Input: Thus, a better understanding of the effects of mutations of this position in Cx32 may have relevance to pathogenesis of a number of different human diseases.


Input: All three mutants associated with CMT1X (R75P, R75Q, and R75W) showed very low levels of coupling similar to those of the cells transfected with vector alone.


Input: Heterotypic pairing with Cx32 WT showed that the absence of coupling for these mutants in the homotypic configuration could be explained by shifts in their hemichannel G (j)-V (j) relations.


Input: Examination of the expression levels and gating characteristics of seven additional mutants (R75A, R75D, R75E, R75H, R75K, R75L, and R75V) at this position suggest that the positive charge at position 75 in Cx32 is required for normal channel function but not for gap junction assembly.


Input: Our studies also suggest that disease treatment strategies for CMT1X, which correct trafficking abnormalities in Cx32, may be ineffective for the group of mutations also conferring changes in gating properties of Cx32 channels.


Input: Simulations of the two-dimensional electronic spectroscopy of the photosystem II reaction center.


Input: We report simulations of the two-dimensional electronic spectroscopy of the Q (y) band of the D1-D2-Cyt b559 photosystem II reaction center at 77 K.


Input: We base the simulations on an existing Hamiltonian that was derived by simultaneous fitting to a wide range of linear spectroscopic measurements and described within modified Redfield theory.


Input: The model obtains reasonable agreement with most aspects of the two-dimensional spectra, including the overall peak shapes and excited state absorption features.


Input: It does not reproduce the rapid equilibration from high energy to low energy excitonic states evident by a strong cross-peak below the diagonal.


Input: We explore modifications to the model to incorporate new structural data and improve agreement with the two-dimensional spectra.


Input: We find that strengthening the system-bath coupling and lowering the degree of disorder significantly improves agreement with the cross-peak feature, while lessening agreement with the relative diagonal/antidiagonal width of the 2D spectra.


Input: We conclude that two-dimensional electronic spectroscopy provides a sensitive test of excitonic models of the photosystem II reaction center and discuss avenues for further refinement of such models.


Input: Stabilization and inhibition of protein-protein interactions: the 14-3-3 case study.


Input: Small-molecule modulation of protein-protein interactions (PPIs) is one of the most exciting but also difficult fields in chemical biology and drug development.


Input: As one of the most important " hub " proteins with at least 200-300 interaction partners, the 14-3-3 proteins are an especially fruitful case for PPI intervention.


Input: Here, we summarize recent success stories in small-molecule modulation, both inhibition and stabilization, of 14-3-3 PPIs.


Input: The chemical breath of modulators includes natural products such as fusicoccin A and derivatives but also compounds identified via high-throughput and in silico screening, which has yielded a toolbox of useful inhibitors and stabilizers for this interesting class of adapter proteins.

fusicoccin A


Input: Protein-protein interactions (PPIs) are involved in almost all biological processes, with any given protein typically engaged in complexes with other proteins for the majority of its lifetime.


Input: Hence, proteins function not simply as single, isolated entities but display their roles by interacting with other cellular components.


Input: These different interaction patterns are presumably as important as the intrinsic biochemical activity status of the protein itself.


Input: The biological role of a protein is therefore decisively dependent on the underlying PPI network that furthermore can show great spatial and temporal variations.


Input: A thorough appreciation and understanding of this concept and its regulation mechanisms could help to develop new therapeutic agents and concepts.


Input: Self-assembly process of soft ferritin-PNIPAAm conjugate bionanoparticles at polar-apolar interfaces.

PNIPAAm


Input: We describe an in-depth investigation on the dynamics and assembly behavior at polar-apolar interfaces of ferritin-PNIPAAm conjugates (poly-N-isopropylacrylamide).

PNIPAAm

poly-N-isopropylacrylamide


Input: The stabilization of oil-water interfaces by the modified ferritin was investigated by dynamic surface tension measurements and compared to the individual components of the bionanoparticle conjugate, namely, unmodified ferritin and pure PNIMAAm of similar molecular weight.

PNIMAAm


Input: It was found that the modified ferritin, even at a low particle concentration, rapidly reduces the interfacial tension.


Input: The difference in interfacial stabilization was also shown by cryo-scanning electron microscopy and scanning force microscopy, which displayed very different morphologies at the polar-apolar interface for the unmodified ferritin, pure PNIPAAm, and the ferritin-PNIPAAm conjugate, respectively.

PNIPAAm

PNIPAAm


Input: The self-assembly of the ferritin-PNIPAAm was further analyzed by cryo-transmission electron microscopy and fluorescence microscopy, for which a fluorescently labeled polymer was used.

PNIPAAm


Input: Both techniques revealed details on the assembly of the protein-polymer conjugate at the oil-water interface.


Input: Simultaneous control of composition and register of an AAB-type collagen heterotrimer.


Input: Control over composition and register of the peptide chains in AAB-type collagen mimetic heterotrimers is critical in developing systems that show fidelity to native collagen.


Input: However, their design is challenging due to the eight competing states possible for a mixture of nonidentical peptides A and B.


Input: Interpeptide salt-bridges have been used previously as keystone interactions to bias the population of competing states to favor a target heterotrimer.


Input: The designed heterotrimers were electroneutral and relied on pairing of acidic and basic residues but could not differentiate between all of the competing states and reported systems populated either multiple heterotrimer compositions or registers.


Input: Here our design methodology includes both positive and negative elements.


Input: First, an excess of acidic or basic residues, which always remain unpaired, introduces a negative design component to destabilize the competing triple helical compositions and registers.


Input: Second, charge pairs introduce a positive design component and stabilize the target assembly.


Input: These antagonistic factors are optimized in the target heterotrimer that forms the maximum number of charge pairs and minimizes unpaired charged residues.


Input: Additionally, we find that not just the number of paired and unpaired residues are important, but also the type.


Input: By a systematic study of different types of charge pairs and unpaired residues, we are able to populate a single composition-single register AAB heterotrimer.


Input: The insights gained here may be useful in designing composition and register specific heterotrimeric ligands with domains that recognize collagen-binding proteins.


Input: Photoreversible micellar solution as a smart drag-reducing fluid for use in district heating/cooling systems.


Input: A photoresponsive micellar solution is developed as a promising working fluid for district heating/cooling systems (DHCs).


Input: It can be reversibly switched between a drag reduction (DR) mode and an efficient heat transfer (EHT) mode by light irradiation.


Input: The DR mode is advantageous during fluid transport, and the EHT mode is favored when the fluid passes through heat exchangers.


Input: This smart fluid is an aqueous solution of cationic surfactant oleyl bis (2-hydroxyethyl) methyl ammonium chloride (OHAC, 3. 4 mM) and the sodium salt of 4-phenylazo benzoic acid (ACA, 2 mM).

oleyl bis (2-hydroxyethyl) methyl ammonium chloride

OHAC

sodium

4-phenylazo benzoic acid

ACA


Input: Initially, ACA is in a trans configuration and the OHAC/ACA solution is viscoelastic and exhibits DR (of up to 80% relative to pure water).

ACA

OHAC

ACA


Input: At the same time, this solution is not effective for heat transfer.


Input: Upon UV irradiation, trans-ACA is converted to cis-ACA, and in turn, the solution is converted to its EHT mode (i. e., it loses its viscoelasticity and DR) but it now has a heat-transfer capability comparable to that of water.

trans-ACA

cis-ACA


Input: Subsequent irradiation with visible light reverts the fluid to its viscoelastic DR mode.


Input: The above property changes are connected to photoinduced changes in the nanostructure of the fluid.


Input: In the DR mode, the OHAC/trans-ACA molecules assemble into long threadlike micelles that impart viscoelasticity and DR capability to the fluid.

OHAC

trans-ACA


Input: Conversely, in the EHT mode the mixture of OHAC and cis-ACA forms much shorter cylindrical micelles that contribute to negligible viscoelasticity and effective heat transfer.

OHAC

cis-ACA


Input: These nanostructural changes are confirmed by cryo-transmission electron microscopy (cryo-TEM), and the photoisomerization of trans-ACA and cis-ACA is verified by (1) H NMR.

trans-ACA

cis-ACA

(1) H


Input: Kinase CK2 inhibition: an update.


Input: Protein kinase CK2 (Casein Kinase 2) is an essential, ubiquitous and highly pleiotropic protein kinase, implicated in several human diseases.


Input: In the last decade, several inhibitors of CK2, have been discovered and characterized to be ATP-competitive compounds.

ATP


Input: However, only one of them, CX-4945, has recently completed Phase I clinical trial as potential anticancer drug.


Input: In this review, we report all chemical classes of CK2 inhibitors available in literature, focusing our attention on conventional ATP-competitive and on non ATP-competitive inhibitors, which could represent a new frontier in CK2 inhibition and, consequently, a promising field of study in discovering new drug candidates.

ATP

ATP


Input: Bioprocessing of plant in vitro systems for the mass production of pharmaceutically important metabolites: paclitaxel and its derivatives.

paclitaxel


Input: Taxol (paclitaxel) and its derivatives are microtubule-stabilizing drugs widely used in the treatment of several types of cancer, including mammary, prostate, ovarian and non-small-cell lung carcinoma, as well as AIDS-associated Kaposi' s sarcoma and other types of tumor.

Taxol

paclitaxel


Input: Taxanes stabilize microtubules by enhancing their polymerization and inhibiting depolymerization.

Taxanes


Input: Microtubule dynamics are crucial to mitotic spindle formation and function; therefore, cells exposed to taxanes are unable to undergo chromosomal separation during mitosis, become arrested in the G2/M phases of the cell cycle, and are subsequently targeted for apoptosis.

taxanes


Input: Plant cell cultures are used for industrial-scale biotechnological production of important bioactive plant secondary metabolites, including the anticancer agent paclitaxel.

paclitaxel


Input: In the last two decades, there have been numerous empirical approaches to improve the biotechnological production of taxanes, leading to the conclusion that treatment of Taxus sp. cells with methyl jasmonate or other elicitors is the most effective strategy.

taxanes

methyl jasmonate


Input: However, little insight has been gained into how the elicitors increase taxane biosynthesis or how this process is regulated.

taxane


Input: In recent years, with the help of " omics " tools, a rational approach has provided new information about taxane metabolism and its control.

taxane


Input: Once pathway bottlenecks have been identified, it will be possible to engineer Taxus sp. cell lines with overexpression of genes that control the flux-limiting steps, thus boosting taxane productivity.

taxane


Input: This review describes the chemical and biological characterization of paclitaxel and its derivatives and discusses future prospects for their biotechnological production.

paclitaxel


Input: The pentacyclic triterpenoids in herbal medicines and their pharmacological activities in diabetes and diabetic complications.

pentacyclic triterpenoids


Input: Pentacyclic triterpenoids including the oleanane, ursane and lupane groups are widely distributed in many medicinal plants, such as Glycyrrhiza species, Gymnema species, Centella asiatica, Camellia sinensis, Crataegus species and Olea europaea, which are commonly used in traditional medicine for the treatment of diabetes and diabetic complications.

Pentacyclic triterpenoids

oleanane

ursane

lupane


Input: A large number of bioactive pentacyclic triterpenoids, such as oleanolic acid, glycyrrhizin, glycyrrhetinic acid, ursolic acid, betulin, betulinic acid and lupeol have shown multiple biological activities with apparent effects on glucose absorption, glucose uptake, insulin secretion, diabetic vascular dysfunction, retinopathy and nephropathy.

pentacyclic triterpenoids

oleanolic acid

glycyrrhizin

glycyrrhetinic acid

ursolic acid

betulin

betulinic acid

lupeol

glucose

glucose


Input: The versatility of the pentacyclic triterpenes provides a promising approach for diabetes management.

pentacyclic triterpenes


Input: Marine natural products with anti-HIV activities in the last decade.


Input: Marine organisms have been proven to be excellent sources of biologically active compounds against HIV.


Input: This review gives an overview of 132 natural products from marine sources obtained during the last decade (2002-2011), which exhibit anti-HIV activity toward different biological targets.


Input: Sponges contribute more than half of all anti-HIV natural products from marine organisms, mainly as alkaloids and cyclic depsipeptides.


Input: In addition, some macromolecules are considered as potential anti-HIV agents, including lectins from algae and marine invertebrates, as well as sulfated polysaccharides from algae.


Input: In the reviewed marine natural products, many active ingredients act as HIV entry inhibitors, one class of new anti-HIV agents, and may be regarded as potential candidates for the development of novel anti-HIV agents.


Input: The other features of development in the marine original anti-HIV natural products in this ten years are also discussed.


Input: Differential action of phytochemicals on platelet apoptosis: a biological overview.


Input: Platelets are anuclear blood cells originating from bone megakaryocytes.


Input: Despite being anuclear, their number is maintained by apoptosis, a process of programmed cell death.


Input: The rate of apoptotic death of platelets is accelerated by oxidative and shear stress, ex vivo storage (blood banking conditions) and certain pathophysiological disorders.


Input: These factors initiate apoptotic events through the mitochondria-mediated intrinsic pathway.


Input: Besides, apoptotic platelets also release phosphatidylserine-positive membrane fractions called microparticles, which cause fibrin deposition and thrombus formation, and are involved in the promulgation of a host of disease conditions including cardiovascular diseases.


Input: In this context, several phytochemicals have been reported to be cardioprotective and work by inhibiting platelet aggregation or by dissolving the fibrin clots.


Input: Besides, ample reports focus on the positive effects of phytochemicals on normal physiology of platelets, but do not focus on their adverse effects on platelets.


Input: Moreover, platelets are reported to be extremely sensitive to therapeutic components in the blood.


Input: For example, resveratrol and thymoquinone are hitherto known compounds to possess proapoptotic effects on platelets.

resveratrol

thymoquinone


Input: In contrast, cinnamtannin B1 and crocin exhibit antiapoptotic effects.

cinnamtannin B1

crocin


Input: Thus, the current review aims to elucidate the underlying mechanisms through which the phytochemicals mediate their effects on platelet apoptosis.


Input: Moreover, the need for scrutiny of therapeutic compounds for their effects on platelet functions before including them in treatment regimen is also being emphasized.


Input: Therapeutically important proteins from in vitro plant tissue culture systems.


Input: Plant cells cultured in liquid medium in bioreactors are now being used commercially to produce biopharmaceutical proteins.


Input: The emergence of in vitro plant cell culture as a production vehicle reflects the importance of key biosafety and biocontainment concerns affecting the competitiveness of alternative systems such as mammalian cell culture and agriculture.


Input: Food plant species are particularly attractive as hosts for in vitro protein production: the risk of transgene escape and food chain contamination is eliminated using containment facilities, while regulatory approval for oral delivery of drugs may be easier than if non-edible species were used.


Input: As in whole plants, proteolysis in cultured plant cells can lead to significant degradation of foreign proteins after synthesis; however, substantial progress has been made to counter the destructive effects of proteases in plant systems.


Input: Although protein secretion into the culture medium is advantageous for product recovery and purification, measures are often required to minimise extracellular protease activity and product losses due to irreversible surface adsorption.


Input: Disposable plastic bioreactors, which are being used increasingly in mammalian cell bioprocessing, are also being adopted for plant cell culture to allow rapid scale-up and generation of saleable product.


Input: This review examines a range of technical and regulatory issues affecting the choice of industrial production platform for foreign proteins, and assesses progress in the development of in vitro plant systems for biopharmaceutical production.


Input: Multi-aspect candidates for repositioning: data fusion methods using heterogeneous information sources.


Input: Drug repositioning, an innovative therapeutic application of an old drug, has received much attention as a particularly costeffective strategy in drug R & D Recent work has indicated that repositioning can be promoted by utilizing a wide range of information sources, including medicinal chemical, target, mechanism, main and side-effect-related information, and also bibliometric and taxonomical fingerprints, signatures and knowledge bases.


Input: This article describes the adaptation of a conceptually novel, more efficient approach for the identification of new possible therapeutic applications of approved drugs and drug candidates, based on a kernel-based data fusion method.


Input: This strategy includes (1) the potentially multiple representation of information sources, (2) the automated weighting and statistically optimal combination of information sources, and (3) the automated weighting of parts of the query compounds.


Input: The performance was systematically evaluated by using Anatomical Therapeutic Chemical Classification System classes in a cross-validation framework.


Input: The results confirmed that kernel-based data fusion can integrate heterogeneous information sources significantly better than standard rank-based fusion can, and this method provides a unique solution for repositioning; it can also be utilized for de novo drug discovery.


Input: The advantages of kernel-based data fusion are illustrated with examples and open problems that are particularly relevant for pharmaceutical applications.


Input: Synthesis and HIV-1 inhibitory activities of dicaffeoyl and digalloyl esters of quinic acid derivatives.

dicaffeoyl and digalloyl esters

quinic acid


Input: Twenty analogues of the anti-HIV-1 integrase (IN) inhibitors dicaffeoylquinic acids (DCQAs) were prepared.

dicaffeoylquinic acids

DCQAs


Input: Their IC (50) values for 3'-end processing and strand transfer against recombinant HIV-1IN were determined in vitro, and their cell toxicities and EC (50) against HIV-1 were measured in cells (ex vivo).


Input: Acetylated or benzylated and/or with cyclohexylidene group compounds exhibited no inhibition of integration in biochemical assays or viral replication in HIV-infected cells, with the exception of 16 and 36.

cyclohexylidene


Input: Removal of these groups, however, correlated with potent inhibition.


Input: Compounds 19, 31, and 38, all digalloyls, exhibited the most robust inhibitory performance in biochemical assays as well as in cell culture and less toxicity than other molecules in the current study.

digalloyls


Input: Histone methyltransferase inhibitors: novel epigenetic agents for cancer treatment.


Input: Epigenetics is defined as heritable changes in gene activity and expression that occur without alteration in DNA sequence.


Input: The gene transcription is strictly correlated to chromatin structure, which could undergo covalent modifications of histones involving acetylation, methylation, phosphorylation and ubiquitination.


Input: Alterations in histones are implicated in many diseases, including cancer, by leading to tumor suppressor silencing or pro-apoptotic proteins downregulation.


Input: Although post-translational addition of methyl groups to the histone lysine has been discovered three decades ago, the importance of this epigenetic modification has emerged only in the last few years.

methyl

lysine


Input: Thenceforward histone methyltransferase inhibitors have been developed as potential therapeutic cancer agents.


Input: It should not be long before some selective inhibitors make their way into clinical trials.


Input: This review is mainly focused on the evolution in the development of new epigenetic modifier molecules modulating histone marks.


Input: Probing of field-induced structures and tunable rheological properties of surfactant capped magnetically polarizable nanofluids.


Input: Oil-based nanofluid containing surfactant-capped magnetite nanoparticles are synthesized by a simple coprecipitation approach, and their magnetorheological properties are studied for different magnetic field strengths and volume fractions.


Input: We observe a distinct " plateau-like region " in the shear thinning viscosity curve, under an external magnetic field, possibly due to a peculiar alignment of the chains with respect to the field direction where the structure is stable against fragmentation.


Input: The observed plateau regime is reminiscent to that of kinetically arrested gel networks.


Input: Interestingly, such a plateau regime has been observed only above certain critical magnetic field when the dipolar interaction strength is much greater than the thermal energy where the aggregation becomes a nonequilibrium transport-limited process.


Input: The good collapse of specific viscosity data against Mason number for different magnetic field strengths onto a single curve suggests the dominance of hydrodynamic and magnetic forces on thermal force above a certain magnetic field strength.


Input: The observed increase in both static and dynamic yield stresses under the magnetic field confirms the formation of columnar structures that hinder the flow behavior.


Input: The hysteresis observed in the magnetic sweep experiments shows the inability of the chains to relax within the measurement time.


Input: The dynamic measurements confirm that the field-induced structures impart elastic behavior to the dispersion, which is found to increase with magnetic field and saturates at higher field strengths.


Input: Effects of dopamine D2/D3 receptor ligands on food-cocaine choice in socially housed male cynomolgus monkeys.

dopamine

cocaine


Input: Dopamine D2/D3 receptor partial agonists have been suggested as medications for cocaine dependence.

Dopamine

cocaine


Input: The present experiments examined the effect of acute and repeated administration of drugs with varying intrinsic efficacy at D2/D3 receptors on the relative reinforcing strength of cocaine.

cocaine


Input: Use of socially housed cynomolgus monkeys permitted the assessment of whether social status, known to alter D2/D3 receptor availability, influenced the behavioral effects of D2/D3 receptor compounds.


Input: The high-efficacy agonist R (-)-norpropylapomorphine [(-)-NPA], low-efficacy agonist aripiprazole (ARI), and antagonist eticlopride (ETIC) were administered acutely to monkeys self-administering cocaine under a food-cocaine choice procedure in which a cocaine self-administration dose-effect curve was determined daily.

R (-)-norpropylapomorphine

(-)-NPA

aripiprazole

ARI

eticlopride

ETIC

cocaine

cocaine

cocaine


Input: The effects of 5-day treatment with ARI and (-)-NPA were characterized under conditions in which monkeys did (ARI) or did not [ARI and (-)-NPA] self-administer cocaine during treatment.

(-)-NPA

ARI

ARI

(-)-NPA

cocaine


Input: When administered acutely, ARI and ETIC increased the choice of low cocaine doses, and only (-)-NPA decreased the choice of higher cocaine doses and cocaine intake; effects were similar across social ranks.

ARI

ETIC

cocaine

(-)-NPA

cocaine

cocaine


Input: When administered repeatedly while self administration occurred only on days 1 and 5 of treatment, ARI, but not (-)-NPA, decreased cocaine choice in dominant monkeys, whereas (-)-NPA, but not ARI, did so in subordinates.

ARI

(-)-NPA

cocaine

(-)-NPA

ARI


Input: When dominant monkeys self-administered cocaine on all five days of ARI treatment, however, these effects were not observed.

cocaine

ARI


Input: The results indicate that the behavioral effects of D2/D3 receptor agonists can differ according to intrinsic efficacy and subject characteristics.


Input: Moreover, these results suggest that exposure to cocaine during treatment can counteract treatment-induced reductions in the reinforcing effects of cocaine.

cocaine

cocaine


Input: Protective effect of 70% ethanolic extract of Lindera obtusiloba Blume on tert-butyl hydroperoxide-induced oxidative hepatotoxicity in rats.

tert-butyl hydroperoxide


Input: Lindera obtusiloba Blume, a native plant of East Asia, has traditionally been used as a folk medicine for liver disease.


Input: We studied the in vitro antioxidant and in vivo hepatoprotective activities of a 70% ethanolic extract of L. obtusiloba (LOE) containing 62. 9% quercitrin and 22. 0% afzelin.

quercitrin

afzelin


Input: LOE prevented tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells.

tert-butyl hydroperoxide

t-BHP


Input: Along with its high antioxidant potency in vitro, our animal study confirmed that pretreatment with LOE (500 or 2000 mg/kg) for 7 days prior to a single dose of t-BHP (i. p.: 0. 5 mmol/kg) significantly lowered the serum levels of alanine and aspartate aminotransferases.

t-BHP

alanine

aspartate


Input: In addition, glutathione levels were increased in the liver, and lipid peroxidation levels were decreased in a dose-dependent manner.

glutathione


Input: The histopathological examinations of rat livers showed that LOE significantly reduced the incidence of liver lesions induced by t-BHP.

t-BHP


Input: Therefore, we concluded that LOE has merit as a potent candidate to protect the liver against oxidative damage.


Input: Steroid receptor coactivator-1 mediates estrogenic actions to prevent body weight gain in female mice.

Steroid


Input: Estrogen receptor-alpha (ER alpha) expressed by hypothalamic proopiomelanocortin and steroidogenic factor-1 neurons largely mediates the antiobesity effects of estrogens in females.

Estrogen

estrogens


Input: However, the critical molecular events that are coupled to ER alpha and mediate estrogenic effects on energy balance remain unknown.


Input: In the current study, we demonstrated that steroid receptor coactivator-1 (SRC1), a nuclear receptor coactivator, is abundantly expressed by both proopiomelanocortin and steroidogenic factor-1 neurons.

steroid


Input: We further showed that central administration of an ER alpha agonist, propyl pyrazole triol, acutely increases physical interaction between SRC1 and ER alpha in the hypothalamus.

propyl pyrazole triol


Input: Finally, we demonstrated that the effects of estrogens on energy homeostasis are significantly blunted in female mice lacking SRC1 globally.

estrogens


Input: Collectively our results indicate that SRC1 is functionally required to mediate the antiobesity effects of estrogen-ER alpha signals.

estrogen


Input: ADP-ribosylation of guanosine by SCO5461 protein secreted from Streptomyces coelicolor.

ADP

guanosine


Input: The Streptomyces coelicolor A3 (2) genome encodes a possible secretion protein, SCO5461, that shares a 30% homology with the activity domains of two toxic ADP-ribosyltransferases, pierisins and mosquitocidal toxin.

ADP


Input: We found ADP-ribosylating activity for the SCO5461 protein product through its co-incubation with guanosine and NAD (+), which resulted in the formation of N (2)-(ADP-ribos-1-yl)-guanosine ((ar2) Guo), with a K (m) value of 110 mu M.

ADP

guanosine

NAD (+)

N (2)-(ADP-ribos-1-yl)-guanosine

(ar2) Guo


Input: SCO5461 was further found to ADP-ribosylate deoxyguanosine, GMP, dGMP, GTP, dGTP, and cyclic GMP with k (cat) values of 150-370 s (-1).

ADP

deoxyguanosine

GMP

dGMP

GTP

dGTP

cyclic GMP


Input: Oligo (dG), oligo (G), and yeast tRNA were also ADP-ribosylated by this protein, although with much lower k (cat) values of 0. 2 s (-1) or less.

ADP


Input: SCO5461 showed maximum ADP-ribosylation activity towards guanosine at 30 degrees C, and maintained 20% of these maximum activity levels even at 0 degrees C.

ADP


Input: This is the first report of the ADP-ribosylation of guanosine and guanine mononucleotides among the family members of various ADP-ribosylating enzymes.

ADP

guanosine

guanine mononucleotides

ADP


Input: We additionally observed secretion of the putative gene product, SCO5461, in liquid cultures of S. coelicolor.


Input: We thus designated the SCO5461 protein product as S. coelicolor ADP-ribosylating protein, ScARP.

ADP


Input: Our current results could offer new insights into not only the ADP-ribosylation of small molecules but also signal transduction events via enzymatic nucleoside modification by toxin-related enzymes.

ADP

nucleoside


Input: New avenues for anticoagulation in atrial fibrillation.


Input: Vitamin K antagonists (VKAs) were, until recently, the only option for chronic anticoagulation in patients with atrial fibrillation.

Vitamin K


Input: Three new oral anticoagulants have been tested for this indication in recent randomized trials: dabigatran, rivaroxaban, and apixaban.

dabigatran

rivaroxaban

apixaban


Input: They offer the promise of consistent effect without the need for monitoring drug levels.


Input: Overall, efficacy and safety appear to be noninferior, and in some instances superior, to warfarin.

warfarin


Input: However, the new drugs have their downsides, and switching from warfarin is not recommended for all patients.

warfarin


Input: This review focuses on the available evidence and attempts to provide guidance to clinicians in the field.


Input: Computation as the mechanistic bridge between precision medicine and systems therapeutics.


Input: Over the past 50 years, like molecular cell biology, medicine and pharmacology have been driven by a reductionist approach.


Input: The focus on individual genes and cellular components as disease loci and drug targets has been a necessary step in understanding the basic mechanisms underlying tissue/organ physiology and drug action.


Input: Recent progress in genomics and proteomics, as well as advances in other technologies that enable large-scale data gathering and computational approaches, is providing new knowledge of both normal and disease states.


Input: Systems-biology approaches enable integration of knowledge from different types of data for precision medicine and systems therapeutics.


Input: In this review, we describe recent studies that contribute to these emerging fields and discuss how together these fields can lead to a mechanism-based therapy for individual patients.


Input: Theoretical study of the reaction of CH2XO (X = F, Cl, Br) radicals with the NO radical.

F

Cl

Br

NO


Input: In this paper, we focus on the multiple-channel reactions of CH (2) XO (X = F, Cl, Br) radicals with the NO radical by means of direct dynamic methods.

CH (2) XO

F

Cl

Br

NO


Input: All structures of the stationary points were obtained at the MP2/6-311 + G (d, p) level and vibrational frequency analysis was also performed at this level of theory.


Input: The minimum energy path (MEP) was obtained via the intrinsic reaction coordinate (IRC) theory at the MP2/6-311 + G (d, p) level, and higher-level energetic information was refined by the MC-QCISD method.


Input: The rate constants for the three hydrogen abstraction reaction channels over the temperature range 200-1, 500 K were calculated by the improved canonical variational transition state theory (ICVT) with a correction for small-curvature tunneling (SCT).

hydrogen


Input: The rate constants calculated in this manner were in good agreement with the available experimental data, and the three-parameter rate-temperature formulae for the temperature range 200-1, 500 K were k (1a) (T) = 0. 32 x 10 (-18) T (1. 83) exp (1748. 54/T), k (2a) (T) = 0. 22 x 10 (-19) T (2. 19) exp (1770. 19/T), k (3a) (T) = 0. 88 x 10 (-20) T (2. 20) exp (1513. 82/T) (in units of cm (3) molecule (-1) s (-1)).


Input: The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits.


Input: Outer hair cells (OHCs) are a mammalian innovation for mechanically amplifying sound energy to overcome the viscous damping of the cochlear partition.


Input: Although the voltage-dependent OHC membrane motor, prestin, has been demonstrated to be essential for mammalian cochlear amplification, the molecular mechanism by which prestin converts electrical energy into mechanical displacement/force remains elusive.


Input: Identifying mutations that alter the motor function of prestin provides vital information for unraveling the energy transduction mechanism of prestin.


Input: We show that the V499G/Y501H mutation does not deprive prestin of its voltage-induced motor activity, but it does significantly impair the fast motor kinetics and voltage operating range.


Input: Furthermore, mutagenesis studies suggest that Val-499 is the primary site responsible for these changes.

Val


Input: We also show that V499G/Y501H prestin forms heteromers with wild-type prestin and that the fast motor kinetics of wild-type prestin is not affected by heteromer formation with V499G/Y501H prestin.


Input: These results suggest that prestin subunits are individually functional within a given multimer.


Input: Adsorption of phenanthrene, 2-naphthol, and 1-naphthylamine to colloidal oxidized multiwalled carbon nanotubes: effects of humic acid and surfactant modification.

phenanthrene

carbon


Input: Carbon nanotubes (CNTs) can exist in the form of colloidal suspension in aquatic environments, particularly in the presence of natural organic matter or surfactants, and may significantly affect the fate and transport of organic contaminants.

Carbon


Input: In the present study, the authors examined the adsorption of phenanthrene, 2-naphthol, and 1-naphthylamine to three colloidal CNTs, including a stable suspension of oxidized multiwalled carbon nanotubes (O-MWNT), a humic acid (HA)-modified colloidal O-MWNT, and a sodium dodecyl sulfate (SDS)-modified colloidal O-MWNT.

phenanthrene

carbon

sodium dodecyl sulfate

SDS


Input: All three colloidal O-MWNTs exhibit strong adsorption affinities to the three test compounds (with K (OC) values orders of magnitude greater than those of natural organic matter), likely resulting from strong nonhydrophobic interactions such as pi-pi electron donor-acceptor interactions and Lewis acid-base interactions.

Lewis acid


Input: When thoroughly mixed, HA (at ~ 310 mg HA/g CNT) and SDS (at ~ 750 mg SDS/g CNT) significantly affected the aggregation properties of O-MWNT, causing individually dispersed tubes to form a loosely entangled network.

SDS

SDS


Input: The effects of HA or SDS modification on adsorption are twofold.

SDS


Input: Adsorption of HA/SDS significantly reduces surface areas of O-MWNT; however, the entangled network allows adsorbate molecules to interact simultaneously with multiple tubes.

SDS


Input: An important implication is that humic substances and surfactant-like materials not only facilitate the formation of colloidal carbon nanoparticles but also affect how these colloidal carbon nanoparticles adsorb organic contaminants.

carbon

carbon


Input: Immunological and reproductive health assessment in herring gulls and black-crowned night herons in the Hudson-Raritan Estuary.


Input: Previous studies have shown inexplicable declines in breeding waterbirds within western New York/New Jersey Harbor between 1996 and 2002 and elevated polychlorinated dibenzo-p-dioxins and polychlorinated biphenyls (PCBs) in double-crested cormorant (Phalacrocorax auritus) eggs.

polychlorinated dibenzo-p-dioxins

polychlorinated biphenyls

PCBs


Input: The present study assessed associations between immune function, prefledgling survival, and selected organochlorine compounds and metals in herring gulls (Larus argentatus) and black-crowned night herons (Nycticorax nycticorax) in lower New York Harbor during 2003.

organochlorine


Input: In pipping gull embryos, lymphoid cells were counted in the thymus and bursa of Fabricius (sites of T and B lymphocyte maturation, respectively).


Input: The phytohemagglutinin (PHA) skin response assessed T cell function in gull and heron chicks.


Input: Lymphocyte proliferation was measured in vitro in adult and prefledgling gulls.


Input: Reference data came from the Great Lakes and Bay of Fundy.


Input: Survival of prefledgling gulls was poor, with only 0. 68 and 0. 5 chicks per nest surviving to three and four weeks after hatch, respectively.


Input: Developing lymphoid cells were reduced 51% in the thymus and 42% in the bursa of gull embryos from New York Harbor.


Input: In vitro lymphocyte assays demonstrated reduced spontaneous proliferation, reduced T cell mitogen-induced proliferation, and increased B cell mitogen-induced proliferation in gull chicks from New York Harbor.


Input: The PHA skin response was suppressed 70 to 80% in gull and heron chicks.


Input: Strong negative correlations (r =-0. 95 to-0. 98) between the PHA response and dioxins and PCBs in gull livers was strong evidence suggesting that these chemicals contribute significantly to immunosuppression in New York Harbor waterbirds.

dioxins

PCBs


Input: Reduced graphene oxide nanoribbon networks: a novel approach towards scalable fabrication of transparent conductive films.

Reduced graphene oxide


Input: An innovative approach is developed for the high-throughput, large-area, and low-cost fabrication of reduced graphene oxide (RGO) nanoribbon networks by using electrospun polymer-based nanowires as the etching mask.

reduced graphene oxide

RGO


Input: Combined with their tunable, controllable structures and transmittance/conductivity properties, the as-fabricated RGO nanoribbon networks exhibit potential as transparent conductive film electrodes, for example, in electrochromic devices.

RGO


Input: Estradiol exerts antiapoptotic effects in skeletal myoblasts via mitochondrial PTP and MnSOD.

Estradiol


Input: 17 beta-Estradiol (E (2)) protects several non-reproductive tissues from apoptosis, including skeletal muscle.

17 beta-Estradiol


Input: We have shown that E (2) at physiological concentrations prevented apoptosis induced by H (2) O (2) in C2C12 skeletal myoblasts.

H (2) O (2)


Input: As we also demonstrated the presence of estrogen receptors in mitochondria, the present work was focused on the effects of E (2) on this organelle.

estrogen


Input: Specifically, we evaluated the actions of E (2) on the mitochondrial permeability transition pore (MPTP) by the calcein-acetoxymethylester/cobalt method using fluorescence microscopy and flow cytometry.

calcein

acetoxymethylester

cobalt


Input: Pretreatment with E (2) prevented MPTP opening induced by H (2) O (2), which preceded loss of mitochondrial membrane potential.

H (2) O (2)


Input: In addition, it was observed that H (2) O (2) induced translocation of Bax to mitochondria; however, in the presence of the steroid this effect was abrogated suggesting that members of the Bcl-2 family may be regulated by E (2) to exert an antiapoptotic effect.

H (2) O (2)

steroid


Input: Moreover, E (2) increased mitochondrial manganese superoxide dismutase protein expression and activity, as part of a mechanism activated by E (2) that improved mitochondrial performance.

superoxide


Input: Our results suggest a role of E (2) in the regulation of apoptosis with a clear action at the mitochondrial level in C2C12 skeletal myoblast cells.


Input: Tracking the mechanism of fibril assembly by simulated two-dimensional ultraviolet spectroscopy.


Input: Alzheimer' s disease (AD) is a neurodegenerative disorder characterized by the accumulation of plaque deposits in the human brain.


Input: The main component of these plaques consists of highly ordered structures called amyloid fibrils, formed by the amyloid beta-peptide (A beta).


Input: The mechanism connecting A beta and AD is yet undetermined.


Input: In a previous study, a coarse-grained united-residue model and molecular dynamics simulations were used to model the growth mechanism of A beta amyloid fibrils.


Input: On the basis of these simulations, a dock/lock mechanism was proposed, in which A beta fibrils grow by adding monomers at either end of an amyloid fibril template.


Input: To examine the structures in the early time-scale formation and growth of amyloid fibrils, simulated two-dimensional ultraviolet spectroscopy is used.


Input: These early structures are monitored in the far ultraviolet regime (lambda = 190-250 nm) in which the computed signals originate from the backbone n pi * and pi pi * transitions.


Input: These signals show distinct cross-peak patterns that can be used, in combination with molecular dynamics, to monitor local dynamics and conformational changes in the secondary structure of A beta-peptides.


Input: The protein geometry-correlated chiral xxxy signal and the non-chiral combined signal xyxy-xyyx were found to be sensitive to, and in agreement with, a dock/lock pathway.


Input: Preparation of functionalized alkynyl magnetic microspheres for the selective enrichment of cell glycoproteins based on click chemistry.

alkynyl


Input: Functionalized alkynyl polyvinyl alcohol magnetic microspheres (PVA MMs) were developed for the specific enrichment of sialic acid-rich glycoproteins by click chemistry.

alkynyl polyvinyl alcohol

PVA

sialic acid


Input: The capture capability for proteins was evaluated through a novel dual-labeled bovine serum albumin (BSA) that utilizes fluorescence resonance energy transfer (FRET).


Input: The PVA MM parameters, including the size and coverage of functionalized groups, were optimized by response surface methodology.

PVA


Input: The optimal parameters obtained were 1. 25-6. 31 mu m in size and 48. 53-73. 05% in coverage.


Input: Then, the optimal PVA MMs were synthesized, and the morphology and surface chemical properties were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR).

PVA


Input: To capture glycoproteins from the cell surface, a bioorthogonal chemical method was applied to metabolically label them with an azide group.

azide


Input: The functionalized alkynyl PVA MMs showed a high specificity and strong binding capability for glycoproteins through a [3 + 2] cycloaddition reaction.

alkynyl PVA


Input: The results indicated that the functionalized alkynyl PVA MMs could be applied to the enrichment of cell glycoproteins, and the merits of the MMs suggested an attractive and potential way to facilitate glycoprotein research.

alkynyl PVA


Input: Functional imaging of legumain in cancer using a new quenched activity-based probe.


Input: Legumain is a lysosomal cysteine protease whose biological function remains poorly defined.

cysteine


Input: Legumain activity is up-regulated in most human cancers and inflammatory diseases most likely as the result of high expression in populations of activated macrophages.


Input: Within the tumor microenvironment, legumain activity is thought to promote tumorigenesis.


Input: To obtain a greater understanding of the role of legumain activity during cancer progression and inflammation, we developed an activity-based probe that becomes fluorescent only upon binding active legumain.


Input: This probe is highly selective for legumain, even in the context of whole cells and tissues, and is also a more effective label of legumain than previously reported probes.


Input: Here we present the synthesis and application of our probe to the analysis of legumain activity in primary macrophages and in two mouse models of cancer.


Input: We find that legumain activity is highly correlated with macrophage activation and furthermore that it is an ideal marker for primary tumor inflammation and early stage metastatic lesions.


Input: Optical pumping of a single electron spin bound to a fluorine donor in a ZnSe nanostructure.

fluorine

ZnSe


Input: Here we demonstrate optical pumping of a single electron within a semiconductor nanostructure comprised of a single fluorine donor located within a ZnSe/ZnMgSe quantum well.

fluorine

ZnSe

ZnMgSe


Input: Experiments were performed to detect optical pumping behavior by observing single photons emitted from the nanostructure when the electron changes spin state.


Input: These results demonstrate initialization and read-out of the electron spin qubit and open the door for coherent optical manipulation of a spin by taking advantage of an unconventional nanostructure.


Input: Improved analysis for determining diffusion coefficients from short, single-molecule trajectories with photoblinking.


Input: Two maximum likelihood estimation (MLE) methods were developed for optimizing the analysis of single-molecule trajectories that include phenomena such as experimental noise, photoblinking, photobleaching, and translation or rotation out of the collection plane.


Input: In particular, short, single-molecule trajectories with photoblinking were studied, and our method was compared to existing analytical techniques applied to simulated data.


Input: The optimal method for various experimental cases was established, and the optimized MLE method was applied to a real experimental system: single-molecule diffusion of fluorescent molecular machines known as nanocars.


Input: Aqueous extracts of Roselle (Hibiscus sabdariffa Linn.) varieties inhibit alpha-amylase and alpha-glucosidase activities in vitro.


Input: This study sought to investigate the inhibitory effect of aqueous extracts of two varieties (red and white) of Hibiscus sabdariffa (Roselle) calyces on carbohydrate hydrolyzing enzymes (alpha-amylase and alpha-glucosidase), with the aim of providing the possible mechanism for their antidiabetes properties.

carbohydrate


Input: Aqueous extracts were prepared (1: 100 w/v) and the supernatant used for the analysis.


Input: The extracts caused inhibition of alpha-amylase and alpha-glucosidase activities in vitro. The IC (50) revealed that the red variety (25. 2 mu g/mL) exhibited higher alpha-glucosidase inhibitory activity than the white variety (47. 4 mu g/mL), while the white variety (90. 5 mu g/mL) exhibited higher alpha-amylase inhibitory activity than the red variety (187. 9 mu g/mL).


Input: However, the alpha-glucosidase inhibitory activities of both calyces were higher than that of their alpha-amylase.


Input: In addition, the red variety possessed higher antioxidant capacity as exemplified by the (*) OH scavenging abilities, Fe (2 +) chelating ability, and inhibition of Fe (2 +)-induced pancreatic lipid peroxidation in vitro.

(*) OH

Fe (2 +)

Fe (2 +)


Input: The enzyme inhibitory activities and antioxidant properties of the roselle extracts agreed with their phenolic content.

phenolic


Input: Hence, inhibition of alpha-amylase and alpha-glucosidase, coupled with strong antioxidant properties could be the possible underlying mechanism for the antidiabetes properties of H. sabdariffa calyces; however, the red variety appeared to be more potent.


Input: Extruder scale-up assessment in the process of extrusion-spheronization: comparison of radial and axial systems by a design of experiments approach.


Input: Scaling-up the extrusion-spheronization process involves the separate scale-up of each of the five process steps: dry mixing, granulation, extrusion, spheronization, and drying.


Input: The aim of the study was to compare two screw extrusion systems regarding their suitability for scaling-up.


Input: Two drug substances of high-and low-solubility in water were retained at different concentrations as formulation variables.


Input: Different spheronization times were tested.


Input: The productivity of the process was followed up using the extrusion rate and yield.


Input: Pellets were characterized by their size and shape, and by their structural and mechanical properties.


Input: A response surface design of experiments was built to evaluate the influence of the different variables and their interactions on each response, and to select the type of extrusion which provides the best results in terms of product quality, the one which shows less influence on the product after scale-up (" scalability ") and when the formula used changes (" robustness "), and the one which allows the possibility to adjust pellet properties with spheronization variables (" flexibility ").


Input: Axial system showed the best characteristics in terms of product quality at lab and industrial scales, the best robustness at industrial scale, and the best scalability, by comparison with radial system.


Input: Axial system thus appeared as the easiest scaled-up system.


Input: Compared to lab scale, the conclusions observed at industrial scale were the same in terms of product quality, but different for robustness and flexibility, which confirmed the importance to test the systems at industrial scale before acquiring the equipment.


Input: Ameliorative effect of aspalathin from rooibos (Aspalathus linearis) on acute oxidative stress in Caenorhabditis elegans.

aspalathin


Input: Rooibos leaves and fine stems (Aspalathus linearis; Fabaceae) are increasingly enjoyed as herbal tea, largely in fermented (oxidised) red-brown form, but also in unfermented (unoxidised) green form.


Input: Rooibos is rich in antioxidant polyphenols, with the dihydrochalcone, aspalathin, as a major active ingredient.

polyphenols

dihydrochalcone

aspalathin


Input: We used Caenorhabditis elegans as model organism to investigate the effect of rooibos extracts against oxidative stress in vivo.


Input: In a high glucose environment, C. elegans treated with rooibos extract exhibited an extended lifespan.

glucose


Input: Furthermore, green rooibos was a more potent antioxidant than red rooibos, probably due to its substantially higher aspalathin content.

aspalathin


Input: In addition, rooibos decreased acute oxidative damage caused by the superoxide anion radical generator, juglone, with aspalathin playing a major role in improving the survival rate of C. elegans.

superoxide

juglone

aspalathin


Input: Quantitative real-time PCR results demonstrated that aspalathin targets stress and ageing related genes, reducing the endogenous intracellular level of ROS.

aspalathin


Input: These findings suggest that rooibos increases stress resistance and promotes longevity under stress, probably mediated via a regulation of the DAF-16/FOXO insulin-like signalling pathway, supporting some of the health claims put forward for rooibos tea.


Input: Synthesis, antimalarial activity and cytotoxic potential of new monocarbonyl analogues of curcumin.

monocarbonyl

curcumin


Input: A series of novel monocarbonyl analogues of curcumin have been designed, synthesized and tested for their activity against Molt4, HeLa, PC3, DU145 and KB cancer cell lines.

monocarbonyl

curcumin


Input: Six of the analogues showed potent cytotoxicity towards these cell lines with IC (50) values below 1 mu M, which is better than doxorubicin, a US FDA approved drug.

doxorubicin


Input: Several analogues were also found to be active against both CQ-resistant (W2 clone) and CQ-sensitive (D6) strains of Plasmodium falciparum in an in-vitro antimalarial screening.


Input: This level of activity warrants further investigation of the compounds for development as anticancer and antimalarial agents.


Input: Combining structure and function to evaluate glaucomatous progression: implications for the design of clinical trials.


Input: The selection of a suitable method for assessment of glaucomatous progression and estimation of rates of change is an essential component of the design of clinical trials investigating neuroprotective therapies for the disease.


Input: Due to the limitations of currently available tests, approaches combining structural and functional tests are essential in order to provide reliable detection of endpoints.


Input: This could also potentially enable shorter clinical trials with relatively smaller sample size requirements.


Input: A recent approach for estimating rates of retinal ganglion cell loss using a combination of structural and functional tests has been shown to perform better than isolated parameters from conventional tests for diagnosing, staging and detecting glaucoma progression and may prove useful as an outcome measure in clinical trials of the disease.


Input: Inhibitory effects of metachromins L-Q and its related analogs against receptor tyrosine kinases EGFR and HER2.

metachromins L-Q

tyrosine


Input: Metachromins are a series of sesquiterpenoid quinones isolated from Okinawan marine sponges.

Metachromins

sesquiterpenoid quinones


Input: Inhibitory effects of metachromins L-Q (1-6), sesquiterpenoid quinones with an amino acid residue, and their related analogs (7-18) prepared from metachromins A (19) and C (20) against receptor tyrosine kinases EGFR and HER2 were investigated.

metachromins L-Q

sesquiterpenoid quinones

amino acid

metachromins

tyrosine


Input: Two analogs 11 and 12 showed relatively stronger inhibitory activity against EGFR, while metachromins L-Q (1-6) and seven analogs (8, 10, 11, and 15-18) showed inhibitory activities against HER2.

metachromins L-Q


Input: Anti-diabetic activities of Gegen Qinlian Decoction in high-fat diet combined with streptozotocin-induced diabetic rats and in 3T3-L1 adipocytes.

streptozotocin


Input: Gegen Qinlian Decoction (GGQLD) is one of the well-known traditional Chinese medicines.


Input: Recently, it was reported that GGQLD had good clinical effects on type 2 diabetes mellitus.


Input: However, few studies have confirmed in detail the anti-diabetic activities of GGQLD in vivo and in vitro.


Input: In the present study, we investigated the anti-diabetic effects of GGQLD in high-fat diet combined with streptozotocin-induced diabetic rats and in 3T3-L1 adipocytes.

streptozotocin


Input: The present results suggested GGQLD (4. 95, 11. 55 and 18. 15 g/kg) decreased significantly fasting blood glucose, glycosylated serum protein, and glycosylated hemoglobin of diabetic rats (p < 0. 05), and GGQLD (4. 95 and 18. 15 g/kg) decreased significantly fasting serum insulin levels of diabetic rats (p < 0. 05); in 3T3-L1 adipocytes, Gegen Qinlian Decoction-containing serum (GGQLD-CS) (4%, 8% and 16%) enhanced glucose consumption, triglyceride (TG) content, adiponectin protein concentration and the mRNA expression of adiponectin.

glucose

glucose

triglyceride


Input: Adiponectin contributes to the regulation of lipid and glucose metabolism, and can play a critical role in the development of diabetes mellitus; the mechanisms of action of GGQLD might be related to augmentation of adiponectin protein concentration and up-regulation of the mRNA expression of adiponectin.

glucose


Input: However, the multi-target mechanisms of action of GGQLD need to be clarified further.


Input: The present study further validated the beneficial effects of GGQLD as an anti-diabetic agent.


Input: These findings provide a new insight into the anti-diabetic application for GGQLD in clinic and display the potential of GGQLD as a new drug candidate for the treatment of diabetes mellitus.


Input: Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma.


Input: Osteosarcoma is characterized by a high malignant and metastatic potential.


Input: Angiogenesis is essential for the caner metastasis.


Input: Interleukin-6 (IL-6) is a multifunctional cytokine that is associated with the disease status and outcomes of cancers.


Input: However, the relationship between IL-6 and vascular endothelial growth factor (VEGF) expression in human osteosarcoma is mostly unknown.


Input: Here we found that the IL-6 and VEGF expression was correlated with tumor stage and significantly higher than that in normal bone.


Input: Incubation of osteosarcoma cells with IL-6 increased VEGF mRNA and protein expression.


Input: Pretreatment of cells with IL-6R antibody reduced IL-6-mediated VEGF production.


Input: The apoptosis signal-regulating kinase 1 (ASK1)/p38/AP-1 pathway was activated after IL-6 treatment, and IL-6-induced VEGF expression was abolished by the specific inhibitor and siRNA of ASK1, p38, and AP-1 cascades.


Input: Importantly, knockdown IL-6 reduced VEGF expression and abolished osteosarcoma conditional medium-mediated angiogenesis.


Input: Taken together, these results indicate that IL-6 occurs through ASK1 and p38, which in turn activates AP-1, resulting in the activations of VEGF expression and contributing the angiogenesis of human osteosarcoma cells.


Input: 4-tert-Octylphenol stimulates the expression of cathepsins in human breast cancer cells and xenografted breast tumors of a mouse model via an estrogen receptor-mediated signaling pathway.

estrogen


Input: Endocrine disrupting chemicals (EDCs) are defined as environmental compounds that modulate steroid hormone receptor-dependent responses an abnormal manner, resulting in adverse health problems for humans such as cancer growth and metastasis.

steroid


Input: Cathepsins are proteases that have been implicated in cancer progression.


Input: However, there have been few studies about the association between cathepsins and estrogenic chemicals during the cancer progression.


Input: In this study, we examined the effect (s) of 4-tert-octylphenol (OP), a potent EDC, on the expression of cathepsins B and D in human MCF-7 breast cancer cells and a xenograft mouse model.


Input: Treatment with OP significantly induced the proliferation MCF-7 cells in an MTT assay.

MTT


Input: In addition, the expression of cathepsins B and D was markedly enhanced in MCF-7 cells at both the transcriptional and the translational levels following treatment with E2 or OP up to 48h.


Input: These results demonstrated the ability of OP to disrupt normal transcriptional regulation of cathepsins B and D in human breast cancer cells.


Input: However, the effects of OP on cell growth or overexpression of cathepsins by inhibiting ER-mediated signaling were abolished by an ER antagonist and siRNA specific for ER alpha.


Input: In conclusion, our findings suggest that OP at 10 (-6) M, like E2, may accelerate breast cancer cell proliferation and the expression of cathepsins through an ER-mediated signaling pathway.


Input: In addition, the breast cancer cells exposed with OP to a xenograft mouse model were more aggressive according to our histological analysis and showed markedly increased expression of cathepsin B.


Input: These effects of mouse model resulted in an increased potential for metastasis in breast cancer.


Input: Taken together, we determined that OP can adversely affect human health by promoting cancer proliferation and metastasis through the amplification of cathepsins B and D via the ER-mediated signaling pathway.


Input: The effect of lead exposure on brain iron homeostasis and the expression of DMT1/FP1 in the brain in developing and aged rats.


Input: The relation between lead (Pb) and iron (Fe) becomes increasingly concerned because they are both divalent metals that are absorbed by the same intestinal mechanism, and Pb exposure and Fe deficiency in the developmental brain, as well as Fe overload in the aged brain, can cause cognitive deficits.

Pb

iron

Fe

Pb

Fe

Fe


Input: However, the interaction between Pb exposure and Fe status in the brain has not been established.

Pb

Fe


Input: Therefore, in the current study, we examined the effects of maternal ingestion of Pb in drinking water during gestation and lactation on the Fe status and the expression of divalent metal transporter 1 (DMT1) and ferroportin 1 (FP1) in the brain of offspring.

Pb

Fe


Input: The offspring were followed through old age, with measurements taken at postnatal week 3 (PNW3), 41 (PNW41) and 70 (PNW70).


Input: Pb exposure increases the Fe content in the old-aged rats' brain, which might be not subjected to DMT1 mediating, but may be associated with the decrease expression of FP1.

Pb

Fe


Input: Furthermore, the effect of Pb on FP1 expression is regulated at transcriptional and posttranscriptional levels.

Pb


Input: The perturbation in Fe homeostasis may contribute to the neurotoxicology consequences induced by Pb exposure, and FP1 may play a role in Pb-induced Fe cumulation in the brain.

Fe

Pb

Pb

Fe


Input: Antiviral activity of (+)-sattabacin against varicella zoster.

(+)-sattabacin


Input: The first report of the antiviral activity of (+)-sattabacin against varicella-zoster virus (VZV) is described.

(+)-sattabacin


Input: Our results show that (+)-sattabacin potently inhibits the growth of VZV at concentrations in the range of other drugs commonly prescribed for VZV infection.

(+)-sattabacin


Input: Experiments detailing the synthesis of (+)-sattabacin, quantification of cytotoxicity and gene expression data in human fibroblast cells are also presented.

(+)-sattabacin


Input: Gene expression data was obtained through microarray analysis from human fibroblast cells exposed to sattabacin in order to identify a possible mechanism by which (+)-sattabacin inhibits VZV replication.

sattabacin

(+)-sattabacin


Input: N-POMC1-28 increases cyclin D expression and inhibits P27 (kip1) in the adrenal cortex.


Input: The Adrenocorticotropic hormone (ACTH) and Pro-opimelanocortin (POMC) 1-28N-terminal peptide (N-POMC1-28) have been shown to act as an adrenal mitogen in vivo.


Input: A possible role for cyclin E in the zona glomerulosa (ZG) proliferation, following ACTH and/or N-POMC1-28 administration, has been previously demonstrated.


Input: In this study, we investigated the effect of ACTH and N-POMC1-28 on the expression of adrenal cortex proteins related to cell cycle control such as cyclins D and P27 (kip1).


Input: The administration of N-POMC upregulated cyclin D1 and D2 expression in the outer zone of the adrenal cortex; cyclin D3 expression was upregulated in the cortex inner zone even after administration of ACTH.


Input: Both ACTH and N-POMC peptides induced a decrease in the P27 (kip1) expression in the ZG.


Input: These novel findings suggest that the POMC-derivate peptides, ACTH and N-POMC, promote proliferation in the adrenal cortex by upregulating the D2 and D3 cyclins and downregulating the P27 (kip1) expression.


Input: 3-Hydroxykynurenine: an intriguing molecule exerting dual actions in the Central Nervous System.


Input: Kynurenine pathway is gaining attention due to the many metabolic processes in which it has been involved.

Kynurenine


Input: The tryptophan conversion into several other metabolites through this pathway provides neuronal and redox modulators useful for maintenance of major functions in the brain.

tryptophan


Input: However, when physiopathological conditions prevail-i. e. oxidative stress, excitotoxicity, and inflammation-preferential formation and accumulation of toxic metabolites could trigger factors for degeneration in neurological disorders.


Input: 3-Hydroxykynurenine has been largely described as one of these toxic metabolites capable of inducing oxidative damage and cell death; consequently, this metabolite has been hypothesized to play a pivotal role in different neurological and psychiatric disorders.


Input: Supporting evidence has shown altered 3-hydroxykynurenine levels in samples of patients from several disorders.


Input: In contrast, some experimental studies have provided evidence of antioxidant and scavenging properties inherent to this molecule.


Input: In this review, we explored most of literature favoring one or the other concept, in order to provide an accurate vision on the real participation of this tryptophan metabolite in both experimental paradigms and human brain pathologies.

tryptophan


Input: Through this collected evidence, we provide an integrative hypothesis on how 3-hydroxykynurenine is exerting its dual actions in the Central Nervous System and what will be the course of investigations in this field for the next years.


Input: 3-(1H-indol-3-yl)-2-[3-(4-nitrophenyl) ureido] propanamide enantiomers with human formyl-peptide receptor agonist activity: molecular modeling of chiral recognition by FPR2.

3-(1H-indol-3-yl)-2-[3-(4-nitrophenyl) ureido] propanamide

formyl


Input: N-formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) that play critical roles in inflammatory reactions, and FPR-specific interactions can possibly be used to facilitate the resolution of pathological inflammatory reactions.

N-formyl


Input: Recent studies indicated that FPRs have stereo-selective preference for chiral ligands.


Input: Here, we investigated the structure-activity relationship of 24 chiral ureidopropanamides, including previously reported compounds PD168368/PD176252 and their close analogs, and used molecular modeling to define chiral recognition by FPR2.

ureidopropanamides


Input: Unlike previously reported 6-methyl-2, 4-disubstituted pyridazin-3 (2H)-ones, whose R-forms preferentially activated FPR1/FPR2, we found that four S-enantiomers in the seven ureidopropanamide pairs tested preferentially activated intracellular Ca (2 +) flux in FPR2-transfected cells, while the R-counterpart was more active in two enantiomer pairs.

6-methyl-2, 4-disubstituted pyridazin-3 (2H)-ones

ureidopropanamide

Ca (2 +)


Input: Thus, active enantiomers of FPR2 agonists can be in either R-or S-configurations, depending on the molecular scaffold and specific substituents at the chiral center.


Input: Using molecular modeling approaches, including field point methodology, homology modeling, and docking studies, we propose a model that can explain stereoselective activity of chiral FPR2 agonists.


Input: Importantly, our docking studies of FPR2 chiral agonists correlated well with the FPR2 pharmacophore model derived previously.


Input: We conclude that the ability of FPR2 to discriminate between the enantiomers is the consequence of the arrangement of the three asymmetric hydrophobic subpockets at the main orthosteric FPR2 binding site with specific orientation of charged regions in the subpockets.


Input: Biological impact of phthalates.

phthalates


Input: Esters of phthalic acid are chemical agents used to improve the plasticity of industrial polymers.

Esters

phthalic acid


Input: Their ubiquitous use in multiple commercial products results in extensive exposure to humans and the environment.


Input: This study investigated cytotoxicity, endocrine disruption, effects mediated via AhR, lipid peroxidation and effects on expression of enzymes of xenobiotic metabolism caused by di-(2-ethy hexyl) phthalate (DEHP), diethyl phthalate (DEP), dibutyl phthalate (DBP) and benzyl butyl phthalate (BBP) in developing fish embryos.

di-(2-ethy hexyl) phthalate

DEHP

diethyl phthalate

DEP

dibutyl phthalate

DBP

benzyl butyl phthalate

BBP


Input: Oxidative stress was identified as the critical mechanism of toxicity (CMTA) in the case of DEHP and DEP, while the efficient removal of DBP and BBP by phase 1 enzymes resulted in lesser toxicity.

DEHP

DEP

DBP

BBP


Input: DEHP and DEP did not mimic estradiol (E (2)) in transactivation studies, but at concentrations of 10mg/L synthesis of sex steroid hormones was affected.

DEHP

DEP

estradiol

steroid


Input: Exposure to 10mg BBP/L resulted in weak transactivation of the estrogen receptor (ER).

estrogen


Input: All phthalates exhibited weak potency as agonists of the aryl hydrocarbon receptor (AhR).

phthalates

aryl hydrocarbon


Input: The order of potency of the 4 phthalates studied was; DEHP > DEP > BBP > DBP.

phthalates

DEHP

DEP

BBP

DBP


Input: The study highlights the need for simultaneous assessment of: (1) multiple cellular targets affected by phthalates and (2) phthalate mixtures to account for additive effects when multiple phthalates modulate the same pathway.

phthalates

phthalate

phthalates


Input: Such cumulative assessment of multiple biological parameters is more realistic, and offers the possibility of more accurately identifying the CMTA.


Input: Doxorubicin decreases paraquat accumulation and toxicity in Caco-2 cells.

Doxorubicin

paraquat


Input: P-glycoprotein (P-gp) is an efflux pump belonging to the ATP-binding cassette transporter superfamily expressed in several organs.

ATP


Input: Considering its potential protective effects, the induction of de novo synthesis of P-gp could be used therapeutically in the treatment of intoxications by its substrates.


Input: The herbicide paraquat (PQ) is a P-gp substrate responsible for thousands of fatal intoxications worldwide that still lacks an effective antidote.

paraquat


Input: The aim of the present work was to evaluate the effectiveness of such an antidote by testing whether doxorubicin (DOX), a known P-gp inducer, could efficiently protect Caco-2 cells against PQ cytotoxicity, 6 h after the incubation with the herbicide, reflecting a real-life intoxication scenario.

doxorubicin

DOX


Input: Cytotoxicity was evaluated by the MTT assay and PQ intracellular concentrations were measured by gas chromatography-ion trap-mass spectrometry (GC-IT-MS).

MTT


Input: Also, the DOX modulatory effect on choline uptake transport system was assessed by measuring the uptake of [(3) H]-choline.

DOX

choline

[(3) H]-choline


Input: The results show that DOX exerts protective effects against PQ cytotoxicity, preventing the intracellular accumulation of the herbicide.

DOX


Input: These protective effects were not completely prevented by the incubation with the UIC2 antibody, a specific P-gp inhibitor, suggesting the involvement of alternative protection mechanisms.


Input: In fact, DOX also efficiently inhibited the choline transport system that influences PQ cellular uptake.

DOX

choline


Input: In conclusion, in this cellular model, DOX effectively protects against PQ toxicity by inducing P-gp and through the interaction with the choline transporter, suggesting that compounds presenting this double feature of promoting the efflux and limiting the uptake of PQ could be used as effective antidotes to treat intoxications.

DOX

choline


Input: Capreomycin supergenerics for pulmonary tuberculosis treatment: preparation, in vitro, and in vivo characterization.

Capreomycin


Input: The pulmonary route is one of the main strategies investigated to improve tuberculosis therapy.


Input: The aim of this study was to develop a simple and scalable method to produce capreomycin inhalable powders to use as supergeneric.

capreomycin


Input: In vitro antimycobacterial activity and in vivo acute toxicity were assessed using agar proportion susceptibility test on Mycobacterium tuberculosis and chicken chorioallantoic membrane assay, respectively.


Input: Capreomycin and three different hydrophobic counterions, namely oleate, linoleate, and linolenate, were combined in solution to obtain hydrophobic ion-pairs that were successively spray-dried.

Capreomycin

oleate

linoleate

linolenate


Input: Ion-pairing efficiency was influenced by the spray-dryer employed to produce the powder.


Input: In the case of capreomycin oleate, both instruments, mini and nano spray-dryer, were suitable to maintain a high ion-paired content, while for capreomycin linoleate and linolenate, mini spray-dryer was the most appropriate instrument.

capreomycin oleate

capreomycin linoleate and linolenate


Input: The three formulations showed morphology and particle sizes potentially suitable for inhalation.


Input: Capreomycin oleate and linoleate showed the same efficacy of capreomycin sulfate against M. tuberculosis, while capreomycin linolenate showed a reduced efficacy, even though strain growth was inhibited at 10 (-4) mycobacterial inoculum.

Capreomycin oleate and linoleate

capreomycin sulfate

capreomycin linolenate


Input: In vivo acute toxicity studies evidenced the lowest toxic potential for capreomycin oleate when compared to the single components or the other two salts.

capreomycin oleate


Input: Overall, capreomycin oleate seems to possess the most promising characteristics to be used as supergenerics in pulmonary tuberculosis treatment.

capreomycin oleate


Input: Evernia prunastri and Pseudoevernia furfuraceae lichens and their major metabolites as antioxidant, antimicrobial and anticancer agents.


Input: The aim of this study is to investigate chemical composition of acetone extracts of the lichens Evernia prunastri and Pseudoevernia furfuraceae and in vitro antioxidant, antimicrobial, and anticancer activities of these extracts and some their major metabolites.

acetone


Input: HPLC-UV method was used for identification of secondary metabolites.


Input: Antioxidant activity was evaluated by free radical scavenging, superoxide anion radical scavenging, reducing power and determination of total phenolic compounds.

superoxide

phenolic


Input: As a result of the study physodic acid had largest antioxidant activities.


Input: Total content of phenol in extracts was determined as pyrocatechol equivalent.

phenol

pyrocatechol


Input: The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method.


Input: The most active was also physodic acid.

physodic acid


Input: Anticancer activity was tested against FemX (human melanoma) and LS174 (human colon carcinoma) cell lines using MTT method.

MTT


Input: Lecithin in mixed micelles attenuates the cytotoxicity of bile salts in Caco-2 cells.

bile salts


Input: This study was designed to investigate the cytotoxicity of bile salt-lecithin mixed micelles on the Caco-2 cell model.

bile salt


Input: Cell viability and proliferation after mixed micelles treatments were evaluated with the MTT assay, and the integrity of Caco-2 cell monolayer was determined by quantitating the transepithelial electrical resistance and the flux of tracer, FITC-dextran 4400.

MTT

FITC


Input: The apoptosis induced by mixed micelles treatments was investigated with the annexin V/PI protocol.


Input: The particle size of mixed micelles was all smaller than 100 nm.


Input: The mixed micelles with lower than 0. 2mM sodium deoxycholate (SDC) had no significant effects on cell viability and proliferation.

sodium deoxycholate

SDC


Input: When the level of SDC was higher than 0. 4mM and the lecithin/SDC ratio was lower than 2: 1, the mixed micelles caused significant changes in cell viability and proliferation.

SDC

SDC


Input: Furthermore, the mixed micelles affected tight junctions in a composition-dependent manner.


Input: Specifically, the tight junctions were transiently opened rather than damaged by the mixed micelles with SDC of between 0. 2 and 0. 6mM.

SDC


Input: The mixed micelles with more lecithin also induced less apoptosis.


Input: These results demonstrate that relatively higher concentrations of mixed micelles are toxic to Caco-2 cells, while phospholipids can attenuate the toxicity of the bile salts.

bile salts


Input: A simple molecular modeling method for the characterization of polymeric drug carriers.


Input: A simple molecular modeling method for the characterization of polymeric drug carriers is presented.


Input: Six biodegradable polymers have been investigated as drug carriers using molecular simulations: l-polylactide, d-polylactide, chitosan, polyglycolic acid, polyethylene glycol and cellulose.

l-polylactide

d-polylactide

polyglycolic acid

polyethylene glycol


Input: Cyclosporine A has been chosen as a model drug substance.

Cyclosporine A


Input: Classical molecular dynamics and docking calculations were employed to model and predict polymer-drug interactions.


Input: These interactions have been analyzed by non-bond interaction energy and interaction parameter calculated using Flory-Huggins theory.


Input: Flexibility of polymer chains has been characterized by the change of gyration radius along the molecular dynamics trajectory.


Input: The relationship between mixing energy, chain length and chain flexibility has been revealed for each polymer/drug system.


Input: Improvement in pelvic pain with botulinum toxin type A-Single vs. repeat injections.


Input: The aim of this prospective study was to report the outcomes of pain and vaginal pressures of successive botulinum toxin type A injections for women with objective pelvic floor muscle overactivity and a two-year history of pelvic pain.


Input: Between 2005 and 2008, 37 women underwent injection of 100 IU of botulinum toxin type A into the puborectalis and pubococcygeous muscles with dysmenorrhoea, dyspareunia, dyschesia, and non-menstrual pelvic pain assessed using a visual analogue scale (VAS), and vaginal pressure measured by vaginal manometry, at 0, 4, 12 and 26 weeks from each injection.


Input: 26 women (70%) had one injection of botulinum toxin type A and 11 (30%) had 2 or more injections.


Input: The second injection was performed at the earliest at 26 weeks after the first, with subsequent injections having a median time to re-injection of 33. 4 weeks (range 9. 4-122. 7 weeks).


Input: Single and repeated injections both demonstrated a statistically significant reduction in dyspareunia by VAS scores from 54 to 30 in the single injection group and from 51 to 23 in the multiple injection group (p =. 001), non-menstrual pelvic pain VAS from 37 to 25 (p =. 04), as well as vaginal pressures; 40 versus 34 cm H (2) O (p =. 02).

H (2) O


Input: No statistically significant difference in dysmenorrhoea or dyschesia was observed for either group from their baseline scores.


Input: Multiple injections of botulinum toxin type A in women with pelvic floor muscle overactivity provide significant relief from dyspareunia and non-menstrual pelvic pain.


Input: The upper limit between re-injection is not yet determined, nor is the maximum number of treatments.


Input: Clinical outcomes for single and subsequent injection of botulinum toxin type A for recurrent pelvic pain are equivalent.


Input: Women who have had benefit from a single injection of botulinum toxin type A can be reassured that if symptoms reoccur, repeated injections can be expected to be equally efficacious.


Input: A polyacetylene-rich extract from Gymnaster koraiensis strongly inhibits colitis-associated colon cancer in mice.

polyacetylene


Input: Gymnaster koraiensis (GK) is a Korean herb used in folk medicine and recently found to positively impact liver health.


Input: Because GK contains polyacetylenes and because other polyacetylenes have been found to exhibit anti-inflammatory and anti-cancer activities, we hypothesized that the polyacetylene gymnasterkoreayne B (GKB), known to increase hepatic detoxification enzymes, may also exert anti-inflammatory and anti-cancer activities.

polyacetylenes

polyacetylenes

polyacetylene gymnasterkoreayne B

GKB


Input: We fed male C57BL/6 mice purified AIN93G diets containing no additions, GKB or the GKB-rich fraction of an ethanol extract (GE) from GK to determine if these diets would slow or prevent either inflammation or inflammation-enhanced colon cancer, using the dextran sulfate sodium/azoxymethane mouse model.

GKB

GKB

ethanol

sodium

azoxymethane


Input: The GKB (500 mu mol/kg diet daily) showed some anti-inflammatory activity, but GE, containing an equal dose of GKB, protected strongly against both inflammation and colon cancer, decreasing adenocarcinomas by 90%.

GKB

GKB


Input: These data support further research into GK as a promising potential anti-cancer agent.


Input: The diverse roles of nonsteroidal anti-inflammatory drug activated gene (NAG-1/GDF15) in cancer.


Input: Nonsteroidal anti-inflammatory drug (NSAID) activated gene-1, NAG-1, is a divergent member of the transforming growth factor-beta (TGF-beta) superfamily that plays a complex but poorly understood role in several human diseases including cancer.


Input: NAG-1 expression is substantially increased during cancer development and progression especially in gastrointestinal, prostate, pancreatic, colorectal, breast, melanoma, and glioblastoma brain tumors.


Input: Aberrant increases in the serum levels of secreted NAG-1 correlate with poor prognosis and patient survival rates in some cancers.


Input: In contrast, the expression of NAG-1 is up-regulated by several tumor suppressor pathways including p53, GSK-3 beta, and EGR-1.


Input: NAG-1 expression is also induced by many drugs and dietary compounds which are documented to prevent the development and progression of cancer in mouse models.


Input: Studies with transgenic mice expressing human NAG-1 demonstrated that the expression of NAG-1 inhibits the development of intestinal tumors and prostate tumors in animal models.


Input: Laboratory and clinical evidence suggest that NAG-1, like other TGF-beta family members, may have different or pleiotropic functions in the early and late stages of carcinogenesis.


Input: Upon understanding the molecular mechanism and function of NAG-1 during carcinogenesis, NAG-1 may serve as a potential biomarker for the diagnosis and prognosis of cancer and a therapeutic target for the inhibition and treatment of cancer development and progression.


Input: The estrogenic effects of benzylparaben at low doses based on uterotrophic assay in immature SD rats.

benzylparaben


Input: Benzylparaben (BzP), a type of parabens being used as a preservative agent in cosmetics, food, and pharmaceutical products, may be ingested by humans.

Benzylparaben

BzP


Input: In this study, we performed an immature uterotrophic assay using Sprague Dawley (SD) rats by intragastric administration to determine the estrogenic effects of BzP and found significant increases in uterine weight with doses of 0. 16 mg/kg body weight and higher (P < 0. 05).

BzP


Input: The in vivo estrogenicity of BzP was supported by in vitro results from the human estrogen receptor alpha (hER alpha)-coactivator recruiting assay and in silico molecular docking analysis performed in this study.

BzP

estrogen


Input: The in vitro estrogenic activity of BzP can be observed at concentrations of 1. 0 x 10 (-8) M and higher.

BzP


Input: Molecular docking analysis showed that BzP fits well into the agonist pocket of hER alpha.

BzP


Input: The lowest observed effect dose (LOED) (0. 16 mg/kg/day) of BzP is much lower than the documented LOEDs of other parabens.

BzP

parabens


Input: Actual risk may exist for people who consume a diet high in BzP or use BzP-laden cosmetics.

BzP

BzP


Input: In addition, we tested the sensitivity of Wistar rats to 17 beta-estradiol by immature uterotrophic assay, and no obvious uterotrophic response was observed in the rats given doses up to 100 mu g/kg body weight.

17 beta-estradiol


Input: MAPK signaling pathways regulate mitochondrial-mediated apoptosis induced by isoorientin in human hepatoblastoma cancer cells.

isoorientin


Input: Isoorientin (ISO) (CAS RN: 4261-42-1) is a flavonoid compound that can be extracted from several plant species, such as Phyllostachys pubescens, Patrinia, and Drosophyllum lusitanicum.

Isoorientin

ISO

flavonoid


Input: ISO is able to induce apoptosis through mitochondrial dysfunction and inhibition of PI3K/Akt signaling pathway in HepG2 cells, however, the effects of ISO on MAPK signaling pathways remain unknown.

ISO

ISO


Input: The present study investigated the effects of ISO on this pathway, and the roles of MAPK kinases on mitochondrial-mediated apoptosis in HepG2 cells.

ISO


Input: The results showed that ISO induced cell death in a dose-and time-dependent manner, and induction apoptosis is main cause for ISO-induced cytotoxicity in HepG2 cells.

ISO

ISO


Input: ISO significantly inhibited the levels of ERK1/2 kinase and increased the expression of JNK and p38 kinases.

ISO


Input: Furthermore, U0126 (an ERK1/2 inhibitor) significantly enhanced the ISO-induced the Bax/Bcl-2 ratio, the release of cytochrome c to the cytosol fraction, and the levels of cleaved caspase-3.

ISO


Input: While SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor) markedly prevented the expression of these proteins induced by ISO.

ISO


Input: Furthermore, the ROS inhibitor (NAC) notably promoted the inhibited effect of ISO on the ERK1/2 kinase.

NAC

ISO


Input: NAC also suppressed the p-JNK and p-p38, but failed to reverse the effects of ISO.

NAC

ISO


Input: These results demonstrated for the first time that ISO induces apoptosis in HepG2 cells through inactivating ERK1/2 kinase and activating JNK and p38 kinases, and ROS stimulated by ISO is able to activate the MAPK singaling pathway as the upstream signaling molecules.

ISO

ISO


Input: Initiating event of the mitochondrial-mediated apoptosis induced by ISO is MAPK signals.

ISO


Input: Hepatic metabolism of sulfur amino acids in db/db mice.

sulfur amino acids


Input: To determine the effect of type-2 diabetes and obesity on the hepatic metabolism of sulfur amino acids, hepatic sulfur amino acid metabolism was determined in db/db mice.

sulfur amino acids

sulfur amino acid


Input: Hepatic methionine was markedly decreased in db/db mice, although the hepatic activity of betaine homocysteine methyltransferase was increased.

methionine

homocysteine


Input: The decrease in hepatic methionine was reflected by decreased sulfur-containing methionine metabolites, including S-adenosylmethionine, homocysteine, cysteine, and hypotaurine in liver and plasma.

methionine

sulfur

methionine

S-adenosylmethionine

homocysteine

cysteine

hypotaurine


Input: In contrast, S-adenosylhomocysteine, putrescine, and spermidine were increased in db/db mice.

S-adenosylhomocysteine

putrescine

spermidine


Input: The hepatic level and activity of methionine adenosyltransferase I/III, an S-adenosylmethionine synthesizing enzyme, were significantly increased.

methionine

S-adenosylmethionine


Input: These results suggest that increased polyamine synthesis, in conjunction with decreased hepatic methionine levels, is partly responsible for the reduction in hepatic S-adenosylmethionine.

polyamine

methionine

S-adenosylmethionine


Input: Decreased homocysteine in liver and plasma may be attributable to the decrease in hepatic methionine and upregulation of hepatic betaine homocysteine methyltransferase.

homocysteine

methionine

homocysteine


Input: Glutathione in liver and plasma did not change despite decreased gamma-glutamylcysteine ligase activity.

Glutathione

gamma-glutamylcysteine


Input: The decreased hepatic hypotaurine may be attributable to the downregulation of cysteine dioxygenase.

hypotaurine

cysteine


Input: The major finding of this study is that db/db mice exhibited decreases in hepatic methionine and its sulfurcontaining metabolites.


Input: Antithrombotic and profibrinolytic activities of isorhamnetin-3-O-galactoside and hyperoside.

hyperoside


Input: The potential anticoagulant activities of two single compounds, isorhamnetin-3-O-galactoside (IMG) and hyperoside, from Oenanthe javanica, were tested.

IMG

hyperoside


Input: The anticoagulant activities were investigated by measuring activated partial thromboplastin time (aPTT) and prothrombin time (PT), and the ability to inhibit production of thrombin and activated factor X (FXa) was investigated in human umbilical vein endothelial cells (HUVECs).


Input: And, the effects of the compounds on expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-(TNF)-alpha activated HUVECs.


Input: Treatment with IMG and hyperoside resulted in significantly prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and IMG or hyperoside inhibited production of thrombin and FXa in HUVECs.

IMG

hyperoside

IMG

hyperoside


Input: In accordance with these anticoagulant activities, both agents elicited anticoagulant effects in mouse.


Input: In addition, treatment with IMG and hyperoside resulted in inhibition of TNF-alpha-induced production of PAI-1, and treatment with IMG resulted in significant reduction of the PAI-1 to t-PA ratio.

IMG

hyperoside

IMG


Input: The anticoagulant and profibrinolytic effects of IMG were greater than those of hyperoside, indicating positive regulation of its anticoagulant function by the methoxy group of IMG.

IMG

hyperoside

methoxy

IMG


Input: IMG and hyperoside possess antithrombotic activities and offer bases for development of a novel anticoagulant.

IMG

hyperoside


Input: Sirtuins as emerging anti-parasitic targets.


Input: Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of NAD (+)-dependent protein N (epsilon)-acetyl-lysine (AcK) deacetylases.

NAD (+)

N (epsilon)-acetyl-lysine

AcK


Input: Sirtuins are also evolutionarily conserved proteins that are present in all kingdoms of life ranging from bacteria to humans.


Input: Interestingly, it was recently found that the sirtuins found in various human parasites (especially the Plasmodium, Trypanosoma, and Leishmania species) were pro-survival for the parasites under various conditions.


Input: Therefore, these parasitic sirtuins have emerged as novel anti-parasitic therapeutic targets.


Input: This article reviews the currently available structural, biochemical, pharmacological, and medicinal chemistry studies on these enzymes, and discusses the perspectives of selectively targeting the parasitic sirtuins as a novel therapeutic strategy for the human parasitic diseases.


Input: Hepatic glucose metabolism in late pregnancy: normal versus high-fat and-fructose diet.

glucose

fructose


Input: Net hepatic glucose uptake (NHGU) is an important contributor to postprandial glycemic control.

glucose


Input: We hypothesized that NHGU is reduced during normal pregnancy and in a pregnant diet-induced model of impaired glucose intolerance/gestational diabetes mellitus (IGT/GDM).

glucose


Input: Dogs (n = 7 per group) that were nonpregnant (N), normal pregnant (P), or pregnant with IGT/GDM (pregnant dogs fed a high-fat and-fructose diet [P-HFF]) underwent a hyperinsulinemic-hyperglycemic clamp with intraportal glucose infusion.

fructose

glucose


Input: Clamp period insulin, glucagon, and glucose concentrations and hepatic glucose loads did not differ among groups.

glucose

glucose


Input: The N dogs reached near-maximal NHGU rates within 30 min; mean +/- SEM NHGU was 105 +/- 9 micro mol. 100 g liver-(1). min-(1).


Input: The P and P-HFF dogs reached maximal NHGU in 90-120 min; their NHGU was blunted (68 +/- 9 and 16 +/- 17 micro mol. 100 g liver-(1). min-(1), respectively).


Input: Hepatic glycogen synthesis was reduced 20% in P versus N and 40% in P-HFF versus P dogs.


Input: This was associated with a reduction (> 70%) in glycogen synthase activity in P-HFF versus P and increased glycogen phosphorylase (GP) activity in both P (1. 7-fold greater than N) and P-HFF (1. 8-fold greater than P) dogs.


Input: Thus, NHGU under conditions mimicking the postprandial state is delayed and suppressed in normal pregnancy, with concomitant reduction in glycogen storage.


Input: NHGU is further blunted in IGT/GDM.


Input: This likely contributes to postprandial hyperglycemia during pregnancy, with potential adverse outcomes for the fetus and mother.


Input: Hot charge-transfer excitons set the time limit for charge separation at donor/acceptor interfaces in organic photovoltaics.


Input: Photocurrent generation in organic photovoltaics (OPVs) relies on the dissociation of excitons into free electrons and holes at donor/acceptor heterointerfaces.


Input: The low dielectric constant of organic semiconductors leads to strong Coulomb interactions between electron-hole pairs that should in principle oppose the generation of free charges.


Input: The exact mechanism by which electrons and holes overcome this Coulomb trapping is still unsolved, but increasing evidence points to the critical role of hot charge-transfer (CT) excitons in assisting this process.


Input: Here we provide a real-time view of hot CT exciton formation and relaxation using femtosecond nonlinear optical spectroscopies and non-adiabatic mixed quantum mechanics/molecular mechanics simulations in the phthalocyanine-fullerene model OPV system.

phthalocyanine

fullerene


Input: For initial excitation on phthalocyanine, hot CT excitons are formed in 10 (-13) s, followed by relaxation to lower energies and shorter electron-hole distances on a 10 (-12) s timescale.

phthalocyanine


Input: This hot CT exciton cooling process and collapse of charge separation sets the fundamental time limit for competitive charge separation channels that lead to efficient photocurrent generation.


Input: Dissociation of Bcl-2-Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes.


Input: Diabetic cardiomyopathy is associated with suppression of cardiac autophagy, and activation of AMP-activated protein kinase (AMPK) restores cardiac autophagy and prevents cardiomyopathy in diabetic mice, albeit by an unknown mechanism.

AMP


Input: We hypothesized that AMPK-induced autophagy ameliorates diabetic cardiomyopathy by inhibiting cardiomyocyte apoptosis and examined the effects of AMPK on the interaction between Beclin1 and Bcl-2, a switch between autophagy and apoptosis, in diabetic mice and high glucose-treated H9c2 cardiac myoblast cells.

glucose


Input: Exposure of H9c2 cells to high glucose reduced AMPK activity, inhibited Jun NH2-terminal kinase 1 (JNK1)-B-cell lymphoma 2 (Bcl-2) signaling, and promoted Beclin1 binding to Bcl-2.

glucose


Input: Conversely, activation of AMPK by metformin stimulated JNK1-Bcl-2 signaling and disrupted the Beclin1-Bcl-2 complex.


Input: Activation of AMPK, which normalized cardiac autophagy, attenuated high glucose-induced apoptosis in cultured H9c2 cells.

glucose


Input: This effect was attenuated by inhibition of autophagy.


Input: Finally, chronic administration of metformin in diabetic mice restored cardiac autophagy by activating JNK1-Bcl-2 pathways and dissociating Beclin1 and Bcl-2.

metformin


Input: The induction of autophagy protected against cardiac apoptosis and improved cardiac structure and function in diabetic mice.


Input: We concluded that dissociation of Bcl-2 from Beclin1 may be an important mechanism for preventing diabetic cardiomyopathy via AMPK activation that restores autophagy and protects against cardiac apoptosis.


Input: Induction of hepatic CYP3A enzymes by pregnancy-related hormones: studies in human hepatocytes and hepatic cell lines.


Input: CYP3A activity is induced by approximately 2-fold during the third trimester of human pregnancy.


Input: Placental growth hormone (PGH), estrogens (primarily 17 beta-estradiol), cortisol, and progesterone have the potential to modulate CYP3A activity.

estrogens

17 beta-estradiol

cortisol

progesterone


Input: Therefore, we determined whether the elevated plasma concentrations of these hormones during pregnancy induce hepatic CYP3A expression.


Input: We incubated sandwich-cultured human hepatocytes (SCHH) from premenopausal female donors (n = 2) with the physiologic (unbound, 1 x total) and the 10 x total third trimester hormone plasma concentrations (individually and in combination) and determined their effect on CYP3A activity and the transcripts of CYP3A4, CYP3A5, and the respective hormone receptors (growth hormone receptor, glucocorticoid receptor, and estrogen receptor alpha).

estrogen


Input: Of all the hormones, cortisol was the most potent inducer of CYP3A activity and CYP3A4, CYP3A5 mRNA expression.

cortisol


Input: The combination of PGH/growth hormone and cortisol induced CYP3A activity and expression significantly more than did cortisol alone.

cortisol

cortisol


Input: When incubated with the unbound or total plasma concentration of all the hormones, CYP3A activity in SCHH was induced to an extent comparable to that observed in vivo during the third trimester.


Input: These hormones had only a modest effect on the mRNA expression of the hormone receptors.


Input: The pattern of induction observed in SCHH was reproduced in HepaRG cells but not in HuH7/HepG2 cells.


Input: SCHH or HepaRG cells could be used to determine the mechanistic basis of CYP3A induction during pregnancy and to predict the magnitude of induction likely to be observed during the first and second trimesters, when phenotyping studies to measure in vivo CYP3A activity are logistically difficult to perform.


Input: Aqueous phase synthesis of copper nanoparticles: a link between heavy metal resistance and nanoparticle synthesis ability in bacterial systems.

copper


Input: We demonstrate aqueous phase biosynthesis of phase-pure metallic copper nanoparticles (CuNPs) using a silver resistant bacterium Morganella morganii.

copper

silver


Input: This is particularly important considering that there has been no report that demonstrates biosynthesis and stabilization of pure copper nanoparticles in the aqueous phase.