Input: 2, 4-Dihydroxybenzophenone (benzophenone-1; BP-1) is an UV stabilizer primarily used to prevent polymer degradation and deterioration in quality due to UV irradiation.

2, 4-Dihydroxybenzophenone


Input: Recently, BP-1 has been reported to bioaccumulate in human bodies by absorption through the skin and has the potential to induce health problems including endocrine disruption.


Input: In the present study, we examined the xenoestrogenic effect of BP-1 on BG-1 human ovarian cancer cells expressing estrogen receptors (ERs) and relevant xenografted animal models in comparison with 17-beta estradiol (E2).

estrogen

17-beta estradiol


Input: In in vitro cell viability assay, BP-1 (10 (-8)-10 (-5) M) significantly increased BG-1 cell growth the way E2 did.


Input: The mechanism underlying the BG-1 cell proliferation was proved to be related with the up-regulation of cyclin D1, a cell cycle progressor, by E2 or BP-1.


Input: Both BP-1 and E2 induced cell growth and up-regulation of cyclin D1 were reversed by co-treatment with ICI 182, 780, an ER antagonist, suggesting that BP-1 may mediate the cancer cell proliferation via an ER-dependent pathway like E2.

ICI 182, 780


Input: On the other hand, the expression of p21, a regulator of cell cycle progression at G1 phase, was not altered by BP-1 though it was down-regulated by E2.


Input: In xenograft mouse models transplanted with BG-1 cells, BP-1 or E2 treatment significantly increased the tumor mass formation compared to a vehicle (corn oil) within 8 weeks.


Input: In histopathological analysis, the tumor sections of E2 or BP-1 group displayed extensive cell formations with high density and disordered arrangement, which were supported by the increased number of BrdUrd positive nuclei and the over-expression of cyclin D1 protein.


Input: Taken together, these results suggest that BP-1 is an endocrine disrupting chemical (EDC) that exerts xenoestrogenic effects by stimulating the proliferation of BG-1 ovarian cancer via ER signaling pathway associated with cell cycle as did E2.


Input: Effects of dopamine D2 agonist quinpirole on neuronal activity of anterior cingulate cortex and striatum in rats.

dopamine

quinpirole


Input: RATIONALE: The influence of acute D2 agonist quinpirole on locomotor activity has been effectively characterized.

quinpirole


Input: However, few studies have addressed the dynamic changes in neuronal activity of the anterior cingulate cortex (ACC) and striatum (STR), two crucial regions for cognitive and motor functions, after quinpirole administration.

quinpirole


Input: OBJECTIVE: This study was conducted in order to acquire detailed information on the evoked activity of the neurons in the ACC and STR after acute quinpirole administration.

quinpirole


Input: METHODS: Multichannel electrophysiological recording was used for tracking neuronal activity in the ACC and STR of urethane-anesthetized rats after administration of saline or 0. 05 or 0. 5 mg/kg quinpirole.

urethane

quinpirole


Input: RESULTS: In contrast to the responses to saline, quinpirole dose-dependently increased the ratio of neurons, the activity of which was inhibited in the ACC and STR.

quinpirole


Input: By examining the ensemble neuronal activities of inhibition-responded neurons, there was no significant activity difference among the " treatments " (saline and low-and high-dose quinpirole), the " periods " (the duration of 0-15 and 16-45 min after i. v. injection), and the interaction between " treatments " and " periods. " Regarding activation-responded neurons, however, there was a significant " periods " difference in both ACC and STR, and the activity of 16-45 min was significantly higher than the activity of 0-15 min after high-dose quinpirole administration in ACC (p < 0. 05) and STR (p < 0. 001).

quinpirole

quinpirole


Input: CONCLUSION: Dose-dependent ACC and STR neuronal responses to quinpirole may offer a possible mechanism for understanding the locomotor responses to quinpirole in behaving rats.

quinpirole

quinpirole


Input: The late excitatory effect of high-dose quinpirole in the STR further suggests that this region would be critical for the activation of locomotor activity.

quinpirole


Input: Differential sensitivity to pro-oxidant exposure in two populations of killifish (Fundulus heteroclitus).


Input: New Bedford Harbor (MA, U. S. A.; NBH) is a Superfund site inhabited by Atlantic killifish (Fundulus heteroclitus) with altered aryl hydrocarbon receptor (Ahr) signaling, leading to resistance to effects of polychlorinated biphenyls (PCBs) and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).

aryl hydrocarbon

polychlorinated biphenyls

PCBs

2, 3, 7, 8-tetrachlorodibenzo-p-dioxin

TCDD


Input: The Ahr is a transcription factor that regulates gene expression of many Phase I and II detoxifying enzymes and interacts with Nrf2, a transcription factor that regulates the response to oxidative stress.


Input: This study tested the hypothesis that PCB-resistant killifish exhibit altered sensitivity to oxidative stress.

PCB


Input: Killifish F (1) embryos from NBH and a clean reference site (Scorton Creek, MA, U. S. A.; SC) were exposed to model pro-oxidant and Nrf2-activator, tert-butylhydroquinone (tBHQ).

tert-butylhydroquinone

tBHQ


Input: Embryos were exposed at specific embryonic developmental stages (5, 7, and 9 days post fertilization) and toxicity was assessed, using a deformity score, survival, heart rate, and gene expression to compare sensitivity between PCB-resistant and-sensitive (reference) populations.

PCB


Input: Acute exposure to tBHQ resulted in transient reduction in heart rate in NBH and SC F (1) embryos.

tBHQ


Input: However, embryos from NBH were more sensitive to tBHQ, with more frequent and severe deformities, including pericardial edema, tail deformities, small body size, and reduced pigment and erythrocytes.

tBHQ


Input: NBH embryos had lower basal expression of antioxidant genes catalase and glutathione-S-transferase alpha (gsta), and upon exposure to tBHQ, exhibited lower levels of expression of catalase, gsta, and superoxide dismutase compared to controls.

glutathione

S

tBHQ

superoxide


Input: This result suggests that adaptation to tolerate PCBs has altered the sensitivity of NBH fish to oxidative stress during embryonic development, demonstrating a cost of the PCB resistance adaptation.

PCBs

PCB


Input: Targeting RET to induce medullary thyroid cancer cell apoptosis: an antagonistic interplay between PI3K/Akt and p38MAPK/caspase-8 pathways.


Input: Mutations in REarranged during Transfection (RET) receptor tyrosine, followed by the oncogenic activation of RET kinase is responsible for the development of medullary thyroid carcinoma (MTC) that responds poorly to conventional chemotherapy.

tyrosine


Input: Targeting RET, therefore, might be useful in tailoring surveillance of MTC patients.


Input: Here we showed that theaflavins, the bioactive components of black tea, successfully induced apoptosis in human MTC cell line, TT, by inversely modulating two molecular pathways: (i) stalling PI3K/Akt/Bad pathway that resulted in mitochondrial transmembrane potential (MTP) loss, cytochrome-c release and activation of the executioner caspases-9 and-3, and (ii) upholding p38MAPK/caspase-8/caspase-3 pathway via inhibition of Ras/Raf/ERK.

theaflavins


Input: Over-expression of either constitutively active myristoylated-Akt-cDNA (Myr-Akt-cDNA) or dominant-negative-caspase-8-cDNA (Dn-caspase-8-cDNA) partially blocked theaflavin-induced apoptosis, while co-transfection of Myr-Akt-cDNA and Dn-caspase-8-cDNA completely eradicated the effect of theaflavins thereby negating the possibility of existence of other pathways.

theaflavins


Input: A search for the upstream signaling revealed that theaflavin-induced disruption of lipid raft caused interference in anchorage of RET in lipid raft that in turn stalled phosphorylation of Ras and PI3Kinase.

theaflavin


Input: In such anti-survival cellular micro-environment, pro-apoptotic signals were triggered to culminate into programmed death of MTC cell.


Input: These findings not only unveil a hitherto unexplained mechanism underlying theaflavin-induced MTC death, but also validate RET as a promising and potential target for MTC therapy.

theaflavin


Input: Operationalizing value-based pricing of medicines: a taxonomy of approaches.


Input: The UK Government is proposing a novel form of price regulation for branded medicines, which it has dubbed' value-based pricing' (VBP).


Input: The specifics of how VBP will work are unclear.


Input: We provide an account of the possible means by which VBP of medicines might be operationalized, and a taxonomy to describe and categorize the various approaches.


Input: We begin with a brief discussion of the UK Government' s proposal for VBP and proceed to define a taxonomy of approaches to VBP.


Input: The taxonomy has five main dimensions: (1) what is identified as being of value, (2) how each element is measured, (3) how it is valued, (4) how the different elements of value are aggregated, and (5) how the result is then used to determine the price of a medicine.


Input: We take as our starting point that VBP will include a measure of health gain and that, as proposed by the UK Government, this will be built on the QALY.


Input: Our principal interest is in the way criteria other than QALYs are taken into account, including severity of illness, the extent of unmet need, and wider societal considerations such as impacts on carers.


Input: We set out to: (1) identify and describe the full range of alternative means by which' value' might be measured and valued, (2) identify and describe the options available for aggregating the different components of value to establish a maximum price, and (3) note the challenges and relative advantages associated with these approaches.


Input: We review the means by which aspects of VBP are currently operationalized in a selection of countries and place these, and proposals for the UK, in the context of our taxonomy.


Input: Finally, we give an initial assessment of the challenges, pros and cons of each approach.


Input: We conclude that identifying where VBP should lie on each of the five dimensions entails value judgements: there are no simple' right or wrong' solutions.


Input: If a wider definition of value than incremental QALYs gained is adopted, as is desirable, then a pragmatic way to aggregate the different elements of value, including both QALYs and benefits unrelated to QALYs, is to use a multi-criteria decision analysis (MCDA) approach.


Input: All approaches to VBP ultimately require the conversion of value, however assessed, into a monetary price.


Input: This requires assessment of the marginal values of all types of benefit, not just of QALYs.


Input: All stages of the VBP process are subject to uncertainty and margins of error.


Input: Consequently, the assessment of overall value can provide bounds to a price negotiation but cannot be expected to identify a precise value-based price.


Input: PXR antagonists and implication in drug metabolism.


Input: Adopted orphan nuclear receptor (NR), pregnane X receptor (PXR), plays a central role in the regulation of xeno-and endobiotic metabolism.

pregnane


Input: Since the discovery of the functional role of PXR in 1998, there is evolving evidence for the role of PXR agonists in abrogating metabolic pathophysiology (e. g., cholestasis, hypercholesterolemia, and inflammation).


Input: However, more recently, it is clear that PXR is also an important mediator of adverse xeno-(e. g., enhances acetaminophen toxicity) and endobiotic (e. g., hepatic steatosis) metabolic phenotypes.

acetaminophen


Input: Moreover, in cancer therapeutics, PXR activation can induce drug resistance, and there is growing evidence for tissue-specific enhancement of the malignant phenotype.


Input: Thus, in these instances, there may be a role for PXR antagonists.


Input: However, as opposed to the discovery efforts for PXR agonists, there are only a few antagonists described.


Input: The mode of action of these antagonists (e. g., sulforaphane) remains less clear.

sulforaphane


Input: Our laboratory efforts have focused on this question.


Input: Since the original discovery of azoles analogs as PXR antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less-toxic PXR antagonists.

azoles


Input: In this review, we describe our published and unpublished findings on recent structure-function studies involving the azole chemical scaffold.

azole


Input: Further work in the future is needed to fully define potent, more-selective PXR antagonists that may be useful in clinical application.


Input: A molecular platinum cluster junction: a single-molecule switch.

platinum


Input: We present a theoretical study of electron transport through single-molecule junctions incorporating a Pt (6) metal cluster bound within an organic framework.

Pt (6)


Input: The insertion of this molecule between a pair of electrodes leads to a fully atomically engineered nanometallic device with high conductance at the Fermi level and two sequential high on/off switching states.


Input: The origin of this property can be traced back to the existence of a degenerate HOMO consisting of two asymmetric orbitals with energies close to the Fermi level of the metal leads.


Input: The degeneracy is broken when the molecule is contacted to the leads, giving rise to two resonances that become pinned to the Fermi level and display destructive interference.


Input: Recent developments in emerging microimmunoassays.


Input: Creative and novel microimmunoassay approaches continue to proliferate across many platforms originating from several fields of study.


Input: These efforts are aimed at improving one or more metrics for clinical tests, including improved sensitivity, increased speed, reduced cost, smaller sample size, the ability to analyze multiple antigens in parallel and ease of use.


Input: Many approaches focus on the production of microarrays that accomplish standard assays in parallel, or mobile solid-support formats to overcome issues of high background noise and long incubation times.


Input: In this article, innovative developments beyond existing commercial tests in the microimmunoassay arena are reviewed, covering January 2008 to April 2012.


Input: These developing experimental platforms are discussed in terms of their ability to augment or replace current commercial approaches.


Input: Polyamine production is downstream and upstream of oncogenic PI3K signalling and contributes to tumour cell growth.

Polyamine


Input: PI3K (phosphoinositide 3-kinase) signalling pathways regulate a large array of cell biological functions in normal and cancer cells.

phosphoinositide


Input: In the present study we investigated the involvement of PI3K in modulating small molecule metabolism.


Input: A LC (liquid chromatography)-MS screen in colorectal cancer cell lines isogenic for oncogenic PIK3CA mutations revealed an association between PI3K activation and the levels of polyamine pathway metabolites, including 5-methylthioadenosine, putrescine and spermidine.

polyamine

putrescine

spermidine


Input: Pharmacological inhibition confirmed that the PI3K pathway controls polyamine production.

polyamine


Input: Despite inducing a decrease in PKB (protein kinase B)/Akt phosphorylation, spermidine promoted cell survival and opposed the anti-proliferative effects of PI3K inhibitors.

spermidine


Input: Conversely, polyamine depletion by an ornithine decarboxylase inhibitor enhanced PKB/Akt phosphorylation, but suppressed cell survival.

polyamine

ornithine


Input: These results suggest that spermidine mediates cell proliferation and survival downstream of PI3K/Akt and indicate that these two biochemical pathways control each other' s activities, highlighting a mechanism by which small molecule metabolism feeds back to regulate kinase signalling.

spermidine


Input: Consistent with this feedback loop having a functional role in these cell models, pharmacological inhibitors of PI3K and ornithine decarboxylase potentiated each other in inhibiting tumour growth in a xenograft model.

ornithine


Input: The results of the present study support the notion that the modulation of spermidine concentrations may be a previously unrecognized mechanism by which PI3K sustains chronic proliferation of cancer cells.

spermidine


Input: Facile fabrication of " dual click " one-and two-dimensional orthogonal Peptide concentration gradients.


Input: Peptides, proteins, and extracellular matrix act synergistically to influence cellular function at the biotic-synthetic interface.


Input: However, identifying the individual and cooperative contributions of the various combinations and concentration regimes is extremely difficult.


Input: The confined channel deposition method we describe affords highly tunable orthogonal reactive concentration gradients that greatly expand the dynamic range, spatial control, and chemical versatility of the reactive silanes that can be controllably deposited.

silanes


Input: Using metal-free " dual click " immobilization chemistries, multiple peptides with a variety of functionality can be immobilized efficiently and reproducibly enabling optimal concentration profiling and the assessment of synergistic interactions.


Input: Hydroxy-terminated conjugated polymer nanoparticles have near-unity bright fraction and reveal cholesterol-dependence of IGF1R nanodomains.

Hydroxy

cholesterol


Input: Fluorescent nanoparticles have enabled many discoveries regarding how molecular machines function.


Input: Quantum dots have been the dominant class of fluorescent nanoparticles but suffer from blinking and from a substantial dark fraction--particles where the fluorescence is never seen--complicating any analysis of biological function.


Input: Nanoparticles composed of conjugated fluorescent polymers (Pdots) have recently been shown to have high brightness and no blinking.


Input: Here we develop a robust and efficient means to measure the dark fraction of Pdots, conjugating Atto dyes to the nanoparticles and testing fluorescence colocalization of dye and Pdot puncta.


Input: This established that the Pdots we generated had minimal dark fraction: ~ 3%.


Input: The application of nanoparticles in biological environments is highly sensitive to surface functionalization.


Input: For Pdots we found that passivation with uncharged hydroxy-terminated polyethylene glycol caused a dramatic reduction in nonspecific cell binding and aggregation compared to a charged coating.

hydroxy

polyethylene glycol


Input: Using carbonyl di-imidazole the hydroxy-Pdots were functionalized efficiently with streptavidin for high stability targeting, allowing specific labeling of mammalian cells.

carbonyl di-imidazole

hydroxy


Input: Type I insulin-like growth factor receptor (IGF1R) regulates cell survival and development, with roles in aging, heart disease, and cancer.


Input: We used hydroxy-Pdots to track the dynamics of IGF1R on a breast cancer cell-line, determining the diffusion characteristics and showing cholesterol-containing membrane nanodomains were important for receptor mobility at the plasma membrane.

hydroxy

cholesterol


Input: The near-unity bright fraction and low nonspecific binding of hydroxy-Pdots, combined with Pdot photostability and lack of blinking, provides many advantages for investigations at the single molecule level.

hydroxy


Input: Acetylcholinesterase immobilized capillary reactors-tandem mass spectrometry: an on-flow tool for ligand screening.


Input: The use of immobilized capillary enzyme reactors (ICERs) for online ligand screening has been adopted as a new technique for high-throughput screening (HTS).


Input: In this work, the selected target was the enzyme acetylcholinesterase (AChE), and the AChE-ICERs produced were used in a liquid chromatograph-tandem ion-trap mass spectrometer.


Input: The activity and kinetic parameters were evaluated by monitoring the choline' s precursor ion (M + H) (+) m/z 104. 0 and its ion fragment (C2H3OH)-(M + H) (+) m/z 60. 0.

choline

H

H


Input: The assay method was validated using the reference AChE inhibitors tacrine and galanthamine.

tacrine

galanthamine


Input: Two new ligands, out of a library of 17 coumarin derivatives, were identified, and the half-maximal inhibitory concentration (IC50), inhibition constant (K (i)), and the inhibition mechanism were determined.

coumarin


Input: A coumarin derivative with IC50 similar to tacrine was highlighted.

coumarin

tacrine


Input: Structure-based design and synthesis of C-1-and C-4-modified analogs of zanamivir as neuraminidase inhibitors.

C

C

zanamivir


Input: In order to exploit the 430-cavity in the active sites of neuraminidases, 22 zanamivir analogs with C-1 and C-4 modification were synthesized, and their inhibitory activities against both group-1 (H5N1, H1N1) and group-2 neuraminidases (H3N2) were determined.

zanamivir

C

C


Input: Compound 9f exerts the most potency, with IC (50) value of 0. 013, 0. 001, and 0. 09 mu M against H3N2, H5N1, and H1N1, which is similar to that of zanamivir (H3N2 IC (50) = 0. 0014 mu M, H5N1 IC (50) = 0. 012 mu M, H1N1 IC (50) = 0. 001 mu M).

zanamivir


Input: Pharmacokinetic studies of compound 9f in rats showed a much longer plasma half-life (t (1/2)) than that of zanamivir following administration (po dose).

zanamivir


Input: Molecular modeling provided information about the binding model between the new inhibitors and neuraminidase, with the elongated groups at the C-1-position being projected toward the 430-loop region.


Input: This study may represent a novel starting point for the future development of improved antiflu agents.


Input: Highly transparent low resistance ZnO/Ag nanowire/ZnO composite electrode for thin film solar cells.

ZnO

Ag

ZnO


Input: We present an indium-free transparent conducting composite electrode composed of silver nanowires (AgNWs) and ZnO bilayers.

indium

silver

ZnO


Input: The AgNWs form a random percolating network embedded between the ZnO layers.

ZnO


Input: The unique structural features of our ZnO/AgNW/ZnO multilayered composite allow for a novel transparent conducting electrode with unprecedented excellent thermal stability (~ 375 degrees C), adhesiveness, and flexibility as well as high electrical conductivity (~ 8. 0 Omega/sq) and good optical transparency (> 91% at 550 nm).

ZnO

ZnO


Input: Cu (In, Ga) (S, Se) 2 (CIGSSe) thin film solar cells incorporating this composite electrode exhibited a 20% increase of the power conversion efficiency compared to a conventional sputtered indium tin oxide-based CIGSSe solar cell.

Cu (In, Ga) (S, Se) 2

CIGSSe

oxide

CIGSSe


Input: The ZnO/AgNW/ZnO composite structure enables effective light transmission and current collection as well as a reduced leakage current, all of which lead to better cell performance.

ZnO

ZnO


Input: Development of a natural products database from the biodiversity of Brazil.


Input: We describe herein the design and development of an innovative tool called the NuBBE database (NuBBEDB), a new Web-based database, which incorporates several classes of secondary metabolites and derivatives from the biodiversity of Brazil.


Input: This natural product database incorporates botanical, chemical, pharmacological, and toxicological compound information.


Input: The NuBBEDB provides specialized information to the worldwide scientific community and can serve as a useful tool for studies on the multidisciplinary interfaces related to chemistry and biology, including virtual screening, dereplication, metabolomics, and medicinal chemistry.


Input: The NuBBEDB site is at http://nubbe. iq. unesp. br/nubbeDB. html.


Input: Effect of headgroup on the physicochemical properties of phospholipid bilayers in electric fields: size matters.


Input: The effect of molecular structure on ensemble structure of phospholipid films has been investigated.


Input: Bilayers of dimyristoyl phosphatidylethanolamine (DMPE) were prepared on Au (111) electrodes using Langmuir-Blodgett and Langmuir-Schaeffer deposition.

dimyristoyl phosphatidylethanolamine

DMPE

Au (111)


Input: Capacitance and charge density measurements were used to investigate the adsorption behavior and barrier properties of the lipid bilayers.


Input: In situ polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) was employed to investigate the organization of the molecules within the bilayer.


Input: DMPE bilayers exhibit lower capacitance than bilayers formed from the related lipid, dimyristoyl phosphatidylcholine (DMPC).

DMPE

dimyristoyl phosphatidylcholine

DMPC


Input: The infrared data show that these results can be explained by structural differences between the bilayers formed from each molecule.


Input: DMPE organizes into bilayers with hydrocarbon chains tilted at a smaller angle to the surface normal, which results in a thicker film.

DMPE

hydrocarbon


Input: The hydrocarbon chains contain few conformational defects.

hydrocarbon


Input: Spectra in the carbonyl and phosphate stretching mode regions indicate low solvent content of DMPE films.

carbonyl

phosphate

DMPE


Input: Both of these effects combine to produce films with lower capacitance and enhanced barrier properties.


Input: The results are explained in terms of the differences in structure between the constituent molecules.


Input: On the origin of thermal untwisting of DNA.


Input: In aqueous solutions, the helical twist of DNA decreases with temperature.


Input: This phenomenon was noticed and studied experimentally several decades ago, but its physical origin remains elusive.


Input: The present paper shows that the thermal untwisting can be predicted from the specific properties of the torsional elasticity of the double helix revealed in recent computational studies.


Input: The temperature coefficient of untwisting estimated using coarse-grained models fitted to all-atom MD data accounts for the experimental results nearly quantitatively.


Input: The agreement is further improved with the computed torsional rigidity scaled to remove the discrepancy from experiment.


Input: The results confirm that the torsional rigidity of DNA is strongly anharmonic.


Input: They indicate that for random DNA, its value grows with small twisting and decreases with untwisting.


Input: Fragment-based design of novel quinazolinon derivatives as human acrosin inhibitors.

quinazolinon


Input: Human acrosin is a promising target for the male contraceptives.


Input: On the basis of the active site of human acrosin, a series of novel quinazolinon compounds were designed by a fragment docking and growing strategy.

quinazolinon


Input: In vitro anti-acrosin assay revealed that all the compounds showed potent human acrosin inhibitory activities.


Input: In particular, compounds 5c and 5g are more active than the known inhibitors.


Input: Molecular docking studies revealed that the quinazolinon inhibitors interacted with human acrosin mainly through hydrogen bonding and hydrophobic interactions.

quinazolinon

hydrogen


Input: The binding mode was also consistent with the structure-activity relationships.


Input: The quinazolinon derivatives in this study can serve as new lead structure for the development of novel male contraceptives.

quinazolinon


Input: 4-Aminoquinoline-Triazine-Based Hybrids with Improved In Vitro Antimalarial Activity Against CQ-Sensitive and CQ-Resistant Strains of Plasmodium falciparum.


Input: A systematic chemical modification in the triazine moiety covalently attached via suitable linkers to 4-amino-7-chloroquinolines yielded a series of new 7-chloro-4-aminoquinoline-triazine hybrids exhibiting high in vitro activity against W2 (chloroquine-resistant) and D6 (chloroquine-sensitive) strains of Plasmodium falciparum without any toxicity against mammalian cell lines (Vero, LLC-PK11, HepG2).

triazine

chloroquine

chloroquine


Input: Many of the compounds (6, 8, 10, 11, 13, 14, 16, 27, 29 and 33) showed excellent potency against chloroquine sensitive and resistant strains.

chloroquine


Input: In particular, compounds 6, 8, 14, 16 and 29 were found to be significantly more active than chloroquine against the chloroquine-resistant strains (W2 clone) of P. falciparum.

chloroquine

chloroquine


Input: Morphological, ecological and genetic aspects associated with endemism in the Fly Orchid group.


Input: The European genus Ophrys (Orchidaceae) is famous for its insect-like floral morphology, an adaptation for a pseudocopulatory pollination strategy involving Hymenoptera males.


Input: A large number of endemic Ophrys species have recently been described, especially within the Mediterranean Basin, which is one of the major species diversity hotspots.


Input: Subtle morphological variation and specific pollinator dependence are the two main perceptible criteria for describing numerous endemic taxa.


Input: However, the degree to which endemics differ genetically remains a challenging question.


Input: Additionally, knowledge regarding the factors underlying the emergence of such endemic entities is limited.


Input: To achieve new insights regarding speciation processes in Ophrys, we have investigated species boundaries in the Fly Orchid group (Ophrys insectifera sensu lato) by examining morphological, ecological and genetic evidence.


Input: Classically, authors have recognized one widespread taxon (O. insectifera) and two endemics (O. aymoninii from France and O. subinsectifera from Spain).


Input: Our research has identified clear morphological and ecological factors segregating among these taxa; however, genetic differences were more ambiguous.


Input: Insights from cpDNA sequencing and amplified fragment length polymorphisms genotyping indicated a recent diversification in the three extant Fly Orchid species, which may have been further obscured by active migration and admixture across the European continent.


Input: Our genetic results still indicate weak but noticeable phylogeographic clustering that partially correlates with the described species.


Input: Particularly, we report several isolated haplotypes and genetic clusters in central and southeastern Europe.


Input: With regard to the morphological, ecological and genetic aspects, we discuss the endemism status within the Fly Orchid group from evolutionary, taxonomical and conservation perspectives.


Input: Food-related impulsivity in obesity and Binge Eating Disorder-a systematic review.


Input: Impulsivity towards food has been recognized as a potential factor leading to increased food intake in obesity.


Input: Patients suffering from binge eating disorder (BED) form a specific subgroup of obese people that might be characterized by increased impulsivity.


Input: These assumptions, although, have yet to be verified.


Input: Therefore, this review evaluates evidence for food-related impulsivity in obese people with and without BED and examines possible differences between both populations.


Input: More precisely, evidence for the two components of impulsivity is analyzed separately: evidence for reward sensitivity, specifically, the urge for appetitive stimuli and evidence for rash-spontaneous behaviour such as acting disinhibited with no regard for the consequences.


Input: Our search resulted in 51 articles demonstrating generally increased food-related impulsivity.


Input: We found particular emphasis on increased reward sensitivity in obese people, which appeared to be more pronounced in people with BED.


Input: There was little and conflicting evidence, however, concerning increased rash-spontaneous behaviour in obese people without BED, but consistent evidence of an increase in obese people with BED.


Input: All in all, the evidence supports the view that BED represents a specific phenotype of obesity with increased food-related impulsivity.


Input: Taking these specific deficits into account can enhance the effectiveness of weight reduction programmes and psychotherapy.


Input: Therapy of obese patients with cardiovascular disease.


Input: Obesity has reached epidemic proportions and is a significant public health concern.


Input: Obesity is associated with increased diabetes, cardiovascular and kidney disease, and associated morbidity and mortality.


Input: Despite the increasing public health problem of obesity, there is a dearth of effective treatment options.


Input: Following the FDA mandated withdrawal of sibutramine, the treatment options for obesity were limited to orlistat as the only pharmacological treatment option for long-term management of obesity.

sibutramine

orlistat


Input: Recently two new medications (Belviq and Qsymia) were approved by FDA for long-term management of obesity.

Belviq

Qsymia


Input: Many other antiobesity drugs are under development.


Input: Bariatric surgery has been shown to be effective in the treatment of obesity and its comorbidities.


Input: The available data suggest that even modest weight loss improves diabetes and cardiovascular disease (CVD) risk factors.


Input: We summarize the treatment options for obesity and the efficacy of these options in ameliorating cardiovascular risk factors.


Input: We also focus on the recently approved antiobesity drugs.


Input: Inactivation of BAD by IKK inhibits TNF alpha-induced apoptosis independently of NF-kappa B activation.


Input: The I kappa B kinase complex (IKK) is a key regulator of immune responses, inflammation, cell survival, and tumorigenesis.


Input: The prosurvival function of IKK centers on activation of the transcription factor NF-kappa B, whose target gene products inhibit caspases and prevent prolonged JNK activation.


Input: Here, we report that inactivation of the BH3-only protein BAD by IKK independently of NF-kappa B activation suppresses TNF alpha-induced apoptosis.


Input: TNF alpha-treated Ikk beta (-/-) mouse embryonic fibroblasts (MEFs) undergo apoptosis significantly faster than MEFs deficient in both RelA and cRel due to lack of inhibition of BAD by IKK.


Input: IKK phosphorylates BAD at serine-26 (Ser26) and primes it for inactivation.

serine


Input: Elimination of Ser26 phosphorylation promotes BAD proapoptotic activity, thereby accelerating TNF alpha-induced apoptosis in cultured cells and increasing mortality in animals.


Input: Our results reveal that IKK inhibits TNF alpha-induced apoptosis through two distinct but cooperative mechanisms: activation of the survival factor NF-kappa B and inactivation of the proapoptotic BH3-only BAD protein.


Input: Green tea catechin leads to global improvement among Alzheimer' s disease-related phenotypes in NSE/hAPP-C105 Tg mice.

catechin


Input: Amyloid beta (Alpha beta) has been reported to be responsible for the functional and structural abnormalities of Alzheimer' s disease (AD) through the induction of oxidative stress.


Input: The aim of this study was to determine whether or not treatment of transgenic (Tg) mice with green tea catechin (GTC), a radical scavenger, improves AD phenotypes.

catechin


Input: To test this, 7-month-old Tg mice were treated with a low (1 mg) or high (10 mg) dose of GTC for 6 months.


Input: Surprisingly, GTC-treated Tg mice exhibited significant decreases in behavioral impairment, A beta-42 production, APP-C99/89 expression, gamma-secretase component and Wnt protein levels, gamma-secretase activity and MAPK activation.


Input: In contrast, the levels of APP-C83 protein and enzyme activities (alpha-secretase, neprilysin and Pin1) were elevated in the GTC-treated groups.


Input: Moreover, GTC-treated groups showed lower levels of total cholesterol and low-density lipoprotein cholesterol, whereas the level of high-density lipoprotein cholesterol increased.

cholesterol

cholesterol

cholesterol


Input: These results provide the first experimental evidence that GTC improves AD phenotypes, thereby suggesting that GTC can be used in the prevention of AD or treatment of AD patients.


Input: Contribution of single-minded 2 to hyperglycaemia-induced neurotoxicity.


Input: Diabetes mellitus is associated to central nervous system damage, which results in impairment of brain functions and cognitive deficits and decline in memory.


Input: However, the mechanisms mediating the actions of glucose on the neurons remained elusive.

glucose


Input: Single-minded 2 (Sim2), a basic helix-loop-helix (bHLH)-PAS transcriptional repressor, is thought to be involved in some symptoms of Down syndrome.


Input: We hypothesized that Sim2 mediated hyperglycaemia-induced neuronal injury and impairment of learning and memory.


Input: It was found that expression of Sim2 protein in cortical neurons was increased in streptozotocin-induced diabetes mellitus rat model.

streptozotocin


Input: Drebrin, down-regulated by Sim2, was subsequently decreased as detected by confocal laser scanning microscopy and Western blot analysis.


Input: The expression pattern of Sim2 and Drebrin correspond to 50mmol/L glucose (hyperglycaemia) was also found in primary cultured neurons.

glucose


Input: Curcumin, one neuroprotective agent, inhibited hyperglycaemia-induced neurotoxicity.

Curcumin


Input: Moreover, curcumin alleviated Sim2 expression, and reversely raised Drebrin expression in neurons treated with hyperglycaemia.

curcumin


Input: Finally, we found that silencing Sim2 expression decreased hyperglycaemia-induced neuronal injury.


Input: In conclusion, Sim2 may mediate neurotoxicity during hyperglycaemia and thereby play a critical role in the development of hyperglycaemia-induced cognitive deficits.


Input: Genistein protection against acetaminophen-induced liver injury via its potential impact on the activation of UDP-glucuronosyltransferase and antioxidant enzymes.

Genistein

acetaminophen

UDP


Input: The purpose of this study was to investigate genistein' s influence on the relationship between the activation of uridine diphosphate glucuronosyltransferase (UGTs) and the protection against acetaminophen-induced liver toxicity.

genistein

uridine diphosphate

acetaminophen


Input: Animal experimental results revealed that genistein (50, 100 or 200mg/BWkg) significantly ameliorated the biomarkers alanine aminotransferase, alanine aminotransferase, lactate dehydrogenase and malondialdehyde, as indicators of acute liver damage caused by APAP (200mg/BWkg).

genistein

alanine

alanine

lactate

malondialdehyde

APAP


Input: The level of GSH declined sharply after treatment with APAP within 1h in both the liver and blood with and without genistein.

GSH

APAP

genistein


Input: However, after 16h, the levels approached or returned to the original level.


Input: Genistein may accelerate and promote APAP glucuronidation as the results showed that APAP-glucuronide increased by 18. 44%, 46. 79%, and 66. 49% for 4h of treatment with genistein dosages of 50, 100 or 200mg/BWkg, respectively, compared with the APAP-only treatment.

Genistein

APAP

APAP

glucuronide

genistein

APAP


Input: The activation of UGTs and glutathione peroxidase and the inhibition of CYP2E1 by genistein were observed, and UGTs mRNA expression level with genistein was measured.

glutathione

genistein

genistein


Input: These findings suggest that genistein can prevent and protect against APAP-induced liver toxicity due to the inhibition of APAP biotransformation and the resistance to oxidative stress via the modulation of the activities of metabolism and the antioxidant enzyme.

genistein

APAP

APAP


Input: Exposure to 1800 MHz radiofrequency electromagnetic radiation induces oxidative DNA base damage in a mouse spermatocyte-derived cell line.


Input: Whether exposure to radiofrequency electromagnetic radiation (RF-EMR) emitted from mobile phones can induce DNA damage in male germ cells remains unclear.


Input: In this study, we conducted a 24h intermittent exposure (5 min on and 10 min off) of a mouse spermatocyte-derived GC-2 cell line to 1800 MHz Global System for Mobile Communication (GSM) signals in GSM-Talk mode at specific absorption rates (SAR) of 1 W/kg, 2 W/kg or 4 W/kg.


Input: Subsequently, through the use of formamidopyrimidine DNA glycosylase (FPG) in a modified comet assay, we determined that the extent of DNA migration was significantly increased at a SAR of 4 W/kg.

formamidopyrimidine


Input: Flow cytometry analysis demonstrated that levels of the DNA adduct 8-oxoguanine (8-oxoG) were also increased at a SAR of 4 W/kg.


Input: These increases were concomitant with similar increases in the generation of reactive oxygen species (ROS); these phenomena were mitigated by co-treatment with the antioxidant alpha-tocopherol.

oxygen

alpha-tocopherol


Input: However, no detectable DNA strand breakage was observed by the alkaline comet assay.


Input: Taking together, these findings may imply the novel possibility that RF-EMR with insufficient energy for the direct induction of DNA strand breaks may produce genotoxicity through oxidative DNA base damage in male germ cells.


Input: Effects of methoxychlor and its metabolite 2, 2-bis (p-hydroxyphenyl)-1, 1, 1-trichloroethane on 11 beta-hydroxysteroid dehydrogenase activities in vitro.

methoxychlor

2, 2-bis (p-hydroxyphenyl)-1, 1, 1-trichloroethane

11 beta-hydroxysteroid


Input: Methoxychlor (MXC) is primarily used as a pesticide and widely present in the environment.

Methoxychlor

MXC


Input: The objective of the present study is to investigate the direct effects of MXC and its metabolite 2-bis (p-hydroxyphenyl)-1, 1, 1-trichloroethane (HPTE) on two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD1 and 11 beta-HSD2) in vitro.

MXC

2-bis (p-hydroxyphenyl)-1, 1, 1-trichloroethane

HPTE

11 beta-hydroxysteroid


Input: Human liver microsome, rat testis microsome and adult Leydig cells were used for the measurement of 11 beta-HSD1 activity.


Input: Human placental and rat kidney microsomes were used for 11 beta-HSD2 activity.


Input: The IC (50) values on human 11 beta-HSD1 by MXC and HPTE were 1. 91 +/- 0. 07 and 8. 88 +/- 0. 08 mu M, respectively.

MXC

HPTE


Input: HPTE inhibited rat 11 beta-HSD1 with IC (50) of 9. 15 +/- 0. 05 mu M, while MXC did not inhibit the enzyme.

HPTE

MXC


Input: MXC and HPTE were competitive inhibitors of 11 beta-HSD1.

MXC

HPTE


Input: HPTE also inhibited human and rat 11 beta-HSD2 with IC (50) values of 55. 57 +/- 0. 08 and 12. 96 +/- 0. 11 mu M, respectively, while MXC did not inhibit 11 beta-HSD2.

HPTE

MXC


Input: In summary, our results showed that MXC and its metabolite HPTE inhibited both isoforms of 11 beta-HSD in a species-and chemical structure-dependent manner.

MXC

HPTE


Input: Viper venom induced inflammation with Montivipera xanthina (Gray, 1849) and the anti-snake venom activities of Artemisia absinthium L. in rat.


Input: The present study was conducted to explore the characterization of Montivipera xanthina crude venom partially by in vitro and in vivo and the anti-snake venom activities of Artemisia absinthium L. in comparison with carrageenan-induced acute inflammation model in rats.


Input: The LD50 value was estimated as 8. 78 mg/kg within 24 h by different venom doses administrated intraperitoneally in mice.


Input: The IC50 value was 0. 43 +/- 0. 18 mu g/ml after 48 h treatment while the calculated value was 0. 73 +/- 0. 10 mu g/ml for the culture media totally refreshed after 2 h treatment with venom.


Input: Wistar rats were treated intraperitoneally with A. absinthium extract, 30 min before venom or carrageenan was injected subplantarly into the left hind paw.


Input: Intraperitoneal administration of 25 and 50 mg/kg extract was inhibited venom induced paw swelling at 0. 5, 1, 2 and 3 h (p < 0. 05) while 12. 5, 25 and 50 mg/kg extract treatment was inhibited carrageenan-induced paw swelling at 2, 3, 4 and 5 h (p < 0. 05).


Input: In conclusion, the in vivo toxicity and inflammatory actions and in vitro cytotoxic actions of crude M. xanthina venom were performed as a first report and inhibition of venom-induced inflammation by methanolic extract of A. absinthium was described.


Input: A success in Toxinology translational research in Brazil: Bridging the gap.


Input: Basic research is fundamental for discovering potential diagnostic and therapeutic tools, including drugs, vaccines and new diagnostic techniques.


Input: On this basis, diagnosis and treatment methods for many diseases have been developed.


Input: Presently, discovering new candidate molecules and testing them in animals are relatively easy tasks that require modest resources and responsibility.


Input: However, crossing the animal-to-human barrier is still a great challenge that most researchers tend to avoid.


Input: Thus, bridging this current gap between clinical and basic research must be encouraged and elucidated in training programmes for health professionals.


Input: This project clearly shows the challenges faced by a group of Brazilian researchers who, after discovering a new fibrin sealant through 20 years of painstaking basic work, insisted on having the product applied clinically.


Input: The Brazilian government has recently become aware of this challenge and has accordingly defined the product as strategic to the public health of the country.


Input: Thus, in addition to financing research and development laboratories, resources were invested in clinical trials and in the development of a virtual platform termed the Virtual System to Support Clinical Research (SAVPC); this platform imparts speed, reliability and visibility to advances in product development, fostering interactions among sponsors, physicians, students and, ultimately, the research subjects themselves.


Input: This pioneering project may become a future model for other public institutions in Brazil, principally in overcoming neglected diseases, which unfortunately continue to afflict this tropical country.


Input: Antibacterial activity of Veronica montana L. extract and of protocatechuic acid incorporated in a food system.

protocatechuic acid


Input: This study was designed to evaluate the antibacterial activity of the Veronica montana L. water extract and its main phenolic compound, protocatechuic acid.

phenolic

protocatechuic acid


Input: The antibacterial activity was determined by microdilution assay against six strains of Gram-positive and Gram-negative bacteria.


Input: Listeria monocytogenes was the most sensitive of the tested bacterial species.


Input: Antibacterial preserving properties of protocatechuic acid were also evaluated after its incorporation in cream cheese, using L. monocytogenes as commonly cheese contaminant.

protocatechuic acid


Input: The compound successfully inhibited L. monocytogenes development in cream cheese, at room temperature and in refrigerator (25 degrees C and 4 degrees C, respectively), after 3days of inoculation.


Input: Sensory evaluation was carried out in order to validate the mentioned food system.


Input: A possible mode of action of the tested compound towards bacterial cells was assessed and appears to be direct lysis of pathogenic cytoplasmic membrane.


Input: Prediction of pharmacokinetic properties was also performed using computational analyzes.


Input: The obtained results can serve as an important platform for the development of effective natural preservatives.


Input: RANKL targeted peptides inhibit osteoclastogenesis and attenuate adjuvant induced arthritis by inhibiting NF-kappa B activation and down regulating inflammatory cytokines.


Input: Peptides designed from osteoprotegerin (OPG) have previously been shown to inhibit receptor activator of NF-kappa B ligand (RANKL) and prevent bone loss without significantly inhibiting inflammation.


Input: The objective of this study was to develop a novel peptide with dual inhibitory activity against bone loss and inflammation using site-directed mutagenesis.


Input: Out of the three putative sites (i. e., Tyr70-Asp78, Tyr82-Glu96, and Leu113-Arg122) available on OPG for RANKL binding, Leu113-Arg122 was used as a template for peptide synthesis.


Input: Peptide mutants of the template sequence (112YLEIEFCLKHR122) were synthesized and initially screened for their inhibitory effect on RANK-RANKL binding by competitive ELISA.


Input: The most active peptide was further evaluated in vitro for RANKL induced osteoclastogenesis in mouse macrophage cells, and in vivo for Freund' s complete adjuvant induced arthritis (AIA) in Lewis rats.


Input: The efficacy of the candidate peptide was compared with that of the standard drug celecoxib.

celecoxib


Input: The peptide YR-11 (YLEIEFSLKHR), obtained by direct substitution of cysteine with a serine residue in the template sequence, significantly (p < 0. 05) inhibited RANK-RANKL binding, and RANKL induced TRAP activity and formation of multinucleated osteoclasts without any cytotoxicity.

cysteine

serine


Input: Administration of YR-11 peptide at the dose of 30mg/kg (i. p.) ameliorated both bone loss and inflammation in AIA rats.


Input: To elucidate the mechanism for inhibition of inflammation in arthritic rats, serum and tissue cytokines (TNF-alpha, IL-1 beta, and IL-6) were analyzed by ELISA and RT-PCR methods.


Input: Results confirmed that YR-11 peptide inhibited pro-inflammatory cytokines in the sera and hind paw tissues of AIA rats through its suppressive effect on RANKL induced nuclear translocation of NF-kappa B.


Input: The results obtained in this study substantiate the therapeutic benefit of this novel peptide in the prevention of bone loss and inflammation in rheumatoid arthritis with reduced side effects.


Input: Surface functionalization of doxorubicin-loaded liposomes with octa-arginine for enhanced anticancer activity.

doxorubicin

octa-arginine


Input: Doxorubicin-loaded PEGylated liposomes (commercially available as DOXIL (R) or Lipodox (R)) were surface functionalized with a cell-penetrating peptide, octa-arginine (R8).

Doxorubicin

DOXIL

Lipodox

octa-arginine


Input: For this purpose, R8-peptide was conjugated to the polyethylene glycol-dioleoyl phosphatidylethanolamine (PEG-DOPE) amphiphilic co-polymer.

polyethylene glycol-dioleoyl phosphatidylethanolamine

PEG-DOPE


Input: The resultant R8-PEG-PE conjugate was introduced into the lipid bilayer of liposomes at 2mol% of total lipid amount via spontaneous micelle-transfer technique.


Input: The liposomal modification did not alter the particle size distribution, as measured by Particle Size Analyzer and transmission electron microscopy (TEM).


Input: However, surface-associated cationic peptide increased zeta potential of the modified liposomes.


Input: R8-functionalized liposomes (R8-Dox-L) markedly increased the intracellular and intratumoral delivery of doxorubicin as measured by flow cytometry and visualizing by confocal laser scanning microscopy (CLSM) compared to unmodified Doxorubicin-loaded PEGylated liposomes (Dox-L).

Dox

doxorubicin

Doxorubicin

Dox


Input: R8-Dox-L delivered loaded Doxorubicin to the nucleus, being released from the endosomes at higher efficiency compared to unmodified liposomes, which had marked entrapment in the endosomes at tested time point of 1h.

Dox

Doxorubicin


Input: The significantly higher accumulation of loaded drug to its site of action for R8-Dox-L resulted in improved cytotoxic activity in vitro (cell viability of 58. 5 +/- 7% for R8-Dox-L compared to 90. 6 +/- 2% for Dox-L at Dox dose of 50 mu g/mL for 4h followed by 24h incubation) and enhanced suppression of tumor growth (348 +/- 53mm (3) for R8-Dox-L, compared to 504 +/- 54mm (3) for Dox-L treatment) in vivo compared to Dox-L.

Dox

Dox

Dox

Dox

Dox

Dox

Dox


Input: R8-modification has the potential for broadening the therapeutic window of pegylated liposomal doxorubicin treatment, which could lead to lower non-specific toxicity.

doxorubicin


Input: Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting.

carbamazepine

Soluplus


Input: Hot-melt extrusion (HME) is a dust-and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic polymers.


Input: Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation.


Input: The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus (R)) by hot-melt extrusion.

carbamazepine

CBZ

polyethyleneglycol

polyvinyl caprolactam

polyvinyl acetate

Soluplus


Input: Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus (R) was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation.

CBZ

Soluplus


Input: It was found that hot-melt extrusion of carbamazepine and Soluplus (R) is feasible on a single-screw hot-melt extruder without the addition of plasticizers.

carbamazepine

Soluplus


Input: DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed ~ 5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ.

CBZ

CBZ

CBZ

CBZ


Input: Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus (R) hot-melt extrudates.

carbamazepine

Soluplus


Input: The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.


Input: Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies.


Input: The effectiveness of Hibiscus sabdariffa L.


Input: (HS) in the treatment of risk factors associated with cardiovascular disease is assessed in this review by taking a comprehensive approach to interpreting the randomized clinical trial (RCT) results in the context of the available ethnomedical, phytochemical, pharmacological, and safety and toxicity information.


Input: HS decoctions and infusions of calyxes, and on occasion leaves, are used in at least 10 countries worldwide in the treatment of hypertension and hyperlipidemia with no reported adverse events or side effects.


Input: HS extracts have a low degree of toxicity with a LD50 ranging from 2, 000 to over 5, 000mg/kg/day.


Input: There is no evidence of hepatic or renal toxicity as the result of HS extract consumption, except for possible adverse hepatic effects at high doses.


Input: There is evidence that HS acts as a diuretic, however in most cases the extract did not significantly influence electrolyte levels.


Input: Animal studies have consistently shown that consumption of HS extract reduces blood pressure in a dose dependent manner.


Input: In RCTs, the daily consumption of a tea or extract produced from HS calyxes significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with pre to moderate essential hypertension and type 2 diabetes.


Input: In addition, HS tea was as effective at lowering blood pressure as the commonly used blood pressure medication Captropril, but less effective than Lisinopril.

Captropril

Lisinopril


Input: Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides were lowered in the majority of normolipidemic, hyperlipidemic, and diabetic animal models, whereas high-density lipoprotein cholesterol (HDL-C) was generally not affected by the consumption of HS extract.

cholesterol

cholesterol

triglycerides

cholesterol


Input: Over half of the RCTs showed that daily consumption of HS tea or extracts had favorable influence on lipid profiles including reduced total cholesterol, LDL-C, triglycerides, as well as increased HDL-C.

cholesterol

triglycerides


Input: Anthocyanins found in abundance in HS calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid.

Anthocyanins

polyphenols

hibiscus acid


Input: A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor.

anthocyanins


Input: This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit.


Input: Antidepressant use and glycemic control.


Input: RATIONALE: Past research on the association of antidepressant medication use with glycemic control abnormalities has produced mixed results.


Input: OBJECTIVE: To examine the association of antidepressant use with glycemic control abnormalities and screen-positive diabetes in a representative population sample of US adults without a diagnosis of diabetes.


Input: METHODS: Using data from adult participants of the National Health and Nutrition Examination Survey (NHANES, 2005-2010), the association of antidepressant use with continuous measures of HbA1c, fasting blood sugar, 2-h oral glucose tolerance test, insulin sensitivity and screen-positive diabetes according to HbA1c, fasting blood sugar and 2-h oral glucose tolerance test were assessed.

sugar

glucose

glucose


Input: RESULTS: Antidepressant use was not associated with increased levels of HbA1c, fasting blood sugar, 2-h oral glucose tolerance test, reduced insulin sensitivity or increased prevalence of screen-positive diabetes.

sugar

glucose


Input: Results were mostly consistent across sociodemographic groups and across different lengths of exposure, different classes of antidepressants and levels of body mass index.


Input: CONCLUSIONS: In this representative population sample, antidepressant use was not associated with an increased risk of abnormalities in glycemic control or undetected diabetes.


Input: Positive findings from past research may be attributable to detection bias, in that individuals prescribed antidepressants may be more likely to be tested and diagnosed with diabetes.


Input: Effects of vitamin B6 metabolism on oncogenesis, tumor progression and therapeutic responses.

vitamin B6


Input: Pyridoxal-5'-phosphate (PLP), the bioactive form of vitamin B6, reportedly functions as a prosthetic group for > 4% of classified enzymatic activities of the cell.

PLP

vitamin B6


Input: It is therefore not surprising that alterations of vitamin B6 metabolism have been associated with multiple human diseases.

vitamin B6


Input: As a striking example, mutations in the gene coding for antiquitin, an evolutionary old aldehyde dehydrogenase, result in pyridoxine-dependent seizures, owing to the accumulation of a metabolic intermediate that inactivates PLP.

aldehyde

pyridoxine

PLP


Input: In addition, PLP is required for the catabolism of homocysteine by transsulfuration.

PLP

homocysteine


Input: Hence, reduced circulating levels of B6 vitamers (including PLP as well as its major precursor pyridoxine) are frequently paralleled by hyperhomocysteinemia, a condition that has been associated with an increased risk for multiple cardiovascular diseases.

PLP

pyridoxine


Input: During the past 30 years, an intense wave of clinical investigation has attempted to dissect the putative links between vitamin B6 and cancer.

vitamin B6


Input: Thus, high circulating levels of vitamin B6, as such or as they reflected reduced amounts of circulating homocysteine, have been associated with improved disease outcome in patients bearing a wide range of hematological and solid neoplasms.

vitamin B6

homocysteine


Input: More recently, the proficiency of vitamin B6 metabolism has been shown to modulate the adaptive response of tumor cells to a plethora of physical and chemical stress conditions.

vitamin B6


Input: Moreover, elevated levels of pyridoxal kinase (PDXK), the enzyme that converts pyridoxine and other vitamin B6 precursors into PLP, have been shown to constitute a good, therapy-independent prognostic marker in patients affected by non-small cell lung carcinoma (NSCLC).

pyridoxal

pyridoxine

vitamin B6

PLP


Input: Here, we will discuss the clinical relevance of vitamin B6 metabolism as a prognostic factor in cancer patients. Oncogene advance online publication, 21 January 2013; doi: 10. 1038/onc. 2012. 623.

vitamin B6


Input: Effects of aging on apoptosis gene expression in oral mucosal tissues.


Input: Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa.


Input: The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues.


Input: This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model.


Input: Macaca mulatta primates from 2 to 23 years of age (n = 23) were used in a cross-sectional study to obtain clinical healthy gingival tissues specimens.


Input: Further, mRNA was prepared and evaluated using the Affymetrix Rhesus GeneChip and 88 apoptotic pathway genes were evaluated.


Input: The results identified significant positive correlations with age in 12 genes and negative correlations with an additional five genes.


Input: The gene effects were predicted to alter apoptosis receptor levels, extrinsic apoptotic pathways through caspases, cytokine effects on apoptotic events, Ca (+ 2)-induced death signaling, cell cycle checkpoints, and potential effects of survival factors.

Ca (+ 2)


Input: Both the positively and negatively correlated genes within the apoptotic pathways provided evidence that healthy tissues in aging animals exhibit decreased apoptotic potential compared to younger animals.


Input: The results suggested that decreased physiologic apoptotic process in the dynamic septic environment of the oral mucosal tissues could increase the risk of aging tissues to undergo destructive disease processes through dysregulated inflammatory responses to the oral microbial burden.


Input: Characterization of osteoblastic and osteolytic proteins in prostate cancer bone metastases.


Input: BACKGROUND: Approximately 90% of patients who die of Prostate Cancer (PCa) have bone metastases, which promote a spectrum of osteoblastic, osteolytic or mixed bone responses.


Input: Numerous secreted proteins have been reported to promote osteoblastic or osteolytic bone responses.


Input: We determined whether previously identified and/or novel proteins were associated with the osteoblastic or osteolytic response in clinical specimens of PCa bone metastases.


Input: METHODS: Gene expression was analyzed on 14 PCa metastases from 11 patients by microarray profiling and qRT-PCR, and protein expression was analyzed on 33 PCa metastases from 30 patients by immunohistochemistry on highly osteoblastic and highly osteolytic bone specimens.


Input: RESULTS: Transcript and protein levels of BMP-2, BMP-7, DKK-1, ET-1, and Sclerostin were not significantly different between osteoblastic and osteolytic metastases.


Input: However, levels of OPG, PGK1, and Substance P proteins were increased in osteoblastic samples.


Input: In addition, Emu1, MMP-12, and sFRP-1 were proteins identified with a novel role of being associated with either the osteoblastic or osteolytic bone response.


Input: CONCLUSIONS: This is the first detailed analysis of bone remodeling proteins in human specimens of PCa bone metastases.


Input: Three proteins not previously shown to be involved may have a role in the PCa bone response.


Input: Furthermore, our data suggests that the relative expression of numerous, rather than a single, bone remodeling proteins determine the bone response in PCa bone metastases.


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


Input: Mineralization of phenanthrene sorbed on multiwalled carbon nanotubes.

phenanthrene

carbon


Input: Carbon nanotubes have attracted attention around the world because of their high sorption capacity for hydrophobic organic compounds (HOCs); however, the bioavailability of HOCs sorbed on carbon nanotubes to bacteria is not well known.

Carbon

carbon


Input: In the present study, (14) C-labeled and unlabeled phenanthrene was spiked onto four kinds of multiwalled carbon nanotubes (MWCNTs) and aged for 60 d, and the mineralization of phenanthrene sorbed on MWCNTs was studied.

(14) C

phenanthrene

carbon

phenanthrene


Input: The mineralization efficiencies of phenanthrene sorbed on the four kinds of MWCNTs were 2. 38, 8. 84, 23. 88, and 31. 47%, respectively, after incubation for 35 d, which were positively correlated with the sum of fast and slow desorption fractions of phenanthrene (p < 0. 05).

phenanthrene

phenanthrene


Input: The authors found that the mineralization efficiencies agreed well with the MWCNT properties; the increasing specific surface area and mesopore and micropore volume of MWCNTs caused a significant decrease in the mineralization efficiency of phenanthrene (p < 0. 05).

phenanthrene


Input: After incubation for 35 d, the density of bacteria had a significant positive correlation with both the desorption and the mineralization efficiencies.


Input: The authors inferred that, although MWCNTs might have toxic effects on the bacteria, the biodegrading ability of bacteria might not decrease significantly under the influence of MWCNTs with low surface area.


Input: Biotinylated phosphoproteins from kinase-catalyzed biotinylation are stable to phosphatases: implications for phosphoproteomics.


Input: Kinase-catalyzed protein phosphorylation is involved in a wide variety of cellular events.


Input: Development of methods to monitor phosphorylation is critical to understand cell biology.


Input: Our lab recently discovered kinase-catalyzed biotinylation, where ATP-biotin is utilized by kinases to label phosphopeptides or phosphoproteins with a biotin tag.

ATP

biotin

biotin


Input: To exploit kinase-catalyzed biotinylation for phosphoprotein purification and identification in a cellular context, the susceptibility of the biotin tag to phosphatases was characterized.

biotinylation


Input: We found that the phosphorylbiotin group on peptide and protein substrates was relatively insensitive to protein phosphatases.

phosphorylbiotin


Input: To understand how phosphatase stability would impact phosphoproteomics research applications, kinase-catalyzed biotinylation of cell lysates was performed in the presence of kinase or phosphatase inhibitors.


Input: We found that biotinylation with ATP-biotin was sensitive to inhibitors, although with variable effects compared to ATP phosphorylation.

ATP

biotin

ATP


Input: The results suggest that kinase-catalyzed biotinylation is well suited for phosphoproteomics studies, with particular utility towards monitoring low-abundance phosphoproteins or characterizing the influence of inhibitor drugs on protein phosphorylation.


Input: Genetic dissection of sesquiterpene biosynthesis by Fusarium fujikuroi.

sesquiterpene


Input: A treasure trove of terpenes: The products of two fungal sesquiterpene synthases from the rice pathogen Fusarium fujikuroi were identified by gene-knockout experiments, genetic engineering of the fungus for production optimization, isolation of the sesquiterpenes, and structure elucidation by spectroscopic methods.

terpenes

sesquiterpene

sesquiterpenes


Input: Synthesis and characterization of conformationally rigid chiral pyridine-N-heterocyclic carbene-based palladacycles with an unexpected Pd-N bond cleavage.

pyridine

N-heterocyclic carbene

palladacycles

Pd

N


Input: The versatility of a previously developed method for the synthesis of chiral carbene-based palladacycles is demonstrated through the synthesis of two new chiral pyridine-functionalized N-heterocyclic carbene palladacycles with different wingtip groups.

carbene

palladacycles

pyridine

N-heterocyclic carbene palladacycles


Input: The efficiency in their resolution with different counter anions and different chiral amino acid salt auxiliaries has been studied.

amino acid


Input: The absolute stereochemistries of all the chiral compounds were confirmed by single crystal X-ray crystallography.


Input: An unexpected Pd-N bond cleavage that resulted in the racemization of the alpha-carbon center in these complexes has also been investigated.

Pd

N

alpha-carbon


Input: TGF-beta 1 Conjugated to Gold Nanoparticles Results in Protein Conformational Changes and Attenuates the Biological Function.


Input: Gold nanoparticles (AuNPs) are widely used as carriers or therapeutic agents due to their great biocompatibility and unique physical properties.


Input: Transforming growth factor-beta 1 (TGF-beta 1), a member of the cysteine-knot structural superfamily, plays a pivotal role in many diseases and is known as an immunosuppressive agent that attenuates immune response resulting in tumor growth.

cysteine


Input: The results reported herein reflect strong interactions between TGF-beta 1 and the surface of AuNPs when incubated with serum-containing medium, and demonstrate a time-and dose-dependent pattern.


Input: Compared with other serum proteins that can also bind to the AuNP surface, AuNP-TGF beta 1 conjugate is a thermodynamically favored compound.


Input: Epithelial cells undergo epithelial-mesenchymal transition (EMT) upon treatment with TGF-beta 1; however, treatment with AuNPs reverses this effect, as detected by cell morphology and expression levels of EMT markers.


Input: TGF-beta 1 is found to bind to AuNPs through S-Au bonds by X-ray photoelectron spectroscopy.

S-Au


Input: Fourier transform infrared spectroscopy is employed to analyze the conformational changes of TGF-beta 1 on the surface of AuNPs.


Input: The results indicate that TGF-beta 1 undergoes significant conformational changes at both secondary and tertiary structural levels after conjugation to the AuNP surface, which results in the deactivation of TGF-beta 1 protein.


Input: An in vivo experiment also shows that addition of AuNPs attenuates the growth of TGF-beta 1-secreting murine bladder tumor 2 cells in syngeneic C3H/HeN mice, but not in immunocompromised NOD-SCID mice, and this is associated with an increase in the number of tumor-infiltrating CD4 (+) and CD8 (+) T lymphocytes and a decrease in the number of intrasplenic Foxp3 (+) lymphocytes.


Input: The findings demonstrate that AuNPs may be a promising agent for modulating tumor immunity through inhibiting immunosuppressive TGF-beta 1 signaling.


Input: Scaffold effects on osteogenic differentiation of equine mesenchymal stem cells: an in vitro comparative study.


Input: The in vitro viability, osteogenic differentiation, and mineralization of four different equine mesenchymal stem cells (MSCs) from bone marrow, periosteum, muscle, and adipose tissue are compared, when they are cultured with different collagen-based scaffolds or with fibrin glue.


Input: The results indicate that bone marrow cells are the best source of MSCs for osteogenic differentiation, and that an electrochemically aggregated collagen gives the highest cell viability and best osteogenic differentiation among the four kinds of scaffolds studied.


Input: Shrinking hydrogel-DNA spots generates 3D microdots arrays.


Input: This report describes a straightforward approach for the achievement of sub-100 micrometers size hydrogel dots supporting DNA immobilization.


Input: Hydrogel-DNA spots are arrayed and UV-crosslinked on PolyShrink, an innovative polymer material having the remarkable property of isotropically shrinking under high temperature.


Input: Curing the microarray enables then spot miniaturization, resulting in 6 micro m thick and 60 micro m wide hydrogel dots in which oligonucleotides are immobilized in a 3D hydrophilic environment.


Input: The probe immobilization within the hydrogel network and its capacity to detect targets specifically and quantitatively is demonstrated using chemiluminescent as well as colorimetric detection techniques.


Input: The hydrogel material improves probe accessibility within the spot, leading to an enhanced sensitivity.


Input: Mimicking native extracellular matrix with phytic Acid-crosslinked protein nanofibers for cardiac tissue engineering.

phytic Acid


Input: A functional scaffold fabricated is developed from natural polymers, favoring regeneration of the ischemic myocardium.


Input: Hemoglobin/gelatin/fibrinogen (Hb/gel/fib) nanofibers are fabricated by electrospinning and are characterized for morphology, scaffold composition, functional groups and hydrophilicity.


Input: It is hypothesized that ex vivo pretreatment of mesenchymal stem cells (MSCs) using 5-azacytidine and such a functional nanofibrous construct having a high oxygen-carrying potential could lead to enhanced cardiomyogenic differentiation of MSCs and result in superior biological and functional effects.

oxygen


Input: The combination of a functional nanofibrous scaffold composed of natural polymers and crosslinked with a natural crosslinking agent, phytic acid, and stem cell biology may prove to be a novel therapeutic device for treatment of myocardial infarction.

phytic acid


Input: Comparison of contact angle hysteresis of different probe liquids on the same solid surface.


Input: Advancing and receding contact angles of water, formamide and diiodomethane were measured on 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) layers deposited on three different solid supports-glass, mica and poly (methyl methacrylate).

formamide

diiodomethane

1, 2-dipalmitoyl-sn-glycero-3-phosphocholine

DPPC

poly (methyl methacrylate)


Input: Up to five statistical monolayers were deposited on the surfaces by spreading DPPC solution.

DPPC


Input: It was found that even on five statistical DPPC monolayers, the hysteresis of a given liquid depends on the kind of solid support.

DPPC


Input: Also on the same solid support the contact angle hysteresis is different for each probe liquid used.


Input: The AFM images show that the heights of roughness of the DPPC films cannot be the primary cause of the observed hysteresis because the heights are too small to cause the observed hystereses.

DPPC


Input: It is believed that the hysteresis is due to the liquid film present right behind the three-phase solid surface/liquid drop/gas (vapour) contact line and the presence of Derjaguin pressure.


Input: The value of contact angle hysteresis depends on both the solid surface and liquid properties as well as on intermolecular interactions between them.


Input: Enhancing macrocyclic diterpenes as multidrug-resistance reversers: structure-activity studies on jolkinol D derivatives.

diterpenes

jolkinol D


Input: The phytochemical study of Euphorbia piscatoria yielded jolkinol D (1) in a large amount, whose derivatization gave rise to 12 ester derivatives (2-13) and hydrolysis to compound 14.

jolkinol D

ester


Input: The in vitro modulation of P-gp of compounds 1-14 was evaluated through a combination of transport and chemosensitivity assays, using the L5178 mouse T lymphoma cell line transfected with the human MDR1 gene.


Input: Apart from jolkinol D, all derivatives (2-14) showed potential as MDR reversal agents.

jolkinol D


Input: In this small library of novel bioactive macrocyclic lathyrane diterpene derivatives, designed to evaluate structure-activity relationships essential in overcoming multidrug resistance (MDR), some correlations between MDR reversal and molecular weight, accessible solvent areas, and octanol/water partition coefficient were identified that can contribute to the development of new selective P-gp reversal agents.

lathyrane diterpene

octanol


Input: Separation and structure elucidation of a new homoflavanol derivative from Pteridium aquilinum (L.) Kuhn.

homoflavanol


Input: A novel homoflavanol derivative (1) with an unprecedented skeleton, as well as two known flavonoids kaempferol (2) and quercetin (3), was isolated from the plant Pteridium aquilinum (L.) Kuhn, and the structure and relative stereochemistry of the new compound (1) were elucidated on the basis of spectroscopic data.

homoflavanol

flavonoids kaempferol

quercetin


Input: Biomimetic polymer brushes containing tethered acetylcholine analogs for protein and hippocampal neuronal cell patterning.

acetylcholine


Input: This paper describes a method to control neuronal cell adhesion and differentiation with both chemical and topographic cues by using a spatially defined polymer brush pattern.


Input: First, biomimetic methacrylate polymer brushes containing tethered neurotransmitter acetylcholine functionalities in the form of dimethylaminoethyl methacrylate or free hydroxyl-terminated poly (ethylene glycol) units were prepared using the " grown from " method through surface-initiated atom transfer radical polymerization reactions.

methacrylate

acetylcholine

dimethylaminoethyl methacrylate

hydroxyl

poly (ethylene glycol)


Input: The surface properties of the resulting brushes were thoroughly characterized with various techniques and hippocampal neuronal cell culture on the brush surfaces exhibit cell viability and differentiation comparable to, or even better than, those on commonly used poly-l-lysine coated glass coverslips.

poly-l-lysine


Input: The polymer brushes were then patterned via UV photolithography techniques to provide specially designed surface features with different sizes (varying from 2 to 200 mu m) and orientations (horizontal and vertical).


Input: Protein absorption experiments and hippocampal neuronal cell culture tests on the brush patterns showed that both protein and neurons can adhere to the patterns and therefore be guided by such patterns.


Input: These results also demonstrate that, because of their unique chemical composition and well-defined nature, the developed polymer brushes may find many potential applications in cell-material interactions studies and neural tissue engineering.


Input: Self-Assembly of Discrete Metal Complexes in Aqueous Solution via Block Copolypeptide Amphiphiles.


Input: The integration of discrete metal complexes has been attracting significant interest due to the potential of these materials for soft metal-metal interactions and supramolecular assembly.


Input: Additionally, block copolypeptide amphiphiles have been investigated concerning their capacity for self-assembly into structures such as nanoparticles, nanosheets and nanofibers.


Input: In this study, we combined these two concepts by investigating the self-assembly of discrete metal complexes in aqueous solution using block copolypeptides.


Input: Normally, discrete metal complexes such as [Au (CN) (2)]-, when molecularly dispersed in water, cannot interact with one another.

[Au (CN) (2)]-


Input: Our results demonstrated, however, that the addition of block copolypeptide amphiphiles such as K (183) L (19) to [Au (CN) (2)]-solutions induced one-dimensional integration of the discrete metal complex, resulting in photoluminescence originating from multinuclear complexes with metal-metal interactions.

[Au (CN) (2)]-


Input: Transmission electron microscopy (TEM) showed a fibrous nanostructure with lengths and widths of approximately 100 and 20 nm, respectively, which grew to form advanced nanoarchitectures, including those resembling the weave patterns of Waraji (traditional Japanese straw sandals).


Input: This concept of combining block copolypeptide amphiphiles with discrete coordination compounds allows the design of flexible and functional supramolecular coordination systems in water.


Input: Crowd computing: using competitive dynamics to develop and refine highly predictive models.


Input: A recent application of a crowd computing platform to develop highly predictive in silico models for use in the drug discovery process is described.


Input: The platform, Kaggle (TM), exploits a competitive dynamic that results in model optimization as the competition unfolds.


Input: Here, this dynamic is described in detail and compared with more-conventional modeling strategies.


Input: The complete and full structure of the underlying dataset is disclosed and some thoughts as to the broader utility of such' gamification' approaches to the field of modeling are offered.


Input: Inhibition of leukemic U937 cell growth by induction of apoptosis, cell cycle arrest and suppression of VEGF, MMP-2 and MMP-9 activities by cytotoxin protein NN-32 purified from Indian spectacled cobra (Naja naja) venom.


Input: A cytotoxin NN-32 (6. 7 kDa) from Indian cobra (Naja naja) venom inhibited human leukemic U937 cell growth as observed by Trypan blue dye exclusion method and cytotoxicity was confirmed by MTT assay.

Trypan blue

MTT


Input: NN-32 induced apoptosis of U937 cell and cell cycle arrest of sub-G1 phase were revealed by FACS analysis.


Input: Increased Bax/Bcl-2 ratio, increased caspase 3 and 9 activities, cleaved PARP, decreased VEGF, MMP-2 and MMP-9 activities were observed after NN-32 treatment of U937 cell.


Input: Antileukemic activity of NN-32 on U937 cell may be due to activation of apoptosis, arresting cell cycle and antiangiogenesis activities.


Input: Pharmacy benefit managers and their obligations during serious prescription drug shortages.


Input: Pharmacy benefit managers are connected to some 215 million Americans and to every prescribing physician and retail pharmacy in the United States.


Input: Many of them have their own large and sophisticated dispensing operations.


Input: These capabilities could be put to use when drug shortages threaten life.


Input: Indeed, these capabilities are such that they confer obligations on pharmacy benefit managers to address such shortages--not only on behalf of their clients but for society in general.


Input: N-1, C-3 substituted indoles as 5-LOX inhibitors--in vitro enzyme immunoaasay, mass spectral and molecular docking investigations.

indoles


Input: Based upon the structures of some known 5-LOX inhibitors, a set of five compounds carrying appropriate substituents at N-1 and C-3 of indole were synthesized and investigated for 5-LOX inhibitory activities.

indole


Input: Fifty percent inhibitory concn (IC (50)) of these compounds ranges from 0. 6 to 5 mu M and found to be comparable to that of clinically used 5-LOX inhibitor, zileuton.

zileuton


Input: The compounds under present investigations exhibited appreciable interactions with 5-LOX as apparent from their association constants calculated from the mass spectral data.


Input: Compound 5a with a tosyl group at N-1 and pyrolidinyl-1, 2-dione substituent at C-3 of indole, exhibiting IC (50) 0. 6 mu M and stoichiometry of 1: 7 in the enzyme-compound complex was identified as highly potent 5-LOX inhibitor and seems to be suitable for further investigations.

tosyl

pyrolidinyl-1, 2-dione

indole


Input: 9 9 mTc-(Me) FGCDEVD, a potential tracer for apoptosis detection.

9 9 mTc-(Me) FGCDEVD


Input: (Me) FGC (Bz) DEVD was radiolabeled with technetium-99m in high yield.

(Me) FGC (Bz) DEVD


Input: This tracer was preferentially accumulated in apoptotic cells in the in vitro studies.


Input: Tumor uptake occurred in vivo after cisplatin injection due to the apoptosis induction, which not observed in the untreated tumors.

cisplatin


Input: Therefore, (99m) Tc-(Me) FGCDEVD is a potential tracer for apoptosis detection.

(99m) Tc-(Me) FGCDEVD


Input: sigma, pi aromaticity and anti-aromaticity as retrieved by the linear response kernel.


Input: The chemical importance of the linear response kernel from conceptual Density Functional Theory (DFT) is investigated for some sigma and pi aromatic and anti-aromatic systems.


Input: The effect of the ring size is studied by looking at some well known aromatic and anti-aromatic molecules of different sizes, showing that the linear response is capable of correctly classifying and quantifying the aromaticity for five-to eight-membered aromatic and anti-aromatic molecules.


Input: The splitting of the linear response in sigma and pi contributions is introduced and its significance is illustrated using some sigma-aromatic molecules.


Input: The linear response also correctly predicts the aromatic transition states of the Diels-Alder reaction and the acetylene trimerisation and shows the expected behavior along the reaction coordinate, proving that the method is accurate not only at the minimum of the potential energy surface, but also in non-equilibrium states.

acetylene


Input: Finally, the reason for the close correlation between the linear response and the Para Delocalisation Index (PDI), found in previous and the present study, is proven mathematically.


Input: These results show the linear response to be a reliable DFT-index to probe the sigma and pi aromaticity or anti-aromaticity of a broad range of molecules.


Input: Exciton diffusion in near-infrared absorbing solution-processed organic thin films.


Input: We report on singlet-singlet annihilation and exciton diffusion in as-prepared p-type and annealed n-type thin films of the low-bandgap quinoidal quaterthiophene [QQT (CN) 4] using ultrafast transient absorption measurements.

quinoidal quaterthiophene

QQT (CN) 4


Input: The decay dynamics of exciton populations are well described by a one-dimensional diffusion-limited bimolecular recombination, indicating that the singlet excitons migrate preferentially along the stacking direction.


Input: Our results show that the exciton diffusion constants in QQT (CN) 4 films do not vary significantly upon thermal annealing.

QQT (CN) 4


Input: Exciton diffusion lengths are measured to be as high as 4 and 5 nm in as-prepared and annealed QQT (CN) 4 films, respectively.

QQT (CN) 4


Input: We also observe an influence of the excitation densities on the singlet exciton diffusion, which is attributed to phonon scattering.


Input: Because of the possibility of patterning p-n regions in QQT (CN) 4 films by thermal nanolithography techniques, this study provides important insight not only into the photophysical properties of quinoidal oligothiophene derivatives but also for their future integration into high-performance p-n nanostructured near infrared light-sensing devices.

QQT (CN) 4

quinoidal oligothiophene


Input: Highly effective Ir (x) Sn (1-x) O2 electrocatalysts for oxygen evolution reaction in the solid polymer electrolyte water electrolyser.

Ir

Sn

oxygen


Input: We developed an advanced surfactant-assistant method for the Ir (x) Sn (1-x) O (2) (0 < x <= 1) nanoparticle (NP) preparation, and examined the OER performances by a series of half-cell and full-cell tests.

Ir

Sn

O (2)


Input: In contrast to the commercial Ir black, the collective data confirmed the outstanding activity and stability of the fabricated Ir (x) Sn (1-x) O (2) (x = 1, 0. 67 and 0. 52) NPs, which could be ascribed to the amorphous structure, good dispersion, high pore volume, solid-solution state and Ir-rich surface for bi-metal oxides, and relatively large size (10-11 nm), while Ir (0. 31) Sn (0. 69) exhibited poor electro-catalytic activity because of the separated two phases, a SnO (2)-rich phase and an IrO (2)-rich phase.

Ir

Sn

O (2)

Ir

bi-metal oxides

Ir

Sn

SnO (2)

IrO (2)


Input: Furthermore, compared with highly active IrO (2), the improved durability, precious-metal Ir utilization efficiency and correspondingly reduced Ir loading were realized by the addition of Sn component.

IrO (2)

Ir

Ir

Sn


Input: When the Ir (0. 52) Sn (0. 48) O (2) cell operated at 80 degrees C using Nafion (R) 115 membrane and less than 0. 8 mg cm (-2) of the noble-metal Ir loading, the cell voltages we achieved were 1. 631 V at 1000 mA cm (-2), and 1. 821 V at 2000 mA cm (-2).

Ir

Sn

O (2)

Nafion

Ir


Input: The IR-free voltage at the studied current density was very close to the onset voltage of oxygen evolution.

oxygen


Input: The only 50 mu V h (-1) of voltage increased for the 500 h durability test at 500 mA cm (-2).


Input: In fact, these results are exceptional compared to the performances for OER in SPEWE cells known so far.


Input: This work highlights the potential of using highly active and stable IrO (2)-SnO (2) amorphous NPs to enhance the electrolysis efficiency, reduce the noble-metal Ir loading and thus the cost of hydrogen production from the solid polymer electrolyte water electrolysis.

IrO (2)

SnO (2)

Ir

hydrogen


Input: Intracameral cefuroxime: prophylaxis of postoperative endophthalmitis after cataract surgery.

cefuroxime


Input: Results of the landmark European Society of Cataract and Refractive Surgeons trial and additional prospective and retrospective studies support the use of intracameral cefuroxime in the prophylaxis of endophthalmitis following cataract surgery.

cefuroxime


Input: Prophylaxis with intracameral cefuroxime at the recommended dose appears to be well tolerated in patients undergoing cataract surgery.

cefuroxime


Input: However, off-label use of intracameral cefuroxime usually requires a two-step dilution process with the potential for dilution errors, and there are also concerns regarding the risk of contamination.

cefuroxime


Input: Aprokam (R) (intracameral cefuroxime) has been approved in the EU for the prophylaxis of postoperative endophthalmitis after cataract surgery.

Aprokam

cefuroxime


Input: After reconstitution of Aprokam (R), no further dilution is required and each vial is only indicated for single-patient use; this has the potential to reduce the risk of both dilution errors and contamination.

Aprokam


Input: The Inhibitory Effects of the Standardized Extracts of Ginkgo biloba on Aromatase Activity in JEG-3 Human Choriocarcinoma Cells.


Input: Breast cancer is the most common cancer in women worldwide.


Input: There are many endocrine adjuvant therapies for breast cancer patients that are categorized according to their mechanisms.


Input: Among them, aromatase inhibitors (AIs) that block the synthesis of estrogens have proven superiority compared with tamoxifen and have replaced it as a first-line hormonal therapy.

estrogens

tamoxifen


Input: However, AIs also have limitations due to their side effects-increased rate of bone loss and musculoskeletal complaints.


Input: We therefore need new candidate AIs with fewer side effects.


Input: The extracts of Ginkgo biloba (EGb), which contain phytochemicals from the tree, had biphasic effects for estrogens and osteoporosis-inhibiting activities in our previous experiments.

estrogens


Input: In this study, we explored the possibility of EGb as an AI and their mechanisms.


Input: Aromatase activities were inhibited by EGb both in JEG-3 cells and in recombinant CYP19 microsomes.


Input: The results of polymerase chain reaction for aromatase from a coding sequence and specific promoter sequences (exon I. a, exon I. c) in JEG-3 cells as well as the results of reporter gene assays showed that EGb dose-dependently decreased the aromatase gene expression.


Input: The decreased protein levels were demonstrated by Western blotting.


Input: From these results, we concluded that EGb could act as an AI at both the enzyme and transcriptional levels.


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


Input: Dendrimer and cancer: a patent review (2006-present).


Input: INTRODUCTION: Dendrimers were widely used in cancer diagnosis and therapy during the past decade.


Input: The surface functionalities allow bioactive molecules such as imaging probes, therapeutic compounds, targeting ligands to be present on dendrimer surface in a multivalent fashion.


Input: In addition, the interior pockets as well as the charged surface of dendrimer can be encapsulated/bound with anti-cancer drugs or therapeutic DNAs/siRNAs.


Input: AREAS COVERED: The combination of dendrimer chemistry and new cancer therapy techniques such as radiotherapy, photodynamic therapy, neuron capture therapy, and photothermal therapy provides promising strategies in future cancer therapy.


Input: Here, we focused on recent advances on this topic in the patents (2006-present) and discussed the advantages of dendrimer technology in these inventions.


Input: EXPERT OPINION: The challenges and perspectives of dendrimer-based theranostics for cancer diagnosis and therapy are discussed.


Input: Future efforts in this area should be focused on designing materials to solve problems such as cancer metastasis, multidrug resistance (MDR) in cancer cells, and early-stage cancer diagnosis.


Input: Comparative single-dose pharmacokinetics of rasagiline in minipigs after oral dosing or transdermal administration via a newly developed patch.

rasagiline


Input: Abstract 1.


Input: A rasagiline transdermal patch was developed for the treatment of early and advanced Parkinson' s disease.

rasagiline


Input: Relevant pharmacokinetic parameters of rasagiline obtained after transdermal administration to minipigs were compared with those of rasagiline after oral administration.

rasagiline

rasagiline


Input: A total of 18 minipigs were randomly divided into three groups (six animals for each group).


Input: A single dose of 1 mg rasagiline tablet was orally administrated to one group.

rasagiline


Input: Meanwhile, single dose of 1. 25 and 2. 5 mg (2 and 4 cm (2)) rasagiline patches were given (at the postauricular skin) to the other two groups, respectively.

rasagiline


Input: The pharmacokinetic parameters such as plasma half-life (t (1/2)), time to peak plasma-concentration (T (max)), mean residence time (MRT), area under the curve (AUC ((0-) (t) ())) were significantly (p < 0. 05) different between transdermal and oral administrations.


Input: The plasma half-life (t (1/2)) of rasagiline (1. 25 mg patch: 11. 8 +/- 6. 5 h, 2. 5 mg patch: 12. 5 +/- 4. 7 h) in minipig following transdermal administration was significantly prolonged as compared with that following the oral administration (1 mg tablet: 4. 7 +/- 2. 5 h).

rasagiline


Input: The dose-normalized relative bioavailability of rasagiline patch in minipig were 178. 5% and 156. 4%, respectively, for 1. 25 and 2. 5 mg patches compared with 1 mg rasagiline tablet.

rasagiline

rasagiline


Input: The prolonged t (1/2) and increased bioavailability of rasagiline patch suggested a possible longer dosing interval compared with oral tablet.

rasagiline


Input: Chemical reactivity and biological activity of chalcones and other alpha, beta-unsaturated carbonyl compounds.

chalcones

alpha, beta-unsaturated carbonyl


Input: Abstract 1.


Input: Chalcones are structural analogues of benzalacetophenone (BAP).

Chalcones

benzalacetophenone

BAP


Input: Several derivatives have been identified in plants and anticarcinogenic and anti-inflammatory properties were attributed to the compounds, probably related to their direct antioxidant activity or stimulatory effects on the expression of endogenous defence enzymes like hemeoxygenase-1 (HO-1).


Input: HO-1 expression is triggered by the Nrf2-Keap1 signalling pathway, initiated by the addition of chalcones to thiol groups of Keap1 via Michael-type reaction.

chalcones

thiol


Input: The present study used a model system estimating the reactivity of different synthetic chalcones and other alpha, beta-unsaturated carbonyl compounds with thiols and compared the chemical reactivity with the biological activity, measured by HO-1 expression in human dermal fibroblasts.

chalcones

alpha, beta-unsaturated carbonyl

thiols


Input: Chemical reactivity with the thiol group of N-acetylcysteine was determined with 5, 5'-dithiobis-(2-nitrobenzoic acid) and followed chemical principles of structure-reactivity relationship.

thiol

N-acetylcysteine

5, 5'-dithiobis-(2-nitrobenzoic acid)


Input: Most reactive were sulforaphane, dimethylfumarate, chalcone 3 ((2E)-1-phenyl-3-pyrimidin-2-ylprop-2-en-1-one) and chalcone 7 (1, 3-diphenylprop-2-yn-1-one).

sulforaphane

dimethylfumarate

chalcone

(2E)-1-phenyl-3-pyrimidin-2-ylprop-2-en-1-one

chalcone

1, 3-diphenylprop-2-yn-1-one


Input: This result demonstrates that alpha, beta-unsaturated carbonyl derivatives react with thiols differently.

alpha, beta-unsaturated carbonyl

thiols


Input: All compounds were also biologically active; however, expression of HO-1 was not only related to the chemical reactivity but also to the lipophilicity of the molecules which likely affected transmembrane uptake.


Input: Most efficient inducers of HO-1 expression were BAP, 4-hydroxynonenal and chalcone 1 (4-[(1E)-3-oxo-3-phenylprop-1-en-1-yl] benzonitrile), chalcone 5 ((2E)-1-phenyl-3-[4-(trifluoromethyl)-phenyl] prop-2-en-1-one) and chalcone 7.

BAP

chalcone

4-[(1E)-3-oxo-3-phenylprop-1-en-1-yl] benzonitrile

chalcone

(2E)-1-phenyl-3-[4-(trifluoromethyl)-phenyl] prop-2-en-1-one

chalcone


Input: Redox-active pi-conjugated organometallic monolayers: pronounced Coulomb blockade characteristic at room temperature.

organometallic


Input: We report the electrical transport characteristics of a series of molecular wires, fc-C = C-C6H4-SAc (fc = ferrocenyl; Ac = acetyl) and AcS-C6H4-C = C-(fc) n-C = C-C6H4-SAc (n = 2, 3), consisting of multiple redox-active ferrocenyl centers.

fc-C = C-C6H4-SAc

ferrocenyl

acetyl

AcS-C6H4-C = C-(fc) n-C = C-C6H4-SAc

ferrocenyl


Input: The self-assembled monolayers of these molecular wires on Au surfaces were comprehensively characterized by electrochemistry and conductive atomic force microscopy techniques.

Au


Input: Characterization of the wires revealed that electron transport is made extremely efficient by the organometallic redox states.

organometallic


Input: There is a strong electronic coupling between ferrocenyl moieties, and superior electron-transport ability exists through these semirigid molecular wires.

ferrocenyl