Input: This result could support the regulatory loop of 1, 25 (OH) (2) D and FGF-23 in human, FGF-23 regulation by 1, 25 (OH) (2) D.

1, 25 (OH) (2) D

1, 25 (OH) (2) D


Input: Purinergic receptor antagonist a438079 protects against acetaminophen-induced liver injury by inhibiting p450 isoenzymes, not by inflammasome activation.

acetaminophen


Input: Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in the western world.

Acetaminophen

APAP


Input: Controversy exists regarding the hypothesis that the hepatocyte injury is amplified by a sterile inflammatory response, rather than being the result of intracellular mechanisms alone.


Input: A recent study suggested that the purinergic receptor antagonist A438079 protects against APAP-induced liver injury by preventing the activation of the Nalp3 inflammasome in Kupffer cells and thereby preventing inflammatory injury.

APAP


Input: To test the hypothesis that A438079 actually affects the intracellular signaling events in hepatocytes, C57Bl/6 mice were treated with APAP (300 mg/kg) and A438079 (80 mg/kg) or saline and GSH depletion, protein adduct formation, c-jun-N-terminal kinase (JNK) activation, oxidant stress, and liver cell necrosis were determined between 0 and 6 h after APAP administration.

APAP

GSH

N

APAP


Input: APAP caused rapid GSH depletion, extensive protein adduct formation in liver homogenates and in mitochondria, JNK phosphorylation and mitochondrial translocation of phospho-JNK within 2 h, oxidant stress, and extensive centrilobular necrosis at 6 h.

APAP

GSH


Input: A438079 significantly attenuated GSH depletion, which resulted in a 50% reduction of total liver and mitochondrial protein adducts and substantial reduction of JNK activation, mitochondrial P-JNK translocation, oxidant stress, and liver injury.

GSH


Input: The same results were obtained using primary mouse hepatocytes.


Input: A438079 did not directly affect JNK activation induced by tert-butyl hydroperoxide and GSH depletion.

tert-butyl hydroperoxide

GSH


Input: However, A438079 dose-dependently inhibited hepatic P450 enzyme activity.


Input: Thus, the protective effect of A438079 against APAP hepatotoxicity in vivo can be explained by its effect on metabolic activation and cell death pathways in hepatocytes without involvement of the Nalp3 inflammasome.

APAP


Input: Protective roles of single-wall carbon nanotubes in ultrasonication-induced DNA base damage.

carbon


Input: The overall level of ultrasonication-induced DNA damage is reduced in the presence of single-wall carbon nanotubes (SWCNTs), particularly for DNA lesions formed by one-electron reduction of intermediate radicals.

carbon


Input: The protective role of SWCNTs observed in this work suggests a contrary view to the general idea that carbon nanotubes have damaging effects on biomolecules.

carbon


Input: Polymer grafting to single-walled carbon nanotubes: effect of chain length on solubility, graft density and mechanical properties of macroscopic structures.

carbon


Input: Single-walled carbon nanotubes are grafted with polystyrene chains employing a graft-to protocol.

carbon

polystyrene


Input: Thermogravimetric analysis allows calculation of the grafted chain density and average interchain separation on the nanotube surface as a function of molecular weight.


Input: The separation scales with molecular weight as a power law with an exponent of ca.


Input: 0. 588, showing the grafted chains to be in a swollen random walk conformation.


Input: This implies that chain packing is controlled by coil size in solution.


Input: In addition, the dispersed concentration of functionalized nanotubes scales with the size of the steric potential barrier that prevents aggregation of polymer functionalized nanotubes.


Input: It is also shown that the molecular weight of the grafted chains significantly affects the mechanical properties of nanotube films.


Input: Withaferin A-stimulated Ca2 + entry, ceramide formation and suicidal death of erythrocytes.

Withaferin A

Ca2 +

ceramide


Input: Withaferin A, a triterpenoid component from Withania somnifera, counteracts malignancy, an effect attributed to stimulation of apoptosis.

Withaferin A

triterpenoid


Input: Withaferin A is partially effective through induction of oxidative stress, altered gene expression and mitochondrial depolarization.

Withaferin A


Input: Erythrocytes lack mitochondria and nuclei but may enter apoptosis-like eryptosis, a suicidal cell death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface.

phosphatidylserine


Input: Triggers of eryptosis include increase of cytosolic Ca (2 +)-activity [Ca (2 +)] (i) following activation of oxidant-sensitive Ca (2 +)-permeable cation channels, ceramide formation and/or ATP-depletion.

Ca (2 +)

Ca (2 +)

Ca (2 +)

ceramide

ATP


Input: The present study explored, whether withaferin A triggers eryptosis.

withaferin A


Input: To this end, [Ca (2 +)] (i) was estimated from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin-V-binding, hemolysis from hemoglobin release, oxidative stress from DCFDA-fluorescence and ceramide abundance utilizing antibodies.

Ca (2 +)

phosphatidylserine

DCFDA

ceramide


Input: A 48 h exposure to withaferin A significantly decreased forward scatter (at >= 10 mu M withaferin concentration) and increased [Ca (2 +)] (i) (>= 5 mu M), ROS-formation (>= 10 mu M) ceramide-formation (>= 10 mu M) as well as annexin-V-binding (>= 5 mu M).

withaferin A

withaferin

Ca (2 +)

ceramide


Input: Withaferin A treatment was followed by slight but significant increase of hemolysis.

Withaferin A


Input: Extracellular Ca (2 +) removal, amiloride, and the antioxidant N-acetyl-l-cysteine significantly blunted withaferin A-triggered annexin-V-binding.

Ca (2 +)

amiloride

N-acetyl-l-cysteine

withaferin A


Input: The present observations reveal that withaferin A triggers suicidal erythrocyte death despite the absence of gene expression and key elements of apoptosis such as mitochondria.

withaferin A


Input: Gut microbiota, immune development and function.


Input: The microbiota of Westerners is significantly reduced in comparison to rural individuals living a similar lifestyle to our Paleolithic forefathers but also to that of other free-living primates such as the chimpanzee.


Input: The great majority of ingredients in the industrially produced foods consumed in the West are absorbed in the upper part of small intestine and thus of limited benefit to the microbiota.


Input: Lack of proper nutrition for microbiota is a major factor under-pinning dysfunctional microbiota, dysbiosis, chronically elevated inflammation, and the production and leakage of endotoxins through the various tissue barriers.


Input: Furthermore, the over-comsumption of insulinogenic foods and proteotoxins, such as advanced glycation and lipoxidation molecules, gluten and zein, and a reduced intake of fruit and vegetables, are key factors behind the commonly observed elevated inflammation and the endemic of obesity and chronic diseases, factors which are also likely to be detrimental to microbiota.


Input: As a consequence of this lifestyle and the associated eating habits, most barriers, including the gut, the airways, the skin, the oral cavity, the vagina, the placenta, the blood-brain barrier, etc., are increasingly permeable.


Input: Attempts to recondition these barriers through the use of so called' probiotics', normally applied to the gut, are rarely successful, and sometimes fail, as they are usually applied as adjunctive treatments, e. g. in parallel with heavy pharmaceutical treatment, not rarely consisting in antibiotics and chemotherapy.


Input: It is increasingly observed that the majority of pharmaceutical drugs, even those believed to have minimal adverse effects, such as proton pump inhibitors and anti-hypertensives, in fact adversely affect immune development and functions and are most likely also deleterious to microbiota.


Input: Equally, it appears that probiotic treatment is not compatible with pharmacological treatments.


Input: Eco-biological treatments, with plant-derived substances, or phytochemicals, e. g. curcumin and resveratrol, and pre-, pro-and syn-biotics offers similar effects as use of biologicals, although milder but also free from adverse effects.

curcumin

resveratrol


Input: Such treatments should be tried as alternative therapies; mainly, to begin with, for disease prevention but also in early cases of chronic diseases.


Input: Pharmaceutical treatment has, thus far, failed to inhibit the tsunami of endemic diseases spreading around the world, and no new tools are in sight.


Input: Dramatic alterations, in direction of a paleolithic-like lifestyle and food habits, seem to be the only alternatives with the potential to control the present escalating crisis.


Input: The present review focuses on human studies, especially those of clinical relevance.


Input: Aryl methylcarbamates: Potency and selectivity towards wild-type and carbamate-insensitive (G119S) Anopheles gambiae acetylcholinesterase, and toxicity to G3 strain An. gambiae.

Aryl methylcarbamates

carbamate


Input: New carbamates that are highly selective for inhibition of Anopheles gambiae acetylcholinesterase (AChE) over the human enzyme might be useful in continuing efforts to limit malaria transmission.

carbamates


Input: In this report we assessed 34 synthesized and commercial carbamates for their selectivity to inhibit the AChEs found in carbamate-susceptible (G3) and carbamate-resistant (Akron) An. gambiae, relative to human AChE.

carbamates

carbamate

carbamate


Input: Excellent correspondence is seen between inhibition potencies measured with carbamate-susceptible mosquito homogenate and purified recombinant wild-type (WT) An. gambiae AChE (AgAChE).

carbamate


Input: Similarly, excellent correspondence is seen between inhibition potencies measured with carbamate-resistant mosquito homogenate and purified recombinant G119S AgAChE, consistent with our earlier finding that the Akron strain carries the G119S mutation.

carbamate


Input: Although high (100-to 500-fold) WT An. gambiae vs human selectivity is observed for several compounds, none of the carbamates tested potently inhibits the G119S mutant enzyme.

carbamates


Input: Finally, we describe a predictive model for WT An. gambiae tarsal contact toxicity of the carbamates that relies on inhibition potency, molecular volume, and polar surface area.

carbamates


Input: Single molecule sensing with solid-state nanopores: novel materials, methods, and applications.


Input: This tutorial review will introduce and explore the fundamental aspects of nanopore (bio) sensing, fabrication, modification, and the emerging technologies and applications that both intrigue and inspire those working in and around the field.


Input: Although nanopores can be classified into two categories, solid-state and biological, they are essentially two sides of the same coin.


Input: For instance, both garner popularity due to their ability to confine analytes of interest to a nanoscale volume.


Input: Due to the vast diversity of nanopore platforms and applications, no single review can cover the entire landscape of published work in the field.


Input: Therefore, in this article focus will be placed on recent advancements and developments taking place in the field of solid-state nanopores.


Input: It should be stated that the intention of this tutorial review is not to cite all articles relating to solid-state nanopores, but rather to highlight recent, select developments that will hopefully benefit the new and seasoned scientist alike.


Input: Initially we begin with the fundamentals of solid-state nanopore sensing.


Input: Then the spotlight is shone on the sophisticated fabrication methods that have their origins in the semiconductor industry.


Input: One inherent advantage of solid-state nanopores is in the ease of functionalizing the surface with a range of molecules carrying functional groups.


Input: Therefore, an entire section is devoted to highlighting various chemical and bio-molecular modifications and explores how these permit the development of novel sensors with specific targets and functions.


Input: The review is completed with a discussion on novel detection strategies using nanopores.


Input: Although the most popular mode of nanopore sensing is based upon what has come to be known as ionic-current blockade sensing, there is a vast, growing literature based around exploring alternative detection techniques to further expand on the versatility of the sensors.


Input: Such techniques include optical, electronic, and force based methods.


Input: It is perhaps fair to say that these new frontiers have caused further excitement within the sensing community.


Input: Meta-analysis of vertebral augmentation compared with conservative treatment for osteoporotic spinal fractures.


Input: Cement augmentation is a controversial treatment for painful vertebral compression fractures (VCF).


Input: Our research questions for the meta-analysis were: Is there a clinical and statistical difference in pain relief, functional improvement, and quality of life between conservative care and cement augmentation for VCF and, if so, are they maintained at longer time points?


Input: We conducted a search of MEDLINE from January 1980 to July 2011 using PubMed, Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL, and EMBASE.


Input: Searches were performed from medical subject headings.


Input: Terms " vertebroplasty " and " compression fracture " were used.


Input: The outcome variables of pain, functional measures, health-related quality of life (HRQOL), and new fracture risk were analyzed.


Input: A random effects model was chosen.


Input: Continuous variables were calculated using the standardized mean difference comparing improvement from baseline of the experimental group with the control group.


Input: New vertebral fracture risk was calculated using log odds ratio.


Input: Six studies met the criteria.


Input: The pain visual analog scale (VAS) mean difference was 0. 73 (confidence interval [CI] 0. 35, 1. 10) for early (< 12 weeks) and 0. 58 (CI 0. 19, 0. 97) for late time points (6 to 12 months), favoring vertebroplasty (p < 0. 001).


Input: The functional outcomes at early and late time points were statistically significant with 1. 08 (CI 0. 33, 1. 82) and 1. 16 (CI 0. 14, 2. 18), respectively.


Input: The HRQOL showed superior results of vertebroplasty compared with conservative care at early and late time points of 0. 39 (CI 0. 16, 0. 62) and 0. 33 (CI 0. 16, 0. 51), respectively.


Input: Secondary fractures were not statistically different between the groups, 0. 065 (CI-0. 57, 0. 70).


Input: This meta-analysis showed greater pain relief, functional recovery, and health-related quality of life with cement augmentation compared with controls.


Input: Cement augmentation results were significant in the early (< 12 weeks) and the late time points (6 to 12 months).


Input: This meta-analysis provides strong evidence in favor of cement augmentation in the treatment of symptomatic VCF fractures.


Input: Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia.


Input: X-linked hypophosphatemia (XLH/HYP)-with renal phosphate wasting, hypophosphatemia, osteomalacia, and tooth abscesses-is caused by mutations in the zinc-metallopeptidase PHEX gene (phosphate-regulating gene with homologies to endopeptidase on the X chromosome).

zinc

phosphate


Input: PHEX is highly expressed by mineralized tissue cells.


Input: Inactivating mutations in PHEX lead to distal renal effects (implying accumulation of a secreted, circulating phosphaturic factor) and accumulation in bone and teeth of mineralization-inhibiting, acidic serine-and aspartate-rich motif (ASARM)-containing peptides, which are proteolytically derived from the mineral-binding matrix proteins of the SIBLING family (small, integrin-binding ligand N-linked glycoproteins).

serine

aspartate


Input: Although the latter observation suggests a local, direct matrix effect for PHEX, its physiologically relevant substrate protein (s) have not been identified.


Input: Here, we investigated two SIBLING proteins containing the ASARM motif-osteopontin (OPN) and bone sialoprotein (BSP)-as potential substrates for PHEX.


Input: Using cleavage assays, gel electrophoresis, and mass spectrometry, we report that OPN is a full-length protein substrate for PHEX.


Input: Degradation of OPN was essentially complete, including hydrolysis of the ASARM motif, resulting in only very small residual fragments.


Input: Western blotting of Hyp (the murine homolog of human XLH) mouse bone extracts having no PHEX activity clearly showed accumulation of an ~ 35 kDa OPN fragment that was not present in wild-type mouse bone.


Input: Immunohistochemistry and immunogold labeling (electron microscopy) for OPN in Hyp bone likewise showed an accumulation of OPN and/or its fragments compared with normal wild-type bone.


Input: Incubation of Hyp mouse bone extracts with PHEX resulted in the complete degradation of these fragments.


Input: In conclusion, these results identify full-length OPN and its fragments as novel, physiologically relevant substrates for PHEX, suggesting that accumulation of mineralization-inhibiting OPN fragments may contribute to the mineralization defect seen in the osteomalacic bone characteristic of XLH/HYP.


Input: Valproic acid but not D-cycloserine facilitates sleep-dependent offline learning of extinction and habituation of conditioned fear in humans.

Valproic acid

D-cycloserine


Input: The effectiveness of D-cycloserine (DCS), an N-methyl-D-aspartate glutamate receptor partial agonist, and valproic acid (VPA), a histone deacetylase inhibitor, in facilitating the extinction of fear-conditioned memory has been explored in humans and animals.

D-cycloserine

DCS

N-methyl-D-aspartate glutamate

valproic acid

VPA


Input: Here, we confirmed whether DCS (100 mg) and VPA (400 mg) act in off-line learning processes during sleep or waking, for further clinical application to anxiety disorders and posttraumatic stress disorder (PTSD).

DCS

VPA


Input: We performed a randomized, blind, placebo-controlled clinical trial in 90 healthy adults.


Input: Visual cues and electric shocks were used as the conditioned stimulus (CS) and unconditioned stimulus (US), respectively.


Input: The extinction effect was observed not in simple recall after the extinction of coupled CS-US, but was observed in the post-re-exposure phase after unexpected re-exposure to reinstatement CS-US coupling.


Input: Newly acquired conditioned fear was also eliminated or habituated by DCS and VPA administration, in line with previous findings.

DCS

VPA


Input: Furthermore, VPA facilitated the off-line learning process of conditioned fear extinction and habituation during sleep, while DCS facilitated this process during waking.

VPA

DCS


Input: These novel findings suggest that DCS and VPA might enhance exposure-based cognitive therapy for anxiety disorders and PTSD by reducing the vulnerability to reinstatement and preventing relapses of fear-conditioned responses, and provide evidence for a peculiarity of the sleep-dependent off-line learning process for conditioned fear extinction.

DCS

VPA


Input: This article is part of a Special Issue entitled' Cognitive Enhancers'.


Input: Acute effects of caffeine on attention: a comparison of non-consumers and withdrawn consumers.

caffeine


Input: Despite the large number of studies on caffeine and attention, interpretation is often difficult because of methodological weaknesses.

caffeine


Input: In the present study, use of a small battery of tests with four key outcome measures, combined with an appropriate sample size, addresses many of these problems.


Input: This methodology was used to examine whether effects of caffeine (a dose of 2 mg/kg) could be explained in terms of reversal of the effects of caffeine withdrawal.

caffeine

caffeine


Input: This was achieved by examining effects in non-consumers (N = 35), who could not be withdrawn, and also in a group of consumers (N = 35) who had undergone withdrawal for a week and no longer reported symptoms of withdrawal.


Input: The results showed no effect of short-term withdrawal on the performance measures, even though subjective reports showed an increase in symptoms after withdrawal.


Input: In contrast, the caffeine challenge carried out on Day 8 showed that ingestion of caffeine was associated with faster simple reaction time, fewer long responses, greater detection of targets in the cognitive vigilance task, and faster encoding of new information.

caffeine

caffeine


Input: These results suggest that it is important to continue to investigate mechanisms underlying these effects of caffeine and to further evaluate the practical implications of such effects.

caffeine


Input: Neurotoxic potential of iron oxide nanoparticles in the rat brain striatum and hippocampus.

iron oxide


Input: It has recently been reported that iron oxide nanoparticles (Fe (3) O (4)-NPs, 30 nm) have the ability to translocate directly from the olfactory nerve to the brain.

iron oxide

Fe (3) O (4)


Input: The striatum and hippocampus are important structures in the brain and are associated with the development of Parkinson' s and Alzheimer' s diseases.


Input: Therefore, it is critical to evaluate Fe (3) O (4)-NPs and their potential to confer striatum and hippocampus neurotoxicity.

Fe (3) O (4)


Input: This study focuses on the effects of Fe (3) O (4)-NPs on the striatum and hippocampus, including oxidative injury and the accumulation and retention of Fe (3) O (4)-NPs.

Fe (3) O (4)

Fe (3) O (4)


Input: This study also explores the molecular mechanism of oxidative damage in dopaminergic neurons; we were able to assess the neurotoxic effects of Fe (3) O (4)-NPs by incubating dopaminergic neurons with radioactive Fe (3) O (4)-NPs.

Fe (3) O (4)

Fe (3) O (4)


Input: A regional distribution of Fe (3) O (4)-NPs was observed in rat brains after the particles were intranasally instilled for seven days.

Fe (3) O (4)


Input: The particles were found to be deposited at particularly high concentrations in the rat striata and hippocampi.


Input: Over half of the Fe (3) O (4)-NPs were retained in the striata for a minimum of 14 days, and may have induced oxidative damage to the region.

Fe (3) O (4)


Input: However, no injuries were observed in the hippocampi.


Input: These in vitro studies demonstrate that Fe (3) O (4)-NPs may decrease neuron viability, trigger oxidative stress, and activate JNK-and p53-mediated pathways to regulate the cell cycle and apoptosis.

Fe (3) O (4)


Input: These results also suggest that environmental exposure to Fe (3) O (4)-NPs may play a role in the development of neurodegenerative diseases.

Fe (3) O (4)


Input: Induction of apoptosis in human ovarian cancer cells by new anticancer compounds, epothilone A and B.

epothilone A and B


Input: Epothilones are a new group of compounds with action mechanisms similar to taxanes.

Epothilones

taxanes


Input: The aim of this study was to compare the effects of epothilone A (Epo A) and epothilone B (Epo B) on ovarian cancer cell line SKOV-3 with those of paclitaxel (PTX), a classic taxane.

epothilone A

Epo A

epothilone B

Epo B

paclitaxel

PTX

taxane


Input: We evaluate glycoprotein P (P-gp) activity in the ovarian cancer cell line.


Input: Apoptotic and necrotic cell levels were measured by double staining with Hoechst 33258 and propidium iodide (PI) as well as Annexin V staining.

Hoechst 33258

propidium iodide


Input: The production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential (Delta Psi m) in cells exposed to Epo A, Epo B and PTX were studied using specific fluorescence probes, DCFH (2)-DA (2', 7'-dichlorodihydrofluorescein diacetate) and JC-1 (5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazolcarbocyanine).

oxygen

Epo A

Epo B

PTX

DCFH (2)-DA

2', 7'-dichlorodihydrofluorescein diacetate

5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazolcarbocyanine


Input: The cytotoxic activity of the drugs was determined by the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide) test.

MTT

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


Input: All probes were analyzed in both the presence and absence of the antioxidant N-acetylcysteine (NAC).

N-acetylcysteine

NAC


Input: The results obtained demonstrated that the antiproliferative capacity of Epo A and Epo B in SKOV-3 cell line (measured as IC (50) after 72 h continuous treatment) was six and five times greater than that of PTX' s respectively.

Epo A

Epo B

PTX


Input: Epothilones induced timecourse-dependent apoptosis and necrosis.

Epothilones


Input: Apoptotic and necrotic events were partially blocked by NAC, indicating ROS played a substantial role in epothilone-induced apoptosis.

NAC

epothilone


Input: Cell death was also associated with a decrease in mitochondrial membrane potential, which was more pronounced after treatment with epothilones as compared to paclitaxel.

epothilones

paclitaxel


Input: Pitch-tunable size reduction patterning with a temperature-memory polymer.


Input: A scalable and pitch-tunable size reduction patterning method is introduced by exploiting the temperature memory effect of shape memory polymer and replica molding of UV-curable materials.


Input: Enhanced oral bioavailability of isradipine via proniosomal systems.

isradipine


Input: The objective of the present research was to develop a proniosomal formulation of isradipine and to evaluate the influence of proniosomal systems on the oral bioavailability of the drug in albino Wistar rats.

isradipine


Input: Proniosomes were prepared by film deposition on carrier' s method using various molar ratios of nonionic surfactants such as span20, span40, span60, and span80 with cholesterol as membrane stabilizing agent and dicetylphosphate as a charge inducer.

cholesterol

dicetylphosphate


Input: The formation of niosomes and surface morphology of proniosome formulations were studied by optical and scanning electron microscopy (SEM), respectively.


Input: The prepared proniosomes have shown higher dissolution of isradipine compared with pure drug powder.

isradipine


Input: Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry studies were performed to understand the solid state properties of the drug.


Input: Ex vivo permeation enhancement assessed from flux, permeability coefficient, and enhancement ratio were significantly higher for proniosomes compared with control.


Input: The pharmacokinetic parameters were evaluated in male albino Wistar rats and a significant enhancement in the bioavailability (2. 3-fold) was observed from optimized proniosome formulation compared with control (oral suspension).


Input: The stability study reveals that the proniosome formulations are stable when stored at 4 degrees C.


Input: A current opinion on electrophoretic deposition in pulsed and alternating fields.


Input: Electrophoretic deposition (EPD) is a colloidal production process developed in the early 20th century.


Input: Industrial scale EPD for the production of electronic components and phosphorescent screens and in the form of cataphoretic painting has known some success.


Input: Despite its limited practical applications, the inherent versatility of EPD has never ceased to fuel research into this technique.


Input: One of the major drives of this research was to render the method more environmentally friendly by enabling deposition from aqueous suspensions.


Input: One particular route, suggested to circumvent the problems caused by the use of water in EPD, is the use of alternating or pulsed fields.


Input: Recently, the use of alternating fields in EPD has been investigated for the deposition of biological matter in the form of cells and molecules.


Input: With this new avenue of research opening up and coinciding with a rise in biotechnological processes, one can expect a renewed interest in traditional EPD and fundamental research on the use of pulsed and alternating fields in this technique.


Input: Hence, this review attempts to summarize a century' s worth of both fundamental and applied research for scientists venturing into the field of EPD.


Input: Combination of beta-cyclodextrin inclusion complex and self-microemulsifying drug delivery system for photostability and enhanced oral bioavailability of methotrexate: novel technique.

beta-cyclodextrin

methotrexate


Input: In the present study, we prepared an inclusion complex of methotrexate (MTX) with beta-cyclodextrin (beta-CD) in order to decrease its photosensitivity and enhance its aqueous solubility.

methotrexate

MTX

beta-cyclodextrin

beta-CD


Input: Then we incorporated this inclusion complex in a self-microemulsifying drug delivery system (SMEDDS) overall to increase its oral bioavailability.


Input: The inclusion complex has been prepared by freeze drying method and characterized by differential scanning calorimetry (DSC), ultraviolet (UV), and infrared (IR) spectroscopy assays.


Input: The proper molecular ratio of MTX/beta-CD was found to be of 1: 7, and the water-solubility of MTX was increased in an average of 10-fold.

MTX

beta-CD

MTX


Input: The photostability studies showed that the MTX became stable on exposure to light.

MTX


Input: Construction of pseudoternary diagrams were investigated to prepare a MTX/beta-CD inclusion complex loaded SMEDDS which was characterized by measuring the particle size and the zeta-potential.

MTX

beta-CD


Input: The optimum formulation of SMEDDS was a system consisting of ethyl oleate, tween 80, and propylene glycol with a mean droplet size of 39. 42 nm.

ethyl oleate

tween 80

propylene glycol


Input: In vitro drug release in different pH media showed that the release profile of MTX from the MTX/beta-CD loaded SMEDDS was influenced by the pH of the release medium and presented the characteristics of a sustained release profile.

MTX

MTX

beta-CD


Input: Finally, in-vivo studies showed an enhancement of the bioavailability of MTX from the MTX/beta-CD loaded SMEDDS form of 1. 57-fold.

MTX

MTX

beta-CD


Input: We concluded that the beta-CD inclusion complex loaded SMEDDS improved the chemical and physiological properties of MTX and could be a promising means for the delivery of MTX and other unstable and lipophilic drugs by oral route.

beta-CD

MTX

MTX


Input: Prospects of personalized medicine in cardiovascular diseases.


Input: Cardiovascular diseases remain the dominant cause of death worldwide.


Input: In the last decades, the remarkable advances in human genetic and genomic research, plus the now common use of genome-wide association studies, have led to the identification of numerous genetic variants associated with specific cardiovascular traits and diseases.


Input: Although the clinical applications are limited because the genetic risk of common cardiovascular disease is still unexplained, and the mechanisms of action of the genetic factor (s) are not known, these research advances have, in turn, widely opened the concept of personalized medicine.


Input: In this paper, the status and prospects of personalized medicine for cardiovascular disease will be presented.


Input: This will be followed by a discussion of issues regarding the implementation of personalized medicine.


Input: Mechanistic systems modeling to guide drug discovery and development.


Input: A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population.


Input: Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials.


Input: Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli.


Input: Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research.


Input: Snake venom metalloproteinases.


Input: Recent proteomic analyses of snake venoms show that metalloproteinases represent major components in most of the Crotalid and Viperid venoms.


Input: In this chapter we discuss the multiple activities of the SVMPs.


Input: In addition to hemorrhagic activity, members of the SVMP family also have fibrin (ogen) olytic activity, act as prothrombin activators, activate blood coagulation factor X, possess apoptotic activity, inhibit platelet aggregation, are pro-inflammatory and inactivate blood serine proteinase inhibitors.


Input: Clearly the SVMPs have multiple functions in addition to their well-known hemorrhagic activity.


Input: The realization that there are structural variations in the SVMPs and the early studies that led to their classification represents an important event in our understanding of the structural forms of the SVMPs.


Input: The SVMPs were subdivided into the P-I, P-II and P-III protein classes.


Input: The noticeable characteristic that distinguished the different classes was their size (molecular weight) differences and domain structure: Class I (P-I), the small SVMPs, have molecular masses of 20-30 kDa, contain only a pro domain and the proteinase domain; Class II (P-II), the medium size SVMPs, molecular masses of 30-60 kDa, contain the pro domain, proteinase domain and disintegrin domain; Class III (P-III), the large SVMPs, have molecular masses of 60-100 kDa, contain pro, proteinase, disintegrin-like and cysteine-rich domain structure.

cysteine


Input: Another significant advance in the SVMP field was the characterization of the crystal structure of the first P-I class SVMP.


Input: The structures of other P-I SVMPs soon followed and the structures of P-III SVMPs have also been determined.


Input: The active site of the metalloproteinase domain has a consensus HEXXHXXGXXHD sequence and a Met-turn.

Met


Input: The " Met-turn " structure contains a conserved Met residue that forms a hydrophobic basement for the three zinc-binding histidines in the consensus sequence.

Met

Met

zinc

histidines


Input: Wogonoside induces autophagy in MDA-MB-231 cells by regulating MAPK-mTOR pathway.

Wogonoside


Input: Previous studies have demonstrated that wogonoside, a bioactive flavonoid extracted from the root of Scutellaria baicalensis Gerogi, has anti-inflammatory and anti-angiogenic activities.

wogonoside

flavonoid


Input: In this study, we evaluated wogonoside-induced autophagy on human breast MDA-MB-231 cells.

wogonoside


Input: We report that wogonoside triggered the formation of microtubule-associated protein-light chain 3 (MAP-LC3) positive autophagosomes and the accumulation of acidic vesicular and autolysosomes in MDA-MB-231 cells.

wogonoside


Input: In addition, cells treated by wogonoside developed autophagosome-like characteristics, including single and double membrane vacuoles containing intact and degraded cellular debris.

wogonoside


Input: The results showed that wogonoside promotes the expression of LC3-II and Beclin-1.

wogonoside


Input: Furthermore, wogonoside inhibited cell growth of MDA-MB-231 cells in a concentration-and time-dependent manner, which was associated with wogonoside-induced autophagy.

wogonoside

wogonoside


Input: Wogonoside also suppressed the activation of mammalian target of rapamycin (mTOR) and p70-S6 kinase (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway.

Wogonoside

rapamycin


Input: Taken together, these results suggest that wogonoside partially inhibits MDA-MB-231 cell growth by inducing autophagy through the MAPK-mTOR pathway and may be a promising anti-tumor agent.

wogonoside


Input: Water extracts of tree Hypericum sps. protect DNA from oxidative and alkylating damage and enhance DNA repair in colon cells.


Input: Diet may induce colon carcinogenesis through oxidative or alkylating DNA damage.


Input: However, diet may also contain anticarcinogenic compounds that contribute to cancer prevention.


Input: DNA damage prevention and/or induction of repair are two important mechanisms involved in cancer chemoprevention by dietary compounds.


Input: Hypericum sps. are widely used in traditional medicine to prepare infusions due to their beneficial digestive and neurologic effects.


Input: In this study, we investigated the potential of water extracts from three Hypericum sps. and some of their main phenolic compounds to prevent and repair oxidative and alkylating DNA damage in colon cells.

phenolic


Input: The results showed that water extracts of Hypericum perforatum, Hypericum androsaemum, Hypericum undulatum, quercetin and rutin have protective effect against oxidative DNA damage in HT29 cells.

quercetin

rutin


Input: Protective effect was also observed against alkylating DNA damage induced by methyl-methanesulfonate, except for H. androsaemum.

methyl-methanesulfonate


Input: With regard to alkylating damage repair H. perforatum, H. androsaemum and chlorogenic acid increased repair of alkylating DNA damage by base excision repair pathway.

chlorogenic acid


Input: No effect was observed on nucleotide excision repair pathway.

nucleotide


Input: Antigenotoxic effects of Hypericum sps. may contribute to colon cancer prevention and the high amount of phenolic compounds present in Hypericum sps. play an important role in DNA protective effects.

phenolic


Input: Ion disturbance and clustering in the NaCl water solutions.

NaCl


Input: Ion clustering and the solvation properties in the NaCl solutions are explored by molecular dynamics simulations with several popular force fields.

NaCl


Input: The existence of ions has a negligible disturbance to the hydrogen bond structures and rotational mobility of water beyond the first ion solvation shells, which is suggested by the local hydrogen bond structures and the rotation times of water.

hydrogen

hydrogen


Input: The potential of mean force (PMF) of ion pair in the dilute solution presents a consistent view with the populations of ion clusters in the electrolyte solutions.


Input: The aggregation level of ions is sensitive to the force field used in the simulations.


Input: The ion-ion interaction potential plays an important role in the forming of the contact ion pair.


Input: The entropy of water increases as the ion pair approaches each other and the association of ion pair is driven by the increment of water entropy according to the results from the selected force fields.


Input: The kinetic transition from the single solvent separated state to the contact ion pair is controlled by the enthalpy loss of solution.


Input: Effect of surfactant and solvent on spin-lattice relaxation dynamics of magnetic nanocrystals.


Input: The effect of varying the surfactant and solvent medium on the dynamics of spin-lattice relaxation in photoexcited Fe3O4 nanocrystals has been investigated by measuring the time-dependent magnetization employing pump-probe transient Faraday rotation technique.


Input: The variation of the surfactants having surface-binding functional groups modified not only the static magnetization but also the dynamics of the recovery of the magnetization occurring via spin-lattice relaxation in the photoexcited Fe3O4 nanocrystals.


Input: The variation of the polarity and size of the solvent molecules can also influence the spin-lattice relaxation dynamics.


Input: However, the effect is limited to the nanocrystals having sufficiently permeable surfactant layer, where the small solvent molecules (e. g., water) can access the surface and dynamically modify the ligand field on the surface.


Input: Lattice Microbes: high-performance stochastic simulation method for the reaction-diffusion master equation.


Input: Spatial stochastic simulation is a valuable technique for studying reactions in biological systems.


Input: With the availability of high-performance computing (HPC), the method is poised to allow integration of data from structural, single-molecule and biochemical studies into coherent computational models of cells.


Input: Here, we introduce the Lattice Microbes software package for simulating such cell models on HPC systems.


Input: The software performs either well-stirred or spatially resolved stochastic simulations with approximated cytoplasmic crowding in a fast and efficient manner.


Input: Our new algorithm efficiently samples the reaction-diffusion master equation using NVIDIA graphics processing units and is shown to be two orders of magnitude faster than exact sampling for large systems while maintaining an accuracy of! 0. 1%.


Input: Display of cell models and animation of reaction trajectories involving millions of molecules is facilitated using a plug-in to the popular VMD visualization platform.


Input: The Lattice Microbes software is open source and available for download at http://www. scs. illinois. edu/schulten/lm


Input: Pituitary metastasis of thyroid cancer.


Input: Pituitary metastases (PM) from thyroid cancer are rare, but their management can represent a difficult challenge for the endocrinologist.


Input: Our aim was to review all reported cases of PM from thyroid cancer.


Input: PubMed was consulted and 19 papers reporting 20 cases were found.


Input: We moreover discuss two of our own cases, which had come to our attention within a few months of one another.


Input: Eleven cases were follicular cancer, eight cases were papillary cancer, two cases were medullary cancer, and one case was an insular cancer.


Input: In nine cases, PM was the first sign of the disease.


Input: Cranial nerve involvement was the most common sign of its presence, and no neuroradiological imaging could lead to a sure diagnosis of PM.


Input: Neurosurgical intervention was performed in almost all cases, and post-surgical treatment comprised radioiodine, external beam radiotherapy, and radiosurgery.

radioiodine


Input: Prognosis was poor for larger metastases, cranial nerve palsy disappeared in only one case, and in only one case of intrasellar metastasis was the disease cured.


Input: PM from thyroid cancer are rare, but are burdened by a poor prognosis.


Input: An early diagnosis appears important, and a comprehensive strategy for treatment (neurosurgery, radioiodine, external radiotherapy, and radiosurgery) appears advisable.

radioiodine


Input: A novel, potent, and selective inhibitor of cardiac late sodium current suppresses experimental arrhythmias.

sodium


Input: Inhibition of cardiac late sodium current (late I (Na)) is a strategy to suppress arrhythmias and sodium-dependent calcium overload associated with myocardial ischemia and heart failure.

sodium

sodium

calcium


Input: Current inhibitors of late I (Na) are unselective and can be proarrhythmic.


Input: This study introduces GS967 (6-[4-(trifluoromethoxy) phenyl]-3-(trifluoromethyl)-[1, 2, 4] triazolo [4, 3-a] pyridine), a potent and selective inhibitor of late I (Na), and demonstrates its effectiveness to suppress ventricular arrhythmias.

6-[4-(trifluoromethoxy) phenyl]-3-(trifluoromethyl)-[1, 2, 4] triazolo [4, 3-a] pyridine


Input: The effects of GS967 on rabbit ventricular myocyte ion channel currents and action potentials were determined.


Input: Anti-arrhythmic actions of GS967 were characterized in ex vivo and in vivo rabbit models of reduced repolarization reserve and ischemia.


Input: GS967 inhibited Anemonia sulcata toxin II (ATX-II)-induced late I (Na) in ventricular myocytes and isolated hearts with IC (50) values of 0. 13 and 0. 21 micro M, respectively.


Input: Reduction of peak I (Na) by GS967 was minimal at a holding potential of-120 mV but increased at-80 mV.


Input: GS967 did not prolong action potential duration or the QRS interval.


Input: GS967 prevented and reversed proarrhythmic effects (afterdepolarizations and torsades de pointes) of the late I (Na) enhancer ATX-II and the I (Kr) inhibitor E-4031 in isolated ventricular myocytes and hearts.

Kr


Input: GS967 significantly attenuated the proarrhythmic effects of methoxamine + clofilium and suppressed ischemia-induced arrhythmias.

methoxamine

clofilium


Input: GS967 was more potent and effective to reduce late I (Na) and arrhythmias than either flecainide or ranolazine.

flecainide

ranolazine


Input: Results of all studies and assays of binding and activity of GS967 at numerous receptors, transporters, and enzymes indicated that GS967 selectively inhibited late I (Na).


Input: In summary, GS967 selectively suppressed late I (Na) and prevented and/or reduced the incidence of experimentally induced arrhythmias in rabbit myocytes and hearts.


Input: Liquid crystalline phase nanodispersions enable skin delivery of siRNA.


Input: The ability of small interfering RNAs (siRNAs) to potently but reversibly silence genes in vivo has made them particularly well suited as a new class of drugs that interfere with disease-causing or disease-promoting genes.


Input: However, the largest remaining hurdle for the widespread use of this technology in skin is the lack of an effective delivery system.


Input: The aim of the present study was to evaluate nanodispersed systems in liquid crystalline phases that deliver siRNA into the skin.


Input: The proposed systems present important properties for the delivery of macromolecules in a biological medium, as they are formed by substances that have absorption-enhancing and fusogenic effects; additionally, they facilitate entrapment by cellular membranes due to their nano-scale structure.


Input: The cationic polymer polyethylenimine (PEI) or the cationic lipid oleylamine (OAM) were added to monoolein (MO)-based systems in different concentrations, and after dispersion in aqueous medium, liquid crystalline phase nanodispersions were obtained and characterized by their physicochemical properties.

polyethylenimine

PEI

oleylamine

OAM

monoolein


Input: Then, in vitro penetration studies using diffusion cell and pig ear skin were carried out to evaluate the effect of the nanodispersions on the skin penetration of siRNA; based on these results, the nanodispersions containing MO/OA/PEI/aqueous phase (8: 2: 5: 85, w/w/w/w) and MO/OA/OAM/aqueous phase (8: 2: 2: 88, w/w/w/w) were selected.

PEI

OAM


Input: These systems were investigated in vivo for skin penetration, skin irritation, and the ability to knockdown glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein levels in animal models.

glyceraldehyde 3-phosphate


Input: The results showed that the studied nanodispersions may represent a promising new non-viral vehicle and can be considered highly advantageous in the treatment of skin disorders; they were effective in optimizing the skin penetration of siRNA and reducing the levels of the model protein GAPDH without causing skin irritation.


Input: Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract.


Input: Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis.


Input: Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate.

sodium dichromate


Input: Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide.

ethidium bromide


Input: The resulting DNA migration trails were obtained using fluorescent microscopy at 400 x magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition.


Input: The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators.

alanine

aspartate


Input: Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue.

hematoxylin

eosin


Input: The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology.


Input: These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds.

methylchavicol


Input: These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications.


Input: Function of the blood-brain barrier and restriction of drug delivery to invasive glioma cells: findings in an orthotopic rat xenograft model of glioma.


Input: Despite aggressive treatment with radiation and chemotherapy, recurrence of glioblastoma multiforme (GBM) is inevitable.


Input: The objective of this study was to show that the blood-brain barrier (BBB), through a combination of tight junctions and active efflux transporters in the brain microvasculature, can significantly restrict delivery of molecularly targeted agents to invasive glioma cells.


Input: Transgenic mice lacking P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) were used to study efflux of erlotinib at the BBB.

erlotinib


Input: A U87 rat xenograft model of GBM was used to investigate the regional distribution of erlotinib to the tumor, and brain regions surrounding the tumor.

erlotinib


Input: The effect of concurrent administration of elacridar on regional tumor distribution of erlotinib was evaluated.

elacridar

erlotinib


Input: We show that erlotinib transport across an intact BBB is significantly restricted due to P-gp-and Bcrp-mediated efflux transport.

erlotinib


Input: We then show that the BBB is sufficiently intact in areas of brain adjacent to the tumor core to significantly restrict erlotinib delivery.

erlotinib


Input: Inhibition of P-gp and Bcrp by the dual inhibitor elacridar dramatically increased erlotinib delivery to the tumor core, rim, and normal brain.

elacridar

erlotinib


Input: These results provide conclusive evidence of the impact that active efflux at the BBB has on the delivery of molecularly targeted therapy to different tumor regions in glioma.


Input: These data also support the possibility that the repeated failure of clinical trials of new drugs for gliomas may be in part due to a failure to achieve effective concentrations in invasive tumor cells that reside behind an intact BBB.


Input: Phenolics profiles of olive fruits (Olea europaea L.) and oils from Ayval i k, Domat and Gemlik varieties at different ripening stages.

Phenolics


Input: Phenolic compounds in olive fruit and oils obtained from Ayval i k, Domat and Gemlik olive varieties collected at different ripening periods were evaluated by High Performance Liquid Chromatography (HPLC).

Phenolic


Input: Gallic acid and p-cumaric acid were identified for Ayval i k and Domat at each period of ripening, respectively.

Gallic acid

p-cumaric acid


Input: In addition, gallic acid, p-cumaric acid, sinapinic and apigenin acids were detected in Gemlik olive fruit.

gallic acid

p-cumaric acid

sinapinic and apigenin acids


Input: Hydroxytyrosol, rutin, oleoropein, luteolin, tyrosol, vanilic acid and gallic acid in Ayval i k olive fruit in all ripening periods were determined.

Hydroxytyrosol

rutin

oleoropein

luteolin

tyrosol

vanilic acid

gallic acid


Input: The tyrasol contents varied between 0. 18 to 1. 57mg/kg.

tyrasol


Input: Luteolin contents of olive oils ranged at the levels between 0. 12 to 2. 28mg/kg.

Luteolin


Input: In contrast, oils had the lowest syringic, p-cumaric, chlorogenic and ferulic acids.

syringic, p-cumaric, chlorogenic and ferulic acids


Input: Vanillic acid contents of oils ranged between 0. 08 to 2. 38mg/kg.

Vanillic acid


Input: Optimization of frozen sour cherries vacuum drying process.


Input: The objective of this research was to optimize the vacuum-drying of frozen sour cherries in order to preserve health-beneficial phytochemicals, as well as textural characteristics.


Input: Investigated range of temperature was 46-74 degrees C and, of pressure, 17-583mbar, in a new design of vacuum-dryer equipment.


Input: The total solids, a (w) value, total phenolics, vitamin C, antioxidant activity, anthocyanin content, total colour change and firmness were used as quality indicators of dried sour cherry.

phenolics

vitamin C

anthocyanin


Input: Within the experimental range of studied variables, the optimum conditions of 54. 03 degrees C and 148. 16mbar were established for vacuum drying of sour cherry.


Input: Separate validation experiments were conducted, under optimum conditions, to verify predictions and adequacy of the second-order polynomial models.


Input: Under these optimal conditions, the predicted amount of total phenolics was 744mg CAE/100 dw, vitamin C 1. 44mg/100g per dry weight (g dw), anthocyanin content 125mg/100g dw, IC (50) 3. 23mg/ml, total solids 70. 72%, a (w) value 0. 646, total colour change 52. 61 and firmness 3395. 4g.

phenolics

vitamin C

anthocyanin


Input: The investigated parameters had a significant effect on the quality of the dried sour cherries.


Input: Occurrence of ochratoxin A in cocoa by-products and determination of its reduction during chocolate manufacture.

ochratoxin A


Input: This work reports an investigation carried out to assess the natural occurrence of ochratoxin A in 168 samples from different fractions obtained during the technological processing of cocoa (shell, nibs, liquor, butter, cake and cocoa powder) and the reduction of ochratoxin A during chocolate manufacture.

ochratoxin A

ochratoxin A


Input: Ochratoxin A analyses were performed with immunoaffinity columns and detection by high performance liquid chromatography.

Ochratoxin A


Input: Concerning the natural ochratoxin A contamination in cocoa by-products, the highest levels of ochratoxin A were found in the shell, cocoa powder and cocoa cake.

ochratoxin A

ochratoxin A


Input: The cocoa butter was the least contaminated, showing that ochratoxin A seems to remain in the defatted cocoa solids.

ochratoxin A


Input: Under the technological conditions applied during the manufacture of chocolate in this study and the level of contamination present in the cocoa beans, this experiment demonstrated that 93. 6% of ochratoxin A present in the beans was reduced during the chocolate producing.

ochratoxin A


Input: Transglutaminase cross-linking effect on sensory characteristics and antioxidant activities of Maillard reaction products from soybean protein hydrolysates.


Input: To improve the yield of Maillard peptides, a microbial transglutaminase (MTGase) was used to increase the content of 1000-5000Da peptides in soybean protein hydrolysates by using a cross-linking reaction.


Input: The sensory characteristics and antioxidant activities of corresponding Maillard Reaction Products (MSPC) was then evaluated.


Input: After cross-linking treatment the content of 1000-5000Da peptides in protein hydrolysates and the yield of Maillard peptides increased by 21. 19% and 8. 71%, respectively, which contributed to the improved mouthfulness of MSPC.


Input: The bitter amino acids were significantly decreased and the umami acids were markedly increased in MSPC.

amino acids


Input: Volatile compounds identified by GC-MS analysis showed that the content of the important meaty flavour compounds (such as 2-methyl-3-furanthiol, bis (2-methyl-3-furyl) disulfide) of MSPC were dramatically higher than that of MRPs from uncross-linking peptides.

bis (2-methyl-3-furyl) disulfide


Input: Combined with sensory evaluation, it was confirmed that MTGase cross-linking improved the flavour Characteristics and did not affect the antioxidant activity of MSPC.


Input: Green and gold kiwifruit peel ethanol extracts potentiate pentobarbital-induced sleep in mice via a GABAergic mechanism.

ethanol

pentobarbital


Input: Kiwifruit is one of the most popular fruits worldwide, and it has various biological properties, including antioxidant, anti-allergic, and cardiovascular protective effects.


Input: The peel of kiwifruit, which is a by-product of processing, is a good source of flavonoids; however, its bioactivity has not been widely investigated.

flavonoids


Input: In this study, we evaluated the hypnotic effects of green (GRPE, Actinidia deliciosa) and gold (GOPE, Actinidia chinensis) kiwifruit peel ethanol extracts and their solvent fractions, and the possible underlying mechanisms.

ethanol


Input: Oral GRPE and GOPE administration (125-1000mg/kg) produced a dose-dependent decrease in sleep latency and an increase in sleep duration in pentobarbital-treated mice.

pentobarbital


Input: Among three different solvent fractions of GRPE and GOPE, ethyl acetate (EA) fractions had the greatest effect on sleep duration at 250mg/kg.

ethyl acetate


Input: The total flavonoid contents of solvent fractions were proportional to sleep duration.

flavonoid


Input: Like diazepam (a GABA (A)-benzodiazepine (BZD) receptor agonist), the hypnotic effects of GRPE, GOPE, and their EA fractions were fully inhibited by flumazenil (a GABA (A)-BZD receptor antagonist).

GABA

benzodiazepine

BZD

flumazenil

GABA

BZD


Input: These results suggest that potentiation effects of GRPE and GOPE on pentobarbital-induced sleep in mice may be modulated by a GABAergic mechanism.

pentobarbital


Input: An investigation into the supramolecular structure, solubility, stability and antioxidant activity of rutin/cyclodextrin inclusion complex.

rutin


Input: The formation of supramolecular inclusion complexes between rutin and four cyclodextrins, namely beta-cyclodextrin (beta-CD), (2-hydroxypropyl)-alpha-cyclodextrin (HP-alpha-CD), (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CD) and (2-hydroxypropyl)-gamma-cyclodextrin (HP-gamma-CD), and the effects of the complexation on the stability and antioxidant activity of rutin were investigated.

rutin

beta-cyclodextrin

beta-CD

HP-alpha-CD

HP-beta-CD

HP-gamma-CD

rutin


Input: Results from phase-solubility studies showed that rutin formed 1: 1 stoichiometric inclusion complexes with HP-alpha-CD, beta-CD, HP-beta-CD and HP-gamma-CD; the complexes formed with HP-gamma-CD and HP-beta-CD had the greatest stability constants, followed by beta-CD and HP-alpha-CD.

rutin

HP-alpha-CD

beta-CD

HP-beta-CD

HP-gamma-CD

HP-gamma-CD

HP-beta-CD

beta-CD

HP-alpha-CD


Input: Thermodynamic studies demonstrate that the inclusion of rutin into HP-beta-CD was an exothermic process which occurred spontaneously.

rutin

HP-beta-CD


Input: Two-dimensional rotating-frame nuclear Overhauser effect spectroscopy (2D ROESY) (1) H NMR analyses show that the A ring of rutin was the part of the molecule that most likely inserted into the cavity of HP-beta-CD, thus forming a supramolecular inclusion complex.

(1) H

rutin

HP-beta-CD


Input: Formation of such an inclusion complex conferred moderate degrees of protection to rutin from degradation by heat and UV radiation during storage, and significantly enhanced its antioxidant capacity as determined by three different procedures.

rutin


Input: A nanosised oxygen scavenger: preparation and antioxidant application to roasted sunflower seeds and walnuts.

oxygen


Input: A novel oxygen scavenger using iron nanoparticle was produced and evaluated as a potential oxygen scavenger.

oxygen

oxygen


Input: Iron nanoparticle was prepared by liquid phase reduction method in microemulsion systems.


Input: The absorption capacity of different kinds of oxygen scavengers was measured as a function of time, and the absorption rate constant was evaluated at 25 degrees C.

oxygen


Input: The absorption kinetic analysis showed that the absorption process followed a first-order reaction.


Input: The absorption rate constant of nanosised and conventional oxygen scavenger were 0. 45 +/- 0. 044h (-1) and 0. 05 +/- 0. 006h (-1), respectively.

oxygen


Input: Successful application of the nanosised oxygen scavenger on roasted sunflower seed and walnut demonstrated its ability to inhibit lipid oxidation in lipid-containing food.

oxygen


Input: Roasted nut treated with nanosised oxygen scavenger possessed the lowest PV and AnV in all treatments after 120 days of storage.

oxygen


Input: Therefore, it has the potential for broad application as an active packaging in a variety of oxygen-sensitive foods.

oxygen


Input: Citrus phenylpropanoids and defence against pathogens.


Input: Part II: gene expression and metabolite accumulation in the response of fruits to Penicillium digitatum infection.


Input: The effect of infection of Citrus sinensis (var. Navelina) fruits with Penicillium digitatum was studied at gene expression and metabolite levels.


Input: In this study, expression of genes involved in the phenylpropanoid pathway was studied in the flavedo (outer coloured part of the peel) and albedo (inner white part) in response to pathogen infection.


Input: Results of the time-course experiment showed that maximal expression of 10 out of 17 phenylpropanoid genes analysed occurred at 48h post-inoculation, when decay symptoms started to appear, and mRNA levels either kept constant or decreased after 72h post-inoculation.


Input: To further investigate the putative involvement of the phenylpropanoid pathway in the defence of citrus fruit, changes in the metabolic profile of both tissues infected with P. digitatum was studied by means of HPLC-PDA-FD.


Input: Metabolite accumulation levels along the time course suggest that flavanones, flavones, polymethoxylated flavones and scoparone are induced in citrus fruit in response to P. digitatum infection, although with different trends depending on the tissue.

flavanones

flavones

polymethoxylated flavones

scoparone


Input: Diuretic effects of cannabinoids.


Input: In vivo effects of cannabinoid (CB) agonists are often assessed using four well-established measures: locomotor activity, hypothermia, cataleptic-like effects, and analgesia.


Input: The present studies demonstrate that doses of CB agonists that produce these effects also reliably increase diuresis.


Input: Diuretic effects of several CB agonists were measured in female rats over 2 hours immediately after drug injection, and results were compared with hypothermic effects.


Input: Direct-acting CB1 agonists, including Delta (9)-tetrahydrocannabinol, WIN 55, 212 [R-(1)-[2, 3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo [1, 2, 3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate], AM2389 [9 beta-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9 beta-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED (50) values for diuresis than for hypothermia.

Delta (9)-tetrahydrocannabinol

WIN 55, 212

R-(1)-[2, 3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo [1, 2, 3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate

9 beta-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol

9 beta-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol


Input: The highest doses of cannabinoid drugs yielded, on average, 26-32 g/kg urine; comparable effects were obtained with 10 mg/kg furosemide and 3. 0 mg/kg trans-(-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide (U50-488).

furosemide

trans-(-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide


Input: Methanandamide (10. 0 mg/kg) had lesser effect than other CB agonists, and the CB2 agonist AM1241 [1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl) indole], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects.

Methanandamide

1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl) indole

anandamide

rimonabant


Input: In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55, 212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl) ethyl]-1H-indol-3-yl] (4-methoxyphenyl) methanone)].

rimonabant

vanilloid

capsazepine

WIN 55, 212

(6-iodo-2-methyl-1-[2-(4-morpholinyl) ethyl]-1H-indol-3-yl] (4-methoxyphenyl) methanone)


Input: These data indicate that cannabinoids have robust diuretic effects in rats that are mediated via CB1 receptor mechanisms.


Input: Anti-breast cancer agents from Chinese herbal medicines.


Input: Chinese Herbal Medicines (CHM) have been used in disease prevention and treatment for centuries in China.


Input: A number of anti-breast cancer agents isolated from CHM recently, showed very interesting structures, although some of the mechanism of action is not quite clear.


Input: These unique chemical structures could be an important information resource for new anti-breast cancer drugs' design and discovery.


Input: This review summarizes these findings on anti-breast cancer agents from CHM.


Input: Role of carbonyl reducing enzymes in the phase I biotransformation of the non-steroidal anti-inflammatory drug nabumetone in vitro.

carbonyl

nabumetone


Input: Nabumetone is a clinically used non-steroidal anti-inflammatory drug, its biotransformation includes major active metabolite 6-methoxy-2-naphtylacetic acid and another three phase I as well as corresponding phase II metabolites which are regarded as inactive.

Nabumetone

6-methoxy-2-naphtylacetic acid


Input: One important biotransformation pathway is carbonyl reduction, which leads to the phase I metabolite, reduced nabumetone.

carbonyl

nabumetone


Input: The aim of this study is the determination of the role of a particular human liver subcellular fraction in the nabumetone reduction and the identification of participating carbonyl reducing enzymes along with their stereospecificities.

nabumetone

carbonyl


Input: Both subcellular fractions take part in the carbonyl reduction of nabumetone and the reduction is at least in vitro the main biotransformation pathway.

carbonyl

nabumetone


Input: The activities of eight cytosolic carbonyl reducing enzymes--CBR1, CBR3, AKR1B1, AKR1B10, AKR1C1-4--toward nabumetone were tested.

carbonyl

nabumetone


Input: Except for CBR3, all tested reductases transform nabumetone to its reduced metabolite.

nabumetone


Input: AKR1C4 and AKR1C3 have the highest intrinsic clearances.


Input: The stereospecificity of the majority of the tested enzymes is shifted to the production of an (+)-enantiomer of reduced nabumetone; only AKR1C1 and AKR1C4 produce predominantly an (-)-enantiomer.

nabumetone


Input: This project provides for the first time evidence that seven specific carbonyl reducing enzymes participate in nabumetone metabolism.

carbonyl

nabumetone


Input: Transport of gemifloxacin, a 4th generation quinolone antibiotic, in the Caco-2 and engineered MDCKII cells, and potential involvement of efflux transporters in the intestinal absorption of the drug.

gemifloxacin

quinolone


Input: The oral (po) bioavailability of gemifloxacin mesylate in rats and its possible association with efflux transporters was investigated.

gemifloxacin mesylate


Input: The apparent permeabilities (Papp) of gemifloxacin across the Caco-2 cell monolayer were 1. 20 +/- 0. 09 x 10 (-5) cm/s for apical to basal (absorptive) transport, and 2. 13 +/- 0. 6 x 10 (-5) cm/s for basal to apical (secretory) transport for a 5-500 mu M concentration range, suggesting the involvement of a carrier-mediated efflux in the secretory transport.

gemifloxacin


Input: The secretory transport in Caco-2 cells was significantly decreased by MRP2 (MK571) and BCRP (Ko143) inhibitors.


Input: The secretory transport was distinct in MDCKII/P-gp, MDCKII/MRP2 and MDCKII/BCRP cells, and the affinity was highest for MRP2, followed by BCRP and P-gp.


Input: The efflux was significantly decreased by verapamil and Ko143, but not significantly by MK571.

verapamil


Input: The comparative po bioavailability in rats was increased by the preadministration of Ko143 (four-fold), MK571 (two-fold) and verapamil (two-fold).

verapamil


Input: Efflux transporters appeared to significantly limit the bioavailability of gemifloxacin in rats, suggesting their possible contribution to the low bioavailability of the drug in the human (70%).

gemifloxacin


Input: A phase I, open-label, single-dose, mass balance study of 14C-labeled abiraterone acetate in healthy male subjects.

14C-labeled abiraterone acetate


Input: 1. Metabolic disposition of (14) C-abiraterone acetate (AA), a prodrug of abiraterone was assessed in a phase I, open-label, single-dose (1000 mg, approximately 100 mu Ci) study in healthy males (18-55 years, N = 8).

(14) C-abiraterone acetate

abiraterone


Input: Blood, urine, and faecal samples were obtained at specified timepoints for determination of abiraterone concentrations in the plasma, total radioactivity (TR), and the metabolite profile.

abiraterone


Input: 2. Most plasma AA concentrations were below the limit of quantification.


Input: The mean maximum plasma concentration (Cmax) of abiraterone was 10. 4 ng/mL, mean area under the plasma concentration-time curve (AUC) from 0 to the last measurable plasma concentration (AUC0-last) was 74. 8 ng. h/mL.

abiraterone


Input: The exposures for TR in plasma (Cmax = 3429 ng. eq/mL; AUC0-last = 26, 683 ng eq. h/mL) and whole blood (Cmax = 1836 ng. eq/mL; AUC0-last = 12, 162 ng. eq. h/mL) were > 300-fold higher than abiraterone exposure in plasma.

abiraterone


Input: The majority of TR resided in the plasma compartment of blood.


Input: 3. Main circulating metabolites were abiraterone sulfate and N-oxide abiraterone sulfate.

abiraterone sulfate

N-oxide abiraterone sulfate


Input: The main metabolite excreted in urine was N-oxide abiraterone sulfate (4. 22% of TR).

N-oxide abiraterone sulfate


Input: Major components of TR in faeces were unchanged AA (55. 3% of TR) and abiraterone (22. 3% of TR).

abiraterone


Input: Mean recovery of TR in faeces was 87. 9%, indicating faeces as primary route of excretion.


Input: Inhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time task.

GABA


Input: Attention deficits are a core cognitive symptom of schizophrenia; the neuropathology underlying these deficits is not known.


Input: Attention is regulated, at least in part, by the prefrontal cortex (PFC), a brain area in which pathology of gamma-aminobutyric acid (GABA) neurons has been consistently observed in post-mortem analysis of the brains of people with schizophrenia.

gamma-aminobutyric acid

GABA


Input: Specifically, expression of the 67-kD isoform of the GABA synthesis enzyme glutamic acid decarboxylase (GAD67) is reduced in parvalbumin-containing fast-spiking GABA interneurons.

GABA

glutamic acid

GABA


Input: Thus it is hypothesized that reduced cortical GABA synthesis and release may contribute to the attention deficits in schizophrenia.

GABA


Input: Here the effect of reducing cortical GABA synthesis with l-allylglycine (LAG) on attention was tested using three different versions of the 5-choice serial reaction time task (5CSRTT).

GABA

l-allylglycine

LAG


Input: Because 5CSRTT performance can be affected by locomotor activity, we also measured this behavior in an open field.


Input: Finally, the expression of Fos protein was used as an indirect measure of reduced GABA synthesis.

GABA


Input: Intra-cortical LAG (10 mu g/0. 5 mu l/side) infusions increased Fos expression and resulted in hyperactivity in the open field.

LAG


Input: Intra-cortical LAG infusions did not affect attention in any version of the 5CSRTT.

LAG


Input: These results suggest that a general decrease in GABA synthesis is not sufficient to cause attention deficits.

GABA


Input: It remains to be tested whether a selective decrease in GABA synthesis in parvalbumin-containing GABA neurons could cause attention deficits.

GABA

GABA


Input: Decreased cortical GABA synthesis did increase locomotor activity; this may reflect the positive symptoms of schizophrenia.

GABA


Input: The PNarec method for detection of ancient recombinations through phylogenetic network analysis.


Input: Recombinations are known to disrupt bifurcating tree structure of gene genealogies.


Input: Although recently occurred recombinations are easily detectable by using conventional methods, recombinations may have occurred at any time.


Input: We devised a new method for detecting ancient recombinations through phylogenetic network analysis, and detected five ancient recombinations in gibbon ABO blood group genes [Kitano et al., 2009. Mol. Phylogenet. Evol., 51, 465-471].


Input: We present applications of this method, now named as " PNarec ", to various virus sequences as well as HLA genes.


Input: Cytisine confers neuronal protection against excitotoxic injury by down-regulating GluN2B-containing NMDA receptors.

Cytisine

NMDA


Input: Cytisine (CYT), one of the principal bioactive components derived from the seeds of Cytisus laborinum L, has been widely used for central nervous system (CNS) diseases treatment.

Cytisine

CYT


Input: The present study investigated the protective effect of CYT on cultured cortical neural injury induced by N-methyl-d-aspartate (NMDA).

CYT

N-methyl-d-aspartate

NMDA


Input: Our data showed that CYT conferred protective effect against loss of cellular viability induced by brief exposure to 200 mu M NMDA in a concentration-dependent manner.

CYT

NMDA


Input: CYT significantly inhibited the neuronal apoptosis induced by NMDA exposure by reversing intracellular Ca (2 +) overload and balancing Bcl-2 and Bax expression levels.

CYT

NMDA

Ca (2 +)


Input: Furthermore, CYT significantly reversed the up-regulation of GluN2B-containing NMDA receptors by exposure to NMDA, but it did not affect the level of GluN2A-containing NMDA receptors.

CYT

NMDA

NMDA

NMDA


Input: These findings suggest that CYT protects cortical neurons, at least partially, by inhibiting the level of GluN2B-containing NMDA receptors and regulating Bcl-2 family.

CYT

NMDA


Input: Inhibition of neurite outgrowth and alteration of cytoskeletal gene expression by sodium arsenite.

sodium arsenite


Input: Arsenic compounds that are often found in drinking water increase the risk of developmental brain disorders.

Arsenic


Input: In this study, we performed live imaging analyses of Neuro-2a cells expressing SCAT3, a caspase-3 cleavage peptide sequence linking two fluorescent proteins; enhanced cyan fluorescence protein (ECFP) and Venus, to determine whether sodium arsenite (NaAsO (2); 0, 1, 5, or 10 mu M) affects both neurite outgrowth and/or induces apoptosis with the same doses and in the same cell cultures.

sodium arsenite

NaAsO (2)


Input: We observed that the area ratio of neurite to cell body in SCAT3-expressing cells was significantly reduced by 5 and 10 mu M NaAsO (2), but not by 1 mu M, although the emission ratio of ECFP to Venus, an endpoint of caspase-3 activity, was not changed.

NaAsO (2)


Input: However, cytological assay using apoptotic and necrotic markers resulted in that apoptosis, but not necrosis, was significantly induced in Neuro-2a cells when NaAsO (2) exposure continued after the significant effects of NaAsO (2) on neurite outgrowth were found by live imaging.

NaAsO (2)

NaAsO (2)


Input: These results suggested that neurite outgrowth was suppressed by NaAsO (2) prior to NaAsO (2)-induced apoptosis.

NaAsO (2)

NaAsO (2)


Input: Next, we examined the effects of NaAsO (2) on cytoskeletal gene expression in Neuro-2a cells.

NaAsO (2)


Input: NaAsO (2) increased the mRNA levels of the light and medium subunits of neurofilament and decreased the mRNA levels of tau and tubulin in a dose-dependent manner; no significant effect was found in the mRNA levels of the heavy subunit of neurofilament, microtubule-associated protein 2, or actin.

NaAsO (2)


Input: The changes in cytoskeletal gene expression are likely responsible for the inhibitory effects of NaAsO (2) on neurite outgrowth.

NaAsO (2)


Input: Association analysis between K and-116A variants of butyrylcholinesterase and Alzheimer' s disease in a Brazilian population.


Input: In Alzheimer' s disease (AD) a reduction in acetylcholinesterase (AChE) and an increase in butyrylcholinesterase (BChE) activity are observed.


Input: K variant (539T) is the most common variant of the BCHE gene and, although controversial, several studies reported association between K variant and AD.


Input: Previous results showed that the K variant alone is not capable of diminishing BChE activity, depending on the presence of the-116A variant.


Input: Considering that, we conducted a case-control association study using a clinically well defined group of AD patients (n = 82) and age and sex matched control subjects (EC; n = 78) in order to test the association with these variations of BCHE gene in a Brazilian population.


Input: The allele, genotype and haplotype frequencies of the K and the-116A variants of BCHE gene were not significantly different between cases and controls.


Input: Although not reaching statistical significance, the results suggested that the presence of-116A variant may have a protective effect against AD.


Input: The association of the K variant with AD in a controversial manner in different surveys is probably caused by its linkage disequilibrium with-116A that, by reducing BChE activity, potentially increases cholinergic transmission in comparison with usual genotypes.


Input: Metabolism of triethylenetetramine and 1, 12-diamino-3, 6, 9-triazadodecane by the spermidine/spermine-N (1)-acetyltransferase and thialysine acetyltransferase.

triethylenetetramine

1, 12-diamino-3, 6, 9-triazadodecane

spermidine

spermine

thialysine


Input: Triethylenetetramine (TETA; Syprine; Merck Rahway, NJ), a drug for Wilson' s disease, is a copper chelator and a charge-deficient analog of polyamine spermidine.

Triethylenetetramine

TETA

Syprine

copper

polyamine spermidine


Input: We recently showed that TETA is metabolized in vitro by polyamine catabolic enzyme spermidine/spermine-N (1)-acetyltransferase (SSAT1) and by thialysine acetyltransferase (SSAT2) to its monoacetylated derivative (MAT).

TETA

polyamine

spermidine

spermine

thialysine


Input: The acetylation of TETA is increased in SSAT1-overexpressing mice compared with wild-type mice.

TETA


Input: However, SSAT1-deficient mice metabolize TETA at the same rate as the wild-type mice, indicating the existence of another N-acetylase respons 2ible for its metabolism in mice.

TETA


Input: Here, we show that siRNA-mediated knockdown of SSAT2 in HEPG2 cells and in primary hepatocytes from the SSAT1-deficient or wild-type mice reduced the metabolism of TETA to MAT.

TETA


Input: By contrast, 1, 12-diamino-3, 6, 9-triazadodecane (SpmTrien), a charge-deficient spermine analog, was an extremely poor substrate of human recombinant SSAT2 and was metabolized by SSAT1 in HEPG2 cells and in wild-type primary hepatocytes.

1, 12-diamino-3, 6, 9-triazadodecane

SpmTrien

spermine


Input: Thus, despite the similar structures of TETA and SpmTrien, SSAT2 is the main acetylator of TETA, whereas SpmTrien is primarily acetylated by SSAT1.

TETA

SpmTrien

TETA

SpmTrien


Input: Picosecond kinetics of strongly coupled excitons and surface plasmon polaritons.


Input: Coupling between excitons of CdSe nanocrystal quantum dots (NQDs) and surface plasmon polaritons (SPPs) of an Ag film attached to a prism have been studied by steady-state and transient reflectivity measurements in the Kretschmann geometry.

CdSe

Ag


Input: In these experiments, the angle of incidence of the probe beam selects hybrid exciton/SPP states with different wavevectors and exciton/SPP compositions.


Input: The dynamics measured in the transient reflectivity experiments are sensitive to the composition of the hybrid states.


Input: Specifically, fast dynamics are observed at probe wavevectors where the lower hybrid state has predominant SPP character.


Input: In contrast, at probe wavevectors where the lower hybrid state is predominantly excitonic, the dynamics are similar to that measured for CdSe NQDs on glass.

CdSe


Input: Phospholipases A2: unveiling the secrets of a functionally versatile group of snake venom toxins.


Input: Phospholipases A (2) (PLA (2) s) are abundant components of snake venoms, where they play toxic and digestive roles.


Input: Despite having a similar three-dimensional structure, venom PLA (2) s exert an amazing variety of toxic and pharmacological effects, which include neurotoxic, myotoxic, hemolytic, edematogenic, hyperalgesic, pro-inflammatory, hypotensive, platelet-aggregation inhibitory, anticoagulant, cytotoxic, and bactericidal activities.


Input: Toxinologists have made significant contributions to deciphering the structure, molecular evolution, mechanisms of action, receptors, role of enzymatic activity for toxicity, structural determinants of toxicity and selectivity, and the impact of these enzymes in the overall pathophysiology of snakebite envenoming.


Input: The present work highlights some of the most relevant contributions in the study of venom PLA (2) s, including the personal accounts of the authors of these studies.


Input: Methamphetamine regulation of sulfotransferase 1A1 and 2A1 expression in rat brain sections.

Methamphetamine


Input: Sulfotransferase catalyzed sulfation regulates the biological activities of various neurotransmitters/hormones and detoxifies xenobiotics.


Input: Rat sulfotransferase rSULT1A1 catalyzes the sulfation of neurotransmitters and xenobiotic phenolic compounds.

phenolic


Input: rSULT2A1 catalyzes the sulfation of hydroxysteroids and xenobiotic alcoholic compounds.

hydroxysteroids

alcoholic


Input: In this work, Western blot and real-time RT-PCR were used to investigate the effect of methamphetamine on rSULT1A1 and rSULT2A1 protein and mRNA expression in rat cerebellum, frontal cortex, hippocampus, and striatum.

methamphetamine


Input: After 1-day treatment, significant induction of rSULT1A1 was observed only in the cerebellum; rSULT2A1 was induced significantly in the cerebellum, frontal cortex, and hippocampus.


Input: After 7 days of exposure, rSULT1A1 was induced in the cerebellum, frontal cortex, and hippocampus, while rSULT2A1 was induced significantly in all four regions.


Input: Western blot results agreed with the real-time RT-PCR results, suggesting that the induction occurred at the gene transcriptional level.


Input: Results indicate that rSULT1A1 and rSULT2A1 are expressed in rat frontal cortex, cerebellum, striatum, and hippocampus.


Input: rSULT1A1 and rSULT2A1are inducible by methamphetamine in rat brain sections in a time dependable manner.

methamphetamine


Input: rSULT2A1 is more inducible than rSULT1A1 by methamphetamine in rat brain sections.

methamphetamine


Input: Induction activity of methamphetamine is in the order of cerebellum > frontal cortex, hippocampus > striatum.

methamphetamine


Input: These results suggest that the physiological functions of rSULT1A1 and rSULT2A1 in different brain regions can be affected by methamphetamine.

methamphetamine


Input: Nanostructured superhydrophobic substrates trigger the development of 3D neuronal networks.


Input: The generation of 3D networks of primary neurons is a big challenge in neuroscience.


Input: Here, a novel method is presented for a 3D neuronal culture on superhydrophobic (SH) substrates.


Input: How nano-patterned SH devices stimulate neurons to build 3D networks is investigated.


Input: Scanning electron microscopy and confocal imaging show that soon after plating neurites adhere to the nanopatterned pillar sidewalls and they are subsequently pulled between pillars in a suspended position.


Input: These neurons display an enhanced survival rate compared to standard cultures and develop mature networks with physiological excitability.


Input: These findings underline the importance of using nanostructured SH surfaces for directing 3D neuronal growth, as well as for the design of biomaterials for neuronal regeneration.


Input: Precision cut lung slices as an efficient tool for in vitro lung physio-pharmacotoxicology studies.


Input: 1. We review the specific approaches for lung tissue slices preparation and incubation systems and the research application fields in which lung slices proved to be a very efficient alternative to animal experimentation for biomechanical, physiological, pharmacological and toxicological approaches.


Input: 2. Focus is made on air-liquid interface dynamic organ culture systems that allow direct tissue exposure to complex aerosol and that best mimic in vivo lung tissue physiology.


Input: 3. A compilation of research applications in the fields of vascular and airway reactivity, mucociliary transport, polyamine transport, xenobiotic biotransformation, chemicals toxicology and complex aerosols supports the concept that precision cut lung slices are a very efficient tool maintaining highly differentiated functions similar to in vivo lung organ when kept under dynamic organ culture.

polyamine


Input: They also have been successfully used for lung gene transfer efficiency assessment, for lung viral infection efficiency assessment, for studies of tissue preservation media and tissue post-conditioning to optimize lung tissue viability before grafting.


Input: 4. Taken all together, the reviewed studies point to a great interest for precision cut lung slices as an efficient and valuable alternative to in vivo lung organ experimentation.


Input: The GARD assay for assessment of chemical skin sensitizers.


Input: Allergic contact dermatitis is a skin disease caused by an immunologic reaction to low molecular weight compounds, so called haptens.


Input: These substances are commonly present in products used by humans in daily life, such as in cosmetics and fragrances, as well as within chemical industry and in pharmaceuticals.


Input: The frequent usage of these compounds in different applications has led to increasing incidences of allergic contact dermatitis, which has become a substantial economic burden for society.


Input: As a consequence, chemicals are routinely tested for their ability to induce skin sensitization, using animal models such as the murine Local Lymph Node Assay.


Input: However, recent legislations regulate the use of animal models within chemical testing.


Input: Thus, there is an urgent need for in vitro alternatives to replace these assays for safety assessment of chemicals.


Input: Recently, we identified a signature of predictive genes, which are differentially regulated in the human myeloid cell-line MUTZ-3 when stimulated with sensitizing compounds compared to non-sensitizing compounds.


Input: Based on these findings, we have formulated a test strategy for assessment of sensitizing compounds, called Genomic Allergen Rapid Detection, GARD.


Input: In this paper, we present a detailed method description of how the assay should be performed.


Input: Natural products as sources of new fungicides (I): synthesis and antifungal activity of acetophenone derivatives against phytopathogenic fungi.

acetophenone


Input: Several series of 45 acetophenone derivatives bearing various alkyl or benzyl substituents were conveniently synthesized and their structures characterized by (1) H and (13) C NMR spectroscopy, HRMS and single-crystal X-ray analysis.

acetophenone

alkyl

benzyl

(1) H

(13) C


Input: Their in vitro antifungal activities against a panel of phytopathogenic fungi were evaluated by mycelial growth rate assay.


Input: Of them, 12 derivatives (e. g., 3a-c, 4c and 4e) exhibited more potent antifungal effects on some phytopathogens than a commercial fungicide hymexazol as positive control.

hymexazol


Input: In particular, compound 3b with IC50 values of 10-19 mu g/mL was found to be the most active in this series and might be a potential lead structure for further optimization.


Input: The preliminary structure-activity relationship (SAR) studies of a series of acetophenones are also discussed.

acetophenones


Input: Droplet Digital (TM) PCR quantitation of HER2 expression in FFPE breast cancer samples.


Input: The human epidermal growth factor receptor 2 (HER2, also known as erbB2) gene is involved in signal transduction for cell growth and differentiation.


Input: It is a cell surface receptor tyrosine kinase and a proto-oncogene.

tyrosine


Input: Overexpression of HER2 is of clinical relevance in breast cancer due to its prognostic value correlating elevated expression with worsening clinical outcome.


Input: At the same time, HER2 assessment is also of importance because successful anti-tumor treatment with Herceptin (R) is strongly correlated with HER2 overexpression in the tumor (approximately 30% of all breast tumors overexpress HER2).


Input: In a comprehensive national study, Wolff et al.


Input: [1] state that " Approximately 20% of current HER2 testing may be inaccurate " which underscores the importance of developing more accurate methods to determine HER2 status.


Input: Droplet Digital (TM) PCR (ddPCR (TM)) has the potential to improve upon HER2 measurements due to its ability to quantitate DNA and RNA targets with high precision and accuracy.


Input: Here we present a study which investigates whether ddPCR can be used to assess HER2 transcript levels in formalin-fixed paraffin embedded (FFPE) human breast tumors and whether these ddPCR measurements agree with prior assessments of these same samples by pathologists using immunohistochemistry (IHC) and in some cases fluorescence in situ hybridization (FISH).

formalin


Input: We also determined the copy number of HER2 in these samples as compared to the CEP17 reference gene.


Input: Results: Clinical FFPE samples were successfully studied using ddPCR and compared to results from standard FISH and IHC methodology.


Input: The results demonstrate that ddPCR can rank order the samples in complete agreement with the current standard methods and that ddPCR has the added benefit of providing quantitative results, rather than relying on the expert skill of a seasoned pathologist for determination.


Input: Lipoprotein (a) metabolism: potential sites for therapeutic targets.


Input: Lipoprotein (a) [Lp (a)] resembles low-density lipoprotein (LDL), with an LDL lipid core and apolipoprotein B (apoB), but contains a unique apolipoprotein, apo (a).


Input: Elevated Lp (a) is an independent risk factor for coronary and peripheral vascular diseases.


Input: The size and concentration of plasma Lp (a) are related to the synthetic rate, not the catabolic rate, and are highly variable with small isoforms associated with high concentrations and pathogenic risk.


Input: Apo (a) is synthesized in the liver, although assembly of apo (a) and LDL may occur in the hepatocytes or plasma.


Input: While the uptake and clearance site of Lp (a) is poorly delineated, the kidney is the site of apo (a) fragment excretion.


Input: The structure of apo (a) has high homology to plasminogen, the zymogen for plasmin and the primary clot lysis enzyme.


Input: Apo (a) interferes with plasminogen binding to C-terminal lysines of cell surface and extracellular matrix proteins.

C


Input: Lp (a) and apo (a) inhibit fibrinolysis and accumulate in the vascular wall in atherosclerotic lesions.


Input: The pathogenic role of Lp (a) is not known.


Input: Small isoforms and high concentrations of Lp (a) are found in healthy octogenarians that suggest Lp (a) may also have a physiological role.


Input: Studies of Lp (a) function have been limited since it is not found in commonly studied small mammals.


Input: An important aspect of Lp (a) metabolism is the modification of circulating Lp (a), which has the potential to alter the functions of Lp (a).


Input: There are no therapeutic drugs that selectively target elevated Lp (a), but a number of possible agents are being considered.


Input: Recently, new modifiers of apo (a) synthesis have been identified.


Input: This review reports the regulation of Lp (a) metabolism and potential sites for therapeutic targets.


Input: Rational design of apoptosis signal-regulating kinase 1 inhibitors: discovering novel structural scaffold.


Input: Increased activity of apoptosis signal-regulating kinase 1 (ASK1) is associated with a number of human disorders and the inhibitors of ASK1 may become important compounds for pharmaceutical application.


Input: Here we report novel ASK1 inhibitor scaffold, namely 5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one, that has been identified using virtual screening and biochemical tests.

5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one


Input: A series of derivatives has been synthesized and evaluated in vitro towards human protein kinase ASK1.


Input: It was revealed that the most active compounds 4-((5Z)-5-{[5-(4-bromophenyl)-2-furyl] methylene}-4-oxo-2-thioxo-1, 3-thiazolidin-3-yl) butanoic acid and 6-((5Z)-5-{[5-(4-bromophenyl)-2-furyl] methylene}-4-oxo-2-thioxo-1, 3-thiazolidin-3-yl) hexanoic acid inhibit ASK1 with IC50 of 0. 2 mu M.

4-((5Z)-5-{[5-(4-bromophenyl)-2-furyl] methylene}-4-oxo-2-thioxo-1, 3-thiazolidin-3-yl) butanoic acid

6-((5Z)-5-{[5-(4-bromophenyl)-2-furyl] methylene}-4-oxo-2-thioxo-1, 3-thiazolidin-3-yl) hexanoic acid


Input: Structure-activity relationships of 33 derivatives of 5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one have been studied and binding mode of this chemical class has been predicted.

5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one


Input: Identification and characterization of novel catalytic bioscavengers of organophosphorus nerve agents.

organophosphorus


Input: In an effort to discover novel catalytic bioscavengers of organophosphorus (OP) nerve agents, cell lysates from a diverse set of bacterial strains were screened for their capacity to hydrolyze the OP nerve agents VX, VR, and soman (GD).

organophosphorus

soman


Input: The library of bacterial strains was identified using both random and rational approaches.


Input: Specifically, two representative strains from eight categories of extremophiles were chosen at random.


Input: For the rational approach, the protein sequence of organophosphorus hydrolase (OPH) from Brevundimonas diminuta was searched against a non-redundant protein database using the Basic Local Alignment Search Tool to find regions of local similarity between sequences.

organophosphorus


Input: Over 15 protein sequences with significant sequence similarity to OPH were identified from a variety of bacterial strains.


Input: Some of these matches were based on predicted protein structures derived from bacterial genome sequences rather than from bona fide proteins isolated from bacteria.


Input: Of the 25 strains selected for nerve agent testing, three bacterial strains had measurable levels of OP hydrolase activity.


Input: These strains are Ammoniphilus oxalaticus, Haloarcula sp., and Micromonospora aurantiaca.


Input: Lysates from A. oxalaticus had detectable hydrolysis of VR; Haloarcula sp. had appreciable hydrolysis of VX and VR, whereas lysates from M. aurantiaca had detectable hydrolysis of VR and GD.


Input: Targeting peroxisome proliferator-activated receptor-beta/delta in colon cancer: how to aim?


Input: Peroxisome proliferator-activated receptor-beta/delta (PPAR delta) is a ubiquitously expressed, ligand-activated transcriptional factor that performs diverse critical functions in normal cells (e. g., fatty acid metabolism, obesity, apoptosis, and inflammation).

fatty acid


Input: Various studies in humans have found that PPAR delta is upregulated in primary colorectal cancers; however, these findings have been challenged by those of other reports.


Input: Similarly, various in vitro and in vivo mechanistic pre-clinical models have yielded data demonstrating that PPAR delta promotes colonic tumorigenesis, but other models have yielded data that contradicts this notion.


Input: Definitive studies are therefore needed to establish the exact role of PPAR delta in human colorectal tumorigenesis and to provide a theoretical basis for PPAR delta therapeutic targeting.


Input: One target-two different binding modes: structural insights into gevokizumab and canakinumab interactions to interleukin-1 beta.


Input: Interleukin-1 beta (IL-1 beta) is a key orchestrator in inflammatory and several immune responses.


Input: IL-1 beta exerts its effects through interleukin-1 receptor type I (IL-1RI) and interleukin-1 receptor accessory protein (IL-1RAcP), which together form a heterotrimeric signaling-competent complex.


Input: Canakinumab and gevokizumab are highly specific IL-1 beta monoclonal antibodies.


Input: Canakinumab is known to neutralize IL-1 beta by competing for binding to IL-1R and therefore blocking signaling by the antigen: antibody complex.


Input: Gevokizumab is claimed to be a regulatory therapeutic antibody that modulates IL-1 beta bioactivity by reducing the affinity for its IL-1RI: IL-1RAcP signaling complex.


Input: How IL-1 beta signaling is affected by both canakinumab and gevokizumab was not yet experimentally determined.


Input: We have analyzed the crystal structures of canakinumab and gevokizumab antibody binding fragment (Fab) as well as of their binary complexes with IL-1 beta.


Input: Furthermore, we characterized the epitopes on IL-1 beta employed by the antibodies by NMR epitope mapping studies.


Input: The direct comparison of NMR and X-ray data shows that the epitope defined by the crystal structure encompasses predominantly those residues whose NMR resonances are severely perturbed upon complex formation.


Input: The antigen: Fab co-structures confirm the previously identified key contact residues on IL-1 beta and provide insight into the mechanisms leading to their distinct modulation of IL-1 beta signaling.


Input: A significant steric overlap of the binding interfaces of IL-1R and canakinumab on IL-1 beta causes competitive inhibition of the association of IL-1 beta and its receptor.


Input: In contrast, gevokizumab occupies an allosteric site on IL-1 beta and complex formation results in a minor reduction of binding affinity to IL-1RI.