they become weakened, while two others become strengthened.

Hyp

Cyt

Hyp

Thy

Hyp

Hyp

Hyp

Hyp

H

O2 H

Hyp

Cyt

O4 H

Hyp

Thy


Input: Zinc deficiency induced in Swiss 3T3 cells by a low-zinc medium impairs calcium entry and two mechanisms of entry are involved.

Zinc

zinc

calcium


Input: Zinc deficiency in 3T3 cells induced by the use of diethylenetriaminepentaacetate (DTPA) has been shown to impair calcium entry associated with failure of proliferation when the cells are stimulated with polypeptide growth factors (GF).

Zinc

diethylenetriaminepentaacetate

DTPA

calcium


Input: These functions of zinc have been evaluated here in the same clone of cells by simple depletion using a low-zinc medium (0. 05 mu mol/L zinc) without chelator.

zinc

zinc

zinc


Input: Confluent cells were maintained for 1 day in the low-zinc medium without GF, then loaded with Fluo-4, and stimulated with GF.

zinc


Input: Calcium entry was measured by the increase in sustained fluorescence.

Calcium


Input: It was preceded by the release of stored calcium as observed in the previous study using DTPA.

calcium

DTPA


Input: Zinc deprivation decreased calcium entry when calcium was added at 0 or 0. 05 mmol/L but not when 0. 1 mmol/L or higher.

Zinc

calcium

calcium


Input: Cell proliferation reflected similar effects of zinc and calcium concentrations.

zinc

calcium


Input: In a newly acquired clone of 3T3 cells, GF did not induce internal calcium release but thapsigargin (TG) did.

calcium

thapsigargin


Input: When added in a low-calcium medium, both agonists stimulated calcium entry when external calcium was added, suggesting that two different mechanisms of entry were impaired by zinc deficiency.

calcium

calcium

calcium

zinc


Input: Zinc deficiency produced by DTPA in the newer clones gave similar results, decreasing calcium entry induced by both agonists.

Zinc

DTPA

calcium


Input: The effects of GF and TG were not additive.


Input: The results confirm the earlier observation that zinc deficiency impairs calcium entry into 3T3 cells when stimulated by GF and show that the cells can take up calcium by either store-operated or receptor-operated mechanisms.

zinc

calcium

calcium


Input: Theoretical investigation into optical and electronic properties of 1, 8-naphthalimide derivatives.

1, 8-naphthalimide


Input: A series of 1, 8-naphthalimide derivatives has been designed to explore their optical, electronic, and charge transport properties as charge transport and/or luminescent materials for organic light-emitting diodes (OLEDs).

1, 8-naphthalimide


Input: The frontier molecular orbitals (FMOs) analysis have shown that the vertical electronic transitions of absorption and emission are characterized as intramolecular charge transfer (ICT) for electron-donating and aromatic groups substituted derivatives.


Input: However, the ICT character of the electron-withdrawing substituted derivatives is not significant.


Input: The calculated results show that their optical and electronic properties are affected by the substituent groups in 4-position of 1, 8-naphthalimide.

1, 8-naphthalimide


Input: Our results suggest that 1, 8-naphthalimide derivatives with electron-donating-OCH3 and-N (CH3) 2 (1 and 2), electron-withdrawing-CN and-COCH3 (3 and 4), 2-(thiophen-2-yl) thiophene (5), 2, 3-dihydrothieno [3, 4-b] [1, 4] dioxine (6), 2-phenyl-1, 3, 4-oxadiazole (7), and benzo [c] [1, 2, 5] thiadiazole (8) fragments are expected to be promising candidates for luminescent materials for OLEDs, particularly for 5 and 7.

1, 8-naphthalimide

-N (CH3) 2

-CN

2-(thiophen-2-yl) thiophene

2, 3-dihydrothieno [3, 4-b] [1, 4] dioxine

2-phenyl-1, 3, 4-oxadiazole

benzo [c] [1, 2, 5] thiadiazole


Input: In addition, 3 and 7 can be used as promising hole transport materials for OLEDs.


Input: This study should be helpful in further theoretical investigations on such kind of systems and also to the experimental study for charge transport and/or luminescent materials for OLEDs.


Input: Polyethylene Glycol and Polyethylenimine Dual-Functionalized Nano-Graphene Oxide for Photothermally Enhanced Gene Delivery.

Polyethylene Glycol

Polyethylenimine

Graphene Oxide


Input: Graphene oxide (GO) has been extensively explored in nanomedicine for its excellent physiochemical, electrical, and optical properties.

Graphene oxide


Input: Here, polyethylene glycol (PEG) and polyethylenimine (PEI) are covalently conjugated to GO via amide bonds, obtaining a physiologically stable dual-polymer-functionalized nano-GO conjugate (NGO-PEG-PEI) with ultra-small size.

polyethylene glycol

PEG

polyethylenimine

PEI

amide

PEG

PEI


Input: Compared with free PEI and the GO-PEI conjugate without PEGylation, NGO-PEG-PEI shows superior gene transfection efficiency without serum interference, as well as reduced cytotoxicity.

PEI

PEI

PEGylation

PEI


Input: Utilizing the NIR optical absorbance of NGO, the cellular uptake of NGO-PEG-PEI is shown to be enhanced under a low power NIR laser irradiation, owing to the mild photothermal heating that increases the cell membrane permeability without significantly damaging cells.

PEG

PEI


Input: As the results, remarkably enhanced plasmid DNA transfection efficiencies induced by the NIR laser are achieved using NGO-PEG-PEI as the light-responsive gene carrier.

PEG

PEI


Input: More importantly, it is shown that our NGO-PEG-PEI is able to deliver small interfering RNA (siRNA) into cells under the control of NIR light, resulting in obvious down-regulation of the target gene, Polo-like kinase 1 (Plk1), in the presence of laser irradiation.

PEG

PEI


Input: This study is the first to use photothermally enhanced intracellular trafficking of nanocarriers for light-controllable gene delivery.


Input: This work also encourages further explorations of functionalized nano-GO as a photocontrollable nanovector for combined photothermal and gene therapies.


Input: Effects of smoking on the oxidant/antioxidant balance and the blood lipids in pesticide sprayers.


Input: The present study was conducted on 80 pesticide male sprayers (42 nonsmokers and 38 smokers).


Input: Our aim was to estimate the smoking effects on blood lipids and oxidant/antioxidant status in pesticide sprayers.


Input: Results revealed that cholesterol, low-density lipoprotein (LDL) and glutathion peroxidase (GPx) enzyme were significantly higher in the 38 smoker sprayers than in the 42 nonsmoker sprayers.

cholesterol

glutathion


Input: Cholesterol and LDL were correlated with smoking index and high-density lipoprotein (HDL), superoxide dismutase (SOD) enzyme and zinc (Zn) were inversely correlated with duration of pesticides' exposure.

Cholesterol

superoxide

zinc

Zn


Input: In nonsmokers, LDL and cholesterol were negatively correlated with SOD and correlated with malondialdehyde (MDA), and cholesterol was negatively correlated with Zn.

cholesterol

malondialdehyde

MDA

cholesterol

Zn


Input: HDL was negatively correlated with MDA in all the sprayers, but was correlated with GPx in smokers and with Zn in nonsmokers.

MDA

Zn


Input: In smokers, LDL was negatively correlated with GPx, HDL was negatively correlated with MDA and triglycerides and very-low-density lipoprotein were negatively correlated with Zn.

MDA

triglycerides

Zn


Input: MDA was negatively correlated with SOD, GPx and Zn.

MDA

Zn


Input: Smoking and pesticide exposure could be responsible for hyperlipidemia and oxidative stress.


Input: Therefore, improvement in the antioxidant status is mandatory for pesticide sprayers especially the ones who smoke.


Input: Agreement between chest radiography and high-resolution computed tomography in diagnosing dust-related interstitial lung fibrosis.


Input: Although it has been suggested that high-resolution computed tomography (HRCT) scans can be obtained when plain radiographs are equivocal for the presence of interstitial lung fibrosis (ILF) caused by inhalation of dust, such as silica, asbestos fibres, etc., the specificity of the findings remains in question.

silica

asbestos


Input: The present study was carried out to compare the relative efficacy of chest radiography by conventional method and HRCT in evaluating ILF which included 22 workers exposed to fibrogenic dust, who were subjected to clinical examination, pulmonary function testing, posteroanterior chest radiography and HRCT.


Input: In the six subjects who had findings suggestive of ILF on HRCT, four had normal chest x-ray (CXR) while one each has been diagnosed as having tuberculosis and ILF on CXR.


Input: The agreement analysis between HRCT and CXR suggests that there was a poor agreement between HRCT and CXR (kappa = 0. 34).


Input: Serum mineral status of long-term cigarette smokers.


Input: This study was carried out to investigate comparatively some serum mineral levels of cigarette smokers.


Input: A total of 25 nonsmokers (control group) and 50 long-term cigarette smokers (smoking for at least 15 years; smoker group) were participated in the study.


Input: Subjects were between 25 and 40 years old.


Input: Control and smoker groups were matched for age, sex and body mass index status.


Input: The blood samples were taken from smokers and nonsmokers after 12 h of fasting period.


Input: The levels of zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg), calcium (Ca), potassium (K), chlorine (Cl), sodium (Na) and phosphorus (P) were measured by autoanalyzer using commercial kits.

zinc

Zn

copper

Cu

iron

Fe

magnesium

Mg

calcium

Ca

potassium

K

chlorine

Cl

sodium

phosphorus

P


Input: Student' s t test was used to compare the control and smoker groups, and p < 0. 05 indicated a significant difference.


Input: Pearson' s correlation coefficient was used to demonstrate the relationship among parameters in smoker and control groups.


Input: Although there was no statistical difference (p > 0. 05) between the groups regarding the levels of K, P, Mg, Na, Cl, Zn, Fe, Ca and Cu, some positive correlations were observed in controls but not in smokers.

K

P

Mg

Cl

Zn

Fe

Ca

Cu


Input: Therefore, it was concluded that smoking does not affect the serum mineral levels.


Input: However, it may negatively affect some important positive correlations among minerals observed in healthy individuals.


Input: Occupational hazards control of hazardous substances in clean room of semiconductor manufacturing plant using CFD analysis.


Input: The manufacturing processes in chip industries are complex, and many kinds of raw materials and solvents of different nature are used, most of which are highly toxic and dangerous.


Input: During the machine preventive maintenance period, these toxic and harmful substances will escape from the sealed reaction chamber to the clean workshop environment and endanger the health of the workers on-site, resulting in occupational diseases.


Input: From the perspective of prevention, the spread and prediction of hydrochloric acid (HCl) that escaped from the metal-etching chamber during maintenance were studied in this article.

hydrochloric acid

HCl


Input: The computational fluid dynamics technology was used for a three-dimensional numerical simulation of the indoor air velocity field and the HCl concentration field, and the simulation results were then compared with the on-site monitoring data to verify the correctness and feasibility.

HCl


Input: The occupational hazards and control measures were analyzed based on the numerical simulation, and the optimal control measure was obtained.


Input: In this article, using the method of ambient air to analyze the occupational exposure can provide a new idea to the field of occupational health research in the integrated circuit industry and had theoretical and practical significance.


Input: Plasmon dynamics in colloidal Au 2 Cd alloy-CdSe core/shell nanocrystals.

Au 2 Cd

CdSe


Input: Metal-semiconductor nanocrystal heterostructures are model systems for understanding the interplay between the localized surface plasmon resonances in the metal domain and the relaxation of the excited carriers in the semiconductor domain.


Input: Here we report the synthesis of colloidal Au 2 Cd (core)/CdSe (shell) nanocrystal heterostructures, which were characterized extensively with several structural and optical techniques, including time-resolved fluorescence and broad-band transient absorption spectroscopy (both below and above the CdSe band gap).

Au 2 Cd

CdSe

CdSe


Input: The dynamics of the transient plasmon peak was dominated by the relaxation of hot carriers in the metal core, its spectral shape was independent of the pump wavelength, and the bleaching lifetime was about half a picosecond, comparable with the value found in the AuCd seeds used for the synthesis.

AuCd


Input: Thermodynamic studies of ionic hydration and interactions for amino acid ionic liquids in aqueous solutions at 298. 15 K.

amino acid


Input: Amino acid ionic liquids are a special class of ionic liquids due to their unique acid-base behavior, biological significance, and applications in different fields such as templates in synthetic chemistry, stabilizers for biological macromolecules, etc.

Amino acid


Input: The physicochemical properties of these ionic liquids can easily be altered by making the different combinations of amino acids as anion along with possible cation modification which makes amino acid ionic liquids more suitable to understand the different kinds of molecular and ionic interactions with sufficient depth so that they can provide fruitful information for a molecular level understanding of more complicated biological processes.

amino acids

amino acid


Input: In this context, volumetric and osmotic coefficient measurements for aqueous solutions containing 1-ethyl-3-methylimidazolium ([Emim]) based amino acid ionic liquids of glycine, alanine, valine, leucine, and isoleucine are reported at 298. 15 K.

Emim

amino acid

glycine

alanine

valine

leucine

isoleucine


Input: From experimental osmotic coefficient data, mean molal activity coefficients of ionic liquids were estimated and analyzed using the Debye-H u ckel and Pitzer models.


Input: The hydration numbers of ionic liquids in aqueous solutions were obtained using activity data.


Input: Pitzer ion interaction parameters are estimated and compared with other electrolytes reported in the literature.


Input: The nonelectrolyte contribution to the aqueous solutions containing ionic liquids was studied by calculating the osmotic second virial coefficient through an application of the McMillan-Mayer theory of solution.


Input: It has been found that the second osmotic virial coefficient which includes volume effects correlates linearly with the Pitzer ion interaction parameter estimated independently from osmotic data as well as the hydrophobicity of ionic liquids.


Input: The enthalpy-entropy compensation effect, explained using the Starikov-Nord e n model of enthalpy-entropy compensation, and partial molar entropy analysis for aqueous [Emim] [Gly] solutions are made by using experimental Gibb' s free energy data and literature enthalpy data.

Emim

Gly


Input: This study highlights that the hydrophobic interaction persists even in the limit of infinite dilution where the hydration effects are usually dominant, implying importance of hydrophobic hydration.


Input: Analysis of the results further shows that the hydration of amino acid ionic liquids occurs through the cooperative H-bond formation with the kosmotropic effect in contrast to the usual inorganic salts or hydrophobic salts like tetraalkylammonium halides.

amino acid

H

tetraalkylammonium halides


Input: Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?


Input: Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks.


Input: Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS).


Input: The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high.


Input: Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future.


Input: The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical.


Input: This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.


Input: Spiroketal formation and modification in avermectin biosynthesis involves a dual activity of AveC.

avermectin


Input: Avermectins (AVEs), which are widely used for the treatment of agricultural parasitic diseases, belong to a family of 6, 6-spiroketal moiety-containing, macrolide natural products.

Avermectins

AVEs

macrolide


Input: AVE biosynthesis is known to employ a type I polyketide synthase (PKS) system to assemble the molecular skeleton for further functionalization.

AVE

polyketide


Input: It remains unknown how and when spiroketal formation proceeds, particularly regarding the role of AveC, a unique protein in the pathway that shares no sequence homology to any enzyme of known function.


Input: Here, we report the unprecedented, dual function of AveC by correlating its activity with spiroketal formation and modification during the AVE biosynthetic process.

AVE


Input: The findings in this study were supported by characterizing extremely unstable intermediates, products and their spontaneous derivative products from the simplified chemical profile and by comparative analysis of in vitro biotransformations and in vivo complementations mediated by AveC and MeiC (the counterpart in biosynthesizing the naturally occurring, AVE-like meilingmycins).

AVE

meilingmycins


Input: AveC catalyzes the stereospecific spiroketalization of a dihydroxy-ketone polyketide intermediate and the optional dehydration to determine the regiospecific saturation characteristics of spiroketal diversity.

dihydroxy-ketone polyketide


Input: These reactions take place between the closures of the hexene ring and 16-membered macrolide and the formation of the hexahydrobenzofuran unit.

hexene

macrolide

hexahydrobenzofuran


Input: MeiC can replace the spirocyclase activity of AveC, but it lacks the independent dehydratase activity.


Input: Elucidation of the generality and specificity of AveC-type proteins allows for the rationalization of previously published results that were not completely understood, suggesting that enzyme-mediated spiroketal formation was initially underestimated, but is, in fact, widespread in nature for the control of stereoselectivity.


Input: Attenuating Staphylococcus aureus Virulence Gene Regulation: A Medicinal Chemistry Perspective.


Input: Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two-component signal transduction systems.


Input: There is now an emerging body of evidence to suggest that the blockade of S. aureus virulence gene expression significantly attenuates infection in experimental models.


Input: In this Perspective, we will provide insights into medicinal chemistry strategies for the development of chemical reagents that have the capacity to inhibit staphylococcal virulence expression.


Input: These reagents can be broadly grouped into four categories: (1) competitive inhibitors of the accessory gene regulator (agr) quorum sensing system, (2) inhibitors of AgrA-DNA interactions, (3) RNAIII transcription inhibitors, and (4) inhibitors of the SarA family of transcriptional regulators.


Input: We discuss the potential of specific examples of antivirulence agents for the management and treatment of staphylococcal infections.


Input: Development of new cyclic plasmin inhibitors with excellent potency and selectivity.


Input: The trypsin-like serine protease plasmin is a target for the development of antifibrinolytic drugs for use in cardiac surgery with cardiopulmonary bypass or organ transplantations to reduce excessive blood loss.

serine


Input: The optimization of our recently described substrate-analogue plasmin inhibitors, which were cyclized between their P3 and P2 side chains, provided a new series with improved efficacy and excellent selectivity.


Input: The most potent inhibitor 8 binds to plasmin with an inhibition constant of 0. 2 nM, whereas K (i) values > 1 mu M were determined for nearly all other tested trypsin-like serine proteases, with the exception of trypsin, which is also inhibited in the nanomolar range.

serine


Input: Docking studies revealed a potential binding mode in the widely open active site of plasmin that explains the strong potency and selectivity profile of these inhibitors.


Input: The dialkylated piperazine-linker segment contributes to an excellent solubility of all analogues.

piperazine


Input: Based on their overall profile the presented inhibitors are well suited for further development as injectable antifibrinolytic drugs.


Input: Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability.

free fatty acid


Input: The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes.

free fatty acid

glucose


Input: Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity.


Input: We have previously reported the FFA1 agonist 3 (TUG-424).


Input: We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability, and appreciable efficacy on glucose tolerance in mice.

glucose


Input: A safety study on single intravenous dose of tetrachloro-diphenyl glycoluril [iodogen] dissolved in dimethyl sulphoxide (DMSO).

tetrachloro-diphenyl glycoluril

iodogen

dimethyl sulphoxide

DMSO


Input: Abstract 1.


Input: Iodogen (tetrachloro-diphenyl glycoluril) dissolved in DMSO (dimethyl sulphoxide) appears indispensable in radioiodination of hypericin for a new anticancer strategy.

Iodogen

tetrachloro-diphenyl glycoluril

DMSO

dimethyl sulphoxide

hypericin


Input: We studied the safety of intravenously administered iodogen/DMSO in mice (n = 132).

iodogen

DMSO


Input: Median lethal dose (LD (50)) of iodogen/DMSO was determined with doses of 40. 0, 50. 0, 55. 0, 60. 0, 65. 0 and 70. 0 mg/kg.

iodogen

DMSO


Input: Next, toxicity of iodogen/DMSO at 30. 0 mg/kg was evaluated using saline and DMSO as controls.

iodogen

DMSO

DMSO


Input: Changes in behaviour, body weight and serum biochemistry were evaluated.


Input: Histopathology of lungs, heart, liver and kidney was performed.


Input: LD (50) values of iodogen/DMSO were 59. 5 mg/kg (95% confidence limits (CI): 54. 1-65. 4 mg/kg) and 61. 0 mg/kg (95% CI: 56. 2-66. 2 mg/kg) for female and male mice, respectively.

iodogen

DMSO


Input: Similar to that of control groups, no animal deaths were encountered after iodogen/DMSO administration at 30. 0 mg/kg.

iodogen

DMSO


Input: Body weights over 24 h were not altered in all groups, but significantly higher in iodogen/DMSO and DMSO groups (p < 0. 05) 14 d post-injection.

iodogen

DMSO

DMSO


Input: Blood urea nitrogen and alkaline phosphatase increased (p < 0. 05) in iodogen/DMSO group without clinical symptoms.

urea nitrogen

iodogen

DMSO


Input: No pathologies were found by gross and microscopic inspection.


Input: A single dose of iodogen/DMSO up to 30. 0 mg/kg, over 3000 times the dose in potential human applications, appears safe, with an LD (50) doubling that dose in mice.

iodogen

DMSO


Input: Fragment-based discovery of new highly substituted 1H-pyrrolo [2, 3-b]-and 3H-imidazolo [4, 5-b]-pyridines as focal adhesion kinase inhibitors.

1H-pyrrolo [2, 3-b]-and 3H-imidazolo [4, 5-b]-pyridines


Input: Focal adhesion kinase (FAK) is considered as an attractive target for oncology, and small-molecule inhibitors are reported to be in clinical testing.


Input: In a surface plasmon resonance (SPR)-mediated fragment screening campaign, we discovered bicyclic scaffolds like 1H-pyrazolo [3, 4-d] pyrimidines binding to the hinge region of FAK.

1H-pyrazolo [3, 4-d] pyrimidines


Input: By an accelerated knowledge-based fragment growing approach, essential pharmacophores were added.


Input: The establishment of highly substituted unprecedented 1H-pyrrolo [2, 3-b] pyridine derivatizations provided compounds with submicromolar cellular FAK inhibition potential.

1H-pyrrolo [2, 3-b] pyridine


Input: The combination of substituents on the bicyclic templates and the nature of the core structure itself have a significant impact on the compounds FAK selectivity.


Input: Structural analysis revealed that the appropriately substituted pyrrolo [2, 3-b] pyridine induced a rare helical DFG-loop conformation.

pyrrolo [2, 3-b] pyridine


Input: The discovered synthetic route to introduce three different substituents independently paves the way for versatile applications of the 7-azaindole core.


Input: Melt granulation in fluidized bed: a comparative study of spray-on versus in situ procedure.


Input: Abstract Objective: The aim of this study was to investigate the influence of process parameters, binder content and binder addition method on characteristics of the granules obtained by melt granulation (MG) in fluidized bed.


Input: Methods: Spray-on experiments were performed according to 2 (3) full factorial design.


Input: The effect of binder content, molten binder feed rate, and spray air pressure on granule size and size distribution, granule shape, fl owability and drug release rate was investigated.


Input: In the in situ experiments, the influence of binder particle size and binder content was evaluated.


Input: Solid-state characterization was performed by means of differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy.


Input: Results: Size of the granules obtained by spray-on procedure was significantly influenced by binder content and spray air pressure, while the width of particle size distribution was mainly affected by binder feed rate.


Input: Spray air pressure showed the most significant influence on granule shape.


Input: It was shown that smooth and spherical particles with good flow properties may be obtained by both procedures, spray-on and in situ MG.


Input: The results obtained indicated the influence of agglomeration mechanism on granule sphericity, with higher degree of granule sphericity observed when immersion and layering was the dominant mechanism.


Input: Paracetamol release from granulates was very rapid, but after compression of the granules into tablets, drug release was considerably slower.

Paracetamol


Input: Solid-state analysis confirmed that the physical form of the granulate components remained unaffected after the MG process.


Input: Conclusion: The results presented indicate that MG in fluidized bed could be a good alternative to conventional granulation techniques.


Input: The mechanism of discrimination between oxidized and reduced coenzyme in the aldehyde dehydrogenase domain of Aldh1l1.

aldehyde


Input: Aldh1l1, also known as 10-formyltetrahydrofolate dehydrogenase (FDH), contains the carboxy-terminal domain (Ct-FDH), which is a structural and functional homolog of aldehyde dehydrogenases (ALDHs).

carboxy

aldehyde


Input: This domain is capable of catalyzing the NADP (+)-dependent oxidation of short chain aldehydes to their corresponding acids, and similar to most ALDHs it has two conserved catalytic residues, Cys707 and Glu673.

NADP (+)

aldehydes


Input: Previously, we demonstrated that in the Ct-FDH mechanism these residues define the conformation of the bound coenzyme and the affinity of its interaction with the protein.


Input: Specifically, the replacement of Cys707 with an alanine resulted in the enzyme lacking the ability to differentiate between the oxidized and reduced coenzyme.

alanine


Input: We suggested that this was due to the loss of a covalent bond between the cysteine and the C4N atom of nicotinamide ring of NADP (+) formed during Ct-FDH catalysis.

cysteine

nicotinamide

NADP (+)


Input: To obtain further insight into the functional significance of the covalent bond between Cys707 and the coenzyme, and the overall role of the two catalytic residues in the coenzyme binding and positioning, we have now solved crystal structures of Ct-FDH in the complex with thio-NADP (+) and the complexes of the C707S mutant with NADP (+) and NADPH.

thio-NADP (+)

NADP (+)

NADPH


Input: This study has allowed us to trap the coenzyme in the contracted conformation, which provided a snapshot of the conformational processing of the coenzyme during the transition from oxidized to reduced form.


Input: Overall, the results of this study further support the previously proposed mechanism by which Cys707 helps to differentiate between the oxidized and reduced coenzyme during ALDH catalysis.


Input: X-ray structure of the V301L aldo-keto reductase 1B10 complexed with NADP (+) and the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity.

NADP (+)

aldose

fidarestat


Input: Only one crystal structure is currently available for tumor marker AKR1B10, complexed with NADP (+) and tolrestat, which is an aldose reductase inhibitor (ARI) of the carboxylic acid type.

NADP (+)

tolrestat

aldose

carboxylic acid


Input: Here, the X-ray structure of the complex of the V301L substituted AKR1B10 holoenzyme with fidarestat, an ARI of the cyclic imide type, was obtained at 1. 60 A resolution by replacement soaking of crystals containing tolrestat.

fidarestat

cyclic imide

tolrestat


Input: Previously, fidarestat was found to be safe in phase III trials for diabetic neuropathy and, consistent with its low in vivo side effects, was highly selective for aldose reductase (AR or AKR1B1) versus aldehyde reductase (AKR1A1).

fidarestat

aldose

aldehyde


Input: Now, inhibition studies showed that fidarestat was indeed 1300-fold more selective for AR as compared to AKR1B10, while the change of Val to Leu (found in AR) caused a 20-fold decrease in the IC50 value with fidarestat.

fidarestat

Val

Leu

fidarestat


Input: Structural analysis of the V301L AKR1B10-fidarestat complex displayed enzyme-inhibitor interactions similar to those of the AR-fidarestat complex.

fidarestat

fidarestat


Input: However, a close inspection of both the new crystal structure and a computer model of the wild-type AKR1B10 complex with fidarestat revealed subtle changes that could affect fidarestat binding.

fidarestat

fidarestat


Input: In the crystal structure, a significant motion of loop A was observed between AR and V301L AKR1B10, linked to a Phe-122/Phe-123 side chain displacement.

Phe

Phe


Input: This was due to the presence of the more voluminous Gln-303 side chain (Ser-302 in AR) and of a water molecule buried in a subpocket located at the base of flexible loop A.

Gln

Ser


Input: In the wild-type AKR1B10 model, a short contact was predicted between the Val-301 side chain and fidarestat, but would not be present in AR or in V301L AKR1B10.

Val

fidarestat


Input: Overall, these changes could contribute to the difference in inhibitory potency of fidarestat between AR and AKR1B10.

fidarestat


Input: Potential monovalent cation-binding sites in aldehyde dehydrogenases.

aldehyde


Input: Potassium ions are non-essential activators of several aldehyde dehydrogenases (ALDHs), whereas a few others require the cation for activity.

Potassium

aldehyde


Input: Two kinds of cation-binding sites, which we named intra-subunit and inter-subunit, have been observed in crystal structures of ALDHs, and based on reported crystallographic data, we here propose the existence of a third kind located in the central cavity of some tetrameric ALDHs.


Input: Given the high structural similarity between these enzymes, cation-binding sites may be present in many other members of this superfamily.


Input: To explore the prevalence of these sites, we compared 37 known crystal structures from 13 different ALDH families and evaluated the possible existence of a cation on the basis of the number, distance and geometry of its potential interactions, as well as of B-factor values of modeled cations obtained in new refinements of some reported crystal structures.


Input: Also, by performing multiple alignments of 855 non-redundant amino acid sequences, we assessed the degree of conservation in their respective families of the amino acid residues putatively relevant for cation binding.

amino acid

amino acid


Input: Among the ALDH enzymes studied, and according to our analyses, potential intra-subunit cation-binding sites seem to be present in most members of ALDH2, ALDH1L, ALDH4, ALDH5, ALDH7, ALDH10, and ALDH25 families, as well as in the bacterial and fungal members of the ALDH9 family and in a few ALDH1, ALDH6, ALDH11 and ALDH26 enzymes; potential inter-subunit sites in members of ALDH1L, ALDH3, ALDH4 from bacillales, ALDH5, ALDH7, ALDH9, ALDH10, ALDH11 and ALDH25 families; and potential central-cavity sites only in some bacterial and animal ALDH9s and in most members of the ALDH1L family.


Input: Because potassium is the most abundant intracellular cation, we propose that these are potassium-binding sites, but the specific structural and/or functional roles of the cation bound to these different sites remain to be investigated.

potassium

potassium


Input: Specific surface area of titanium dioxide (TiO2) particles influences cyto-and photo-toxicity.

titanium dioxide


Input: The aim of this study is to examine how different specific surface areas of similar-sized titanium dioxide (TiO (2)) particles could influence both cytotoxicity and phototoxicity.

titanium dioxide

TiO (2)


Input: TiO (2) particles of different specific surface areas were compared for their toxic effects on RAW264. 7 cells in the absence and presence of UV light.

TiO (2)


Input: From the results, TiO (2) particles with larger specific surface area were found to induce higher cyto-(UV absent) and photo-toxicity (UV activated) to cells after 24h incubation.

TiO (2)


Input: The observed cytotoxicity from TiO (2) particles with larger surface area could be explained from their interactions with biomolecules.

TiO (2)


Input: Upon photoactivation, a larger number of hydroxyl radicals were detected from TiO (2) particles with larger surface area, again suggesting a surface area dependent phototoxic effect.

hydroxyl

TiO (2)


Input: On the other hand, pre-adsorbing TiO (2) particles with extracellular proteins were found to decrease toxicity effects.

TiO (2)


Input: Lack of transient receptor potential melastatin 8 activation by phthalate esters that enhance contact hypersensitivity in mice.

phthalate esters


Input: We studied the involvement of sensory neurons in skin sensitization to allergens using a mouse model in which the T-helper type 2 response is essential.


Input: Skin sensitization to fluorescein isothiocyanate (FITC) has been shown to be enhanced by several phthalate esters, including dibutyl phthalate (DBP).

fluorescein isothiocyanate

FITC

phthalate esters

dibutyl phthalate

DBP


Input: For different types of phthalate esters, we found a correlation between the ability of transient receptor potential (TRP) A1 activation and that of enhancing skin sensitization.

phthalate esters


Input: A TRPA1-specific antagonist, HC-030031, was shown to suppress skin sensitization in the presence of DBP.

DBP


Input: However, since phthalate esters also activate TRPV1, phthalate esters could activate other types of TRP channels non-selectively.

phthalate esters

phthalate esters


Input: Furthermore, sensitization to FITC is also enhanced by menthol, which activates TRPA1 and TRPM8.

FITC

menthol


Input: Here we established an in vitro system for measuring TRPM8 activation.


Input: The selectivity for TRPM8 was established by the fact that two TRPM8 agonists (menthol and icilin) induced calcium mobilization, whereas agonists of TRPA1 and TRPV1 did not.

menthol

icilin

calcium


Input: We demonstrated that phthalate esters do not activate TRPM8.

phthalate esters


Input: TRPA1-antagonist HC-030031 did not inhibit TRPM8 activation induced by menthol or icilin.

menthol

icilin


Input: These results show that phthalate esters activate TRPA1 and TRPV1 with selectivity.

phthalate esters


Input: TRPM8 activation is not likely to be involved in the sensitization to FITC.

FITC


Input: The genotoxicity of PEI-based nanoparticles is reduced by acetylation of polyethylenimine amines in human primary cells.

PEI

polyethylenimine amines


Input: The ultrasmall size and unique properties of polymeric nanoparticles (NPs) have led to raising concerns about their potential cyto-and genotoxicity on biological systems.


Input: Polyethylenimine (PEI) is a highly positive charged polymer and is known to have varying degree of toxic effect to cells based on its chemical structure (i. e., amount of primary and secondary amine).

Polyethylenimine

PEI

primary and secondary amine


Input: Herein, drug delivery carriers such as PEI-PLGA nanoparticles (PEI-NPs) and acetylated PEI-PLGA nanoparticles (AcPEI-NPs) were utilized to examine the effect of acetylation on NPs biocompatibility and genotoxicity, using human primary cells as in vitro model.

PEI

PLGA

PEI

acetylated PEI

PLGA

AcPEI


Input: Cell uptake of NPs was characterized along with their effects on cellular viability.


Input: The results indicate that both NPs showed an equivalent behavior in terms of uptake and biocompatibility.


Input: In depth analysis of NP uptake on cell biology evidenced that these nanoparticles induced dose dependant genotoxic effects.


Input: This phenomenon was significantly reduced by PEI acetylation.

PEI


Input: Endocytosed PEI-NPs trigger an oxidative stress on cells by inducing the production of reactive oxygen species (ROS), which cause DNA damage without apparently affecting cell viability.

PEI

oxygen


Input: Thus, the genotoxicity of nanoparticles, that could be used as non-viral drug carriers, should be evaluated based on the intracellular level of ROS generation and DNA damage even in absence of a significant cell death.


Input: Graphene oxide for effective radionuclide removal.

Graphene oxide


Input: Here we show the efficacy of graphene oxide (GO) for rapid removal of some of the most toxic and radioactive long-lived human-made radionuclides from contaminated water, even from acidic solutions (pH < 2).

graphene oxide


Input: The interaction of GO with actinides including Am (III), Th (IV), Pu (IV), Np (V), U (VI) and typical fission products Sr (II), Eu (III) and Tc (VII) were studied, along with their sorption kinetics.

actinides

Am (III)

Th (IV)

Pu (IV)

Np (V)

U (VI)

Sr (II)

Eu (III)

Tc (VII)


Input: Cation/GO coagulation occurs with the formation of nanoparticle aggregates of GO sheets, facilitating their removal.


Input: GO is far more effective in removal of transuranium elements from simulated nuclear waste solutions than other routinely used sorbents such as bentonite clays and activated carbon.

transuranium

bentonite

carbon


Input: These results point toward a simple methodology to mollify the severity of nuclear waste contamination, thereby leading to effective measures for environmental remediation.


Input: Ebullition rates and mercury concentrations in St.

mercury


Input: Lawrence river sediments and a benthic invertebrate.


Input: Ebullition, the release of gas from anaerobic decomposition in sediments, was recorded in a mercury-contaminated depositional zone (Zone 1) of the St.

mercury


Input: Lawrence River Area of Concern in Cornwall, Ontario, Canada.


Input: The aim of the present study was to test if this disturbance affected the bioavailability of total mercury (THg) and methylmercury (MeHg) in surficial sediments to a benthic invertebrate (Echinogammarus ischnus).

mercury

methylmercury

MeHg


Input: Ebullition rates ranged from < 1 to 2, 800 ml/m (2) daily, with methane gas comprising 29 to 84% of the total.

methane


Input: No direct effects of ebullition were found on either abiotic (sediment or pore water THg or MeHg concentrations) or biotic (amphipod THg or MeHg concentrations) variables measured.

MeHg

MeHg


Input: Instead, amphipod MeHg concentrations were best predicted by pore water THg and MeHg concentrations, organic matter of surficial sediments, and water depth and location.

MeHg

MeHg


Input: Trend surface analyses demonstrated that a shallow, southwestern part of Zone 1 was most contaminated with pore water mercury, which decreased in a gradient toward the northeast.

mercury


Input: Further study is needed to determine if the amount of sediment resuspended by ebullition affects the spatial distribution of mercury.

mercury


Input: Ab initio molecular dynamics simulation on the formation process of He @C 6 0 synthesized by explosion.

He

C 6 0


Input: The applications of endohedral non-metallic fullerenes are limited by their low production rate.

fullerenes


Input: Recently, an explosive method developed in our group shows promise to prepare He @C 6 0 at fairly high yield, but the mechanism of He inserting into C 6 0 cage at explosive conditions was not clear.

He

C 6 0

He

C 6 0


Input: Here, ab initio molecular dynamics analysis has been used to simulate the collision between C 6 0 molecules at high-temperature and high-pressure induced by explosion.

C 6 0


Input: The results show that defects formed on the fullerene cage by collidsion can effectively decrease the reaction barrier for the insertion of He into C 6 0, and the self-healing capability of the defects was also observed.

fullerene

He

C 6 0


Input: Biomimetic Methodology to Produce Polymeric Multilayered Particles for Biotechnological and Biomedical Applications.


Input: The production of multi-compartmented particles for biomedical and biotechnological applications is challenging and the existing methods usually involve wet and aggressive conditions that compromise the encapsulation efficiency of bioactive agents and the viability of cells.


Input: Biomimetic superhydrophobic surfaces allow construction of concentric multilayered polymeric systems, adding sequential layers where molecules or cells may be separately confined in compartments with high efficiency.


Input: Cynomolgus monkey as a potential model to assess drug interactions involving hepatic organic anion transporting polypeptides: in vitro, in vivo, and in vitro-to-in vivo extrapolation.


Input: Organic anion-transporting polypeptides (OATP) 1B1, 1B3, and 2B1 can serve as the loci of drug-drug interactions (DDIs).


Input: In the present work, the cynomolgus monkey was evaluated as a potential model for studying OATP-mediated DDIs.


Input: Three cynomolgus monkey OATPs (cOATPs), with a high degree of amino acid sequence identity (91. 9, 93. 5, and 96. 6% for OATP1B1, 1B3, and 2B1, respectively) to their human counterparts, were cloned, expressed, and characterized.

amino acid


Input: The cOATPs were stably transfected in human embryonic kidney cells and were functionally similar to the corresponding human OATPs (hOATPs), as evident from the similar uptake rate of typical substrates (estradiol-17 beta-d-glucuronide, cholecystokinin octapeptide, and estrone-3-sulfate).

estradiol-17 beta-d-glucuronide


Input: Moreover, six known hOATP inhibitors exhibited similar IC (50) values against cOATPs.


Input: To further evaluate the appropriateness of the cynomolgus monkey as a model, a known hOATP substrate [rosuvastatin (RSV)]-inhibitor [rifampicin (RIF)] pair was examined in vitro; the monkey-derived parameters (RSV K (m) and RIF IC (50)) were similar (within 3. 5-fold) to those obtained with hOATPs and human primary hepatocytes.

rosuvastatin

RSV

rifampicin

RIF

RSV

RIF


Input: In vivo, the area under the plasma concentration-time curve of RSV (3 mg/kg, oral) given 1 hour after a single RIF dose (15 mg/kg, oral) was increased 2. 9-fold in cynomolgus monkeys, consistent with the value (3. 0-fold) reported in humans.

RSV

RIF


Input: A number of in vitro-in vivo extrapolation approaches, considering the fraction of the pathways affected and free versus total inhibitor concentrations, were also explored.


Input: It is concluded that the cynomolgus monkey has the potential to serve as a useful model for the assessment of OATP-mediated DDIs in a nonclinical setting.


Input: Pesticides in urban streams and early life stages of pacific coho salmon.


Input: Pesticides are frequently detected in urban streams and are believed to be primarily the result of homeowner use.


Input: Although concentrations in most cases are low (< 1 micro g/L), there is concern that pesticide inputs threaten efforts to restore and enhance salmon habitat.


Input: The authors exposed early life stages of coho salmon (Oncorhynchus kisutch) to a pesticide mixture (" cocktail ") representative of those pesticides most frequently reported in urban streams in western Washington State, USA.


Input: Life stages were continuously exposed to pulses of the cocktail simulating those in urban streams in fall and winter when coho salmon eggs and sac fry are present.


Input: Nominal concentrations of eight herbicides, two insecticides, a fungicide, and a breakdown product were the maximum detected.


Input: Fertilization, hatching success, survival, deformities, and growth of fry were not significantly affected.


Input: A reduction in fertilization success (19-25%) was not reproducible even when gametes were exposed to 100 times the maximum concentrations detected.


Input: Based on the end points examined in the present study, the results suggest that direct exposure to the pesticides most frequently detected in urban streams in western Washington does not impair early life stages of coho salmon and is not a major factor governing the recovery of salmon populations.


Input: The extent to which pesticide exposure would affect smoltification, outmigration, and ocean survival needs to be determined.


Input: Resveratrol improves cardiomyopathy in dystrophin-deficient mice through SIRT1 protein-mediated modulation of p300 protein.

Resveratrol


Input: Cardiomyopathy is the main cause of death in Duchenne muscular dystrophy.


Input: Here, we show that oral administration of resveratrol, which leads to activation of an NAD (+)-dependent protein deacetylase SIRT1, suppresses cardiac hypertrophy and fibrosis and restores cardiac diastolic function in dystrophin-deficient mdx mice.

resveratrol

NAD (+)


Input: The pro-hypertrophic co-activator p300 protein but not p300 mRNA was up-regulated in the mdx heart, and resveratrol administration down-regulated the p300 protein level.

resveratrol


Input: In cultured cardiomyocytes, cardiomyocyte hypertrophy induced by the alpha (1)-agonist phenylephrine was inhibited by the overexpression of SIRT1 as well as resveratrol, both of which down-regulated p300 protein levels but not p300 mRNA levels.

phenylephrine

resveratrol


Input: In addition, activation of atrial natriuretic peptide promoter by p300 was inhibited by SIRT1.


Input: We found that SIRT1 induced p300 down-regulation via the ubiquitin-proteasome pathway by deacetylation of lysine residues for ubiquitination.

lysine


Input: These findings indicate the pathological significance of p300 up-regulation in the dystrophic heart and indicate that SIRT1 activation has therapeutic potential for dystrophic cardiomyopathy.


Input: The dynamics of dendrimers by NMR relaxation: interpretation pitfalls.


Input: NMR is a powerful tool to study the dynamics of dendrimers.


Input: By analogy to linear polymers, shorter T (1) relaxation times have been traditionally associated to less mobile nuclei and hence, dendrimers described with reduced local motions at either the core or the periphery.


Input: Herein we report a NMR relaxation study [(1) H and (13) C T (1), T (2); (13) C {(1) H} NOE; various fields and temperatures] which reveals profound differences between the relaxation behavior of dendrimers and linear polymers.

(1) H

(13) C

(13) C

(1) H


Input: Dendrimers show slower dynamics at internal layers and on increasing generation and may display internal nuclei in the slow motional regime with larger T (1) values than the periphery.


Input: In contrast to the relaxation properties of linear polymers, these T (1) increments should not be interpreted as resulting from faster dynamics.


Input: Only the recording of T (1) data at various temperatures (alternatively, T (2) or NOE at one temperature) ensures the correct interpretation of dendrimer dynamics.


Input: All-trans retinoic acid protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating collagen 8A2.

All-trans retinoic acid


Input: As a therapeutic or chemopreventative agent for various cancers, all-trans retinoic acid (atRA) has been reported to inhibit growth, induce apoptosis or cause differentiation.

all-trans retinoic acid

atRA


Input: It was found that atRA could protect hepatocellular carcinoma (HCC) cells against cell death induced by serum starvation.

atRA


Input: Furthermore, it was found that atRA could enhance cell adhesion, but had no effect on the cell cycle and apoptosis.

atRA


Input: Using an Illumina Human HT-12 v4 expression microarray, 207 upregulated and 173 downregulated genes were identified in HepG2 cells treated with atRA.

atRA


Input: The most upregulated genes are cytochrome P450 family 26 subfamily A polypeptide 1 (CYP26A1), histidine triad nucleotide binding protein 3 (HINT3), miR-1282 and cytochrome P450 family 26 subfamily B polypeptide 1 (CYP26B1), which showed more than fivefold greater expression.

histidine


Input: Using Gene Ontology analysis, the greatest significance was found in extracellular-matrix-related molecular functions and the cellular component in upregulated genes.


Input: The upregulation of collagen 8A2 (COL8A2) was further confirmed using quantitative RT-PCR and western blotting.


Input: Knockdown of COL8A2 blocked enhancement in the early stage of cell adhesion by atRA treatment.

atRA


Input: Re-expression of COL8A2 in COL8A2-knocked-down HCC cells reversed the effect of small interfering RNA-COL8A2.


Input: In addition, COL8A2 could increase HCC cell migration and invasion.


Input: Thus, COL8A2 was identified as the key protein involved in the enhancement of cell adhesion of atRA under serum-free conditions.

atRA


Input: In conclusion, atRA protects HCC cells against serum-starvation-induced cell death by enhancing cell adhesion, and COL8A2 plays an important role in HCC cell migration and invasion.

atRA


Input: Systemic leptin increases the electrical activity of supraoptic nucleus oxytocin neurones in virgin and late pregnant rats.

oxytocin


Input: In the rat hypothalamus, fasting attenuates the expression of oxytocin and this can be reversed by exogenous leptin administration.

oxytocin


Input: In the present study, we investigated the effects of systemically administered leptin on the electrical activity of magnocellular neurones in the supraoptic nucleus of urethane-anaesthetised rats.

urethane


Input: In virgin female rats, systemic leptin significantly excited identified oxytocin neurones with no detected effects on the patterning of activity, as reflected by hazard function analyses.

oxytocin


Input: The lowest dose that was consistently effective was 100 mu g/i. v., and this dose had no significant effect on vasopressin neurones.

vasopressin


Input: In virgin rats fasted overnight, the spontaneous firing rate of oxytocin neurones was significantly lower than in unfasted rats, although leptin had a similar excitatory effect as in unfasted rats.

oxytocin


Input: In late pregnant rats (days 19-21 of pregnancy), spontaneous firing rates of oxytocin neurones were higher than in virgins, and the initial response to leptin was similar to that in virgin rats, although the increase in activity was more persistent.

oxytocin


Input: In fasted pregnant rats, the mean spontaneous firing rate of oxytocin neurones was again lower than in unfasted rats, although leptin had no significant effect even at the higher dose of 1 mg/rat.

oxytocin


Input: Thus, fasting reduced the spontaneous firing rates of oxytocin neurones in nonpregnant rats, and this effect could be reversed by the excitatory effects of leptin.

oxytocin


Input: Pregnant rats showed some evidence of leptin resistance but only after an overnight fast.


Input: Design and synthesis of potent inhibitor of apoptosis (IAP) proteins antagonists bearing an octahydropyrrolo [1, 2-a] pyrazine scaffold as a novel proline mimetic.

octahydropyrrolo [1, 2-a] pyrazine

proline


Input: To develop novel inhibitor of apoptosis (IAP) proteins antagonists, we designed a bicyclic octahydropyrrolo [1, 2-a] pyrazine scaffold as a novel proline bioisostere.

bicyclic octahydropyrrolo [1, 2-a] pyrazine

proline


Input: This design was based on the X-ray co-crystal structure of four N-terminal amino acid residues (AVPI) of the second mitochondria-derived activator of caspase (Smac) with the X-chromosome-linked IAP (XIAP) protein.

N

amino acid


Input: Lead optimization of this scaffold to improve oral absorption yielded compound 45, which showed potent cellular IAP1 (cIAP1 IC (50): 1. 3 nM) and XIAP (IC (50): 200 nM) inhibitory activity, in addition to potent tumor growth inhibitory activity (GI (50): 1. 8 nM) in MDA-MB-231 breast cancer cells.


Input: X-ray crystallographic analysis of compound 45 bound to XIAP and to cIAP1 was achieved, revealing the various key interactions that contribute to the higher cIAPI affinity of compound 45 over XIAP.


Input: Because of its potent IAP inhibitory activities, compound 45 (T-3256336) caused tumor regression in a MDA-MB-231 tumor xenograft model (T/C:-53% at 30 mg/kg).


Input: Smart mesoporous SiO2 nanoparticles for the DNAzyme-induced multiplexed release of substrates.


Input: The fluorescent dyes methylene blue, MB (+), and thionine, Th (+), can be trapped in the pores of mesoporous silica, MP-SiO (2), by means of functional nanostructures consisting of the Mg (2 +)-or Zn (2 +)-dependent DNAzyme sequences.

methylene blue

thionine

silica

SiO (2)

Mg (2 +)

Zn (2 +)


Input: In the presence of Mg (2 +) or Zn (2 +) ions the respective DNAzymes are activated, leading to the specific cleavage of the respective caps, and the selective release of MB (+) or Th (+).

Mg (2 +)

Zn (2 +)


Input: The enlargement of the conserved loop domains of the Mg (2 +)-or Zn (2 +)-dependent DNAzyme sequences with foreign nucleotides prohibits the formation of active DNAzymes and eliminates the release of the respective dyes.

Mg (2 +)

Zn (2 +)

nucleotides


Input: This is due to the flexibility of the loops that lacks affinity for the association of the ions.


Input: The insertion of aptamer sequences (e. g., the adenosine-5'-triphosphate (ATP) aptamer) or ion-binding sequences (e. g., T-rich Hg (2 +) ion-binding domains) as foreign components to the loop regions allows the formation of active Mg (2 +)-or Zn (2 +)-dependent DNAzyme structures through the cooperative formation of aptamer-ATP complexes or T-Hg (2 +)-T bridges.

ATP

Hg (2 +)

Mg (2 +)

Zn (2 +)

ATP

Hg (2 +)


Input: These aptamer-substrate complexes or T-Hg (2 +)-T bridges allosterically stabilize and activate the DNAzymes, thus allowing the selective release of the fluorescent substrates MB (+) or Th (+).

Hg (2 +)


Input: The metal ion-driven DNAzyme release of substrates from the pores of MP-SiO (2), and particularly the allosteric activation of the DNAzymes through cooperative aptamer-substrate complexes or metal-ion bridges, has important future nanomedical implications for targeted release of drugs.

SiO (2)


Input: This is demonstrated with the triggered release of the anticancer drug, doxorubicin, by the Mg (2 +)-DNAzyme-locked pores or by the aptamer-ATP complex-triggered activation of the Mg (2 +)-dependent DNAzyme.

doxorubicin

Mg (2 +)

ATP

Mg (2 +)


Input: Polymeric " smart " coatings to prevent foreign body response to implantable biosensors.


Input: Application of implantable glucose biosensors for " real-time " monitoring is reliant on controlling the negative tissue reaction at the sensor tissue interphase.

glucose


Input: A novel polymer coating consisting of poly (lactic-co-glycolic) acid (PLGA) microsphere dispersed in poly (vinyl alcohol) (PVA) hydrogels was evaluated in combination with dummy sensors as a " smart " drug eluting biocompatible coating for implantable biosensors to prevent the foreign body response, and thus enhance sensor performance in vivo.

poly (lactic-co-glycolic) acid

PLGA

poly (vinyl alcohol)

PVA


Input: The polymeric microspheres slowly release tissue-modifying drugs at the implantation sites to control the inflammation and fibrous encapsulation, while the hydrogel allows rapid analyte diffusion to the sensing elements.


Input: Dummy sensors with identical dimensions to that of the functional glucose sensors (0. 5 x 0. 5 x 5mm) were coated with the PLGA/PVA composites using a mold fabrication process.

glucose

PLGA

PVA


Input: Both normal and diabetic rats were used in the current study to investigate the effect of the diabetic state on tissue sensor interactions.


Input: It was evident that the PLGA/PVA hydrogel composite was able to form a uniform coating around the dummy sensor and stayed intact throughout the course of the study (one month).

PLGA

PVA


Input: Tissue samples containing dummy sensors that were coated with dexamethasone free composites exhibited acute and chronic inflammation as well as fibrous encapsulation in both normal and diabetic rats.

dexamethasone


Input: However, the diabetic rats exhibited decreased intensity and delayed onset of the foreign body response following implantation of drug free dummy sensors in comparison to those of normal rats.


Input: On the other hand, tissues containing dummy sensors that were coated with dexamethasone containing composites remained normal (i. e. similar to untreated tissues), with no inflammatory reaction or fibrous encapsulation occurring over the one-month period in both the normal and diabetic rats.

dexamethasone


Input: The feasibility of utilizing PLGA microsphere/PVA hydrogel composites as coatings for implantable biosensors was demonstrated.

PLGA

PVA


Input: This polymeric composite is an innovative approach to control the foreign body reaction at the tissue-device interface to prolong biosensor lifetime.


Input: Facile sonochemical synthesis of novel pyrazolyne derivates at ambient conditions.

pyrazolyne


Input: Claisen-Schmidt condensation reaction of 4-acetamidoacetophenone with aromatic aldehydes under ultrasonic irradiation affords acetylaminochalcones (yields: 71-90%) which also under ultrasonic irradiation and in the presence of sodium acetate and acetic acid aqueous undergo facile and clean cyclocondensation with hydrazine to afford 3-(4-acetamidophenyl)-5-(aryl)-1-H-pyrazolines.

aromatic aldehydes

acetylaminochalcones

sodium acetate

acetic acid

hydrazine

3-(4-acetamidophenyl)-5-(aryl)-1-H-pyrazolines


Input: The pyrazolines were obtained in good to excellent yields (81-89%), and were characterized by conventional spectral data.

pyrazolines


Input: The work-up is simple and the results obtained indicate that, unlike classical heating, ultrasonic irradiation results in higher yields, shorter reaction times (1. 5-2. 3 h) and milder conditions.


Input: Pharmacokinetic and pharmacodynamic modeling of hedgehog inhibitor TAK-441 for the inhibition of Gli1 messenger RNA expression and antitumor efficacy in xenografted tumor model mice.


Input: 6-Ethyl-N-[1-(hydroxyacetyl) piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2, 2, 2-trifluoroethoxy)-4, 5-dihydro-1H-pyrrolo [3, 2-c] pyridine-2-carboxamide (TAK-441) is a potent, selective hedgehog signaling pathway inhibitor that binds to Smo and is being developed for the treatment of cancer.

6-Ethyl-N-[1-(hydroxyacetyl) piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2, 2, 2-trifluoroethoxy)-4, 5-dihydro-1H-pyrrolo [3, 2-c] pyridine-2-carboxamide


Input: The objectives of these studies were to explore the possibility of establishing of a link between the pharmacokinetics of TAK-441 and the responses of Gli1 mRNA in tumor-associated stromal or skin cells and the antitumor effect of hedgehog inhibition.


Input: To this end, we built pharmacokinetic and pharmacodynamic models that describe the relationship of the concentrations of TAK-441 plasma to the responses of Gli1 mRNA in the tumor (target) and skin (surrogate) and to tumor growth inhibition in mice bearing xenografts of human pancreatic tumors (PAN-04).


Input: The responses of Gli1 mRNA and tumor growth were described by an indirect response model and an exponential tumor growth model, respectively.


Input: The IC50 values for Gli1 mRNA inhibition in the tumor and skin by TAK-441 were estimated to be 0. 0457 and 0. 113 mu g/ml, respectively.


Input: The IC90 value for tumor growth inhibition was estimated to be 0. 68 mu g/ml.


Input: These results suggest that a > 83% inhibition of Gli1 mRNA expression in the skin or a > 94% inhibition of Gli1 mRNA expression in the tumor would be required to sufficiently inhibit (> 90%) hedgehog-related tumor growth in the xenografted model mice.


Input: We conclude that Gli1 mRNA expression in the tumor and skin could be a useful biomarker for predicting the antitumor effect of hedgehog inhibitors.


Input: Alternative splicing in the aldo-keto reductase superfamily: implications for protein nomenclature.


Input: The aldo-keto reductase superfamily contains 173 proteins which are present in all phyla.


Input: Examination of the human and mouse genomes has identified that in some instances a single AKR gene can give rise to alternatively spliced mRNA variants which in some cases can give rise to more than one protein isoform.


Input: This is currently well documented in the AKR6A subfamily which contains the beta-subunits of the voltage-gated potassium ion channels.

potassium


Input: With the emergence of second generation sequencing it is likely that the occurrence of transcript variants and protein isoforms from a single AKR gene may become common place.


Input: To deal with this issue we recommend that the Ensembl data-base nomenclature be used to annotate the transcript variants from a single AKR gene.


Input: However, since multiple transcript variants could give rise to either the same or multiple protein isoforms from the same AKR gene we also propose to expand the nomenclature of the AKR protein superfamily, so that when a protein isoform is shown to be expressed and is functional it would be assigned the standard AKR name followed by a " period or full-stop " and a number for that unique isoform.


Input: Numbers will be assigned chronologically and linked to the respective transcripts annotated in Ensembl e. g. AKR6A5. 1 (Kv beta 2. 1) (AKR6A5-001,-006 and-201), followed by AKR6A5. 2 (Kv beta 2. 2) (AKR6A5-002,-202).


Input: This nomenclature is expandable and it enables multiple protein isoforms to be assigned to their respective transcripts when they arise from the same AKR gene or for a single protein isoform to be assigned to multiple transcripts when the transcripts encode the same AKR protein.


Input: Protective effects of alpha lipoic acid versus N-acetylcysteine on ifosfamide-induced nephrotoxicity.

alpha lipoic acid

N-acetylcysteine

ifosfamide


Input: Ifosfamide (IFO) is a highly effective chemotherapeutic agent for treating a variety of pediatric solid tumors.

Ifosfamide

IFO


Input: However, its use is limited due to its serious side effect on kidneys.


Input: The side-chain oxidation of IFO in renal tubular cells produces a reactive toxic metabolite that is believed to be responsible for its nephrotoxic effect.

IFO


Input: Therefore, this study was carried out to investigate the possible underlying mechanisms that may be involved in IFO-induced nephrotoxicity, including free radical generation and the possible role of alpha lipoic acid (ALA) versus N-acetylcysteine (NAC) in protection against this toxicity.

IFO

alpha lipoic acid

ALA

N-acetylcysteine

NAC


Input: Male albino rats were injected intraperitoneally with saline, IFO (50 mg/kg daily for 5 days), IFO + ALA (100 mg/kg daily for 8 days) and IFO + NAC (200 mg/kg daily for 8 days).

IFO

IFO

ALA

IFO

NAC


Input: Kidney malondialdehyde, nitric oxide and glutathione contents and serum biochemical parameters and histopathological analysis were determined.

malondialdehyde

nitric oxide

glutathione


Input: Both ALA and NAC markedly reduced the severity of renal dysfunction induced by IFO.

ALA

NAC

IFO


Input: NAC was more nephroprotective than ALA.

NAC

ALA


Input: This study suggests that oxidative stress is possibly involved in the IFO-induced nephrotoxicity in rats.

IFO


Input: The study also suggests the potential therapeutic role for ALA and NAC against IFO-induced nephrotoxicity.

ALA

NAC

IFO


Input: Antioxidative, antiapoptotic, and proliferative effect of curcumin on liver regeneration after partial hepatectomy in rats.

curcumin


Input: The aim of the present study was to assess the influence of curcumin on liver regeneration after partial hepatectomy (PH) in rats.

curcumin


Input: A total of 24 male Sprague Dawley rats were divided into three groups: sham-operated (SH), PH, and PH + curcumin; each group contains eight animals.

curcumin


Input: The rats in curcumin-treated groups were given curcumin (in a dose of 100 mg/kg body weight) once a day orally for 7 days, starting 3 days prior to hepatectomy operation.

curcumin

curcumin


Input: At 7 days after resection, liver samples were collected.


Input: The malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were estimated in liver homogenates.

malondialdehyde

MDA

superoxide

glutathione

GSH


Input: Moreover, histopathological examination, mitotic index (MI), proliferating cell nuclear antigen labeling, proliferation index (PI), transferase-mediated 2'-deoxyuridine, 5'-triphosphate nick end-labeling assay, and apoptotic index (AI) were evaluated at 7 days after hepatectomy.


Input: As a result, curcumin significantly increased MI and PI and significantly decreased AI in PH rats.

curcumin


Input: Additionally, curcumin remarkably inhibited MDA elevation, restored impaired antioxidant SOD activity and GSH level and also attenuated hepatic vacuolar degeneration and sinusoidal congestion.

curcumin

MDA

GSH


Input: These results suggested that curcumin treatment had a beneficial effect on liver regenerative capacity of the remnant liver tissue after hepatectomy, probably due to its antioxidative, antiapoptotic, and proliferative properties.

curcumin


Input: Structure-based redesign of proteins for minimal T-cell epitope content.


Input: The protein universe displays a wealth of therapeutically relevant activities, but T-cell driven immune responses to non-" self " biological agents present a major impediment to harnessing the full diversity of these molecular functions.


Input: Mutagenic T-cell epitope deletion seeks to mitigate the immune response, but can typically address only a small number of epitopes.


Input: Here, we pursue a " bottom-up " approach that redesigns an entire protein to remain native-like but contain few if any immunogenic epitopes.


Input: We do so by extending the Rosetta flexible-backbone protein design software with an epitope scoring mechanism and appropriate constraints.


Input: The method is benchmarked with a diverse panel of proteins and applied to three targets of therapeutic interest.


Input: We show that the deimmunized designs indeed have minimal predicted epitope content and are native-like in terms of various quality measures, and moreover that they display levels of native sequence recovery comparable to those of non-deimmunized designs.


Input: Long-range corrected functionals satisfy Koopmans' theorem: calculation of correlation and relaxation energies.


Input: In this article, we show that the long-range-corrected (LC) density functionals LC-BOP and LCgau-BOP reproduce frontier orbital energies and highest-occupied molecular orbital (HOMO)-lowest-unoccupied molecular orbital (LUMO) gaps better than other density functionals.


Input: The negative of HOMO and LUMO energies are compared with the vertical ionization potentials (IPs) and electron affinities, respectively, using CCSD (T)/6-311 + + G (3df, 3pd) for 113 molecules, and we found LC functionals to satisfy Koopmans' theorem.


Input: We also report that the frontier orbital energies and the HOMO-LUMO gaps of LC-BOP and LCgau-BOP are better than those of recently proposed omega M05-D (Lin et al., J. Chem. Phys. 2012, 136, 154109).


Input: We express the exact IP in terms of orbital relaxation, and correlation energies and hence calculate the relaxation and correlation energies for the same set of molecules.


Input: It is found that the LC functionals, in general, includes more relaxation effect than Hartree-Fock and more correlation effect than the other density functionals without LC scheme.


Input: Finally, we scan mu parameter in LC scheme from 0. 1 to 0. 6 bohr (-1) for the above test set molecules with LC-BOP functional and found our parameter value, 0. 47 bohr (-1), is usefully applicable to our tested systems.


Input: Simultaneous determination and characterization of tannins and triterpene saponins from the fruits of various species of Terminalia and Phyllantus emblica using a UHPLC-UV-MS method: application to triphala.

tannins

triterpene saponins


Input: Terminalia species are a rich source of tannins.

tannins


Input: Many preparations of these species are used in traditional medicine and have many different ethnobotanical applications.


Input: A simple UHPLC method was developed for the simultaneous analysis of such hydrolysable tannins and triterpene saponins from the fruit rinds of different species of Terminalia (T. chebula, T. arjuna, T. bellirica) and Phyllantus emblica.

tannins

triterpene saponins


Input: A separation by LC was achieved using a reversed-phase column and a water/acetonitrile mobile phase, both containing formic acid, using a gradient system and a temperature of 40 degrees C.

acetonitrile

formic acid


Input: Eight hydrolysable tannins (gallic acid, gallic acid methyl ester, corilagin, chebulagic acid, 1, 2, 3, 6-tetra-O-galloyl-beta-D-glucose, ellagic acid, chebulinic acid, and 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose) and six triterpene saponins (arjunglucoside-I, arjunglucoside-III, chebuloside II, bellericoside, arjunetin, and arjunglucoside-II) could be separated within 20 minutes.

tannins

gallic acid

gallic acid methyl ester

corilagin

chebulagic acid

1, 2, 3, 6-tetra-O-galloyl-beta-D-glucose

ellagic acid

chebulinic acid

1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose

triterpene saponins

arjunglucoside-I

arjunglucoside-III

chebuloside II

bellericoside

arjunetin

arjunglucoside-II


Input: The wavelength used for detection with the diode array detector was 254 and 275 nm for tannins and 205 nm for triterpene saponins.

tannins

triterpene saponins


Input: The method was validated for linearity, repeatability, limits of detection, and limits of quantification.


Input: The developed method is economical, fast, and especially suitable for quality control analysis of tannins and triterpene saponins in various plant samples and commercial products of Terminalia.

tannins

triterpene saponins


Input: Fetal and neonatal outcomes in women reporting ingestion of licorice (Glycyrrhiza uralensis) during pregnancy.


Input: Maternal intake of licorice from dietary sources has been associated with adverse maternal and fetal outcomes.


Input: We prospectively studied the outcome of 185 singleton pregnancies who took over-the-counter or naturopathic formulations containing licorice during their pregnancy, and 370 age-matched singleton pregnant controls that were not exposed to any potential teratogen.


Input: The indication in 56. 8% of the women taking licorice was for cough and cold control, with the maximum dose of 2104 mg/day and exposure occurring between the 4th day and 25th week of gestation.


Input: The rate of stillbirths was marginally higher among women who took licorice than those who did not (OR = 7. 9; 95% CI 0. 9-71. 5; p = 0. 048), and significantly higher when compared to the general population in the Republic of Korea (OR = 13. 3; 95% CI 4. 9-35. 8; p < 0. 001).


Input: Other fetal outcomes assessed in the study were similar between the two study groups, e. g., the OR of major malformations was 3. 9 (95% CI 0. 4-43. 5; p = 0. 27).


Input: In conclusion, the present study suggests that licorice is not a major teratogen.


Input: However, whether licorice may increase the risk of stillbirths requires careful consideration in further studies with a larger sample size.


Input: Antibodies against Yariv' s reagent for immunolocalization of arabinogalactan-proteins in aerial parts of Echinacea purpurea.


Input: Arabinogalactan-proteins are glycoproteins that occur in higher plants and are involved in important processes like cell differentiation and plant growth.


Input: In the medicinal plant Echinacea purpurea L., they belong to the putative immunomodulating compounds and are structurally well characterized.


Input: For microscopic localization of arabinogalactan-proteins, synthetic (beta-D-Glc) 3 Yariv phenylglycoside that specifically binds to most plant arabinogalactan-proteins was used to label arabinogalactan-proteins in fresh cut sections of stems and petioles of Echinacea purpurea.

(beta-D-Glc) 3 Yariv phenylglycoside


Input: Polyclonal antibodies against (beta-D-Glc) 3 Yariv phenylglycoside were used to detect the arabinogalactan-protein-(beta-D-Glc) 3 Yariv phenylglycoside complex.

(beta-D-Glc) 3 Yariv phenylglycoside

(beta-D-Glc) 3 Yariv phenylglycoside


Input: After addition of fluorescein isothiocyanate-conjugated secondary antibodies, the sections were analyzed by confocal laser scanning microscopy.

fluorescein isothiocyanate


Input: Arabinogalactan-proteins are localized mainly in the central cylinder in the collateral vascular bundles, especially in the area of the xylem.


Input: In cell walls of fully differentiated vessels and tracheids, arabinogalactan-proteins have been detected mainly at the inner area of the wall close to the cell lumina.


Input: Intense labeling occurs around pit canals connecting adjacent vessels.


Input: Furthermore, arabinogalactan-proteins are present in the lumina of cells of the sclerenchyma caps and in companion cells of the phloem.


Input: An in vitro model of human acute ethanol exposure that incorporates CXCR3-and CXCR4-dependent recruitment of immune cells.

ethanol


Input: Alcoholic liver disease (ALD) is one of the commonest causes of cirrhosis and liver failure in the developed world.


Input: Hepatic inflammation is the critical stage in progression of both ALD and non-ALD, but it remains difficult to study the underlying mechanisms in a human system, and current animal models do not fully recapitulate human liver disease.


Input: We developed a human tissue-based system to study lymphocyte recruitment in response to ethanol challenge.

ethanol


Input: Precision-cut liver slices (PCLS) from human livers were incubated in culture, and hepatic function was determined by albumin production, 3-(4, 5-dimethylthiazol)-2, 5-diphenyl tetrazolium bromide assay, glucose uptake responses, and morphometric assessment.

3-(4, 5-dimethylthiazol)-2, 5-diphenyl tetrazolium bromide

glucose


Input: Responses of tissue and lymphocytes to ethanol exposure were determined by PCR, flow cytometry, histology, and lymphocyte infiltration assays.

ethanol


Input: Human PCLS demonstrated appropriate upregulation of CYP2E1, ADH1 alpha, and ADH3 in response to ethanol treatment.

ethanol


Input: Ethanol also induced expression of endothelial VCAM-1 and ICAM-1, production of sICAM-1 and CXCL8, and the chemokine receptors CXCR3 and CXCR4 on CD4 and CD8 lymphocytes.

Ethanol


Input: CXCR3-and CXCR4-dependent migration of lymphocytes into the tissue increased significantly in response to treatment with ethanol.

ethanol


Input: We have demonstrated that ethanol increases chemokine receptor expression and lymphocyte recruitment into human liver tissue, suggesting that it may operate directly to promote hepatitis in ALD.

ethanol


Input: The physiological and pathophysiological responses of the PCLS to ethanol in vitro highlight the potential of this assay for dissecting the molecular mechanisms underlying human liver inflammation and as a screening tool for novel therapeutics.

ethanol


Input: Identification of propofol binding sites in a nicotinic acetylcholine receptor with a photoreactive propofol analog.

propofol

acetylcholine

propofol


Input: Propofol, a widely used intravenous general anesthetic, acts at anesthetic concentrations as a positive allosteric modulator of gamma-aminobutyric acid type A receptors and at higher concentration as an inhibitor of nicotinic acetylcholine receptors (nAChRs).

Propofol

gamma-aminobutyric acid

acetylcholine


Input: Here, we characterize propofol binding sites in a muscle-type nAChR by use of a photoreactive analog of propofol, 2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl] phenol (AziPm).

propofol

propofol

2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl] phenol

AziPm


Input: Based upon radioligand binding assays, AziPm stabilized the Torpedo nAChR in the resting state, whereas propofol stabilized the desensitized state.

AziPm

propofol


Input: nAChR-rich membranes were photolabeled with [(3) H] AziPm, and labeled amino acids were identified by Edman degradation.

[(3) H] AziPm

amino acids


Input: [(3) H] AziPm binds at three sites within the nAChR transmembrane domain: (i) an intrasubunit site in the delta subunit helix bundle, photolabeling in the nAChR desensitized state (+ agonist) delta M2-18' and two residues in delta M1 (delta Phe-232 and delta Cys-236); (ii) in the ion channel, photolabeling in the nAChR resting, closed channel state (-agonist) amino acids in the M2 helices (alpha M2-6', beta M2-6' and-13', and delta M2-13') that line the channel lumen (with photolabeling reduced by > 90% in the desensitized state); and (iii) at the gamma-alpha interface, photolabeling alpha M2-10'.

[(3) H] AziPm

delta Phe

delta Cys

amino acids


Input: Propofol enhanced [(3) H] AziPm photolabeling at alpha M2-10'.

Propofol

[(3) H] AziPm


Input: Propofol inhibited [(3) H] AziPm photolabeling within the delta subunit helix bundle at lower concentrations (IC50 = 40 mu m) than it inhibited ion channel photolabeling (IC50 = 125 mu m).

Propofol

[(3) H] AziPm


Input: These results identify for the first time a single intrasubunit propofol binding site in the nAChR transmembrane domain and suggest that this is the functionally relevant inhibitory binding site.

propofol


Input: BSTA promotes mTORC2-mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation.


Input: Phosphorylation and activation of Akt1 is a crucial signaling event that promotes adipogenesis.


Input: However, neither the complex multistep process that leads to activation of Akt1 through phosphorylation at Thr (3) 0 8 and Ser 4 7 (3) nor the mechanism by which Akt1 stimulates adipogenesis is fully understood.

Thr

Ser


Input: We found that the BSD domain-containing signal transducer and Akt interactor (BSTA) promoted phosphorylation of Akt1 at Ser 4 7 (3) in various human and murine cells, and we uncovered a function for the BSD domain in BSTA-Akt1 complex formation.

Ser


Input: The mammalian target of rapamycin complex 2 (mTORC2) facilitated the phosphorylation of BSTA and its association with Akt1, and the BSTA-Akt1 interaction promoted the association of mTORC2 with Akt1 and phosphorylation of Akt1 at Ser 4 7 (3) in response to growth factor stimulation.

Ser


Input: Furthermore, analyses of bsta gene-trap murine embryonic stem cells revealed an essential function for BSTA and phosphorylation of Akt1 at Ser 4 7 (3) in promoting adipocyte differentiation, which required suppression of the expression of the gene encoding the transcription factor FoxC2.

Ser


Input: These findings indicate that BSTA is a molecular switch that promotes phosphorylation of Akt1 at Ser 4 7 (3) and reveal an mTORC2-BSTA-Akt1-FoxC2-mediated signaling mechanism that is critical for adipocyte differentiation.

Ser


Input: Amino acid grafted chitosan for high performance gene delivery: comparison of amino acid hydrophobicity on vector and polyplex characteristics.

Amino acid

amino acid


Input: To develop a safe, effective, and biocompatible gene delivery vector, a series of hydrophobic amino acid grafted chitosan (AGC) derivatives were synthesized by carbodiimide mediated coupling reaction.

amino acid

carbodiimide


Input: Chemical characterization of AGC polymers was performed by NMR and elemental analysis.


Input: AGC polymers demonstrated excellent blood compatibility and cell viability, as evaluated by hemolysis and MTT assay, respectively.

MTT


Input: AGC polymers could effectively bind and condense plasmid DNA (pDNA) to form polyplexes in the size range of 161-263 nm and possessed net cationic charge.


Input: The resultant polyplex showed 3. 4-5. 4-fold greater cellular uptake and 13-30-fold higher transfection efficiency in HEK 293 cells as compared to unmodified chitosan.


Input: Moreover, both cellular uptake and transfection efficiency improved with the increasing amino acid hydrophobicity.

amino acid


Input: Hydrophobic amino acid substitution contributed to the enhance pDNA release at cytosolic pH.

amino acid


Input: These data demonstrate AGC polymers as a promising novel nonviral gene delivery vector.


Input: Improved self-healing of polyethylene/carbon black nanocomposites by their shape memory effect.

polyethylene

carbon black


Input: In this work, the improved self-healing of cross-linked polyethylene (PE) (cPE)/carbon black (CB) nanocomposites by their shape memory effect (SME) is investigated.

polyethylene

carbon black


Input: CB nanoparticles are found to be homogeneously dispersed in the PE matrix and significantly increase the strength of the materials.


Input: Compared with the breaking of linear PE (lPE) at the melting temperature (T (m)), the cPE and cPE/CB nanocomposites still have high strength above T (m) due to the formation of networks.


Input: The cPE and cPE/CB nanocomposites show both high strain fixity ratio (R (f)) and high strain recovery ratio (R (r)).


Input: Crystallization-induced elongation is observed for all the prepared shape memory polymer (SMP) materials and the effect becomes less remarkable with increasing volume fraction of CB nanoparticles (v (CB)).


Input: The scratch self-healing tests show that the cross-linking of PE matrix, the addition of CB nanoparticles, and the previous stretching in the direction perpendicular to the scratch favor the closure of the scratch and its complete healing.


Input: This SME-aided self-healing could have potential applications in diverse fields such as coating and structure materials.


Input: Formulation study of a patch containing propranolol by design of experiments.

propranolol


Input: Abstract Objective: To evaluate the feasibility of a transdermal patch containing propranolol (PR).

propranolol


Input: Method: Skin penetration enhancers (SPEs) able to improve the skin permeability of PR were selected and a quality by design approach was applied to the development of the patch by a 2 (4) full factorial design.


Input: The permeation profile of PR from the formulations was assessed in in vitro permeation studies performed by using Franz diffusion cells and human epidermis as membrane.


Input: Finally, skin irritation was evaluated by the Draize test.


Input: Results: N-methyl pyrrolidone (NMP) resulted as the best SPE: in addition, the critical factors influencing the PR diffusion through the human epidermis when loaded in the patch resulted in the matrix thickness (X (1), p = 0. 0957) and PR content (X (3), p = 0. 0004) which improved the flux; conversely, NMP lacked its enhancement effect when loaded in the patch and the increase in its concentration (X (4), p = 0. 006) affected the drug permeation through human epidermis.

N-methyl pyrrolidone

NMP

NMP


Input: The flux of optimal formulation was 12. 7 mu g/cm (2)/h.


Input: On the basis of the steady-state concentration and clearance of PR, the estimated patch surface was 100-120 cm (2), since the activity of PR is related to its Senantiomer and no in vivo bioconversion occurs.


Input: Conclusion: A patch containing (S)-PR was prepared and the (S)-PR flux (13. 3 mu g/cm (2)/h) permitted to confirm the suitability of a transdermal administration of PR.

(S)-PR

(S)-PR


Input: In particular, the use of a 50 mu m thick methacrylic matrix containing 8% (S)-PR and 15% NMP can allow to develop a patch non-irritating to the skin, in order to ensure a constant permeation flux of PR over 48 h.

methacrylic

(S)-PR

NMP


Input: Nanoscale Dynamics and Protein Adhesivity of Alkylamine Self-Assembled Monolayers on Graphene.

Alkylamine

Graphene


Input: Atomic-scale molecular dynamics computer simulations are used to probe the structure, dynamics, and energetics of alkylamine self-assembled monolayer (SAM) films on graphene and to model the formation of molecular bilayers and protein complexes on the films.

alkylamine

graphene


Input: Routes toward the development and exploitation of functionalized graphene structures are detailed here, and we show that the SAM architecture can be tailored for use in emerging applications (e. g., electrically stimulated nerve fiber growth via the targeted binding of specific cell surface peptide sequences on the functionalized graphene scaffold).

graphene

graphene


Input: The simulations quantify the changes in film physisorption on graphene and the alkyl chain packing efficiency as the film surface is made more polar by changing the terminal groups from methyl (-CH (3)) to amine (-NH (2)) to hydroxyl (-OH).

graphene

alkyl

methyl

CH (3)

amine

NH (2)

hydroxyl

OH


Input: The mode of molecule packing dictates the orientation and spacing between terminal groups on the surface of the SAM, which determines the way in which successive layers build up on the surface, whether via the formation of bilayers of the molecule or the immobilization of other (macro) molecules (e. g., proteins) on the SAM.


Input: The simulations show the formation of ordered, stable assemblies of monolayers and bilayers of decylamine-based molecules on graphene.

decylamine

graphene


Input: These films can serve as protein adsorption platforms, with a hydrophobin protein showing strong and selective adsorption by binding via its hydrophobic patch to methyl-terminated films and binding to amine-terminated films using its more hydrophilic surface regions.

methyl

amine


Input: Design rules obtained from modeling the atomic-scale structure of the films and interfaces may provide input into experiments for the rational design of assemblies in which the electronic, physicochemical, and mechanical properties of the substrate, film, and protein layer can be tuned to provide the desired functionality.


Input: Inelastic X-ray scattering studies of the short-time collective vibrational motions in hydrated lysozyme powders and their possible relation to enzymatic function.


Input: High-resolution inelastic X-ray scattering was used to investigate the collective vibrational excitations in hydrated lysozyme powders as a function of hydration level and temperature.


Input: It is found that the samples with strong enzymatic function are " soft ", in the sense that they exhibit low frequency and large amplitude intraprotein collective vibrational motions on certain length scales.


Input: This is not the case for samples with weak or no enzymatic activity.


Input: Thus, we identify a possible correlation between the short-time intraprotein collective vibrational motions and the establishment of enzymatic function in hydrated lysozyme powders, and bring new insight to notions of protein " conformational flexibility " and " softness " in terms of these motions.


Input: In vitro evaluation of (99m) Tc-EDDA/tricine-HYNIC-Q-Litorin in gastrin-releasing peptide receptor positive tumor cell lines.

(99m) Tc-EDDA/tricine-HYNIC-Q-Litorin


Input: Abstract Bombesin and its derivatives exhibit a high affinity for gastrin-releasing peptide receptor (GRPr), which is over-expressed in a variety of human cancers (prostate, pancreatic, lung, etc.).

Bombesin


Input: The aim of this study was to investigate the in vitro potential of the hydrazinonicotinamide (HYNIC)-Q-Litorin.

hydrazinonicotinamide

HYNIC

Litorin


Input: (99m) Tc labeling was performed by using different co-ligands: tricine and ethylenediamine diacetic acid (EDDA).

(99m) Tc

tricine

ethylenediamine diacetic acid

EDDA


Input: The radiochemical stability of radiolabeled peptide conjugates was checked at room temperature and in cysteine solution up to 24 h.

cysteine


Input: The in vitro cell uptake of (99m) Tc-EDDA-HYNIC-Q-Litorin and (99m) Tc-tricine-HYNIC-Q-Litorin were evaluated on pancreatic tumor and control cell lines.

(99m) Tc-EDDA-HYNIC-Q-Litorin

(99m) Tc-tricine-HYNIC-Q-Litorin


Input: Optimum specific activity and incubation time were determined for all the cell lines.


Input: The results showed that the cell uptake of the radiolabeled peptide conjugates in tumor cell lines were higher than in the control cell line.


Input: The findings of this study indicated the need for further development of in vivo study as a radiopharmaceutical for pancreatic tumor imaging.