Input: These results show that the administration of successive doses of the venoms for more than 6 months results in an antivenin with higher avidity that is able to recognize a greater number of antigens present in the venoms.


Input: These characteristics indicate a more efficient and potent antivenin than what has been described in other studies.


Input: A review of mouse critical size defect models in weight bearing bones.


Input: Current and future advances in orthopedic treatment are aimed at altering biological interactions to enhance bone healing.


Input: Currently, several clinical scenarios exist for which there is no definitive treatment, specifically segmental bone loss from high-energy trauma or surgical resection-and it is here that many are aiming to find effective solutions.


Input: To test experimental interventions and better understand bone healing, researchers employ critical size defect (CSD) models in animal studies.


Input: Here, an overview of CSDs is given that includes the specifications of varying models, a discussion of current scaffold and bone graft designs, and current outcome measures used to determine the extent of bone healing.


Input: Many promising graft designs have been discovered along with promising adjunctive treatments, yet a graft that offers biomechanical support while allowing for neovascularization with eventual complete resorption and remodeling remains to be developed.


Input: An overview of this important topic is needed to highlight current advances and provide a clear understanding of the ultimate goal in CSD research-develop a graft for clinical use that effectively treats the orthopedic conundrum of segmental bone loss.


Input: Autophagy in ageing and ageing-associated diseases.


Input: Autophagy is a cell self-digestion process via lysosomes that clears " cellular waste ", including aberrantly modified proteins or protein aggregates and damaged organelles.


Input: Therefore, autophagy is considered a protein and organelle quality control mechanism that maintains normal cellular homeostasis.


Input: Dysfunctional autophagy has been observed in ageing tissues and several ageing-associated diseases.


Input: Lifespan of model organisms such as yeast, worms, flies, and mice can be extended through promoting autophagy, either by genetic manipulations such as over-expression of Sirtuin 1, or by administrations of rapamycin, resveratrol or spermidine.

rapamycin

resveratrol

spermidine


Input: The evidence supports that autophagy may play an important role in delaying ageing or extending lifespan.


Input: In this review, we summarize the current knowledge about autophagy and its regulation, outline recent developments ie the genetic and pharmacological manipulations of autophagy that affects the lifespan, and discuss the role of autophagy in the ageing-related diseases.


Input: Excess androgen during puberty disrupts circadian organization in female rats.

androgen


Input: Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis.


Input: Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated.


Input: Polycystic ovary syndrome (PCOS) is a particularly devastating endocrinopathy, affecting approximately 10% of women at childbearing age.


Input: Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen.

androgen


Input: Approximately 40% of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia.


Input: It has been suggested that excess androgen is a critical factor in the etiology of PCOS.

androgen


Input: We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo-pituitary-ovarian axes.

androgen


Input: Female period1-luciferase (per1-luc) rats were exposed to androgen (5 alpha-dihydrotestosterone [DHT]) or placebo for 4-6 weeks (short term) or 9-15 weeks (long term).

androgen

5 alpha-dihydrotestosterone

DHT


Input: As expected, DHT-treated animals gained more weight than controls and had disrupted estrous cycles.

DHT


Input: At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1-luc expression in each was recorded.


Input: Analysis of per1-luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals.

DHT


Input: These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes.

androgen


Input: Estimating population-level HC5 for copper using a species sensitivity distribution approach.

copper


Input: Estimation of population-level benchmark concentrations for protecting aquatic organisms from chemicals is important for value-relevant ecological risk assessments.


Input: By employing a species sensitivity distribution (SSD) approach, the authors aimed to derive the population-level hazardous concentration for 5% of species (PHC5) for copper.

copper


Input: Based on available information on copper toxicity and population models, the authors estimated population threshold concentrations at which the population size is stable (that is, 0 net population growth) for 13 freshwater species (3 algal, 6 invertebrate, and 4 fish species).

copper


Input: The PHC5 for copper was then estimated (6. 8 micro g/L; 95% confidence interval [CI], 1. 8-13. 6 micro g/L), by fitting a log-normal distribution to the population threshold concentrations obtained.

copper


Input: The close overlap between the present study' s estimate of the PHC5 and a field-derived threshold concentration suggests that the population-level SSD approach provides a reasonable level of protection for species richness in the natural environment.


Input: By contrast, and counterintuitively, the authors' estimate was comparable with the individual-level HC5 reported in the European Union risk assessment.


Input: Although the present study cannot determine the underlying reasons for the similar figures, the result provides an indication that the margin between individual-level and population-level benchmarks derived from SSD approaches can be very small.


Input: The results therefore suggest that attention is needed to achieve population-level protection using an individual-level SSD approach.


Input: Environ Toxicol Chem 2013; 32: 1396-1402.


Input: (c) 2013 SETAC.


Input: Determination of mercury speciation in fish tissue with a direct mercury analyzer.

mercury

mercury


Input: Knowledge of Hg speciation in tissue is valuable for assessing potential toxicological effects in fish.

Hg


Input: Direct Hg analyzers, which use thermal decomposition and atomic absorption spectrometry, have recently gained popularity for determining organic Hg after procedural solvent extraction from some environmental media, although quantitative recovery from lipid-rich materials, such as fish liver, has been problematic.

Hg

Hg


Input: The authors developed a new method by which organic Hg in fish liver and muscle is estimated by the difference between direct measurements of inorganic Hg in an acid extract and total Hg in whole tissue.

Hg

Hg

Hg


Input: The method was validated by analysis of a certified reference material (DOLT-4 dogfish liver) and naturally contaminated fish tissues with comparison to an established Hg speciation method (gas chromatography cold vapor atomic fluorescence spectrometry).

Hg


Input: Recovery of organic Hg from DOLT-4, estimated by difference, averaged 99 +/- 5% of the mean certified value for methylmercury.

Hg

methylmercury


Input: In most liver samples and all muscle samples, estimates of organic Hg from the proposed method were indiscernible from direct speciation measurements of methylmercury (99% +/- 6%).

Hg

methylmercury


Input: Estimation of organic Hg by the difference between total Hg and inorganic Hg was less accurate in liver samples with a high percentage of inorganic Hg (90%).

Hg

Hg

Hg

Hg


Input: This was because of the increased uncertainty that results from estimating a third value (i. e., organic Hg) by using the difference between two large concentrations (inorganic and total Hg).

Hg

Hg


Input: The proposed method is a useful tool for examining the speciation of Hg in fish muscle and liver, and by extension, potentially other tissues and environmental media.

Hg


Input: Environ Toxicol Chem 2013; 32: 1237-1241.


Input: (c) 2013 SETAC.


Input: Versatile Nanostructured Materials via Direct Reaction of Functionalized Catechols.

Catechols


Input: A facile one-step polymerization strategy is explored to achieve novel catechol-based materials.

catechol


Input: Depending on the functionality of the catechol, the as-prepared product can be used to modify at will the surface tension of nano and bulk structures, from oleo-/hydrophobic to highly hydrophilic.

catechol


Input: A hydrophobic catechol prepared thus polymerized shows the ability to self-assemble as solid nanoparticles with sticky properties in polar solvent media.

catechol


Input: Such a versatile concept is ideal for the development of catechol-based multifunctional materials.

catechol


Input: Structural insights into the recovery of aldolase activity in N-acetylneuraminic acid lyase by replacement of the catalytically active lysine with gamma-thialysine by using a chemical mutagenesis strategy.

N-acetylneuraminic acid

lysine

gamma-thialysine


Input: Chemical modification has been used to introduce the unnatural amino acid gamma-thialysine in place of the catalytically important Lys165 in the enzyme N-acetylneuraminic acid lyase (NAL).

amino acid gamma-thialysine

N-acetylneuraminic acid


Input: The Staphylococcus aureus nanA gene, encoding NAL, was cloned and expressed in E. coli.


Input: The protein, purified in high yield, has all the properties expected of a class I NAL.


Input: The S. aureus NAL which contains no natural cysteine residues was subjected to site-directed mutagenesis to introduce a cysteine in place of Lys165 in the enzyme active site.

cysteine

cysteine


Input: Subsequently chemical mutagenesis completely converted the cysteine into gamma-thialysine through dehydroalanine (Dha) as demonstrated by ESI-MS.

cysteine

gamma-thialysine

dehydroalanine

Dha


Input: Initial kinetic characterisation showed that the protein containing gamma-thialysine regained 17% of the wild-type activity.

gamma-thialysine


Input: To understand the reason for this lower activity, we solved X-ray crystal structures of the wild-type S. aureus NAL, both in the absence of, and in complex with, pyruvate.

pyruvate


Input: We also report the structures of the K165C variant, and the K165-gamma-thialysine enzyme in the presence, or absence, of pyruvate.

gamma-thialysine

pyruvate


Input: These structures reveal that gamma-thialysine in NAL is an excellent structural mimic of lysine.

gamma-thialysine

lysine


Input: Measurement of the pH-activity profile of the thialysine modified enzyme revealed that its pH optimum is shifted from 7. 4 to 6. 8.

thialysine


Input: At its optimum pH, the thialysine-containing enzyme showed almost 30% of the activity of the wild-type enzyme at its pH optimum.

thialysine


Input: The lowered activity and altered pH profile of the unnatural amino acid-containing enzyme can be rationalised by imbalances of the ionisation states of residues within the active site when the pK (a) of the residue at position 165 is perturbed by replacement with gamma-thialysine.

amino acid

gamma-thialysine


Input: The results reveal the utility of chemical mutagenesis for the modification of enzyme active sites and the exquisite sensitivity of catalysis to the local structural and electrostatic environment in NAL.


Input: Cytophilic/Cytophobic Design of Nanomaterials at Biointerfaces.


Input: To control interactions between cells and nanomaterials has been a great challenge because numerous nanomaterials have been intensively explored in the fields of biology and medicine.


Input: However, current surface modification of nanomaterials is mainly carried out in an empirical way.


Input: Herein, a general strategy to tune the surface chemistry of nanomaterials is proposed based on cell affinity, that is, cytophilic or cytophobic.


Input: The cell affinity of nanomaterials directly affects cellular response to materials at the very early stage of cell-material interactions before other events, such as endocytosis, cell spreading, and cell differentiation, occur.


Input: In this Concept, it is suggested that there is a developing library of cytophilic and cytophobic moieties, and how the cell affinity of nanomaterials functions at biointerfaces is discussed by exemplifying several applications, namely therapy, tissue engineering, and biosensors.


Input: It is believed that control of the cytophilic/cytophobic property will be helpful in guiding the design of functional nanomaterials for their biomedical applications.


Input: Forty-seven days of decay does not change persistent organic pollutant levels in loggerhead sea turtle eggs.


Input: Reptile and bird eggs are priority samples for specimen banking programs that assess spatial and temporal trends of environmental contaminants.


Input: From endangered species, such as sea turtles, nonlethal sampling is required (e. g., unhatched eggs collected postemergence).


Input: Previous contaminant monitoring studies have used unhatched sea turtle eggs, but no study has tested whether their concentrations represent levels found in fresh eggs (e. g., eggs collected within 24 h of oviposition).


Input: The author analyzed three fresh eggs from different nest depths and up to three unhatched eggs from 10 loggerhead sea turtle (Caretta caretta) nests in South Carolina, USA, for a suite of persistent organic pollutants (POPs).


Input: Lipid-normalized POP concentrations were not significantly different (p > 0. 05) between fresh and unhatched eggs or among different depths from the same nest.


Input: The POP concentrations in loggerhead eggs from South Carolina were higher than previously measured concentrations in eggs from Florida and slightly lower than concentrations in eggs from North Carolina.


Input: This pattern agrees with previously observed trends of increasing POP concentrations in loggerhead turtles inhabiting northern latitudes along the U. S.


Input: East Coast.


Input: Contaminant profiles are discussed, including a higher chlorinated pattern of polychlorinated biphenyls possibly associated with a Superfund site in nearby Brunswick, Georgia, USA, and unusual polybrominated diphenylether patterns seen in this and previous sea turtle studies.

polychlorinated biphenyls

polybrominated diphenylether


Input: Concentrations correlated with one of eight measurements of reproductive success; levels were negatively correlated with egg mass (p < 0. 05), which may have implications for hatchling fitness.


Input: The present study suggests that unhatched eggs can be used for POP-monitoring projects.


Input: Lifelong exposure to bisphenol a alters cardiac structure/function, protein expression, and DNA methylation in adult mice.

bisphenol a


Input: Bisphenol A (BPA) is an estrogenizing endocrine disruptor compound of concern.

Bisphenol A

BPA


Input: Our objective was to test whether lifelong BPA would impact cardiac structure/function, calcium homeostasis protein expression, and the DNA methylation of cardiac genes.

BPA

calcium


Input: We delivered 0. 5 and 5. 0 micro g/kg/day BPA lifelong from gestation day 11 or 200 micro g/kg/day from gestation day 11 to postnatal day 21 via the drinking water to C57bl/6n mice.

BPA


Input: BPA 5. 0 males and females had increased body weight, body mass index, body surface area, and adiposity.

BPA


Input: Echocardiography identified concentric remodeling in all BPA-treated males.

BPA


Input: Systolic and diastolic cardiac functions were essentially similar, but lifelong BPA enhanced male and reduced female sex-specific differences in velocity of circumferential shortening and ascending aorta velocity time integral.

BPA


Input: Diastolic blood pressure was increased in all BPA females.

BPA


Input: The calcium homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), sodium calcium exchanger-1, phospholamban (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation.

calcium

sodium calcium

phospholamban


Input: Changes in their expression suggest increased calcium mobility in males and reduced calcium mobility in females supporting the cardiac function changes.

calcium

calcium


Input: DNA methyltransferase 3a expression was increased in all BPA males and BPA 0. 5 females and reduced in BPA 200 females.

BPA

BPA

BPA


Input: Global DNA methylation was increased in BPA 0. 5 males and reduced in BPA 0. 5 females.

BPA

BPA


Input: BPA induced sex-specific altered DNA methylation in specific CpG pairs in the calsequestrin 2 CpG island.

BPA

CpG


Input: These results suggest that continual exposure to BPA impacts cardiac structure/function, protein expression, and epigenetic DNA methylation marks in males and females.

BPA


Input: The sorting of proglucagon to secretory granules is mediated by carboxypeptidase E and intrinsic sorting signals.


Input: Proglucagon is expressed in pancreatic alpha cells, intestinal L cells and brainstem neurons.


Input: Tissue-specific processing of proglucagon yields the peptide hormones glucagon in the alpha cell and glucagon-like peptide (GLP)-1 and GLP-2 in L cells.


Input: Both glucagon and GLP-1 are secreted in response to nutritional status and are critical for regulating glycaemia.


Input: The sorting of proglucagon to the dense-core secretory granules of the regulated secretory pathway is essential for the appropriate secretion of glucagon and GLP-1.


Input: We examined the roles of carboxypeptidase E (CPE), a prohormone sorting receptor, the processing enzymes PC1/3 and PC2 and putative intrinsic sorting signals in proglucagon sorting.


Input: In Neuro 2a cells that lacked CPE, PC1/3 and PC2, proglucagon co-localised with the Golgi marker p115 as determined by quantitative immunofluorescence microscopy.


Input: Expression of CPE, but not of PC1/3 or PC2, enhanced proglucagon sorting to granules.


Input: siRNA-mediated knockdown of CPE disrupted regulated secretion of glucagon from pancreatic-derived alphaTC1-6 cells, but not of GLP-1 from intestinal cell-derived GLUTag cells.


Input: Mutation of the PC cleavage site K70R71, the dibasic R17R18 site within glucagon or the alpha-helix of glucagon, all significantly affected the sub-cellular localisation of proglucagon.


Input: Protein modelling revealed that alpha helices corresponding to glucagon, GLP-1 and GLP-2, are arranged within a disordered structure, suggesting some flexibility in the sorting mechanism.


Input: We conclude that there are multiple mechanisms for sorting proglucagon to the regulated secretory pathway, including a role for CPE in pancreatic alpha cells, initial cleavage at K70R71 and multiple sorting signals.


Input: Development of a cell-based high-throughput peroxisome proliferator-activated receptors (PPARs) screening model and its application for evaluation of the extracts from Rhizoma Coptis.


Input: To date, peroxisome proliferator-activated receptors (PPARs) are becoming the new therapeutic targets for the treatment of metabolic diseases, such as Type 2 diabetes, obesity, and cardiovascular disease.


Input: In this study, a cell-based high-throughput PPARs (PPAR alpha/beta/gamma) model was developed for the screening of PPARs agonists.


Input: The screening conditions were evaluated through analyzing the expression value of luciferase.


Input: Finally, 24 h of drug acting time, 5 times of the dilution factor of luciferase zymolyte, and about 2 x 10 (4) cells/well on HeLa cells in 96-well plates were used, respectively.


Input: Furthermore, the quality of high-throughput screening (HTS) in stability and reliability was evaluated by the Z'-factor.


Input: Additionally, different extracts of Rhizoma Coptis and berberine were tested by the developed method.

berberine


Input: The results suggested that both the EtOAc extract and berberine were able to activate PPAR alpha/beta/gamma, and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.

EtOAc

berberine

berberine


Input: In conclusion, the developed HTS assay is a simple, rapid, stable, and specific method for the screening of PPARs natural agonists.


Input: Salidroside attenuates myocardial ischemia-reperfusion injury via PI3K/Akt signaling pathway.

Salidroside


Input: To investigate the cardioprotective effects of salidroside on myocardial ischemia-reperfusion injury (IRI) in rabbits and the underlying action mechanisms in PI3K/Akt signaling pathway, a rabbit ischemia/reperfusion model was created by ligating the left anterior descending coronary arterial branch for 30 min and by releasing the ligature to allow reperfusion for 120 min.

salidroside


Input: Salidroside or salidroside + PI3K inhibitor (LY294002) was administered via intracoronary injections at the onset of reperfusion.

Salidroside

salidroside


Input: Apoptosis of cardiomyocytes was assessed by terminal dUTP nick-end labeling assay, and the expression of apoptosis-related proteins was observed by immunohistochemistry.

dUTP


Input: The expressions of total Akt and phosphorylated Akt (p-Akt) were detected by western blot analysis.


Input: The results showed that intracoronary injection of salidroside at the onset of reperfusion markedly reduced the apoptosis of cardiomyocytes, significantly increasing Bcl-2 and p-Akt proteins expressions and decreasing Bax and caspase-3 expressions in the hearts subjected to ischemia followed by 120-min reperfusion.

salidroside


Input: However, the anti-apoptotic effect induced by salidroside was inhibited by LY294002, which blocked the activation of Akt.

salidroside


Input: These results suggested that intracoronary administration of salidroside at the onset of reperfusion could significantly reduce the IRI-induced apoptosis of cardiomyocytes, and this protective mechanism seemed to be mediated by the PI3K-Akt signaling pathway.

salidroside


Input: A new antibacterial denitroaristolochic acid from the tubers of Stephania succifera.

denitroaristolochic acid


Input: A new denitroaristolochic acid, demethylaristofolin C (1), together with six known alkaloids, crebanine N-oxide (2), (-)-sukhodianine-beta-N-oxide (3), palmatine (4), corydalmine (5), dehydrocorydalmine (6), and corynoxidine (7), was isolated from the tubers of Stephania succifera.

denitroaristolochic acid

demethylaristofolin C

crebanine N-oxide

(-)-sukhodianine-beta-N-oxide

palmatine

corydalmine

dehydrocorydalmine

corynoxidine


Input: The structure of demethylaristofolin C was elucidated by spectroscopic techniques (UV, IR, 1D, and 2D NMR) and HR-ESI-MS analyses.

demethylaristofolin C


Input: These compounds exhibited antibacterial activities against Staphylococcus aureus and methicillin-resistant S. aureus strains in different degrees.

methicillin


Input: Preparation and characterization of progesterone dispersions using supercritical carbon dioxide.

progesterone

carbon dioxide


Input: Abstract Context: Supercritical fluid methods offer an alternative to conventional mixing methods, particularly for heat sensitive drugs and where an organic solvent is undesirable.


Input: Objective: To design, develop and construct a unit for the particles from a gas-saturated suspension/solution (PGSS) method and form endogenous progesterone (PGN) dispersion systems using SC-CO (2).

progesterone

PGN

CO (2)


Input: Materials and methods: The PGN dispersions were manufactured using three selected excipients: polyethylene glycol (PEG) 400/4000 (50: 50), Gelucire 44/14 and D-alpha-tocopheryl PEG 1000 succinate (TPGS).

PGN

polyethylene glycol

PEG

Gelucire

D-alpha-tocopheryl PEG 1000 succinate

TPGS


Input: Semisolid dispersions of PGN prepared by PGSS method were compared to the conventional methods; comelting (CM), cosolvent (CS) and physical mixing (PM).

PGN


Input: The dispersion systems made were characterized by Raman and Fourier transform infrared (FTIR) spectroscopies, X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), PGN recovery, uniformity and in vitro dissolution, analyzed by high-performance liquid chromatography (HPLC).

PGN


Input: Results: Raman spectra revealed no changes in the crystalline structure of PGN treated with SC-CO (2) compared to that of untreated PGN.

PGN

CO (2)

PGN


Input: XRPD and FTIR showed the presence of peaks and bands for PGN confirming that PGN has been incorporated well with each individual excipient.

PGN

PGN


Input: All PGN dispersions prepared by the PGSS method resulted in the improvement of PGN dissolution rates compared to that prepared by the conventional methods and untreated PGN after 60 min (p value < 0. 05).

PGN

PGN

PGN


Input: Conclusion: The novel PGN dispersions prepared by the PGSS method offer the great potential to enhance PGN dissolution rate, reduce preparation time and form stable crystalline dispersion systems over those prepared by conventional methods.

PGN

PGN


Input: Incorporation of rapid thermodynamic data in fragment-based drug discovery.


Input: Fragment-based drug discovery (FBDD) has enjoyed increasing popularity in recent years.


Input: We introduce SITE (single-injection thermal extinction), a novel thermodynamic methodology that selects high-quality hits early in FBDD.


Input: SITE is a fast calorimetric competitive assay suitable for automation that captures the essence of isothermal titration calorimetry but using significantly fewer resources.


Input: We describe the principles of SITE and identify a novel family of fragment inhibitors of the enzyme ketosteroid isomerase displaying high values of enthalpic efficiency.

ketosteroid


Input: In vivo drug interactions of the teratogen thalidomide with midazolam: heterotropic cooperativity of human cytochrome P450 in humanized TK-NOG mice.

thalidomide

midazolam


Input: In vivo drug interactions of the teratogen thalidomide with the model cytochrome P450 (P450) 3A substrate midazolam were investigated in mice with humanized livers.

thalidomide

midazolam


Input: The clearance of midazolam (administered intravenously, 10 mg kg (-1)) in chimeric mice was enhanced by orally co-administered thalidomide (100 mg kg (-1)).

midazolam

thalidomide


Input: A larger area under the curve of the major metabolite 1'-hydroxymidazolam (1. 7-fold) was obtained with thalidomide because of the heterotropic cooperativity of human P450 3A enzymes.

thalidomide


Input: A larger area under the curve of the minor metabolite 4-hydroxymidazolam (3. 5-fold) was seen with daily pretreatment with thalidomide for 3 days, presumably because of human P450 3A induction.

thalidomide


Input: These results demonstrate that livers of humanized mice mediate drug interactions of thalidomide and suggest interactions of therapeutic agents during therapies with thalidomide.

thalidomide

thalidomide


Input: Electrically conductive gold-and copper-metallized DNA origami nanostructures.

copper


Input: This work demonstrates the use of a circuit-like DNA origami structure as a template to fabricate conductive gold and copper nanostructures on Si surfaces.

copper

Si


Input: We improved over previous results by using multiple Pd seeding steps to increase seed uniformity and density.

Pd


Input: Our process has also been characterized through atomic force microscopy, particle size distribution analysis, and scanning electron microscopy.


Input: We found that four successive Pd seeding steps yielded the best results for electroless metal plating on DNA origami.

Pd


Input: Electrical resistance measurements were done on both Au-and Cu-metallized nanostructures, with each showing ohmic behavior.

Au

Cu


Input: Gold-plated DNA origami structures made under optimal conditions had an average resistivity of 7. 0 x 10 (-5) Omega. m, whereas copper-metallized structures had a resistivity as low as 3. 6 x 10 (-4) Omega. m.

copper


Input: Importantly, this is the first demonstration of electrically conductive Cu nanostructures fabricated on either DNA or DNA origami templates.

Cu


Input: Although resistivities for both gold and copper samples were larger than those of the bulk metal, these metal nanostructures have the potential for use in electrically connecting small structures.

copper


Input: In addition, these metallized objects might find use in surface-enhanced Raman scattering experiments.


Input: Temporal relationship between aquaporin-4 and glial fibrillary acidic protein in cerebellum of neonate and adult rats administered a BBB disrupting spider venom.


Input: Two astrocyte markers, the glial water channel aquaporin-4 (AQP4) and the glial fibrillary acidic protein (GFAP), have been implicated in several physiological and pathological conditions in the central nervous system (CNS) as well as in blood-brain barrier breakdown (BBBb).


Input: By color segmentation the immunoreactivity of both proteins, we demonstrate that the expression of AQP4 and GFAP was increased in the cerebellum of neonate (14-day-old, P14) and adult (8-week-old) rats administered Phoneutria nigriventer spider venom (PNV) known to cause perivascular edema, BBBb and convulsion.


Input: In the cerebellum' s gray matter, PNV produced a major response, especially in the granular layer.


Input: Parallel increases in AQP4 and GFAP expression occurred 24 h after envenomation in the white matter of P14 and in the molecular layer of adults, as well as in the granular layer 2 h after envenomation.


Input: In the Purkinje layer there was a tendency of increased AQP4, for both, neonates (5 h), and adults (2 and 24 h).


Input: Moreover, PNV also provoked nonparallel upregulation of both markers with prevalence of upregulation of AQP 4 for P14 rats, and GFAP for adults.


Input: The major expression of both proteins was in the gray matter.


Input: The data indicates a venom effect in water/electrolyte balance in the cerebellum and the participation of AQP4 in these effects.


Input: Age-related and time-related regional differences probably reflect specificity in AQP4 distribution in different astrocytic membrane domains as well as its participation in K (+) buffering and neural activity.

K (+)


Input: This study is the first to associate astrocytic AQP4 expression and reactive gliosis in a model of BBB permeability promoted by P. nigriventer venom.


Input: Our data provide compelling evidence that AQP4 expression was increased in the cerebellum of rats administered PNV.


Input: Pelargonidin activates the AhR and induces CYP1A1 in primary human hepatocytes and human cancer cell lines HepG2 and LS174T.

Pelargonidin


Input: We examined the effects of anthocyanidins (cyanidin, delphinidin, malvidin, peonidin, petunidin, pelargonidin) on the aryl hydrocarbon receptor (AhR)-CYP1A1 signaling pathway in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cells.

anthocyanidins

cyanidin

delphinidin

malvidin

peonidin

petunidin

pelargonidin

aryl hydrocarbon


Input: AhR-dependent reporter gene expression in transfected HepG2 cells was increased by pelargonidin in a concentration-dependent manner at 24h.

pelargonidin


Input: Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2, 3, 7, 8-tetrachlorodibenzodioxin (TCDD), the most potent activator of AhR.

pelargonidin

2, 3, 7, 8-tetrachlorodibenzodioxin

TCDD


Input: CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme.

pelargonidin

TCDD


Input: Ligand binding analysis demonstrated that pelargonidin was a weak ligand of AhR.

pelargonidin


Input: Enzyme kinetic analyses using human liver microsomes revealed inhibition of CYP1A1 activity by delphinidin (IC50 78 mu M) and pelargonidin (IC50 33 mu M).

delphinidin

pelargonidin


Input: Overall, although most anthocyanidins had no effects on AhR-CYP1A1 signaling, pelargonidin can bind to and activate the AhR and AhR-dependent gene expression, and pelargonidin and delphinidin inhibit the CYP1A1 catalytic activity.

anthocyanidins

pelargonidin

pelargonidin

delphinidin


Input: Metformin and Sulfonylureas in Relation to Cancer Risk in Type II Diabetes Patients: A Meta-analysis using primary data of published studies.

Metformin

Sulfonylureas


Input: INTRODUCTION: Accumulating evidence suggests that patients with type 2 diabetes mellitus (T2DM) and hyperinsulinemia are at increased risk for developing malignancies.


Input: It remains to be fully elucidated whether use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affect cancer incidence in subjects with T2DM.

metformin

sulfonylureas


Input: MATERIAL & METHODS: We performed a meta-analysis using PubMed, of randomized control trials (RCTs), cohorts, and case-control studies published through July 2012 that assess effects of metformin and/or sulfonylurea sulfonylureas on cancer risk at any site, in subjects with T2DM.

metformin

sulfonylurea sulfonylureas


Input: Fixed and random effects meta-analysis models were used, and the effect size was summarized as relative risk (RR) for RCTs/cohorts and as odds ratio (OR) for the case-control studies.


Input: RESULTS: Analysis of 24 metformin studies in subjects with T2DM showed that metformin use is associated with reduced risk for the development of cancer, in both cohort (RR = 0. 70 [95% CI = 0. 67-0. 73]) and case-control studies (OR = 0. 90 [95% CI = 0. 84-0. 98]), but this finding was not supported by RCTs (RR = 1. 01 [95% CI = 0. 81-1. 26]).

metformin

metformin


Input: Data from 18 sulfonylurea studies in subjects with T2DM showed that sulfonylurea use is associated with an increase in all-cancer risk, in cohort studies (RR = 1. 55 [95% CI = 1. 48-1. 63]), though data from RCTs (RR = 1. 17 [95% CI = 0. 95-1. 45]) and case-control studies (OR = 1. 02 [95% CI = 0. 93-1. 13]) failed to demonstrate a statistically significant effect.

sulfonylurea

sulfonylurea


Input: CONCLUSIONS: This analysis using pooled primary data demonstrates that metformin use reduces, while sulfonylurea use may be associated with an increased cancer risk in subjects with T2DM.

metformin

sulfonylurea


Input: These findings need to be confirmed in large-scale RCTs before they are translated into clinical practice.


Input: Dextran-pegylated microparticles for enhanced cellular uptake of hydrophobic drugs.


Input: Polyethylene glycol monosubstituted with a polymerizable acrylic moiety was linked to 6-carboxy free position on dextran side chains and then subjected to radical polymerization with a comonomer in order to obtain microspheres for the oral controlled release of ketoconazole, a hydrophobic model drug.

Polyethylene glycol

acrylic

ketoconazole


Input: Microparticles were submitted to studies on their ability to absorb and retain water.


Input: Cell uptake studies, in the presence and absence of mucus, across two different monolayers, respectively, HT29-MTX-E12 and Caco-2, were done.


Input: Cytotoxicity studies were carried out to calculate the IC50 value.


Input: The ability of microspheres to open monolayers tight junctions was tested by measuring their TEER values.


Input: Images of cell uptake were visualized by CLSM.


Input: In HT29-MTX-E12 cells, more mucoadhesion and drug internalization is seen thanks to the presence of PEG and dextran chains.

PEG


Input: The transdermal delivery of fentanyl.

fentanyl


Input: The fentanyl patch is one of the great commercial successes in transdermal drug delivery.

fentanyl


Input: The suitability of this molecule for delivery through skin had been identified in the 1970s, and subsequently, a number of transdermal formulations became available on the market.


Input: This article reviews the development of fentanyl patch technology with particular emphasis on the pharmacokinetics and disposition of the drug when delivered through the skin.

fentanyl


Input: The various patch designs are considered as well as the bioequivalence of the different designs.


Input: The influence of heat on fentanyl permeation is highlighted.

fentanyl


Input: Post-mortem redistribution of fentanyl is discussed in light of the reported discrepancies in serum levels reported in patients after death compared with therapeutic levels in living subjects.

fentanyl


Input: Finally, alternatives to patch technology are considered, and recent novel transdermal formulations are highlighted.


Input: Optimization of cell receptor-specific targeting through multivalent surface decoration of polymeric nanocarriers.


Input: Treatment of tuberculosis is impaired by poor drug bioavailability, systemic side effects, patient non-compliance, and pathogen resistance to existing therapies.


Input: The mannose receptor (MR) is known to be involved in the recognition and internalization of Mycobacterium tuberculosis.

mannose


Input: We present a new assembly process to produce nanocarriers with variable surface densities of mannose targeting ligands in a single step, using kinetically-controlled, block copolymer-directed assembly.

mannose


Input: Nanocarrier association with murine macrophage J774 cells expressing the MR is examined as a function of incubation time and temperature, nanocarrier size, dose, and PEG corona properties.

PEG


Input: Amphiphilic diblock copolymers are prepared with terminal hydroxyl, methoxy, or mannoside functionality and incorporated into nanocarrier formulations at specific ratios by Flash NanoPrecipitation.

hydroxyl

methoxy

mannoside


Input: Association of nanocarriers protected by a hydroxyl-terminated PEG corona with J774 cells is size dependent, while nanocarriers with methoxy-terminated PEG coronas do not associate with cells, regardless of size.

hydroxyl

PEG

methoxy

PEG


Input: Specific targeting of the MR is investigated using nanocarriers having 0-75% mannoside-terminated PEG chains in the PEG corona.

mannoside

PEG

PEG


Input: This is a wider range of mannose densities than has been previously studied.

mannose


Input: Maximum nanocarrier association is attained with 9% mannoside-terminated PEG chains, increasing uptake more than 3-fold compared to non-targeted nanocarriers with a 5kgmol (-1) methoxy-terminated PEG corona.

mannoside

PEG

methoxy

PEG


Input: While a 5kgmol (-1) methoxy-terminated PEG corona prevents non-specific uptake, a 1. 8kgmol (-1) methoxy-terminated PEG corona does not sufficiently protect the nanocarriers from nonspecific association.

methoxy

PEG

methoxy

PEG


Input: There is continuous uptake of MR-targeted nanocarriers at 37 degrees C, but a saturation of association at 4 degrees C.


Input: The majority of targeted nanocarriers associated with J774E cells are internalized at 37 degrees C and uptake is receptor-dependent, diminishing with competitive inhibition by dextran.


Input: This characterization of nanocarrier uptake and targeting provides promise for optimizing drug delivery to macrophages for TB treatment and establishes a general route for optimizing targeted formulations of nanocarriers for specific delivery at targeted sites.


Input: Psychopharmacology of theobromine in healthy volunteers.

theobromine


Input: BACKGROUND: Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate.

Theobromine

methylxanthine

caffeine


Input: However, current evidence for this is limited.


Input: OBJECTIVES: We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1, 000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants.

theobromine

caffeine


Input: RESULTS: Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters.

Caffeine


Input: Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses.

Theobromine


Input: It also dose-dependently increased heart rate.


Input: In secondary analyses, we also examined individual differences in the drug' s effects in relation to genes related to their target receptors, but few associations were detected.


Input: CONCLUSIONS: This study represents the highest dose of theobromine studied in humans.

theobromine


Input: We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.

theobromine


Input: Theoretical studies on the thermodynamic properties, densities, detonation properties, and pyrolysis mechanisms of trinitromethyl-substituted aminotetrazole compounds.

trinitromethyl-substituted aminotetrazole


Input: Trinitromethyl-substituted aminotetrazoles with-NH (2),-NO (2),-N (3), and-NHC (NO (2)) (3) groups were investigated at the B3LYP/6-31G (d) level of density functional theory.

Trinitromethyl-substituted aminotetrazoles

NH (2)

NO (2)

N (3)

NHC (NO (2)) (3)


Input: Their sublimation enthalpies, thermodynamic properties, and heats of formation were calculated.


Input: The thermodynamic properties of these compounds increase with temperature as well as with the number of nitro groups attached to the tetrazole ring.

nitro

tetrazole


Input: In addition, the detonation velocities and detonation pressures of these compounds were successfully predicted using the Kamlet-Jacobs equations.


Input: It was found that these compounds exhibit good detonation properties, and that compound G (D = 9. 2 km/s, P = 38. 8 GPa) has the most powerful detonation properties, which are similar to those of the well-known explosive HMX (1, 3, 5, 7-tetranitro-1, 3, 5, 7-tetrazocine).

HMX

1, 3, 5, 7-tetranitro-1, 3, 5, 7-tetrazocine


Input: Finally, the electronic structures and bond dissociation energies of these compounds were calculated.


Input: The BDEs of their C-NO (2) bonds were found to range from 101. 9 to 125. 8 kJ/mol (-1).

C-NO (2)


Input: All of these results should provide useful fundamental information for the design of novel HEDMs.


Input: TiO2 nanowire electron transport pathways inside organic photovoltaics.


Input: Charge transport is one of the five main steps in the operation of organic photovoltaics, but achieving balanced hole and electron transport with high mobility has been challenging in devices.


Input: Here, we report improved charge transport in organic photovoltaics via incorporation of nanostructured inorganic electron transport materials into the active layers of devices.


Input: Co-depositing TiO2 nanowires with the organic active layer solution embeds the nanowires directly within active layers of the solar cell.


Input: The ability of these nanowires to transport electrons is compared with neat P3HT: PCBM active layers and also devices containing TiO2 nanotube aggregates.

PCBM


Input: Incorporation of TiO2 nanowires yields a six-fold increase in the electron mobility relative to unmodified devices, leading to a 19% improvement in the power conversion efficiency.


Input: Lower energetic disorder of the film and more balanced charge transport are also observed upon incorporating TiO2 nanowires.


Input: These advantageous effects correlate with the TiO2 nanowire length.


Input: Protein-specific force field derived from the fragment molecular orbital method can improve protein-ligand binding interactions.


Input: Accurate computational estimate of the protein-ligand binding affinity is of central importance in rational drug design.


Input: To improve accuracy of the molecular mechanics (MM) force field (FF) for protein-ligand simulations, we use a protein-specific FF derived by the fragment molecular orbital (FMO) method and by the restrained electrostatic potential (RESP) method.


Input: Applying this FMO-RESP method to two proteins, dodecin, and lysozyme, we found that protein-specific partial charges tend to differ more significantly from the standard AMBER charges for isolated charged atoms.


Input: We did not see the dependence of partial charges on the secondary structure.


Input: Computing the binding affinities of dodecin with five ligands by MM PBSA protocol with the FMO-RESP charge set as well as with the standard AMBER charges, we found that the former gives better correlation with experimental affinities than the latter.


Input: While, for lysozyme with five ligands, both charge sets gave similar and relatively accurate estimates of binding affinities.


Input: (c) 2013 Wiley Periodicals, Inc.


Input: Systematic and efficient side chain optimization for molecular docking using a cheapest-path procedure.


Input: Molecular docking of small-molecules is an important procedure for computer-aided drug design.


Input: Modeling receptor side chain flexibility is often important or even crucial, as it allows the receptor to adopt new conformations as induced by ligand binding.


Input: However, the accurate and efficient incorporation of receptor side chain flexibility has proven to be a challenge due to the huge computational complexity required to adequately address this problem.


Input: Here we describe a new docking approach with a very fast, graph-based optimization algorithm for assignment of the near-optimal set of residue rotamers.


Input: We extensively validate our approach using the 40 DUD target benchmarks commonly used to assess virtual screening performance and demonstrate a large improvement using the developed side chain optimization over rigid receptor docking (average ROC AUC of 0. 693 vs. 0. 623).


Input: Compared to numerous benchmarks, the overall performance is better than nearly all other commonly used procedures.


Input: Furthermore, we provide a detailed analysis of the level of receptor flexibility observed in docking results for different classes of residues and elucidate potential avenues for further improvement.


Input: (c) 2013 Wiley Periodicals, Inc.


Input: Potential Genotoxicity of Traditional Chinese Medicinal Plants and Phytochemicals: An Overview.


Input: In the last decades, cases of poisoning due to herbal medicines have occurred in many countries; Chinese herbal medicines (CHMs) are occasionally involved.


Input: The experience gained from traditional use is efficient to detect immediate or near-immediate relationship between administration and toxic effects but is quite unlikely to detect medium-to long-term toxicities; thorough investigations of herbal medicines (toxicity assessments, active pharmacovigilance) appear then essential for their safe use.


Input: Genotoxicity is an especially insidious toxicity that may result in carcinoma development years after exposure; it can arise from multiple compounds, with or without metabolic activation.


Input: The present work reviews traditional CHMs and phytochemicals that have been shown to present a genotoxic hazard.


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


Input: Once-daily initiation of basal insulin as add-on to metformin: a 26-week, randomized, treat-to-target trial comparing insulin detemir with insulin glargine in patients with type 2 diabetes.

metformin


Input: AIMS: This study assessed the efficacy and safety of once-daily insulin initiation using insulin detemir (detemir) or insulin glargine (glargine) added to existing metformin in type 2 diabetes (T2D).

metformin


Input: METHODS: This 26-week, multinational, randomized, treat-to-target trial involved 457 insulin-na i ve adults with T2D (HbA1c 7-9%).


Input: Detemir or glargine was added to current metformin therapy [any second oral antidiabetic drug (OAD) discontinued] and titrated to a target fasting plasma glucose (FPG) <= 90 mg/dl (<= 5. 0 mmol/l).

metformin

glucose


Input: Primary efficacy endpoint was change in HbA1c.


Input: RESULTS: Mean (s. d.) HbA1c decreased with detemir and glargine by 0. 48 and 0. 74%-points, respectively, to 7. 48% (0. 91%) and 7. 13% (0. 72%) [estimated between-treatment difference, 0. 30 (95% CI: 0. 14-0. 46)].


Input: Non-inferiority for detemir at the a priori level of 0. 4%-points was not established.


Input: The proportions of patients reaching HbA1c <= 7% at 26 weeks were 38% and 53% (p = 0. 026) with detemir and glargine, respectively.


Input: FPG decreased ~ 43. 2 mg/dl (~ 2. 4 mmol/l) in both groups [non-significant (NS)].


Input: Treatment satisfaction was good for both insulins.


Input: Hypoglycaemia, which occurred infrequently, was observed less with detemir than glargine [rate ratio 0. 73 (95% CI 0. 54-0. 98)].


Input: The proportions of patients reaching HbA1c <= 7% without hypoglycaemia in the detemir and glargine groups were 32% and 38% (NS), respectively.


Input: Weight decreased with detemir [-0. 49 (3. 3) kg] and increased with glargine [+ 1. 0 (3. 1) kg] (95% CI for difference:-2. 17 to-0. 89 kg).


Input: CONCLUSION: While both detemir and glargine, when added to metformin therapy, improved glycaemic control, glargine resulted in greater reductions in HbA1c, while detemir demonstrated less weight gain and hypoglycaemia.

metformin


Input: Impact of model perfume molecules on the self-assembly of anionic surfactant sodium dodecyl 6-benzene sulfonate.

sodium dodecyl 6-benzene sulfonate


Input: The impact of two model perfumes with differing degrees of hydrophobicity/hydrophilicity, linalool (LL) and phenylethanol (PE), on the solution structure of anionic surfactant sodium dodecyl 6-benzene sulfonate, LAS-6, has been studied by small angle neutron scattering, SANS.

linalool

phenylethanol

sodium dodecyl 6-benzene sulfonate


Input: For both types of perfume molecules, complex phase behavior is observed.


Input: The phase behavior depends upon the concentration, surfactant/perfume composition, and type of perfume.


Input: The more hydrophilic perfume PE promotes the formation of more highly curved structures.


Input: At relatively low surfactant concentrations, small globular micelles, L1, are formed.


Input: These become perfume droplets, L (sm), stabilized by the surfactant at much higher perfume solution compositions.


Input: At higher surfactant concentrations, the tendency of LAS-6 to form more planar structures is evident.


Input: The more hydrophobic linalool promotes the formation of more planar structures.

linalool


Input: Combined with the greater tendency of LAS-6 to form planar structures, this results in the planar structures dominating the phase behavior for the LAS-6/linalool mixtures.

linalool


Input: For the LAS-6/linalool mixture, the self-assembly is in the form of micelles only at the lowest surfactant and perfume concentrations.

linalool


Input: Over most of the concentration-composition space explored, the structures are predominantly lamellar, L (alpha), or vesicle, L (v), or in the form of a lamellar/micellar coexistence.


Input: At low and intermediate amounts of LL, a significantly different structure is observed, and the aggregates are in the form of small, relatively monodisperse vesicles (i. e., nanovesicles), L (sv).


Input: (M)-and (P)-Bicelaphanol A, Dimeric Trinorditerpenes with Promising Neuroprotective Activity from Celastrus orbiculatus.

(M)-and (P)-Bicelaphanol A

Trinorditerpenes


Input: (M)-Bicelaphanol A (1) and (P)-bicelaphanol A (2), two unprecedented dimeric trinorditerpenes existing as atropisomers, together with their monomer celaphanol A (3), were isolated from the root bark of Celastrus orbiculatus.

(M)-Bicelaphanol A

(P)-bicelaphanol A

celaphanol A


Input: The structures and absolute configurations of 1 and 2 were determined by spectroscopic and single-crystal X-ray diffraction analyses.


Input: Compound 1 exhibited a significant in vitro neuroprotective effect against a hydrogen peroxide-induced cell viability decrease in PC12 cells at 1 mu M, while compounds 2 and 3 showed such effects at 10 mu M.

hydrogen peroxide


Input: Novel microbial transformation of desacetylcinobufagin by Fusarium avenaceum AS 3. 4594.

desacetylcinobufagin


Input: In this paper, the microbial transformation of desacetylcinobufagin (1) by Fusarium avenaceum AS 3. 4594 was investigated, and four metabolites were isolated and characterized as 3-keton-desacetylcinobufagin (2), 3-epi-desacetylcinobufagin (3), bufadienolide A (4), and 15 beta, 16 alpha-dihydroxyl-17 beta H-bufalin (5), respectively.

desacetylcinobufagin

bufadienolide A

15 beta, 16 alpha-dihydroxyl-17 beta H-bufalin


Input: Among them, 4 and 5 are new compounds.


Input: The cytotoxicities of transformed products (2-5) against Hela cells were also investigated.


Input: Dorsamin-A' s, Glycerolipids Carrying a Dehydrophenylalanine Ester Moiety from the Seed-Eating Larvae of the Bruchid Beetle Bruchidius dorsalis.

Dorsamin-A

Dehydrophenylalanine Ester


Input: Using a TLC autographic assay for radical-scavenging activity with the ABTS radical, the presence of lipophilic antioxidants in the larvae of the wild bruchid seed beetle Bruchidius dorsalis was detected.

ABTS


Input: Assay-guided fractionation of the CHCl (3)-soluble fraction of the larvae resulted in the isolation of new glycerolipids, designated dorsamin-A763,-A737,-A765,-A739, and-A767, comprising 1, 2-diacyl-sn-glycero-3-dehydrophenylalanine ester structural units.

CHCl (3)

dorsamin-A763,-A737,-A765,-A739, and-A767

1, 2-diacyl-sn-glycero-3-dehydrophenylalanine ester


Input: The ABTS radical scavenging activity of the dorsamin-A' s was comparable with or stronger than that of Trolox.

ABTS

dorsamin-A

Trolox


Input: Colloidal nanoplasmonics: from building blocks to sensing devices.


Input: Nanoplasmonics is a rapidly developing field of research and technology that is based on the ability of small metal particles to interact strongly with light of wavelength significantly larger than their size.


Input: The development of nanoplasmonics has been closely associated with the application of colloid science to the controlled growth of metal nanocrystals in solution and to directing the self-assembly of such nanocrystals into organized arrays with enhanced collective properties.


Input: Engineering the morphology and the assembly of metal nanoparticles is a key step toward the fabrication of devices with great potential in detection and diagnosis as well as in a wide variety of other fields.


Input: In this Feature Article, we provide an overview of the recent work in our laboratory, which in our view somehow reflects the evolution of the field itself and provides guidelines for future research.


Input: Four new eudesmane-type sesquiterpenoid lactones from atractylenolide II by biotransformation of rat hepatic microsomes.

eudesmane

sesquiterpenoid lactones

atractylenolide II


Input: The biotransformation of atractylenolide II, a major bioactive principle of the rhizomes of Atractylodes macrocephala Koidz., was investigated in vitro by incubation with rat hepatic microsomes pretreated with sodium phenobarbital.

atractylenolide II

sodium phenobarbital


Input: The biotransformation products were extracted and purified by chromatographic methods.


Input: Seven biotransformation products (BP1-BP7) were obtained and their structures were elucidated by NMR and MS data analyses and by comparison with the previously reported values, including four new compounds, namely 4 (R), 15-epoxy-atractylenolide II (BP1), 4 (R), 15-epoxy-13-hydroxyatractylenolide II (BP5), 4 (R), 15-epoxy-1 beta-hydroxyatractylenolide II (BP6), and 4 (R), 15-dihydroxyatractylenolide II (BP7).

4 (R), 15-epoxy-atractylenolide II

4 (R), 15-epoxy-13-hydroxyatractylenolide II

4 (R), 15-epoxy-1 beta-hydroxyatractylenolide II

4 (R), 15-dihydroxyatractylenolide II


Input: The biotransformation pathway of atractylenolide II by hepatic microsomes was deducted based on the structure resolution of the products.

atractylenolide II


Input: Resveratrol enhances exercise training responses in rats selectively bred for high running performance.

Resveratrol


Input: High Capacity Runner (HCR) rats have been developed by divergent artificial selection for treadmill endurance running capacity to explore an aerobic biology-disease connection.


Input: The beneficial effects of resveratrol supplementation have been demonstrated in endurance running and the antioxidant capacity of resveratrol is also demonstrated.

resveratrol

resveratrol


Input: In this study we examine whether 12weeks of treadmill exercise training and/or resveratrol can enhance performance in HCR.

resveratrol


Input: Indeed, resveratrol increased aerobic performance and strength of upper limbs of these rats.

resveratrol


Input: Moreover, we have found that resveratrol activated the AMP-activated protein kinase, SIRT1, and mitochondrial transcription factor A (p < 0. 05).

resveratrol

AMP


Input: The changes in mitochondrial fission/fusion and Lon protease/HSP78 levels suggest that exercise training does not significantly induce damage of proteins.


Input: Moreover, neither exercise training nor resveratrol supplementation altered the content of protein carbonyls.

resveratrol


Input: Changes in the levels of forkhead transcription factor 1 and SIRT4 could suggest increased fat utilization and improved insulin sensitivity.


Input: These data indicate, that resveratrol supplementation enhances aerobic performance due to the activation of the AMPK-SIRT1-PGC-1 alpha pathway.

resveratrol


Input: Antimicrobial, antiviral and antioxidant activities of " a gua-mel " from Portugal.


Input: " A gua-mel " is a honey-based product produced in Portugal for ancient times.


Input: Several attributes have been reported to " a gua-mel " particularly in the alleviation of simple symptoms of upper respiratory tract.


Input: Samples of " a gua-mel " from diverse beekeepers from different regions of Portugal were studied in what concerns antimicrobial, antioxidant and antiviral properties.


Input: The amounts of phenol and brown pigment were also evaluated and correlated with the antioxidant activities.

phenol


Input: A great variability on the levels of these compounds was found among samples which were responsible for the variability detected also on the antioxidant activities, independent on the method used.


Input: Generally, antioxidant activity correlated better with brown pigments' amount than with phenols' content.

phenols


Input: The antimicrobial activity found for " a gua-mel " samples confirm the virtues reported by popular findings.


Input: In addition, this work also reveals the antiviral properties of " a gua-mel " evidenced by a decrease on the infectivity of the Q beta bacteriophage.


Input: Lanostane-type triterpenoid and steroid from the stem bark of Klainedoxa gabonensis.

Lanostane

triterpenoid

steroid


Input: A new lanostane triterpenoid, 2-hydroxy-24-methylenelanostan-1, 8-dien-3-one named klainedoxalanostenone (1) with one new steroid, 6-O-acyl-beta-d-glucosyl-beta-sitosterol named klainedoxasterol (2) together with ten known compounds including six triterpenoids (3-8), two steroids (9, 10) and two tanins (11, 12) were isolated from the stem bark of Klainedoxa gabonensis.

lanostane triterpenoid

2-hydroxy-24-methylenelanostan-1, 8-dien-3-one

klainedoxalanostenone

steroid

6-O-acyl-beta-d-glucosyl-beta-sitosterol

klainedoxasterol

triterpenoids

steroids

tanins


Input: To the best of our knowledge, this is the first report of lanostane-type triterpenoids from this genus.

lanostane

triterpenoids


Input: Their structures were determined by extensive analysis of spectroscopic data (1D and 2D NMR, MS) and by comparison with literature data.


Input: The xanthine oxidase inhibitory activity of nine compounds (1-6, 8, 10 and 11) were evaluated.

xanthine


Input: Compound 5 showed a good xanthine oxidase inhibitory activity; the other tested compounds were moderately active.

xanthine


Input: Cytotoxic sesquiterpenes from Hedychium spicatum: Isolation, structure elucidation and structure-activity relationship studies.

sesquiterpenes


Input: Phytochemical investigation of chloroform extract from rhizomes of Hedychium spicatum resulted in the isolation of six new sesquiterpenes (1-6) along with fifteen known compounds (7-21).

chloroform

sesquiterpenes


Input: Their structures were elucidated on the basis of the extensive spectroscopic analyses (IR, Mass and NMR) and by comparison of the data with those reported in the literature.


Input: Further, cytotoxic activities of all the isolates were evaluated by determining their inhibitory effects against A-549, B-16, Hela, HT-29, NCI-H460, PC-3, IEC-6 and L-6 cancer cell lines.


Input: Results indicated that compounds 1 and 3 may serve as an important natural lead compounds for future development as they showed potent cytotoxic activity against Hela cell lines with an IC50 value of 0. 3 mu g/mL and 1. 80 mu g/mL, respectively.


Input: Investigation of the cumulative body burden of estrogen-3, 4-quinone in breast cancer patients and controls using albumin adducts as biomarkers.

estrogen-3, 4-quinone


Input: Both 17 beta-estradiol-2, 3-quinone (E2-2, 3-Q) and 17 beta-estradiol-3, 4-quinone (E2-3, 4-Q) are reactive metabolites of estrogen.

17 beta-estradiol-2, 3-quinone

E2-2, 3-Q

17 beta-estradiol-3, 4-quinone

E2-3, 4-Q

estrogen


Input: Elevation of E2-3, 4-Q to E2-2, 3-Q ratio is thought to be an important indicator of estrogen-induced carcinogenesis.

E2-3, 4-Q

E2-2, 3-Q

estrogen


Input: Our current study compared the cumulative body burden of these estrogen quinones in serum samples taken from Taiwanese women with breast cancer (n = 152) vs healthy controls (n = 75) by using albumin (Alb) adducts as biomarkers.

estrogen quinones


Input: Results clearly demonstrated the presence of cysteinyl adducts of E2-2, 3-Q-4-S-Alb and E2-3, 4-Q-2-S-Alb in all study population at levels ranging from 61. 7-1330 to 66. 6-1, 590 pmol/g, respectively.

cysteinyl

E2-2, 3-Q

E2-3, 4-Q


Input: Correlation coefficient between E2-2, 3-Q-4-S-Alb and E2-3, 4-Q-2-S-Alb was 0. 610 for controls and 0. 767 for breast cancer patients (p < 0. 001).

E2-2, 3-Q

E2-3, 4-Q


Input: We also noticed that in premenopausal subjects with body mass index (BMI) less than 27, background levels of E2-3, 4-Q-2-S-Alb was inversely proportional to BMI with about 25% increase in E2-3, 4-Q-2-S-Alb per 5 kg/m (2) decrease in BMI (p < 0. 001).

E2-3, 4-Q

E2-3, 4-Q


Input: In addition, we confirmed that mean levels of E2-3, 4-Q-2-S-Alb in breast cancer patients were ~ 5-fold greater than in those of controls (p < 0. 001).

E2-3, 4-Q


Input: Overall, this evidence suggests that disparity in estrogen disposition and the subsequent elevation of cumulative body burden of E2-3, 4-Q may play a role in the development of breast cancer.

estrogen

E2-3, 4-Q


Input: Co-extrusion as manufacturing technique for multilayer mini-matrices with dual drug release.


Input: The aim of this work was to develop by means of co-extrusion a multilayered dosage form characterized by a dual release profile of the same drug.


Input: Co-extrudates consisted of two concentric polymer matrices: a core having a lipophilic character and a coat with a hydrophilic character.


Input: Diclofenac sodium (DS) was incorporated as model drug in both layers.

Diclofenac sodium


Input: Several polymers were screened on the basis of their processability via hot melt extrusion (HME) and in vitro drug release.


Input: Polymer combinations with suitable properties (i. e., similar extrusion temperature, appropriate drug release profile) were processed via co-extrusion.


Input: (Co-) extruded samples were characterized in terms of solid state (XRD, SEM), in vitro drug release, core/coat adhesion, and bioavailability.


Input: Based on the polymer screening, two polymer combinations were selected for co-extrusion: ethylcellulose (core) combined with Soluplus (R) (coat) and polycaprolactone (core) with PEO (coat).

Soluplus

polycaprolactone

PEO


Input: These combinations were successfully co-extruded.


Input: XRD revealed that DS remained crystalline during extrusion in ethylcellulose, Soluplus (R), polycaprolactone, and PEO.

Soluplus

polycaprolactone

PEO


Input: The polycaprolactone/PEO combination could be processed at a lower temperature (70 degrees C), vs. 140 degrees C for ethylcellulose/Soluplus (R).

polycaprolactone

PEO

Soluplus


Input: The maximum drug load in core and coat depended on the extrusion temperature and the die dimensions, while adhesion between core and coat was mainly determined by the drug load and by the extrusion temperature.


Input: In vitro drug release from the co-extruded formulations was reflected in the in vivo behavior: formulations with a higher DS content in the coat (i. e., faster drug release) resulted in higher Cmax and higher AUC values.


Input: Co-extrusion is a viable method to produce in a single step a multilayer dosage form with dual drug release.


Input: NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage sites.


Input: ATR and ATM kinases are central to the checkpoint activation in response to DNA damage and replication stress.


Input: However, the nature of the signal, which initially activates these kinases in response to UV damage, is unclear.


Input: Here, we have shown that DDB2 and XPC, two early UV damage recognition factors, are required for the damage-specific ATR and ATM recruitment and phosphorylation.


Input: ATR and ATM physically interacted with XPC and promptly localized to the UV damage sites.


Input: ATR and ATM recruitment and their phosphorylation were negatively affected in cells defective in DDB2 or XPC functions.


Input: Consequently, the phosphorylation of ATR and ATM substrates, Chk1, Chk2, H2AX, and BRCA1 was significantly reduced or abrogated in mutant cells.


Input: Furthermore, UV exposure of cells defective in DDB2 or XPC resulted in a marked decrease in BRCA1 and Rad51 recruitment to the damage site.


Input: Conversely, ATR-and ATM-deficiency failed to affect the recruitment of DDB2 and XPC to the damage site, and therefore did not influence the NER efficiency.


Input: These findings demonstrate a novel function of DDB2 and XPC in maintaining a vital cross-talk with checkpoint proteins, and thereby coordinating subsequent repair and checkpoint activation.


Input: Balancing societal needs and regulatory certainty: the case study of peramivir in Japan.

peramivir


Input: Regulators must balance societal and medical requirements against the need for certainty about benefit and risk for new medicines.


Input: This is described in a case study of the expedited review and approval of peramivir, a novel neuraminidase inhibitor, in Japan in the context of the emergence of new strain of influenza in 2009.

peramivir


Input: The case illustrates the importance of regulatory science and transparency in supporting such decision making.


Input: Characterisation of non-warfarin-associated bleeding events reported to the Norwegian spontaneous reporting system.

warfarin


Input: OBJECTIVE: The aim of the study was to analyse non-warfarin-associated bleeding adverse drug events reported to the Norwegian spontaneous reporting system, with characterisation of the bleeding locations, outcome and drug interactions.

warfarin


Input: In addition, concordance in assessments between reporters and evaluators, trend shifts in reporting, and detection of potentially new adverse drug interaction signals were studied.


Input: METHODS: Data on bleeding events reported between 1 January 2003 and 31 December 2005 were retrieved from the Norwegian spontaneous reporting system database.


Input: RESULTS: Of 327 case reports of non-warfarin-associated bleeding events, 270 reports (82. 6%) were characterised as serious and 69 (21. 1%) had a fatal outcome.

warfarin


Input: One hundred and eighty-seven bleeds (57. 5%) were gastrointestinal, 57 (17. 4%) were cerebral, and 81 (24. 8%) were from other bleeding sites.


Input: The bleeding sites differed with respect to the patient' s age, drug use, diagnoses and outcomes.


Input: Of drugs associated with bleeding, nonsteroidal anti-inflammatory drugs (NSAIDs)/COX-2 inhibitors (145 reports) and acetylsalicylic acid (128 reports) were most frequently used.

acetylsalicylic acid


Input: Only fibrinolytics were associated with increased mortality.


Input: There was a 67. 4% correlation between reporters and evaluators in assessment of drugs associated with bleeding (P < 0. 001), with considerable variation in concordance between drug groups.


Input: CONCLUSION: Non-warfarin-associated bleeding events are associated with substantial mortality.

warfarin


Input: Old age, cerebral bleeds, number of drugs used, and use of fibrinolytics are all independently associated with increased mortality.


Input: The recognition of the bleeding risk of commonly used drugs such as acetylsalicylic acid and heparins may be insufficient among prescribers.

acetylsalicylic acid


Input: Translational repression of thymidylate synthase by targeting its mRNA.


Input: Resistance to drugs targeting human thymidylate synthase (TS) poses a major challenge in the field of anti-cancer therapeutics.


Input: Overexpression of the TS protein has been implicated as one of the factors leading to the development of resistance.


Input: Therefore, repressing translation by targeting the TS mRNA could help to overcome this problem.


Input: In this study, we report that the compound Hoechst 33258 (HT) can reduce cellular TS protein levels without altering TS mRNA levels, suggesting that it modulates TS expression at the translation level.

Hoechst 33258


Input: We have combined nuclear magnetic resonance, UV-visible and fluorescence spectroscopy methods with docking and molecular dynamics simulations to study the interaction of HT with a region in the TS mRNA.


Input: The interaction predominantly involves intercalation of HT at a CC mismatch in the region near the translational initiation site.


Input: Our results support the use of HT-like compounds to guide the design of therapeutic agents targeting TS mRNA.


Input: An investigation of the photophysical properties of minor groove bound and intercalated DAPI through quantum-mechanical and spectroscopic tools.

DAPI


Input: The fluorescent probe 4', 6-diamidino-2-phenylindole (DAPI) is a dye known to interact with polynucleotides in a non-univocal manner, both intercalation and minor groove binding modes being possible, and to specifically change its photophysical properties according to the different environments.

4', 6-diamidino-2-phenylindole

DAPI


Input: To investigate this behavior, quantum-mechanical calculations using time-dependent density functional theory (TDDFT), coupled with polarizable continuum and/or atomistic models, were performed in combination with spectroscopic measurements of the probe in the different environments, ranging from a homogeneous solution to the minor groove or intercalation pockets of double stranded nucleic acids.


Input: According to our simulation, the electronic transition involves a displacement of the electron charge towards the external amidine groups and this feature makes the absorption energies very environment-sensitive while a much smaller sensitivity is seen in the fluorescence energies.

amidine


Input: Moreover, the calculations show that the DAPI molecule, when minor groove bound to the nucleic acid, presents both a reduced geometrical flexibility because of the rigid DNA pocket and a reduced polarization due to the very " apolar " microenvironment.

DAPI


Input: All these effects can be used to better understand the observed enhancement of the fluorescence, which makes it an excellent marker for DNA.


Input: Type 2 Diabetes With Partial Lipodystrophy of the Limbs: A new lipodystrophy phenotype.


Input: OBJECIVELipodystrophies are categorized by the extent of fat loss (generalized vs. partial) and by inheritance (congenital vs. acquired).


Input: We examined whether a group of patients with partial lipodystrophy of the limbs (PLL), type 2 diabetes mellitus (T2DM), and an absence of a family history of lipodystrophy constitute a new clinical subtype. RESEARCH AND DESIGN METHODSTen women with T2DM and PLL were identified in academic diabetes clinics and were matched by age, sex, BMI, ethnicity, and diabetes status with 10 women with control T2DM without lipodystrophy.


Input: All patients were characterized by clinical evaluation and hyperinsulinemic clamp. RESULTSPatients with T2DM and PLL exhibited symmetrical loss of subcutaneous fat in forearms, or forearms plus calves, and acanthosis nigricans.


Input: Maximally stimulated glucose disposal rates were markedly reduced by 56% in the T2DM with PLL group compared with the control T2DM patients, whether normalized by body weight or surface area.

glucose


Input: Most PLL patients exhibited little or no insulin-mediated glucose uptake after subtraction of non-insulin-mediated glucose uptake.

glucose

glucose


Input: The T2DM with PLL group also had greater elevations in hepatic transaminases and triglycerides and earlier onset of diabetes compared with control T2DM. CONCLUSIONST2DM with PLL represents a previously unrecognized phenotype of lipodystrophy and of T2DM.

triglycerides


Input: These T2DM patients exhibit symmetrical lipodystrophy of the distal limbs, acanthosis nigricans, marked insulin resistance with little insulin-mediated glucose uptake, hypertriglyceridemia, and hepatic transaminase elevations, which are greater in severity than observed in patients with common T2DM.

glucose


Input: 5-Aza-2'-deoxycytidine inhibited PDGF-induced rat airway smooth muscle cell phenotypic switching.


Input: Airway smooth muscle (ASM) cell phenotypic switching played an important role in airway remodeling in asthma.


Input: In vitro platelet-derived growth factor (PDGF) induced ASM cell phenotypic switching from a mature to pro-remodeling phenotype, but the mechanism remained incompletely understood.


Input: This study was to explore the effect of DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (Aza-CdR) on PDGF-induced rat ASM cell phenotypic switching and biological behaviors.

Aza-CdR


Input: Rat airway smooth muscle (RASM) cells were obtained by primary explant techniques.


Input: Western blot, 3-dimensional gel contraction, transwell and wound healing assay, and MTT were applied to detect cell phenotypic switching, contractility, migration and proliferation, respectively.

MTT


Input: Cytoskeleton rearrangement was observed by immunofluorescence.


Input: Results showed Aza-CdR inhibited PDGF-induced down-regulation of contractile markers in RASM cells and increased cell contractility.

Aza-CdR


Input: Aza-CdR inhibited PDGF-induced RASM cell migration by abrogating cell morphology change and cytoskeletal reorganization and attenuated the effect of PDGF on proliferating cell nuclear antigen expression and cell cycle progression, ultimately cell proliferation.

Aza-CdR


Input: PDGF-induced DNA methyltransferase 1 (DNMT1) expression was mediated by activation of PI3K/Akt and ERK signaling in RASM cells.


Input: Selective depletion of DNMT1 protein by Aza-CdR inhibited PDGF-induced RASM cell phenotypic switching, revealing DNMT1-mediated DNA methylation was implicated in asthmatic ASM remodeling.

Aza-CdR


Input: We proposed for the first time that DNMT1 played a key role in PDGF-induced RASM cell phenotypic switching and Aza-CdR is promising in intervening ASM remodeling in asthma.

Aza-CdR


Input: Although study of abnormal DNA methylation in PDGF-stimulated ASM cells is in its infancy, this work contributes to providing new insights into the mechanism of ASM remodeling and may be helpful for developing effective treatments for airway remodeling in asthma.


Input: Use of gene expression data to determine effects on gonad phenotype in japanese medaka after exposure to trenbolone or estradiol.

trenbolone

estradiol


Input: Various aquatic bioassays using one of several fish species have been developed or are in the process of being developed by organizations like the US Environmental Protection Agency and the Office of Economic Cooperation and Development for testing potential endocrine-disrupting chemicals (EDCs).


Input: Often, these involve assessment of the gonad phenotype of individuals as a key endpoint that is inputted into a risk or hazard assessment.


Input: Typically, gonad phenotype is determined histologically, which involves specialized and time-consuming techniques.


Input: The methods detailed here utilize an entirely different methodology, reverse-transcription quantitative polymerase chain reaction, to determine the relative expression levels of 4 genes after exposure to either 17 beta-estradiol or 17 beta-trenbolone and, by extension, the effects of EDCs on the phenotypic status of the gonad.

17 beta-estradiol

17 beta-trenbolone


Input: The 4 genes quantified, Sox9b, protamine, Fig1 alpha, and ZPC1, are all involved in gonad development and maintenance in Japanese medaka (Oryzias latipes); these data were then inputted into a permutational multivariate analysis of variance to determine whether significant differences exist between treatment groups.


Input: This information in conjunction with the sexual genotype, which can be determined in medaka, can be used to determine adverse effects of exposure to EDCs in a similar fashion to the histologically determined gonad phenotype.


Input: Environ Toxicol Chem 2013; 32: 1344-1353.


Input: (c) 2013 SETAC.


Input: Absorption, distribution, and biotransformation of hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine in B6C3F1 mice (Mus musculus).

hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine


Input: Absorption, distribution, and biotransformation are 3 critical aspects affecting toxicant action in animals.


Input: In the present study, B6C3F1 mice (Mus musculus) were exposed for 28 d to contaminated feed that contained 1 of 5 different hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine (RDX) concentrations: 0 mg/kg, 0. 5 mg/kg, 5 mg/kg, 50 mg/kg, and 500 mg/kg.

hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine


Input: The authors quantified RDX and its reductive transformation products hexahydro-1-nitroso-3, 5-dinitro-1, 3, 5-triazine (MNX), hexahydro-1, 3-dinitroso-5-nitro-1, 3, 5-triazine (DNX), and hexahydro-1, 3, 5-trinitroso-1, 3, 5-triazine (TNX) in the stomach, intestine, plasma, liver, and brain of these mice.

hexahydro-1-nitroso-3, 5-dinitro-1, 3, 5-triazine

hexahydro-1, 3-dinitroso-5-nitro-1, 3, 5-triazine

hexahydro-1, 3, 5-trinitroso-1, 3, 5-triazine


Input: Average RDX concentrations followed a dose-dependent pattern for all matrices tested.


Input: No controls had concentrations above limits of detection.


Input: Average RDX concentrations in tissues of exposed mice ranged from 11. 1 ng/mL to 182 ng/mL, 25. 6 ng/g to 3319 ng/g, 123 ng/g to 233 ng/g, 144 ng/g to 35 900 ng/g, and 51. 1 ng/g to 2697 ng/g in the plasma, brain, liver, stomach, and intestine, respectively.


Input: A considerable amount of RDX was present in the brain, especially in the highest-exposure group.


Input: This is consistent with the widely observed central nervous system effects caused by gamma-aminobutyric acid inhibition associated with RDX exposure.

gamma-aminobutyric acid


Input: N-nitroso metabolites of RDX were also present in tested tissues in a dose-dependent pattern.

N-nitroso


Input: Average MNX concentrations in the stomachs of mice exposed to RDX ranged from nondetectable in control exposures to 490 ng/g in the highest-exposure groups.


Input: In the brain, MNX accumulated at a maximum average concentration of 165. 1 ng/g, suggesting the potential formation of MNX from RDX within the brain.


Input: At higher exposures, DNX and TNX were present in the stomach, plasma, and brain of mice.


Input: The presence of RDX metabolites at notable amounts in different tissues suggests that RDX can transform into its N-nitroso metabolites in vivo by an undefined mechanism.

N-nitroso


Input: Environ Toxicol Chem 2013; 32: 1295-1303.


Input: (c) 2013 SETAC.


Input: Cytotoxic triterpenoid saponins from the stems of Gordonia longicarpa.

triterpenoid saponins


Input: Nine new triterpenoid saponins named longicarposides A-I (1-9), together with three known saponins (10-12), were isolated from the stems of Gordonia longicarpa.

triterpenoid saponins

longicarposides A-I

saponins


Input: The structures of the saponins were elucidated by a combination of 1D and 2D NMR techniques, mass spectrometry, and chemical methods.

saponins


Input: They were characterized to be oleanane-type saponins with sugar moieties linked to C-3 of the aglycone.

oleanane

saponins

sugar


Input: Cytotoxic activities of these saponins were evaluated against five human tumor cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780) by using the MTT in vitro assay.

saponins

MTT


Input: Compounds 5, 7, 8, 10, and 11 exhibited potent cytotoxic activity with IC50 values of 1. 42-8. 42 micro M, while 6, 9, and 12 showed selective cytotoxic activity toward the tested cell lines.


Input: Bioavailability-based chronic toxicity measurements of permethrin to Chironomus dilutus.

permethrin


Input: Compared with acute toxicity, chronic exposures to low levels of contaminants are more environmentally relevant, but fewer data are available.


Input: In the present study, sediment toxicity of the pyrethoid permethrin to Chironomus dilutus was determined.

pyrethoid permethrin


Input: The whole-life-cycle toxicity testing was conducted with the endpoints covering survival, growth, emergence, and reproduction.


Input: Permethrin caused 50% lethality in C. dilutus at 1. 83 +/- 1. 13 micro g/g organic carbon (OC) and 1. 20 +/- 0. 55 micro g/g OC after exposures of 20 d (before pupation) and 58 d (the end of the testing), respectively.

Permethrin

carbon


Input: The 5% and median effect concentrations (EC5 and EC50) represented the marginal and toxic levels of the sublethal effects, respectively, and effect data were all normalized to the controls before Probit analysis.


Input: The EC5s for growth, emergence, and reproduction were 0. 034 +/- 0. 006 micro g/g OC, 0. 016 +/- 0. 008 micro g/g OC, and 0. 009 +/- 0. 008 micro g/g OC, respectively; the respective EC50s were 1. 09 +/- 0. 56 micro g/g OC, 0. 838 +/- 0. 077 micro g/g OC, and 0. 039 +/- 0. 105 micro g/g OC.


Input: In addition, a 24-h Tenax extraction was employed to better assess permethrin bioavailability.

permethrin


Input: Ultimately, response spectra with a series of endpoints were developed for permethrin using either OC-normalized bulk sediment concentrations or bioavailability-based Tenax extractable concentrations as the dose metric.

permethrin


Input: The development of bioavailability-based chronic toxicity endpoints for sediment-associated permethrin would provide valuable benchmarks for evaluating ecological risk of this contaminant and contributing to improve sediment management policies.


Input: Environ Toxicol Chem 2013; 32: 1403-1411.


Input: (c) 2013 SETAC.


Input: Air-plant exchange of brominated flame retardants at a rural site: Influencing factor, interspecies difference, and forest scavenging.


Input: Brominated flame retardants (BFRs) in eucalyptus leaves and pine needles from a rural site in southern China were measured to investigate the air-plant exchange.


Input: Mean concentrations of BFRs were higher in pine needles (79. 8 ng/g dry wt) than in eucalyptus leaves (74. 5 ng/g), whereas an inverse result was found for the leaf surface particles, with mean concentrations of 3490 ng/g and 5718 ng/g, respectively.


Input: For most of the BFRs, the correlations between their concentrations in plants and those in the vapor phase, atmospheric particles, leaf surface particles, and the environmental variables (temperature, wind speed, and relative humidity) at this site were in contrast to the results the authors observed at an electronic waste site previously, indicating that ambient air level plays a vital role in the relationships.


Input: The interspecies difference in the BFR profiles and the correlations above implied that pine needles likely have more advantages for uptake of BFRs from gaseous deposition than eucalyptus leaves, for which particle-bound deposition is more important.


Input: Like the electronic waste site, the leaf scavenging ratios of BFRs were also controlled by their octanol-air partition coefficient.


Input: It was estimated that approximately 154 kg of BFRs in the atmosphere are scavenged annually by forest in this region, which was 1. 7 times larger than that via atmospheric deposition to nonforest ground.


Input: Environ Toxicol Chem 2013; 32: 1248-1253.


Input: (c) 2013 SETAC.


Input: Rutin-and Selenium-attenuated cadmium-induced testicular pathophysiology in rats.

Rutin

Selenium

cadmium


Input: Cadmium (Cd) is known to cause oxidative damage in the testes of rats.

Cadmium

Cd


Input: The aim of this study was to investigate the protective role of rutin (RUT, 30 mg/kg) and selenium (Se, 0. 15 ppm) alone or in combination against Cd (200 ppm)-induced lipid peroxidation, steroidogenesis and changes in antioxidant defence system in the rat testes.

rutin

RUT

selenium

Se

Cd


Input: The obtained results showed that Cd increased lipid peroxidation and abnormal sperm count and decreased plasma testosterone, lactate dehydrogenase, acid phosphatase, alkaline phosphatase and testicular steroidogenic enzymes: 3 beta-hydroxysteroid dehydrogenase (HSD), 17 beta-HSD activities as well as epididymal sperm counts and motility, while RUT and Se treatment reversed this change to control values.

Cd

testosterone

lactate

3 beta-hydroxysteroid

RUT

Se


Input: Acute intoxication with Cd was also followed by significantly decreased activity of the antioxidant defence system (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione (GSH), and glutathione-S-transferase (GST)).

Cd

superoxide

glutathione

GSH

glutathione

glutathione

GSH

glutathione

S


Input: Treatment with RUT and Se reversed Cd-induced alterations of antioxidant defence system and significantly prevented Cd-induced testes damage and depletion of plasma and testicular Se levels.

RUT

Se

Cd

Cd

Se


Input: RUT and Se appear not to have more profound effects than their separate effects against Cd-induced testicular toxicity, although Se was more potent than RUT in the recovery of testosterone levels.

RUT

Se

Cd

Se

RUT

testosterone


Input: These results suggest that both RUT and Se do not have synergistic role against Cd-induced testicular injury.

RUT

Se

Cd


Input: Probucol and the cholesterol synthesis inhibitors simvastatin and triparanol regulate Iks channel function differently.

Probucol

cholesterol

simvastatin

triparanol


Input: Channels responsible for slowly activating delayed-rectifier potassium current (I (Ks)) are composed of KCNQ1 and KCNE1 subunits, and these channels play a role in the repolarization of cardiac action potentials.

potassium


Input: Recently, we showed that the antihyperlipidemic drug probucol, which induces QT prolongation, decreases the I (Ks) after 24-h treatment.

probucol


Input: In the present study, we investigated the effects of three cholesterol-lowering agents (probucol, an enhancer of cholesterol efflux; simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor; and triparanol, a 3 beta-hydroxysterol-^ 24-reductase inhibitor) on cholesterol synthesis, the KCNQ1 current (I (KCNQ1)), and the I (Ks) to clarify the differences in the modes of action of these agents on the I (Ks).

cholesterol

probucol

cholesterol

simvastatin

triparanol

3 beta-hydroxysterol

cholesterol


Input: Probucol did not inhibit cholesterol synthesis and had no effect on I (KCNQ1), while I (Ks) decreased after 24-h treatment.

Probucol

cholesterol


Input: Simvastatin inhibited cholesterol synthesis and decreased I (KCNQ1) and I (Ks).

Simvastatin

cholesterol


Input: Additionally, the activation kinetics of I (Ks) became faster, compared with that of control I (Ks).


Input: Triparanol inhibited cholesterol synthesis but did not reduce I (KCNQ1) and I (Ks).

Triparanol

cholesterol


Input: However, the activation kinetics of I (Ks) became faster.


Input: Our data indicated that the mechanism by which probucol inhibits I (Ks) was not mediated by the inhibition of cholesterol synthesis but depended on an interaction with the KCNQ1/KCNE1 complex.

probucol

cholesterol


Input: Meanwhile, the reduction in cholesterol induced by simvastatin and triparanol is one of the mechanisms that affects the kinetics of I (ks).

cholesterol

simvastatin

triparanol


Input: Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation.

Resveratrol

methotrexate


Input: Hepatotoxicity is one of the major complications of methotrexate (MTX) therapy.

methotrexate

MTX


Input: This study was carried out to evaluate the possible protective effect of resveratrol (trans-3, 5, 4'-trihydroxystilbene, RVT) against MTX-induced hepatotoxicity.

resveratrol

trans-3, 5, 4'-trihydroxystilbene

RVT

MTX


Input: Rats were randomly divided into four groups as control, MTX treated (7 mg/kg/day, intraperitoneally (i. p.), once daily for 3 consecutive days), MTX + RVT treated (20 mg/kg/day, i. p.), and RVT treated.

MTX

MTX

RVT

RVT


Input: First dose of RVT was administrated 3 days before the MTX injection and continued for 3 days.

RVT

MTX


Input: Histopathology of liver was evaluated by light microscopy.


Input: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury.

Aspartate

alanine

MTX


Input: The levels of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and activities of hepatic antioxidant enzymes such as catalase (CAT) and glutathione-S-transferase (GST) were used to analyze the oxidative stress-mediated lipid peroxidation in liver sections.

thiobarbituric acid

glutathione

S


Input: Our results showed that MTX administration significantly increased ALT, ASP, and ALP levels.

MTX


Input: TBARS, CAT, and GST levels were also markedly increased in liver after MTX administration.

MTX


Input: RVT treatment significantly prevented MTX-induced hepatotoxicity, as indicated by AST, ALT, and ALP levels and liver histopathology.

RVT

MTX


Input: Moreover, administration of RVT significantly decreased the elevated levels of TBARS and activities of CAT and GST in the liver compared to MTX-treated group.

RVT

MTX


Input: These results revealed that RVT may have a protective effect against MTX-induced hepatotoxicity by inhibiting oxidative stress-mediated lipid peroxidation.

RVT

MTX


Input: Consequently, RVT treatment might be a promising strategy against MTX-induced hepatotoxicity.

RVT

MTX


Input: Protective effect of the roots extract of Platycodon grandiflorum on bile duct ligation-induced hepatic fibrosis in rats.


Input: The aim of the present study was to evaluate the protective effect of aqueous extract from Platycodon grandiflorum (BC703) on bile duct ligation (BDL)-induced hepatic fibrosis in rats.


Input: BDL rats were divided into three groups, which orally received distilled water or BC703 (10 or 50 mg/kg/day) for consecutive 28 days.


Input: Antifibrotic effects of BC703 on BDL-induced hepatic fibrosis in rats were estimated by assessing serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood urea nitrogen (BUN), transforming growth factor-beta 1 (TGF-beta 1) and hepatic levels of malondialdehyde (MDA), glutathione (GSH), total superoxide dismutase (SOD) and nitric oxide (NO).

alanine

aspartate

bilirubin

urea nitrogen

malondialdehyde

MDA

glutathione

GSH

superoxide

nitric oxide

NO


Input: The biochemical observations were supplemented by histopathological examination of liver samples stained with hematoxylin and eosin and Masson' s trichrome stain.

hematoxylin

eosin


Input: ALT, AST, TBIL and BUN were elevated in the group treated with BDL alone than in the sham-operated group.


Input: These elevations were significantly decreased by BC703 treatment.


Input: Hepatic GSH and SOD levels, depressed by BDL, were also increased in the BC703 group.

GSH


Input: In addition, increases in hepatic MDA and NO levels in the BDL-induced cholestasis were attenuated by BC703 treatment.

MDA

NO


Input: Furthermore, BC703 treatment significantly reduced the serum level of fibrogenic cytokine, TGF-beta 1.


Input: Histopathological studies further substantiated the protective effect of BC703 on BDL-induced hepatic fibrosis in rat.


Input: BC703 may have beneficial effects not only on hepatic fibrosis by cholestasis but also on hepatic fibrosis development in patients with chronic hepatic disease.


Input: Clinical development of biosimilars: an evolving landscape.


Input: Biosimilars, or similar biological medicinal products, can provide a meaningful option for patients and physicians provided they deliver the therapeutic value of a reference product at a more modest cost.


Input: Unlike generic small-molecule drugs that require primarily the demonstration of pharmaceutical equivalence, the complex nature of protein therapeutics warrants a rigorous evaluation of both pharmaceutical and therapeutic equivalence to the reference product in an abbreviated clinical program.


Input: Furthermore, the lack of comprehensive structure-activity relationship data increases the burden on appropriately designed human clinical studies with predefined acceptance criteria to demonstrate the absence of clinically meaningful differences between the biosimilar and reference product.


Input: Although a number of biosimilar proteins have been approved, especially in Europe, issues on substitutability, extrapolation to other disease indications, and selection of reference standards and comparators, remains to be standardized at a global level.


Input: Structure of iron ions in some acetone based electrolytes.

iron

acetone


Input: X-ray absorption, M o ssbauer, and Raman spectroscopy were combined to determine the local environment of iron ions in acetone based solutions of FeCl2.

acetone


Input: It is shown that part of the Fe (II) ions change their oxidation state, accompanied by symmetry change from octahedral Fe (H2O) 6 (2 +) to tetrahedral [FeCl4] (-) at large acetone concentrations.

Fe (II)

Fe (H2O) 6 (2 +)

[FeCl4] (-)

acetone


Input: The ratio of Fe (II)/Fe (III) determined by M o ssbauer spectroscopy agrees well with that determined by the X-ray absorption studies.

Fe (II)

Fe (III)


Input: Raman measurements confirm quantitative estimations of [FeCl4] (-) species in acetone rich solutions.

[FeCl4] (-)

acetone


Input: Biotransformation of ursolic acid by Syncephalastrum racemosum CGMCC 3. 2500 and anti-HCV activity.

ursolic acid


Input: Microbial transformation of ursolic acid (UA, 3 beta-hydroxy-urs-12-en-28-oic acid, 1) by filamentous fungus Syncephalastrum racemosum CGMCC 3. 2500 was conducted.

ursolic acid

3 beta-hydroxy-urs-12-en-28-oic acid


Input: Five metabolites 3 beta, 7 beta, 21 beta-trihydroxy-urs-12-en-28-oic acid (2); 3 beta, 21 beta-dihydroxy-urs-11-en-28-oic acid-13-lactone (3); 1 beta, 3 beta, 21 beta-trihydroxy-urs-12-en-28-oic acid (4); 3 beta, 7 beta, 21 beta-trihydroxy-urs-1-en-28-oic acid-13-lactone (5); and 21-oxo-1 beta, 3 beta-dihydroxy-urs-12-en-28-oic acid (6) were afforded.

3 beta, 7 beta, 21 beta-trihydroxy-urs-12-en-28-oic acid

3 beta, 21 beta-dihydroxy-urs-11-en-28-oic acid-13-lactone

1 beta, 3 beta, 21 beta-trihydroxy-urs-12-en-28-oic acid

3 beta, 7 beta, 21 beta-trihydroxy-urs-1-en-28-oic acid-13-lactone

21-oxo-1 beta, 3 beta-dihydroxy-urs-12-en-28-oic acid


Input: Elucidation of the structures of these metabolites was primarily based on 1D and 2D NMR and HR-MS data.


Input: Metabolite 2 was a new compound.


Input: In addition, the anti-HCV activity of compounds 1-6 was evaluated.


Input: Biomarkers of Exposure and Effect in Human Lymphoblastoid TK6 Cells Following [13C2]-Acetaldehyde Exposure.


Input: The dose-response relationship for biomarkers of exposure (N (2)-ethylidene-dG adducts) and effect (cell survival and micronucleus formation) was determined across 4. 5 orders of magnitude (50nM-2mM) using [(13) C2]-acetaldehyde exposures to human lymphoblastoid TK6 cells for 12h.

N (2)-ethylidene-dG

[(13) C2]-acetaldehyde


Input: There was a clear increase in exogenous N (2)-ethylidene-dG formation at exposure concentrations >= 1 micro M, whereas the endogenous adducts remained nearly constant across all exposure concentrations, with an average of 3. 0 adducts/10 (7) dG.

N (2)-ethylidene-dG


Input: Exogenous adducts were lower than endogenous adducts at concentrations <= 10 micro M and were greater than endogenous adducts at concentrations >= 250 micro M.


Input: When the endogenous and exogenous adducts were summed together, statistically significant increases in total adduct formation over the endogenous background occurred at 50 micro M.


Input: Cell survival and micronucleus formation were monitored across the exposure range and statistically significant decreases in cell survival and increases in micronucleus formation occurred at >= 1000 micro M.


Input: This research supports the hypothesis that endogenously produced reactive species, including acetaldehyde, are always present and constitute the majority of the observed biological effects following very low exposures to exogenous acetaldehyde.

acetaldehyde

acetaldehyde


Input: These data can replace default assumptions of linear extrapolation to very low doses of exogenous acetaldehyde for risk prediction.

acetaldehyde


Input: The role of de novo catecholamine synthesis in mediating methylmercury-induced vesicular dopamine release from rat pheochromocytoma (PC12) cells.

catecholamine

methylmercury

dopamine


Input: The purpose of this study was to characterize methylmercury (MeHg)-induced dopamine (DA) release from undifferentiated pheochromocytoma (PC12) cells and to examine the potential role for DA synthesis in this process.

methylmercury

MeHg

dopamine