Input: However, when mice are exposed to diet-induced insulin resistance, pharmacologic secretagogue stimulation of beta-cells with an incretin hormone glucagon-like peptide-1 analogue or with a Fatty Acid Receptor 1/GPR40 selective activator, EPAC2A is required for the increased beta-cell response to secretory demand.

Fatty Acid


Input: Under these circumstances, EPAC2A is required for potentiating the early dynamic increase in islet calcium levels after glucose stimulation, which is reflected in potentiated first phase insulin secretion.

calcium

glucose


Input: These studies broaden our understanding of EPAC2A function and highlight its significance during increased secretory demand or drive on beta-cells.


Input: Our findings advance the rationale for developing EPAC2A selective pharmacologic activators for beta-cell targeted pharmacotherapy in type 2 diabetes mellitus.


Input: Salicylic acid alleviates copper toxicity in rice (Oryza sativa L.) seedlings by up-regulating antioxidative and glyoxalase systems.

Salicylic acid

copper


Input: The present study investigated the effect of salicylic acid (SA) on toxic symptoms, lipid peroxidation, reactive oxygen species generation and responses of antioxidative and glyoxalase systems in rice seedlings grown hydroponically under copper (Cu) stress for 48 h.

salicylic acid

oxygen

copper

Cu


Input: Exposures of 75 and 150 mu M Cu (2 +) caused toxicity symptoms (chlorosis, necrosis and rolling in leaves), sharp increases in malondialdehyde (MDA), hydrogen peroxide (H2O2) contents and lipoxygenase (LOX) activity with concomitant reductions of chlorophyll (Chl) and relative water content (RWC).

Cu (2 +)

malondialdehyde

MDA

hydrogen peroxide


Input: Both levels of Cu decreased ascorbic acid (AsA), glutathione (GSH), non-protein thiol (NPT) and proline contents in roots but rather increased in leaves except that AsA decreased in leaves too.

Cu

ascorbic acid

AsA

glutathione

GSH

thiol

proline

AsA


Input: These results together with overaccumulation of superoxide (O 2 (*-)) and H2O2 in leaves revealed that Cu exposures induced oxidative stress.

superoxide

O 2 (*-)

Cu


Input: Contrary, SA-pretreatment (100 mu M for 24 h) reduced toxicity symptoms and diminished Cu-induced increases in LOX activity, H2O2, MDA and proline contents while the levels of RWC, Chl, AsA and redox ratios were elevated.

Cu

MDA

proline

AsA


Input: Higher levels of GSH and NPT were also observed in roots of SA-pretreated Cu-exposed seedlings.

GSH

Cu


Input: SA-pretreatment also exerted its beneficial role by inhibiting the Cu upward process.

Cu


Input: Studies on antioxidant enzymes showed that SA further enhanced the activities of superoxide dismutase, ascorbate peroxidase, glutathione reductase and glutathione peroxidase, and also elevated the depressed activities of catalase, dehydroascorbate reductase and glutathione S-transferase particularly at 150 mu M Cu (2 +) stress.

superoxide

ascorbate

glutathione

glutathione

dehydroascorbate

glutathione S

Cu (2 +)


Input: In addition, the activity of glyoxalase system (glyoxalase I and II) was further elevated by SA pretreatment in the Cu-exposed seedlings.

Cu


Input: These results concluded that SA-mediated retention of Cu in roots and enhanced capacity of both antioxidative and glyoxalase systems might be associated with the alleviation of Cu-toxicity in rice seedlings.

Cu

Cu


Input: Endowing carbon nanotubes with superparamagnetic properties: applications for cell labeling, MRI cell tracking and magnetic manipulations.

carbon


Input: Coating of carbon nanotubes (CNTs) with magnetic nanoparticles (NPs) imparts novel magnetic, optical, and thermal properties with potential applications in the biomedical domain.

carbon


Input: Multi-walled CNTs have been decorated with iron oxide superparamagnetic NPs.

iron oxide


Input: Two different approaches have been investigated based on ligand exchange or " click chemistry ".


Input: The presence of the NPs on the nanotube surface allows conferring magnetic properties to CNTs.


Input: We have evaluated the potential of the NP/CNT hybrids as a contrast agent for magnetic resonance imaging (MRI) and their interactions with cells.


Input: The capacity of the hybrids to magnetically monitor and manipulate cells has also been investigated.


Input: The NP/CNTs can be manipulated by a remote magnetic field with enhanced contrast in MRI.


Input: They are internalized into tumor cells without showing cytotoxicity.


Input: The labeled cells can be magnetically manipulated as they display magnetic mobility and are detected at a single cell level through high resolution MRI.


Input: The lack of association between components of metabolic syndrome and treatment resistance in depression.


Input: RATIONALE: Although a number of studies investigated the link between major depressive disorder (MDD) and metabolic syndrome (MetS), the association between MetS and treatment-resistant depression (TRD) is still not clear.


Input: OBJECTIVES: The aim of the study was to investigate the relationship between TRD and MetS and/or components of MetS and cardiovascular risk factors.


Input: Given the high prevalence of both conditions, the hypothesis was that TRD would be significantly associated with MetS.


Input: METHODS: This cross-sectional study included 203 inpatients with MDD, assessed for the treatment resistance, MetS and its components, and severity of MDD.


Input: Diagnoses and evaluations were made with SCID based on DSM-IV, National Cholesterol Education Program Adult Treatment Panel III criteria, and the Hamilton Depression Rating Scale.

Cholesterol


Input: RESULTS: TRD prior to study entry was found in 26. 1% of patients, while MetS was observed in 33. 5% of patients.


Input: The prevalence of MetS did not differ significantly between TRD and non-TRD patients.


Input: In addition, the frequency of the altered values of particular components of the MetS or cardiovascular risk factors was not associated with treatment resistance in depressed patients.


Input: Patients with TRD were older, had a higher number of lifetime episodes of depression and suicide attempts, and longer duration of MDD compared to non-TRD patients.


Input: CONCLUSIONS: The occurrence of either MetS or the particular components of the MetS and other cardiovascular risk factors was similar between TRD and non-TRD patients.


Input: Although there is a bidirectional relationship between depression and MetS, neither MetS nor its components appear to influence treatment resistance to antidepressants.


Input: The efficacy of metformin in pregnant women with polycystic ovary syndrome: a meta-analysis of clinical trials.

metformin


Input: Objectives: The role of metformin in the treatment of pregnant women with polycystic ovary syndrome is controversial.

metformin


Input: Therefore, we evaluated whether the use of metformin during pregnancy in women with polycystic ovary syndrome could reduce pregnancy-related complications.

metformin


Input: Research design and methods: MEDLINE was searched to retrieve relevant trials.


Input: In addition, reviews and reference lists of the retrieved articles were scanned for further appropriate studies.


Input: The primary outcome measure was the incidence of complications of pregnancy, which included early pregnancy loss, gestational diabetes, preeclampsia and preterm delivery.


Input: Results: In total, eight studies with 1106 patients were included.


Input: The pooled ORs (95% CIs) of outcome for pregnant women with polycystic ovary syndrome prescribed metformin were 0. 32 (0. 19-0. 55) for early pregnancy loss, 0. 37 (0. 25-0. 56) for gestational diabetes, 0. 53 (0. 30-0. 95) for preeclampsia and 0. 30 (0. 13-0. 68) for preterm delivery.

metformin


Input: Conclusions: Metformin therapy throughout pregnancy decreased the ORs of early pregnancy loss, gestational diabetes, preeclampsia and preterm delivery in pregnant PCOS women with no serious detrimental sideeffects.

Metformin


Input: Application of Ultra-Performance Liquid Chromatography/Mass Spectrometry-Based Metabonomic Techniques to Analyze the Joint Toxic Action of Long-Term Low-Level Exposure to a Mixture of Organophosphate Pesticides on Rat Urine Profile.

Organophosphate


Input: In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate and phorate) to rats using metabonomic technology at their corresponding no observed adverse effect level (NOAEL).

organophosphate

dichlorvos

dimethoate

acephate

phorate


Input: Results show that a single pesticide elicits no toxic response.


Input: The present study aimed to determine whether chronic exposure to a mixture of the above four pesticides (at their corresponding NOAEL) can lead to joint toxic action in rats using the same technology.


Input: Pesticides were administered daily to rats through drinking water for 24 weeks.


Input: The above mixture of the four pesticides showed joint toxic action at the NOAEL of each pesticide.


Input: The metabonomic profiles of rats urine were analyzed by ultra-performance liquid chromatography/mass spectrometry.


Input: The 16 metabolites statistically significantly changed in all treated groups compared with the control group.


Input: Dimethylphosphate and dimethyldithiophosphate exclusively detected in all treated groups can be used as early, sensitive biomarkers for exposure to a mixture of the OP pesticides.

Dimethylphosphate

dimethyldithiophosphate


Input: Moreover, exposure to the OP pesticides resulted in increased 7-methylguanine, ribothymidine, cholic acid, 4-pyridoxic acid, kynurenine and indoxyl sulfate levels, as well as decreased hippuric acid, creatinine, uric acid, gentisic acid, C18-dihydrosphingosine, phytosphingosine, suberic acid and citric acid.

ribothymidine

cholic acid

4-pyridoxic acid

kynurenine

indoxyl sulfate

hippuric acid

creatinine

uric acid

gentisic acid

phytosphingosine

suberic acid

citric acid


Input: The results indicated that a mixture of OP pesticides induced DNA damage, oxidative stress, disturbed the metabolism of lipids as well as interfered with the tricarboxylic acid cycle.

tricarboxylic acid


Input: Ensuring food safety requires not only the toxicology test data of each pesticide for the calculation of the acceptable daily intake, but also the joint toxic action.


Input: Anti-Ulcerative Colitis Activity of Compounds from Euphorbia granuleta Forssk.


Input: The aim of the present study was to evaluate the anti-ulcerative colitis (UC) activity of the total alcohol extracts of Euphorbia granuleta Forssk.

alcohol


Input: (Euphorpiaceae), isolate and identify the active compounds that could be responsible for the activity, in addition to determination of the possible mechanism of action.


Input: Six compounds were isolated and identified from this plant: three phenolic compounds (kampferol, kampferol-3-glucoside and kampferol-3-galactoside) in addition to three steroidal compounds (1-ethoxypentacosane, heptacosan-1-ol and beta-sitosterol).

phenolic

kampferol

beta-sitosterol


Input: Three compounds (heptacosan-1-ol, beta-sitosterol and kampferol-3-galactoside) were found to be responsible for the anti-UC activity of E. granuleta extract.

beta-sitosterol


Input: The anti-UC activity of these compounds may be explained by reducing the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), in addition to reduction of colonic malondialdehyde (MDA) contents.

malondialdehyde

MDA


Input: No side effects were reported on liver and kidney functions.


Input: The active compounds reduced both serum TNF-alpha and mucosal MDA levels.

MDA


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


Input: Decursin Exerts Anti-cancer Activity in MDA-MB-231 Breast Cancer Cells Via Inhibition of the Pin1 Activity and Enhancement of the Pin1/p53 Association.

Decursin


Input: The peptidyl-prolyl cis/trans isomerase Pin1 is overexpressed in a wide variety of cancer cells and thus considered as an important target molecule for cancer therapy.

prolyl


Input: This study demonstrates that decursin, a bioactive compound from Angelica gigas, exert the anti-cancer effect against breast cancer cells via regulation of Pin1 and its related signaling molecules.

decursin


Input: We observed that decursin induced G1 arrest with decrease in cyclin D1 level in Pin1-expressing breast cancer cells MDA-MB-231, but not Pin1-non-expressing breast cancer cells MDA-MB-157.

decursin


Input: In addition, decursin significantly reduced protein expression and enzymatic activity of Pin1 in MDA-MB-231 cells.

decursin


Input: Further, we found that decursin treatment enhanced the p53 expression level and failed to down-regulate Pin1 in the cells transfected with p53 siRNA, indicating the importance of p53 in the decursin-mediated Pin1 inhibition in MDA-MB-231 cells.

decursin

decursin


Input: Decursin stimulated association between Pin1 to p53.

Decursin


Input: Moreover, decursin facilitated p53 transcription in MDA-MB-231 cells.

decursin


Input: Overall, our current study suggests the potential of decursin as an attractive cancer therapeutic agent for breast cancer by targeting Pin1 protein.

decursin


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


Input: Pharmacological Inhibition of Platelet-tumor Cell Cross-talk Prevents Platelet-induced Overexpression of Cyclooxygenase-2 in HT29 Human Colon Carcinoma Cells.


Input: Cyclooxygenase (COX)-2-derived prostanoids can influence several processes that are linked to carcinogenesis.

prostanoids


Input: We aimed to address the hypothesis that platelets contribute to aberrant COX-2 expression in HT29 colon carcinoma cells and to reveal the role of platelet-induced COX-2 on the expression of proteins involved in malignancy and marker genes of epithelial-mesenchymal transition (EMT).


Input: Human platelets co-cultured with HT29 cells rapidly adhered to cancer cells and induced COX-2 mRNA expression, but not protein synthesis which required the late release of platelet PDGF and COX-2 mRNA stabilization.


Input: Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21 (WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by rofecoxib (a selective COX-2 inhibitor) and rescued by exogenous PGE2.

rofecoxib


Input: Galectin-3, highly expressed in HT29 cells, is unique among galectins because it contains a collagen-like domain.


Input: Thus, we studied the role of galectin-3 and platelet collagen receptors in platelet-induced COX-2 overexpression.


Input: Inhibitors of galectin-3 function (beta-lactose, a dominant-negative form of galectin-3, Gal-3C, and anti-galectin-3 antibody M3/38) or collagen receptor-mediated platelet adhesion (revacept, a dimeric collagen receptor GPVI-Fc) prevented aberrant COX-2 expression.

beta-lactose


Input: Inhibition of platelet-cancer cell interaction by revacept was more effective than rofecoxib in preventing platelet-induced mRNA changes of EMT markers suggesting that direct cell-cell contact and aberrant COX-2 expression synergistically induced gene expression modifications associated with EMT.

rofecoxib


Input: In conclusion, our findings provide the rationale for testing blockers of collagen binding sites, such as revacept, and galectin-3 inhibitors in the prevention of colon cancer metastasis in animal models followed by studies in patients.


Input: The absence of ER beta results in altered gene expression in ovarian granulosa cells isolated from in vivo preovulatory follicles.


Input: Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation.

estrogen


Input: Estrogen receptor (ER) beta is highly expressed in ovarian granulosa cells and mice lacking ER beta (beta ERKO) are subfertile due to inefficient ovulation.

Estrogen


Input: Previous work has focused on isolated granulosa cells or cultured follicles and while informative, provides confounding results due to the heterogeneous cell types present including granulosa, theca and oocytes and exposure to in vitro conditions.


Input: Herein, we isolated preovulatory granulosa cells from WT and ER beta-null mice using laser capture microdissection to examine the genomic transcriptional response downstream of PMSG (mimicking FSH) and PMSG/hCG (mimicking LH) stimulation.


Input: This allows for a direct comparison of in vivo granulosa cells at the same stage of development from both WT and ER beta-null ovaries.


Input: ER beta-null granulosa cells showed altered expression of genes known to be regulated by FSH (Akap12 and Runx2) as well as not previously reported (Arnt2 and Pou5f1) in WT granulosa cells.


Input: Our analysis also identified 304 genes not previously associated with ER beta in granulosa cells.


Input: LH responsive genes including Abcb1b and Fam110c show reduced expression in ER beta-null granulosa cells; however novel genes including Rassf2 and Megf10 were also identified as being downstream of LH signaling in granulosa cells.


Input: Collectively, our data suggests that granulosa cells from ER beta-null ovaries may not be appropriately differentiated and are unable to respond properly to gonadotropin stimulation.


Input: Caspase-14 suppresses GCM1 acetylation and inhibits placental cell differentiation.


Input: Glial cell missing 1 (GCM1) transcription factor regulates placental cell fusion into the syncytiotrophoblast.


Input: Caspase-14 is proteolytically activated to mediate filaggrin processing during keratinocyte differentiation.


Input: Interestingly, altered expression of nonactivated caspase-14 proenzyme is associated with tumorigenesis and diabetic retinopathy, suggesting that caspase-14 may perform physiological functions independently of its protease activity.


Input: Here, we performed tandem affinity purification coupled with mass spectrometry analysis to identify caspase-14 proenzyme as a GCM1-interacting protein that suppresses GCM1 activity and syncytiotrophoblast differentiation.


Input: Immunohistochemistry revealed that caspase-14 and GCM1 colocalize to placental cytotrophoblast cells at 8 wk of gestation and syncytiotrophoblast layer at term.


Input: Further, we demonstrated that caspase-14 mRNA level is decreased by 40% in placental BeWo cells treated with forskolin (FSK).

forskolin

FSK


Input: To the contrary, stimulation of GCM1-regulated placental cell fusion and human chorionic gonadotropin beta (hCG beta) expression by FSK is enhanced by caspase-14 knockdown.


Input: Indeed, GCM1 protein level is increased by 40% in the caspase-14-knockdown BeWo cells.


Input: Because GCM1 is stabilized by acetylation, we subsequently showed that caspase-14 impedes the interaction between GCM1 and cAMP response element-binding protein (CREB)-binding protein (CBP) to suppress CBP-mediated acetylation and transcriptional coactivation of GCM1.

cAMP


Input: Therefore, caspase-14 can suppress placental cell differentiation through down-regulation of GCM1 activity.-Wu, Y.-H., Lo, H.-F., Chen, S.-H., Chen, H.


Input: Caspase-14 suppresses GCM1 acetylation and inhibits placental cell differentiation.


Input: Patchy surfaces stabilize dextran-polyethylene glycol aqueous two-phase system liquid patterns.

polyethylene glycol


Input: This paper analyzes surface chemistry effects to stably pattern aqueous two-phase system (ATPS) droplets on chemically modified poly (dimethylsiloxane) (PDMS).

poly (dimethylsiloxane)

PDMS


Input: Polyethylene glycol (PEG) and dextran (DEX) are used as phase-forming polymers for the ATPS.

Polyethylene glycol

PEG


Input: PDMS surface modifications studied include primary amine groups, carboxylic acid groups, and neutral polymer surfaces.

PDMS

primary amine

carboxylic acid


Input: The PDMS surfaces were characterized by fluorescent measurement, water and DEX contact angle measurements, and X-ray photoelectron spectroscopy (XPS) analysis to confirm surface properties.

PDMS


Input: While homogeneous surfaces of different functional groups affect DEX droplet pinning somewhat, the most stable patterns were realized using surfaces with chemical heterogeneity.


Input: Arbitrary DEX solution patterning was achieved on a chemically patchy surface.


Input: A Butterfly-Shaped Pyrene Derivative of Cholesterol and Its Uses as a Fluorescent Probe.

Pyrene

Cholesterol


Input: A butterfly-shaped pyrene derivative of cholesterol, namely, N, N'-(ethane-1, 2-diyl)-bis (N-(2-(chol-amino) ethyl) pyrene-1-sulfonamide) (ECPS), has been designed and synthesized.

cholesterol

N, N'-(ethane-1, 2-diyl)-bis (N-(2-(chol-amino) ethyl) pyrene-1-sulfonamide)

ECPS


Input: Solvent effect studies revealed that in good solvents such as n-hexane, benzene, and 1, 4-dioxane, the profile of the fluorescence emission of the compound is characterized by pyrene monomer emission, but in poor solvent such as water, the emission is dominated by pyrene excimer emission.

n-hexane

benzene

1, 4-dioxane

pyrene


Input: Quantitatively speaking, the ratio of the excimer emission to monomer emission changes from 50 to 0 when ECPS is dissolved in water and n-hexane, respectively.

n-hexane


Input: In contrast, for a commonly used polarity probe pyrene, the ratio of I3/I1 varies only from ~ 0. 6 to ~ 1. 7, where I3 and I1 stand for the intensities of the fluorescence emission at peak 3 and peak 1, respectively.

pyrene


Input: This value suggests that a more powerful discriminating ability of the new compound in polarity sensing.


Input: Furthermore, unlike the main components of the compound, pyrene and cholesterol, its main chain is composed of multiple hydrophilic structures, and it is this structure that makes the emission of the compound in organic solvents sensitive to the presence of water.

pyrene

cholesterol


Input: Accordingly, the applicability of the compound in determination of the trace amount of water in some organic solvents was evaluated.


Input: As expected, the detection limit of the compound toward water in acetonitrile reaches 7 ppm, a result never reached before.

acetonitrile


Input: Furthermore, the fluorescence emission of the compound is also sensitive to viscosity variation.


Input: Therefore, it is assumed that ECPS may be used both as a polarity probe and a viscosity probe.

ECPS


Input: On the bases of a series of steady-state and time-resolved fluorescence, as well as dynamic light scattering studies, a structural model was proposed to rationalize the fluorescence behavior of the compound in different solvents and its polarity and viscosity probing performances.


Input: Enhanced Optical Second-Harmonic Generation from the Current-Biased Graphene/SiO2/Si (001) Structure.

Graphene

Si


Input: We find that optical second-harmonic generation (SHG) in reflection from a chemical-vapor-deposition graphene monolayer transferred onto a SiO2/Si (001) substrate is enhanced about 3 times by the flow of direct current electric current in graphene.

graphene

Si

graphene


Input: Measurements of rotational-anisotropy SHG revealed that the current-induced SHG from the current-biased graphene/SiO2/Si (001) structure undergoes a phase inversion as the measurement location on graphene is shifted laterally along the current flow direction.

graphene

Si

graphene


Input: The enhancement is due to current-associated charge trapping at the graphene/SiO2 interface, which introduces a vertical electric field across the SiO2/Si interface that produces electric field-induced SHG.

graphene

Si


Input: The phase inversion is due to the positive-to-negative polarity switch in the current direction of the trapped charges at the current-biased graphene/SiO2 interface.

graphene


Input: Exciplex Formation in Blended Spin-Cast Films of Fluorene-Linked Dyes and Bisphthalimide Quenchers.

Fluorene

Bisphthalimide


Input: Spin-cast films of dyes (donor-pi-donor, donor-pi-acceptor, and acceptor-pi-acceptor type, where the donor is Ph2N-, the acceptor is 2-benzothiazoyl, and the pi-linker is 9, 9-diethylfluorene) blended with nonconjugated bisphthalimides were prepared.

9, 9-diethylfluorene

bisphthalimides


Input: Upon visible-light excitation of the dyes, quenching of the excited state occurs by exciplex formation between dye and bisphthalimide molecules or, in some cases, by excimer formation or aggregation-induced emission between two dye molecules.

bisphthalimide


Input: The extent of exciplex formation is dependent on the driving force, which can be calculated using the energy difference between the lowest unoccupied molecular orbitals (LUMOs) of the dyes and bisphthalimides.

bisphthalimides


Input: The results show that complete exciplex formation occurs when this driving force is greater than 0. 57 eV whereas partial exciplex formation occurs when the driving force is between 0. 28 and 0. 57 eV.


Input: The exciplex emission energies can also be predicted by calculating the difference between the LUMO level of the bisphthalimide and the highest occupied molecular orbital (HOMO) of the dye.

bisphthalimide


Input: These calculated values, which were obtained from the electrochemically determined energy levels, showed good agreement with the observed emission energies.


Input: The exciplex lifetimes were found to be significantly longer than the lifetimes of the lone dyes.


Input: These exciplexes formed from nonlinked donors and acceptors in the solid state might have potential uses in nonlinear photonics.


Input: Condensation of DNA-A putative obstruction for repair process in abasic clustered DNA damage.


Input: Clustered DNA damages are defined as two or more closely located DNA damage lesions that may be present within a few helical turns of the DNA double strand.


Input: These damages are potential signatures of ionizing radiation and are often found to be repair resistant.


Input: Types of damaged lesions frequently found inside clustered DNA damage sites include oxidized bases, abasic sites, nucleotide dimers, strand breaks or their complex combinations.

nucleotide dimers


Input: In this study, we used a bistranded two-lesion abasic cluster DNA damage model to access the repair process of DNA in condensate form.


Input: Oligomer DNA duplexes (47bp) were designed to have two deoxyuridine in the middle of the sequences, three bases apart in opposite strands.

deoxyuridine


Input: The deoxyuridine residues were converted into abasic sites by treatment with UDG enzyme creating an abasic clustered damage site in a precise position in each of the single strand of the DNA duplex.

deoxyuridine


Input: This oligomer duplex having compatible cohesive ends was ligated to pUC19 plasmid, linearized with HindIII restriction endonuclease.


Input: The plasmid-oligomer conjugate was transformed into condensates by treating them with spermidine.

spermidine


Input: The efficiency of strand cleavage action of ApeI enzyme on the abasic sites was determined by denaturing PAGE after timed incubation of the oligomer duplex and the oligomer-plasmid conjugate in presence and absence of spermidine.

spermidine


Input: The efficiency of double strand breaks was determined similarly by native PAGE.


Input: Quantitative gel analysis revealed that rate of abasic site cleavage is reduced in the DNA condensates as compared to the oligomer DNA duplex or the linear ligated oligomer-plasmid conjugates.


Input: Generation of double strand break is significantly reduced also, suggesting that their creation is not proportionate to the number of abasic sites cleaved in the condensate model.


Input: All these suggest that the ApeI enzyme have difficulty to access the abasic sites located deep into the condensates leading to repair refractivity of the damages.


Input: In addition, we found that presence of a polyamine such as spermidine has no notable effect in the incision activity of ApeI enzyme in linear oligomer DNA duplexes in our experimental concentration.

polyamine

spermidine


Input: Synthesis and antitumor activity of 1, 3, 4-oxadiazole possessing 1, 4-benzodioxan moiety as a novel class of potent methionine aminopeptidase type II inhibitors.

1, 3, 4-oxadiazole

1, 4-benzodioxan

methionine


Input: A series of 1, 3, 4-oxadiazole derivatives containing 1, 4-benzodioxan moiety (7a-7q) have been designed, synthesized and evaluated for their antitumor activity.

1, 3, 4-oxadiazole

1, 4-benzodioxan


Input: Most of the synthesized compounds were proved to have potent antitumor activity and low toxicity.


Input: Among them, compound 7a showed the most potent biological activity against Human Umbilical Vein Endothelial cells, which was comparable to the positive control.


Input: The results of apoptosis and flow cytometry (FCM) demonstrated that compound 7a induce cell apoptosis by the inhibition of MetAP2 pathway.


Input: Molecular docking was performed to position compound 7a into MetAP2 binding site in order to explore the potential target.


Input: Nr4a1-Dependent Ly6C (low) Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal.


Input: The functions of Nr4a1-dependent Ly6C (low) monocytes remain enigmatic.


Input: We show that they are enriched within capillaries and scavenge microparticles from their lumenal side in a steady state.


Input: In the kidney cortex, perturbation of homeostasis by a TLR7-dependent nucleic acid " danger " signal, which may signify viral infection or local cell death, triggers G alpha i-dependent intravascular retention of Ly6C (low) monocytes by the endothelium.


Input: Then, monocytes recruit neutrophils in a TLR7-dependent manner to mediate focal necrosis of endothelial cells, whereas the monocytes remove cellular debris.


Input: Prevention of Ly6C (low) monocyte development, crawling, or retention in Nr4a1 (-/-), Itgal (-/-), and Tlr7 (host-/-BM +/+) and Cx3cr1 (-/-) mice, respectively, abolished neutrophil recruitment and endothelial killing.


Input: Prevention of neutrophil recruitment in Tlr7 (host +/+ BM-/-) mice or by neutrophil depletion also abolished endothelial cell necrosis.


Input: Therefore, Ly6C (low) monocytes are intravascular housekeepers that orchestrate the necrosis by neutrophils of endothelial cells that signal a local threat sensed via TLR7 followed by the in situ phagocytosis of cellular debris.


Input: The anti-diabetic effects and pharmacokinetic profiles of berberine in mice treated with Jiao-Tai-Wan and its compatibility.

berberine


Input: Jiao-Tai-Wan (JTW), a classical Chinese prescription, has been clinically employed to treat diabetes mellitus in recent years.


Input: To investigate the comparative evaluations on anti-diabetic effects and pharmacokinetics of the active ingredient berberine in mice treated with JTW in various combinations of its constituent herbs.

berberine


Input: In our study, the anti-diabetic study was carried out in diabetic mice induced by intraperitoneal injection of streptozotocin.

streptozotocin


Input: The diabetic mice were randomly assigned to three therapy groups and orally administered with different prescription proportions of Rhizoma Coptidis and Cinnamomum cassia respectively.


Input: The level of plasma glucose, lipid profile and parameters related to oxidative stress were determined.

glucose


Input: The concentrations of berberine in non-diabetic mice plasma were determined using HPLC, and main pharmacokinetic parameters were investigated.

berberine


Input: The results indicated that the compatibility effects of ingredients present in Cinnamomum cassia could affect the anti-diabetic ability and pharmacokinetics of berberine in JTW.

berberine


Input: Quercetin suppressed CYP2E1-dependent ethanol hepatotoxicity via depleting heme pool and releasing CO.

Quercetin

ethanol

CO


Input: Naturally occuring quercetin protects hepatocytes from ethanol-induced oxidative stress, and heme oxygenase-1 (HO-1) induction and carbon monoxide (CO) metabolite may be implicated in the beneficial effect.

quercetin

ethanol

heme

carbon monoxide

CO


Input: However, the precise mechanism by which quercetin counteracts CYP2E1-mediated ethanol hepatotoxicity through HO-1 system is still remained unclear.

quercetin

ethanol


Input: To explore the potential mechanism, herein, ethanol (4. 0g/kg. bw.) was administrated to rats for 90 days.

ethanol


Input: Our data showed that chronic ethanol over-activated CYP2E1 but suppressed HO-1 with concurrent hepatic oxidative damage, which was partially normalized by quercetin (100mg/kg. bw.).

ethanol

quercetin


Input: Quercetin (100 mu M) induced HO-1 and depleted heme pool when incubated to human hepatocytes.

Quercetin


Input: Ethanol-stimulated (100mM) CYP2E1 upregulation was suppressed by quercetin but further enhanced by HO-1 inhibition with resultant heme accumulation.

Ethanol

quercetin

heme


Input: CO scavenging blocked the suppression of quercetin only on CYP2E1 activity.

CO

quercetin


Input: CO donor dose-dependently inactivated CYP2E1 of ethanol-incubated microsome, which was mimicked by HO-1 substrate but abolished by CO scavenger.

CO

ethanol

CO


Input: Thus, CYP2E1-mediated ethanol hepatotoxicity was alleviated by quercetin through HO-1 induction.

ethanol

quercetin


Input: Depleted heme pool and CO releasing limited protein synthesis and inhibited enzymatic activity of CYP2E1, respectively.

CO


Input: Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox4.

Quinone

NADPH


Input: NADPH oxidase Nox4 is expressed in a wide range of tissues and plays a role in cellular signaling by providing reactive oxygen species (ROS) as intracellular messengers.

NADPH

oxygen


Input: Nox4 oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific quinone derivatives could modulate this activity.

quinone


Input: In fact, we demonstrated a significant stimulation of Nox4 activity by 4 quinone derivatives (AA-861, tBuBHQ, tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx (TM), and chondrocyte cell lines.

quinone

tBuBHQ

tBuBQ

duroquinone


Input: Our results indicate that the effect is specific toward Nox4 versus Nox2.


Input: Furthermore, we showed that NAD (P) H: quinone oxidoreductase (NQO1) may participate in this stimulation.

NAD (P) H

quinone


Input: Interestingly, Nox4 activity is also stimulated by reducing agents that possibly act by reducing the disulfide bridge (Cys226, Cys270) located in the extracellular E-loop of Nox4.

disulfide


Input: Such model of Nox4 activity regulation could provide new insight into the understanding of the molecular mechanism of the electron transfer through the enzyme, i. e., its potential redox regulation, and could also define new therapeutic targets in diseases in which quinones and Nox4 are implicated.

quinones


Input: Phenolic compounds present in Sardinian wine extracts protect against the production of inflammatory cytokines induced by oxysterols in CaCo-2 human enterocyte-like cells.

Phenolic

oxysterols


Input: Cholesterol auto-oxidation products, namely oxysterols, are widely present in cholesterol-rich foods.

Cholesterol

oxysterols

cholesterol


Input: They are thought to potentially interfere with homeostasis of the human digestive tract, playing a role in intestinal mucosal damage.


Input: This report concerns the marked up-regulation in differentiated CaCo-2 colonic epithelial cells of two key inflammatory interleukins, IL-6 and IL-8, caused by a mixture of oxysterols representative of a high cholesterol diet.

oxysterols

cholesterol


Input: This strong pro-inflammatory effect appeared to be dependent on the net imbalance of red-ox equilibrium with the production of excessive levels of reactive oxygen species through the colonic NADPH-oxidase NOX1 activation.

oxygen

NADPH


Input: Induction of NOX1 was markedly while not fully inhibited by CaCo-2 cell pre-incubation with phenolic extracts obtained from well-selected wines from typical grape varieties grown in Sardinia.


Input: Oxysterol-dependent NOX1 activation, as well as interleukin synthesis, were completely prevented by Cannonau red wine extract that contains an abundant phenolic fraction, in particular phenolic acids and flavonoids.

Oxysterol

phenolic acids

flavonoids


Input: Conversely, cell pre-treatment with Vermentino white wine extract with smaller phenolic fraction showed only a partial NOX1 down-regulation and was ineffective in interleukin synthesis induced by dietary oxysterols.

oxysterols


Input: It is thus likely that the effects of Sardinian wine extracts against intestinal inflammation induced by dietary oxysterols are mainly due to their high phenolic content: low doses of phenolics would be responsible only for direct scavenging oxysterol-dependent ROS production.

oxysterols

phenolics

oxysterol


Input: Besides this direct activity, an excess of phenolic compounds detectable in red wine, may exert an additional indirect action by blocking oxysterol-related NOX1 induction, thus totally preventing the pro-oxidant and pro-inflammatory events triggered by dietary oxysterols.

phenolic

oxysterol

oxysterols


Input: Simonols A and B, two novel sesqui-neolignans from the fruits of Illicium simonsii.

Simonols A and B

sesqui-neolignans


Input: Two new sesqui-neolignans with novel conjugation way, simonol A (1), featuring a unique motif of a 5, 5-dihydro-pyran with a hemiketal carbon, while simonol B (2) possessing two dihydronfuran rings in the same direction, were isolated from the ethanol extract of the fruits of Illicium simonii.

sesqui-neolignans

simonol A

5, 5-dihydro-pyran

hemiketal carbon

simonol B

dihydronfuran

ethanol


Input: Their structures were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, and calculation of electronic circular dichroism (ECD) using density functional theory (DFT).


Input: The two isolates were evaluated for their inhibitory activities against the growth of four lines of human cancer cells (NCI-H460, SMMC-7721, MCF-7, BGC-823): 1 showed strong activities comparable to 5-Fluorouracil, and 2 to a less content.


Input: In addition, plausible biosynthetic routes for the two compounds were also proposed.


Input: A comprehensive machine-readable view of the mammalian cholesterol biosynthesis pathway.

cholesterol


Input: Cholesterol biosynthesis serves as a central metabolic hub for numerous biological processes in health and disease.

Cholesterol


Input: A detailed, integrative single-view description of how the cholesterol pathway is structured and how it interacts with other pathway systems is lacking in the existing literature.

cholesterol


Input: Here we provide a systematic review of the existing literature and present a detailed pathway diagram that describes the cholesterol biosynthesis pathway (the mevalonate, the Kandutch-Russell and the Bloch pathway) and shunt pathway that leads to 24 (S), 25-epoxycholesterol synthesis.

cholesterol

mevalonate

24 (S), 25-epoxycholesterol


Input: The diagram has been produced using the Systems Biology Graphical Notation (SBGN) and is available in the SBGN-ML format, a human readable and machine semantically parsable open community file format.


Input: Molecular mechanisms for the anti-cancer effects of diallyl disulfide.

diallyl disulfide


Input: Considerable evidence in recent years suggests that garlic has anti-proliferative effects against various types of cancer.


Input: Garlic contains water-soluble and oil-soluble sulfur compounds.


Input: Oil-soluble compounds such as diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS) and ajoene are more effective than water-soluble compounds in protection against cancer.

diallyl sulfide

DAS

diallyl disulfide

DADS

diallyl trisulfide

DATS

ajoene


Input: DADS, a major organosulfur compound derived from garlic, can decrease carcinogen-induced cancers in experimental animals and inhibit the proliferation of various types of cancer cells.

DADS

organosulfur


Input: Its mechanisms of action include: the activation of metabolizing enzymes that detoxify carcinogens; suppression of the formation of DNA adducts; antioxidant effects; regulation of cell-cycle arrest; induction of apoptosis and differentiation; histone modification; and inhibition of angiogenesis and invasion.


Input: These topics are discussed in depth in this review.


Input: Particle sizing measurements in pharmaceutical applications: Comparison of in-process methods versus off-line methods.


Input: It has been previously described that when a sample' s particle size is determined using different sizing techniques, the results can differ considerably.


Input: The purpose of this study was to review several in-process techniques for particle size determination (Spatial Filtering Velocimetry, Focused Beam Reflectance Measurements, Photometric Stereo Imaging, and the Eyecon (R) technology) and compare them to well-known and widespread off-line reference methods (laser diffraction and sieve analysis).


Input: To start with, a theoretical explanation of the working mechanism behind each sizing technique is presented, and a comparison between them is established.


Input: Secondly, six batches of granules and pellets (i. e., spherical particles) having different sizes were measured using these techniques.


Input: The obtained size distributions and related D10, D50, and D90 values were compared using the laser diffraction wet dispersion method as reference technique.


Input: As expected, each technique provided different size distributions with different D values.


Input: These dissimilarities were examined and explained considering the measurement principles behind each sizing technique.


Input: The particle property measured by each particle size analyzer (particle size or chord length) and how it is measured as well as the way in which size information is derived and calculated from this measured property and how results are presented (e. g., volume or mass distributions) are essential for the interpretation of the particle size data.


Input: Interdependency of protein-release completeness and polymer degradation in PLGA-based implants.

PLGA


Input: Release of BSA (model protein) from hot-melt extruded poly (lactide-co-glycolide) (PLGA)-based implants was incomplete.

poly (lactide-co-glycolide)

PLGA


Input: A residual mass of covalent BSA-PLGA adducts was still present after 6months.

PLGA


Input: The objective of this study was to increase the completeness of BSA release.


Input: BSA reduced the PLGA degradation and erosion rate as well as the extent of erosion.

PLGA


Input: An increased uptake of release medium in the presence of BSA in addition to the early outflux of PLGA oligomers resulted in a reduction of the matrix acidity and thus reduction of autocatalysis effects.

PLGA


Input: PLGA mass loss was incomplete at 60% and 80% for 10% and 25% BSA-containing implants.

PLGA


Input: The extent of PLGA mass loss was correlated with the total releasable protein.

PLGA


Input: The same release was obtained from implants prepared with pre-degraded PLGA suggesting that the induction phase did not affect the release completeness.

PLGA


Input: Thus, the focus was on the erosion phase to enhance outflux of soluble oligomers.


Input: BSA release completeness increased by increasing the porosity of the implants at the onset of erosion phase.


Input: This could be obtained with a higher initial porosity, formation of porosity upon higher diffusional release and/or incorporation of pore-formers/plasticizers.


Input: Accordingly, the BSA release completeness could be improved by enhancing the outflux of soluble PLGA degradation products.

PLGA


Input: Thermal stability of oligodeoxynucleotide duplexes containing l-deoxynucleotide at termini.

l-deoxynucleotide


Input: The effects of substituting l-deoxynucleotide for d-deoxynucleotide at duplex termini were evaluated and the terminal substitutions were found to show much less effects on duplex destabilization and to show a similar tendency in base pairing selectivity, compared with internal chiral substitutions.

l-deoxynucleotide

d-deoxynucleotide


Input: Agonistic activity of ICI 182 780 on activation of GSK 3 beta/AKT pathway in the rat uterus during the estrous cycle.

ICI 182 780


Input: We examined the ability of ICI 182, 780 (ICI) to block uterine cell proliferation via protein kinase b/AKT pathway in the uterus of the rat during the estrous cycle.

ICI 182, 780

ICI


Input: Intact rats, with regular estrous cycles, received a subcutaneous (s. c.) injection of either vehicle or ICI at 08: 00h on the day of proestrus or at 00: 00h on the day of estrus and sacrificed at 13: 00h of metaestrus.

ICI


Input: Estradiol (E2) and progesterone (P4) plasma levels were measured by radioimmunoassay.

Estradiol

progesterone


Input: Both ICI treatments, induced a significant decrease (p < 0. 01) in uterine estrogen receptor alpha (ER alpha) content, had no effect on uterine progesterone receptor (PR) protein expression and caused marked nuclear localization of cyclin D1, in both luminal and glandular uterine epithelium, as compared to vehicle-treated animals.

ICI

estrogen

progesterone


Input: Furthermore, we detected that ICI treatment induced glycogen synthase kinase (Gsk3-beta) Ser 9 phosphorylation, which correlates with cyclin D1 nuclear localization.

ICI


Input: However, some differences were observed between the two different time schedules of administration.


Input: We observed that the administration of ICI at 08: 00h on proestrus day produced a 15% inhibition of luminal epithelial cell proliferation, reduced uterine wet weight by 21% and caused reduction of Akt phosphorylation at Ser 473 as compared to vehicle-treated animals, whereas ICI treatment at 00: 00h on estrus day had no effect on these parameters.

ICI

Ser

ICI


Input: The overall results indicate that ICI may exert agonistic and antagonistic effects on uterine cell proliferation through differential activation of the Akt pathway depending on the administration period during the estrous cycle, and indicates that the mechanism of cell proliferation during the physiological conditions of the estrous cycle, is under a different and more complex regulation than in the ovariectomized + E2 animal model.

ICI


Input: Skin penetration enhancing properties of the plant N-alkylamide spilanthol.

N-alkylamide spilanthol


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Plants are often used for skin diseases in different ethnopharmacological systems.


Input: Local and systemic effects of topically applied compounds can be significantly increased by plant constituents having skin penetration enhancers.


Input: MATERIALS AND METHODS: In this study, we examined the proposed penetration enhancing properties of spilanthol, an N-alkylamide abundantly present in several Asteraceae plants like Spilanthes acmella L., on three model drugs (caffeine, testosterone and ibuprofen).

spilanthol

N-alkylamide

caffeine

testosterone

ibuprofen


Input: Moreover, as plants are frequently contaminated with toxic environmental substances, the mutual influence on the transdermal behavior between spilanthol and six model mycotoxins (aflatoxin B1, ochratoxin A, fumonisin B1, citrinin, zearalenone, T-2 toxin) was investigated.

spilanthol

aflatoxin B1

ochratoxin A

fumonisin B1

citrinin

zearalenone

T-2 toxin


Input: RESULTS: Spilanthol exhibits component and concentration dependent penetration enhancing effects.

Spilanthol


Input: No significant penetration enhancing effect for ibuprofen has been observed, but with increasing spilanthol concentration (from 0 up to 1w/V%), the permeability of caffeine increased, resulting in an enhancing ratio (ER) of 4. 60.

ibuprofen

spilanthol

caffeine


Input: For testosterone, a maximal penetration enhancing concentration of 0. 5% spilanthol was found (ER = 4. 13).

testosterone

spilanthol


Input: Next to its beneficial applicability to increase local as well as systemic pharmacological effects of dermally co-administrated drug, this N-alkylamide negatively influences human health risk if spilanthol containing formulations are polluted with mycotoxins: the presence of spilanthol (0. 3w/V%) induced a significant increase of permeability coefficient Kp of five investigated mycotoxins, with ER values ranging between 1. 57 and 6. 37.

N-alkylamide

spilanthol

spilanthol


Input: On the other hand, mycotoxins themselves do not significantly influence the transdermal behavior of spilanthol.

spilanthol


Input: CONCLUSIONS: The existence of a significant mutual influence of compounds towards skin penetration should always be considered during the development or as part of the functional quality evaluation of topical products.


Input: Biopharmaceutical classification of poorly soluble drugs with respect to " enabling formulations "


Input: The large number of drug candidates with poor dissolution characteristics seen in the past decade, has fostered interest in so-called " enabling formulations ", i. e., formulations which shall make such drugs bio-available.


Input: Development of enabling formulations is currently being guided by the following (simplified) hypothesis: If a poorly soluble drug (BCS class II drug) can be transferred into a solubilized state, one can achieve an absorption profile close to that of a soluble drug (BCS class I drug).


Input: Thus, formulation development typically endeavors to achieve the most robust solubility enhancement.


Input: Here we critically review both common in vitro approaches and experimental data available in literature pertaining to the solubility and permeability of poorly soluble drugs from enabling formulations, and discuss their interplay.


Input: Recent in vitro data indicate, that commonly employed surfactants as well as endogenous surfactants present in the intestine, although enhancing drug solubility, mostly hamper drug permeation.


Input: Mechanistic studies demonstrate a direct correlation between passive transcellular diffusion and the concentration of molecularly dissolved drug.


Input: The latter may be reduced due to partitioning into micelles or other solubilizing carriers, but enhanced in supersaturating formulations.


Input: We conclude thus that biopharmaceutical assessment approaches that rely on the amount of molecularly dissolved drug should guide us towards successful enabling formulations.


Input: Dietary nimodipine delays the onset of methylmercury neurotoxicity in mice.

nimodipine

methylmercury


Input: Adult-onset exposure is thought to result primarily in sensory and motor deficits but effects on learning are poorly understood.


Input: One mechanism by which chronic MeHg may exert its neurotoxicity is via sustained disruption of intracellular calcium homeostasis, with a consequent increase of intracellular Ca (2 +) ions in vulnerable neurons.

MeHg

calcium

Ca (2 +)


Input: A biochemically heterogeneous group of compounds, calcium channel blockers, have been shown in vitro to attenuate MeHg' s toxicity.

calcium

MeHg


Input: To evaluate the role of calcium antagonism in MeHg toxicity in vivo, adult BALB/c mice were exposed chronically to 0 or 15ppm of Hg (as MeHg) via drinking water and to nimodipine, a dihydropryidine, L-type Ca (2 +) channel blocker with action in the CNS.

calcium

MeHg

Hg

MeHg

nimodipine

dihydropryidine

Ca (2 +)


Input: Nimodipine was administered orally in diets (0, 20, or 200ppm, producing approximately 0, 2, or 20mg/kg/day of nimodipine).

Nimodipine

nimodipine


Input: An incremental repeated acquisition (IRA) of response chains procedure was used to detect MeHg-induced deficits in learning or motoric function and to evaluate possible neuroprotection by nimodipine.

MeHg

nimodipine


Input: MeHg impaired performance on the IRA task, and this was partially or completely blocked by dietary nimodipine, depending on dose.

MeHg

nimodipine


Input: Measures of learning co-varied with measures of motoric function as indicated by overall response rate.


Input: Nimodipine delayed or prevented the behavioral toxicity of MeHg exposure as evidenced by IRA performance; effects on learning seemed secondary to response rate decreases.

Nimodipine

MeHg


Input: Acute and subacute toxicity studies on triptolide and triptolide-loaded polymeric micelles following intravenous administration in rodents.

triptolide

triptolide


Input: Except its anti-tumour effects, triptolide (TP) also shows multiple pharmacological side activities, such as immune-suppressive and male anti-fertility.

triptolide


Input: To increase the therapeutic index of TP, a novel polymeric micelle system containing TP (TP-PM) has been developed to treat tumour.


Input: Our previous studies have demonstrated the good anti-tumour efficacy of TP-PM.


Input: This paper investigated the acute toxicity in mice and subacute toxicity in rats of TP-PM and TP.


Input: Results demonstrated that the LD50 for TP-PM and TP administered intravenously were 1. 06mg/kg and 0. 83mg/kg in mice, respectively.


Input: In subacute toxicity study, TP-PM and TP were administered intravenously at the dose levels of 0. 1mg/kg and 0. 3mg/kg for 14d.


Input: Compared to the control, there was significant decrease in the serum AST activities, the testis ACP activities, thymus index, testis index, and significant increase in spleen index, and obvious histopathological changes in rats treated with TP, however, the toxicities of TP-PM on liver, kidney, testis and spleen are slighter than TP.


Input: Compared to TP, TP-PM significantly increased the ACP activity of the testis and decreased the MDA level in serum.

MDA


Input: So, the polymeric micelles may be a novel drug delivery carrier of TP for reducing the toxicities of TP.


Input: Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-kappa B pathway inhibition: Contribution of chlorogenic acid.

chlorogenic acid


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (DC) Stapf leaves infusion is used in traditional medicine for the treatment of inflammatory conditions, however little is known about their bio-active compounds.


Input: AIM OF THE STUDY: Investigate the compounds responsible for anti-inflammatory potential of Cymbopogon citratus (Cy) on cytokines production induced by lipopolysaccharide in human and mouse macrophages, and the action mechanisms involved.


Input: MATERIALS AND METHODS: An essential oil-free infusion of Cy was prepared and polyphenol-rich fractions (PFs) were obtained from it by column chromatography.

polyphenol


Input: Chlorogenic acid was identified, by HPLC/PDA/ESI-MS (n).

Chlorogenic acid


Input: The expression of cytokines, namely TNF-alpha and CCL5, was analyzed by real-time RT-PCR, on lipopolysaccharide-stimulated human macrophages.


Input: Activation of nuclear factor-kappa B, a master regulator of inflammation, was investigated by western blot and gene reporter assay.


Input: Proteasome activity was assessed using a fluorogenic peptide.


Input: RESULTS: Cymbopogon citratus extract and its polyphenols inhibited the cytokine production on human macrophages.

polyphenols


Input: This supports the anti-inflammatory activity of Cy polyphenols in physiologically relevant cells.

polyphenols


Input: Concerning the effect on the activation of nuclear factor (NF)-kappa B pathway, the results pointed to an inhibition of LPS-induced NF-kappa B activation by Cy and PFs.


Input: Chlorogenic acid was identified, by HPLC/PDA/ESI-MS (n), as the main phenolic acid of the Cy infusion, and it demonstrated to be, at least in part, responsible by that effect.

Chlorogenic acid

phenolic acid


Input: Additionally, it was verified for the first time that Cy and PFs inhibited the proteasome activity, a complex that controls NF-kappa B activation, having CGA a strong contribution.


Input: CONCLUSIONS: The results evidenced, for the first time, the anti-inflammatory properties of Cymbopogon citratus through proteasome inhibition and, consequently NF-kappa B pathway and cytokine expression.


Input: Additionally, Cy polyphenols, in particular chlorogenic acid, were highlighted as bio-active compounds.

polyphenols

chlorogenic acid


Input: Effect of bioactive peptide of Carapax Trionycis on TGF-beta 1-induced intracellular events in hepatic stellate cells.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicines for hepatic fibrosis therapy, Carapax Trionycis is used usually as an indispensable component and has a long history of medical use in China.


Input: Previous studies have demonstrated that extracts of Carapax Trionycis were able to protect liver against fibrosis in CCl4 animal models.


Input: AIM OF THE STUDY: The purpose of this study is to verify the inhibitory effect and the underlying mechanisms of Carapax Trionycis extract peptide (CTEP) on activated hepatic stellate cells which play a central role in liver fibrogenesis.


Input: MATERIALS AND METHODS: Hepatic stellate cells induced by TGF-beta 1 were applied to evaluate the anti-fibrotic effect of CTEP in vitro.


Input: MTS assay, enzyme-linked immunosorbent assay and western blotting were then used to further investigate the molecular mechanisms.

MTS


Input: RESULTS: The results show that the contents of collagen I, collagen III and TIMP-1 were significantly inhibited and the level of collagen I, collagen III, p-Smad 3, TIMP-1 and alpha-SMA proteins decreased significantly in a concentration-dependence manner after treatment with CTEP.


Input: Interestingly, the level of Smad 3 protein was not different significantly.


Input: CONCLUSIONS: Our data indicate that CTEP efficiently inhibits cultured HSC-T6 cell activation and proliferation via the TGF-beta 1/Smad pathway as well as by the elimination of the extracellular matrix.


Input: Design, synthesis and biological evaluation of new classes of thieno [3, 2-d] pyrimidinone and thieno [1, 2, 3] triazine as inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2).

thieno [3, 2-d] pyrimidinone

thieno [1, 2, 3] triazine


Input: Driven by a multidisciplinary approach combination (Structure-Based (SB) Three-Dimensional Quantitative Structure-Activity Relationships (3-D QSAR), molecular modeling, organic chemistry and various biological evaluations) here is reported the disclosure of new thienopyrimidines 1-3 as inhibitors of KDR activity and human umbilical vein endothelial cell (HUVEC) proliferation.

thienopyrimidines


Input: More specifically, compound 2f represents a new lead compound that inhibits VEGFR-2 and HUVEC at mu M concentration.


Input: Moreover by the mean of an endothelial cell tube formation in vitro model 2f tartaric acid salt proved to block angiogenesis of HUVEC at mu M level.

tartaric acid


Input: A microfluidic D-subminiature connector.


Input: Standardized, affordable, user-friendly world-to-chip interfaces represent one of the major barriers to the adoption of microfluidics.


Input: We present a connector system for plug-and-play interfacing of microfluidic devices to multiple input and output lines.


Input: The male connectors are based on existing standardized housings from electronics that are inexpensive and widely available.


Input: The female connectors are fabricated using familiar replica molding techniques that can easily be adopted by microfluidic developers.


Input: Meclofenamic acid blocks the gap junction communication between the retinal pigment epithelial cells.

Meclofenamic acid


Input: Aim: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage the pain and inflammation.


Input: NSAIDs can cause serious side effects, including vision problems.


Input: However, the underlying mechanisms are still unclear.


Input: Therefore, we aimed to investigate the effect of meclofenamic acid (MFA) on retinal pigment epithelium (RPE).

meclofenamic acid

MFA


Input: Materials and methods: In our study, we applied image analysis and whole-cell patch clamp recording to directly measure the effect of MFA on the gap junctional coupling between RPE cells.

MFA


Input: Results: Analysis of Lucifer yellow (LY) transfer revealed that the gap junction communication existed between RPE cells.

Lucifer yellow


Input: Functional experiments using the whole-cell configuration of the patch clamp technique showed that a gap junction conductance also existed between this kind of cells.


Input: Importantly, MFA largely inhibited the gap junction conductance and induced the uncoupling of RPE cells. Other NSAIDs, like aspirin and flufenamic acid (FFA), had the same effect.

MFA

aspirin

flufenamic acid

FFA


Input: Conclusion: The gap junction functionally existed in RPE cells, which can be blocked by MFA.

MFA


Input: These findings may explain, at least partially, the vision problems with certain clinically used NSAIDs.


Input: A simple, sensitive and accurate method for rat paw volume measurement and its expediency in preclinical animal studies.


Input: Several methods are used to evaluate the inflammatory changes.


Input: Measurement of edema is the most commonly used method for evaluating artificially induced inflammation in rat model.


Input: In this context, we present a method for the measurement of volume of rat paw, in which two glass columns containing fluid are connected by a glass tube.


Input: Paw is immersed in one column and the other column is placed on weighing balance.


Input: Upon immersion of paw, equal volume of fluid displaced applies a force F, which shows specific and proportional increment in the level of fluid in both the columns, which could then be detected by weighing balance, as' Force = Weight' of displaced fluid, using the specific gravity of the fluid and the volume of paw, and thus the change in the volume of paw can be calculated.


Input: The rat paw immersed in column without touching the wall of the column facilitates the accurate measurement of volume of paw when measured several times.


Input: Present method is validated for its accuracy and reproducibility when internal radii of both the columns were same or different.


Input: Presented method is also cost-effective and hence can be used for the academic and the commercial animal research purpose, without compromising the precision of the evaluation.


Input: Insulin-and glucagon-like peptide-1-induced changes in heart rate and vagosympathetic activity: why they matter.


Input: Heart rate (HR) predicts cardiovascular morbidity and mortality in individuals either with or without diabetes.


Input: In type 2 diabetic patients, cardiac autonomic neuropathy is a risk marker for cardiac morbidity and mortality.


Input: A major pathogenic potential may be attributed to vagal depression and sympathetic predominance.


Input: In this issue of Diabetologia, Berkelaar et al (DOI: 10. 1007/s00125-013-2848-6) examined the effects of euglycaemic, and hyperglycaemic clamp with the addition of glucagon-like-peptide-1 (GLP-1) and arginine, on cardiac vagal control in a large number of healthy subjects.

arginine


Input: After adjustments for age, BMI and insulin sensitivity, insulin associations with HR remained partially intact while those with vagal control disappeared.


Input: This suggested that BMI and insulin sensitivity, but not insulin levels, were the main drivers of cardiac vagal control.


Input: GLP-1 infusion during hyperglycaemia increased HR and BP and produced a statistically non-significant decrease in measures of cardiac vagal control compared with values before any manipulation of insulin levels.


Input: This commentary summarises how, and to what extent, insulin and GLP-1 affect autonomic nervous system activity, HR and BP.


Input: More information is needed on the mechanisms through which acute administration of, and long-term treatment with, GLP-1 may affect haemodynamics and autonomic activity in diabetic and obese patients, since this may influence cardiovascular outcomes.


Input: Photocytotoxicity of copper (II) complexes of curcumin and N-ferrocenylmethyl-l-amino acids.

copper (II)

curcumin

N-ferrocenylmethyl-l-amino acids


Input: Copper (II) complexes [Cu (Fc-aa) (cur)] (1-3) of curcumin (Hcur) and N-ferrocenylmethyl-l-amino acids (Fc-aa), viz., ferrocenylmethyl-l-tyrosine (Fc-TyrH), ferrocenylmethyl-l-tryptophan (Fc-TrpH) and ferrocenylmethyl-l-methionine (Fc-MetH), were prepared and characterized.

Copper (II)

[Cu (Fc-aa) (cur)]

curcumin

Hcur

N-ferrocenylmethyl-l-amino acids

Fc-aa

ferrocenylmethyl-l-tyrosine

Fc-TyrH

ferrocenylmethyl-l-tryptophan

Fc-TrpH

ferrocenylmethyl-l-methionine

Fc-MetH


Input: The DNA photocleavage activity, photocytotoxicity and cellular localization in HeLa and MCF-7 cancer cells of these complexes were studied.


Input: Acetylacetonate (acac) complexes [Cu (Fc-aa) (acac)] (4-6) were prepared and used as controls.

Acetylacetonate

acac

[Cu (Fc-aa) (acac)]


Input: The chemical nuclease inactive complexes showed efficient pUC19 DNA cleavage activity in visible light.


Input: Complexes 1-3 showed high photocytotoxicity with low dark toxicity thus giving remarkable photodynamic effect.


Input: FACScan analysis showed apoptosis of the cancer cells.


Input: Fluorescence microscopic studies revealed primarily cytosolic localization of the complexes.


Input: Chronic Administration of Small Non-Erythropoietic Peptide Sequence of Erythropoietin Effectively Ameliorates the Progression of Post Myocardial Infarction Dilated Cardiomyopathy.


Input: The cardioprotective properties of erythropoietin (EPO) in pre-clinical studies are well documented, but erythropoietic and prothrombotic properties of EPO preclude its use in chronic heart failure (CHF).


Input: We tested the effect of long-term treatment with a small peptide sequence within the EPO molecule, Helix B surface peptide (HBSP), that possess tissue-protective, but not erythropoietic properties of EPO, on mortality and cardiac remodeling in post-myocardial infarction dilated cardiomyopaty in rats.


Input: Starting two weeks after permanent left coronary artery ligation, rats received i. p. injections of HBSP (60 micro g/kg) or saline 2 times/week for 10 months.


Input: Treatment did not elicit an immune response, and did not affect the hematocrit.


Input: Compared to untreated rats, HBSP treatment reduced mortality by 50% (p < 0. 05).


Input: Repeated echocardiography demonstrated remarkable attenuation of left ventricular dilatation (EDV: 41% vs. 86%; ESV: 44% vs. 135%; p < 0. 05), LV functional deterioration (EF:-4% vs.-63%; p < 0. 05) and MI expansion (3% vs. 38%; p < 0. 05).


Input: A hemodynamic assessment at study termination demonstrated normal preload independent stroke work (63 +/- 5 vs. 40 +/- 4; p < 0. 05) and arterio-ventricular coupling (1. 2 +/- 0. 2 vs. 2. 7 +/- 0. 7; p < 0. 05).


Input: Histological analysis revealed reduced apoptosis (p < 0. 05) and fibrosis (p < 0. 05), increased cardiomyocyte density (p < 0. 05), and increased number of cardiomyocytes in myocardium among HBSP-treated rats.


Input: The results indicate that HBSP effectively reduces mortality, ameliorates the MI expansion and CHF progression, and preserves systolic reserve in the rat post MI model.


Input: There is also a suggestion that HBSP promoted the increase of the myocytes number in the myocardial wall remote from the infarct.


Input: Thus HBSP peptide merits consideration for clinical testing.


Input: Diamond-Lipid Hybrids Enhance Chemotherapeutic Tolerance and Mediate Tumor Regression.

Diamond


Input: Self-assembled nanodiamond-lipid hybrid particles (NDLPs) harness the potent interaction between the nanodiamond (ND)-surface and small molecules, while providing a mechanism for cell-targeted imaging and therapy of triple negative breast cancers.


Input: Epidermal growth factor receptor-targeted NDLPs are highly biocompatible particles that provide cell-specific imaging, promote tumor retention of ND-complexes, prevent epirubicin toxicities and mediate regression of triple negative breast cancers.

epirubicin


Input: Alkane Oxidation by an Immobilized Nickel Complex Catalyst: Structural and Reactivity Differences Induced by Surface-Ligand Density on Mesoporous Silica.

Alkane

Nickel

Silica


Input: Immobilized nickel catalysts SBA *-L-x/Ni (L = bis (2-pyridylmethyl) (1H-1, 2, 3-triazol-4-ylmethyl) amine) with various ligand densities (L content (x) = 0. 5, 1, 2, 4 mol% Si) have been prepared from azidopropyl-functionalized mesoporous silicas SBA-N3-x.

nickel

Ni

bis (2-pyridylmethyl) (1H-1, 2, 3-triazol-4-ylmethyl) amine

Si

azidopropyl

silicas


Input: Related homogeneous ligand L (t) (Bu) and its Ni (II) complexes, [Ni (L (t) (Bu)) (OAc) 2 (H2 O)] (L (t) (Bu)/Ni) and [Ni (L (t) (Bu)) 2] BF4 (2 L (t) (Bu)/Ni), have been synthesized.

L (t) (Bu)

Ni (II)

[Ni (L (t) (Bu)) (OAc) 2 (H2 O)] (L (t) (Bu)/Ni)

[Ni (L (t) (Bu)) 2] BF4 (2 L (t) (Bu)/Ni)


Input: The L/Ni ratio (0. 9-1. 7: 1) in SBA *-L-x/Ni suggests the formation of an inert [NiL2] site on the surface at higher ligand loadings.

Ni

Ni


Input: SBA *-L-x/Ni has been applied to the catalytic oxidation of cyclohexane with m-chloroperbenzoic acid (mCPBA).

Ni

cyclohexane

m-chloroperbenzoic acid

mCPBA


Input: The catalyst with the lowest loading shows high activity in its initial use as the homogeneous L (t) (Bu)/Ni catalyst, with some metal leaching.

L (t) (Bu)

Ni


Input: As the ligand loading increases, the activity and Ni leaching are suppressed.

Ni


Input: The importance of site-density control for the development of immobilized catalysts has been demonstrated.


Input: Simulating Lifetime Outcomes Associated with Complications for People with Type 1 Diabetes.


Input: OBJECTIVES: The aim of this study was to develop a discrete-time simulation model for people with type 1 diabetes mellitus, to estimate and compare mean life expectancy and quality-adjusted life-years (QALYs) over a lifetime between intensive and conventional blood glucose treatment groups.

glucose


Input: METHODS: We synthesized evidence on type 1 diabetes patients using several published sources.


Input: The simulation model was based on 13 equations to estimate risks of events and mortality.


Input: Cardiovascular disease (CVD) risk was obtained from results of the DCCT (diabetes control and complications trial).


Input: Mortality post-CVD event was based on a study using linked administrative data on people with diabetes from Western Australia.


Input: Information on incidence of renal disease and the progression to CVD was obtained from studies in Finland and Italy.


Input: Lower-extremity amputation (LEA) risk was based on the type 1 diabetes Swedish inpatient registry, and the risk of blindness was obtained from results of a German-based study.


Input: Where diabetes-specific data were unavailable, information from other populations was used.


Input: We examine the degree and source of parameter uncertainty and illustrate an application of the model in estimating lifetime outcomes of using intensive and conventional treatments for blood glucose control.

glucose


Input: RESULTS: From 15 years of age, male and female patients had an estimated life expectancy of 47. 2 (95% CI 35. 2-59. 2) and 52. 7 (95% CI 41. 7-63. 6) years in the intensive treatment group.


Input: The model produced estimates of the lifetime benefits of intensive treatment for blood glucose from the DCCT of 4. 0 (95% CI 1. 2-6. 8) QALYs for women and 4. 6 (95% CI 2. 7-6. 9) QALYs for men.

glucose


Input: Absolute risk per 1, 000 person-years for fatal CVD events was simulated to be 1. 37 and 2. 51 in intensive and conventional treatment groups, respectively.


Input: CONCLUSIONS: The model incorporates diabetic complications risk data from a type 1 diabetes population and synthesizes other type 1-specific data to estimate long-term outcomes of CVD, end-stage renal disease, LEA and risk of blindness, along with life expectancy and QALYs.


Input: External validation was carried out using life expectancy and absolute risk for fatal CVD events.


Input: Because of the flexible and transparent nature of the model, it has many potential future applications.


Input: tert-Butylhydroquinone reduces lipid accumulation in C57BL/6 mice with lower body weight gain.

tert-Butylhydroquinone


Input: tert-Butylhydroquinone (tBHQ) is a commonly used antioxidant additive that is approved for human use by both the Food and Agriculture Organization and the World Health Organization (FAO/WHO).

tert-Butylhydroquinone

tBHQ


Input: In this study, we examined the effect of tBHQ on body weight gain and found that food supplementation with 0. 001% (w/w) tBHQ inhibited 61. 4% (P < 0. 01) of body weight gain in high-fat diet (HFD)-induced C57BL/6 mice, and the oral administration of tBHQ (1. 5 mg/kg) reduced 47. 5% (P < 0. 05) of body weight gain in normal diet fed db/db mice.

tBHQ

tBHQ

tBHQ


Input: The HFD increased lipid deposit in adipocytes, but these were reduced significantly by tBHQ treatment in C57BL/6 mice.

tBHQ


Input: tBHQ supplementation significantly lowered the plasma triglyceride and total cholesterol, with reduced size of accumulated fat mass.

tBHQ

triglyceride

cholesterol


Input: The rate limiting enzyme of beta-oxidation (ACOX1) was significantly over-expressed in the liver with tBHQ treatment.

tBHQ


Input: These results indicate that tBHQ suppresses body weight gain in mice, possibly at least related to the up-regulation of ACOX1 gene expression.

tBHQ


Input: Tandem Assays of Protein and Glucose with Functionalized Core/Shell Particles Based on Magnetic Separation and Surface-Enhanced Raman Scattering.

Glucose


Input: Tandem assays of protein and glucose in combination with mannose-functionalized Fe3 O4 @SiO2 and Ag @SiO2 tag particles have promising potential in effective magnetic separation and highly sensitive and selective SERS assays of biomaterials.

glucose

mannose

Fe3 O4

Ag


Input: It is for the first time that tandem assay of glucose is developed using SERS based on the Con A-sandwiched microstructures between the functionalized magnetic and tag particles.

glucose


Input: De-repression of FOXO3a death axis by microRNA-132 and-212 causes neuronal apoptosis in Alzheimer' s disease.


Input: Alzheimer' s disease (AD) is a multifactorial and fatal neurodegenerative disorder for which the mechanisms leading to profound neuronal loss are incompletely recognized.


Input: MicroRNAs (miRNAs) are recently discovered small regulatory RNA molecules that repress gene expression and are increasingly acknowledged as prime regulators involved in human brain pathologies.


Input: Here we identified two homologous miRNAs, miR-132 and miR-212, downregulated in temporal cortical areas and CA1 hippocampal neurons of human AD brains.


Input: Sequence-specific inhibition of miR-132 and miR-212 induces apoptosis in cultured primary neurons, whereas their overexpression is neuroprotective against oxidative stress.


Input: Using primary neurons and PC12 cells, we demonstrate that miR-132/212 controls cell survival by direct regulation of PTEN, FOXO3a and P300, which are all key elements of AKT signaling pathway.


Input: Silencing of these three target genes by RNAi abrogates apoptosis caused by the miR-132/212 inhibition.


Input: We further demonstrate that mRNA and protein levels of PTEN, FOXO3a, P300 and most of the direct pro-apoptotic transcriptional targets of FOXO3a are significantly elevated in human AD brains.


Input: These results indicate that the miR-132/miR-212/PTEN/FOXO3a signaling pathway contributes to AD neurodegeneration.


Input: Inhibition of Ras-Effector Interaction by Cyclic Peptides.


Input: A combinatorial library of 6 x 10 (6) cyclic peptides was synthesized in the one bead-two compound format, with each bead displaying a unique cyclic peptide on its surface and a linear peptide encoding tag in its interior.


Input: Screening of the library against K-Ras identified compounds that bound K-Ras with submicromolar affinity and disrupted its interaction with effector proteins.


Input: Using in Situ X-ray Reflectivity to Study Protein Adsorption on Hydrophilic and Hydrophobic Surfaces: Benefits and Limitations.


Input: We have employed in situ X-ray reflectivity (IXRR) to study the adsorption of a variety of proteins (lysozyme, cytochrome c, myoglobin, hemoglobin, serum albumin, and immunoglobulin G) on model hydrophilic (silicon oxide) and hydrophobic surfaces (octadecyltrichlorosilane self-assembled monolayers), evaluating this recently developed technique for its applicability in the area of biomolecular studies.

silicon oxide

octadecyltrichlorosilane


Input: We report herein the highest resolution depiction of adsorbed protein films, greatly improving on the precision of previous neutron reflectivity (NR) results and previous IXRR studies.


Input: We were able to perform complete scans in 5 min or less with the maximum momentum transfer of at least 0. 52 A (-1), allowing for some time-resolved information about the evolution of the protein film structure.


Input: The three smallest proteins (lysozyme, cytochrome c, and myoglobin) were seen to deposit as fully hydrated, nondenatured molecules onto hydrophilic surfaces, with indications of particular preferential orientations.


Input: Time evolution was observed for both lysozyme and myoglobin films.


Input: The larger proteins were not observed to deposit on the hydrophilic substrates, perhaps because of contrast limitations.


Input: On hydrophobic surfaces, all proteins were seen to denature extensively in a qualitatively similar way but with a rough trend that the larger proteins resulted in lower coverage.


Input: We have generated high-resolution electron density profiles of these denatured films, including capturing the growth of a lysozyme film.


Input: Because the solution interface of these denatured films is diffuse, IXRR cannot unambiguously determine the film extent and coverage, a drawback compared to NR.


Input: X-ray radiation damage was systematically evaluated, including the controlled exposure of protein films to high-intensity X-rays and exposure of the hydrophobic surface to X-rays before adsorption.


Input: Our analysis showed that standard measuring procedures used for XRR studies may lead to altered protein films; therefore, we used modified procedures to limit the influence of X-ray damage.


Input: Quantitative Determination of Lateral Concentration and Depth Profile of Histidine-Tagged Recombinant Proteins Probed by Grazing Incidence X-ray Fluorescence.

Histidine


Input: We have demonstrated that the complementary combination of grazing incidence X-ray fluorescence (GIXF) with specular X-ray reflectivity (XRR) can be used to quantitatively determine the density profiles of Ni (2) (+) ions complexed with chelator headgroups as well as S atoms in recombinant proteins anchored to lipid monolayers at the air/water interface.

Ni (2) (+)

S


Input: First, we prepared phospholipid monolayers incorporating chelator lipid anchors at different molar fractions at the air/water interface.


Input: The fine-structures perpendicular to the global plane of monolayers were characterized by XRR in the presence of Ni (2) (+) ions, yielding the thickness, roughness, and electron density of the stratified lipid monolayers.

Ni (2) (+)


Input: X-ray fluorescence intensities from Ni K alpha core levels recorded at the incidence angles below and above the critical angle of total reflection allow for the determination of the position and lateral density of Ni (2) (+) ions associated with chelator headgroups with a high spatial accuracy (+/- 5 A).

Ni

Ni (2) (+)


Input: The coupling of histidine-tagged Xenopus cadherin 11 (Xcad-11) can also be identified by changes in the fines-structures using XRR.

histidine


Input: Although fluorescence intensities from S K alpha level were much weaker than Ni K alpha signals, we could detect the location of S atoms in recombinant Xcad-11 proteins.

S

Ni

S


Input: Ligand Based Approach to L-Type Calcium Channel by Imidazo [2, 1-b] thiazole-1, 4-Dihydropyridines: from Heart Activity to Brain Affinity.

Calcium

Imidazo [2, 1-b] thiazole-1, 4-Dihydropyridines


Input: The synthesis, characterization, and functional in vitro assay in cardiac and smooth muscle (vascular and nonvascular) of a series of 4-imidazo [2, 1-b] thiazole-1, 4-dihydropyridines are reported.

4-imidazo [2, 1-b] thiazole-1, 4-dihydropyridines


Input: To define the calcium blocker nature of the imidazo [2, 1-b] thiazole-1, 4-DHPs and their selectivity on Cav1. 2 and Cav1. 3 isoforms we performed binding studies on guinea pig atrial and ventricular membranes, on intact cells expressing the cloned Cav1. 2a subunit and on rat brain cortex.

calcium

imidazo [2, 1-b] thiazole-1, 4-DHPs


Input: To get major insights into the reasons for the affinity for Cav1. 2 and/or Cav1. 3 molecular modelling studies were also undertaken.


Input: Some physicochemical and pharmacokinetic properties of selected compounds were calculated and compared.


Input: All the biological data collected and reported herein allowed us to rationalize the structure-activity relationship of the 4-imidazo [2, 1-b] thiazole-1, 4-DHPs and to identify which of these enhanced the activity at the central level.

4-imidazo [2, 1-b] thiazole-1, 4-DHPs


Input: Synthesis of chemicals using solar energy with stable photoelectrochemically active heterostructures.


Input: Efficient and cost-effective conversion of solar energy to useful chemicals and fuels could lead to a significant reduction in fossil hydrocarbon use.

hydrocarbon


Input: Artificial systems that use solar energy to produce chemicals have been reported for more than a century.


Input: However the most efficient devices demonstrated, based on traditionally fabricated compound semiconductors, have extremely short working lifetimes due to photocorrosion by the electrolyte.


Input: Here we report a stable, scalable design and molecular level fabrication strategy to create photoelectrochemically active heterostructure (PAH) units consisting of an efficient semiconductor light absorber in contact with oxidation and reduction electrocatalysts and otherwise protected by alumina.

alumina


Input: The functional heterostructures are fabricated by layer-by-layer, template-directed, electrochemical synthesis in porous anodic aluminum oxide membranes to produce high density arrays of electronically autonomous, nanostructured, corrosion resistant, photoactive units (~ 10 (9)-10 (10) PAHs per cm (2)).

aluminum oxide


Input: Each PAH unit is isolated from its neighbor by the transparent electrically insulating oxide cellular enclosure that makes the overall assembly fault tolerant.

oxide


Input: When illuminated with visible light, the free floating devices have been demonstrated to produce hydrogen at a stable rate for over 24 h in corrosive hydroiodic acid electrolyte with light as the only input.

hydrogen

hydroiodic acid


Input: The quantum efficiency (averaged over the solar spectrum) for absorbed photons-to-hydrogen conversion was 7. 4% and solar-to-hydrogen energy efficiency of incident light was 0. 9%.

hydrogen

hydrogen


Input: The fabrication approach is scalable for commercial manufacturing and readily adaptable to a variety of earth abundant semiconductors which might otherwise be unstable as photoelectrocatalysts.


Input: The role of external defects in chemical sensing of graphene field-effect transistors.

graphene


Input: A fundamental understanding of chemical sensing mechanisms in graphene-based chemical field-effect transistors (chemFETs) is essential for the development of next generation chemical sensors.

graphene


Input: Here we explore the hidden sensing modalities responsible for tailoring the gas detection ability of pristine graphene sensors by exposing graphene chemFETs to electron donor and acceptor trace gas vapors.

pristine graphene

graphene


Input: We uncover that the sensitivity (in terms of modulation in electrical conductivity) of pristine graphene chemFETs is not necessarily intrinsic to graphene, but rather it is facilitated by external defects in the insulating substrate, which can modulate the electronic properties of graphene.

pristine graphene

graphene

graphene


Input: We disclose a mixing effect caused by partial overlap of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of adsorbed gas molecules to explain graphene' s ability to detect adsorbed molecules.

graphene


Input: Our results open a new design space, suggesting that control of external defects in supporting substrates can lead to tunable graphene chemical sensors, which could be developed without compromising the intrinsic electrical and structural properties of graphene.

graphene


Input: Study of the microcharacter of ultrastable aqueous foam stabilized by a kind of flexible connecting bipolar-headed surfactant with existence of magnesium ion.

magnesium


Input: In this paper, ultrastable aqueous foam stabilized by a kind of flexible connecting bipolar-headed surfactant alkyl polyoxyethylene sulfate (AE3S) with coexisting Mg (2 +) was reported.

alkyl polyoxyethylene sulfate

Mg (2 +)


Input: Detailed molecular behaviors of AE3S in foam film with coexisting divalent cationic Ca (2 +) or Mg (2 +) were investigated by molecular dynamic simulation, comparing with the traditional surfactant sodium dodecyl sulfate (SDS), to find out how the microcharacter and array behavior of molecules in the foam film determined by molecular interaction effect the foam stability.

Ca (2 +)

Mg (2 +)

sodium dodecyl sulfate

SDS


Input: It was found that the ultrastable foam film obtained by the cooperation of magnesium ions and AE3S was driven from two aspects: one is the favorable arrangement of surfactant molecules, and the other is the increase of capacity of foam films for resolutely holding water molecules deduced by a dipolar pair formed by the flexible connecting head groups of AE3S and hydrated Mg (2 +) via intermolecular coactions, both related to the presence of magnesium ions.

magnesium

hydrated Mg (2 +)

magnesium


Input: Foam lamella stability measurement and foam decay method were both used to evaluate the stability of foam.


Input: Fourier transform infrared (FT-IR) was used to detect the composition variation of foam film in the drainage process; the vibration peak of OH for water molecule shifted from the 3390 cm (-1) (being assigned to the bulk water integrated by hydrogen bonds) to 3685 cm (-1) (being assigned to the vibration of isolated water molecules) for the ultrastable foam film after complete drainage, which agreed very well with the molecular simulation results.

OH

hydrogen


Input: Quinoline Drug-Heme Interactions and Implications for Antimalarial Cytostatic versus Cytocidal Activities.

Quinoline

Heme


Input: Historically, the most successful molecular target for antimalarial drugs has been heme biomineralization within the malarial parasite digestive vacuole.


Input: Heme released from catabolized host red blood cell hemoglobin is toxic, so malarial parasites crystallize heme to nontoxic hemozoin.

Heme

heme


Input: For years it has been accepted that a number of effective quinoline antimalarial drugs (e. g., chloroquine, quinine, amodiaquine) function by preventing hemozoin crystallization.

quinoline

chloroquine

quinine

amodiaquine


Input: However, recent studies over the past decade have revealed a surprising molecular diversity in quinoline-heme molecular interactions.

quinoline

heme


Input: This diversity shows that even closely related quinoline drugs may have quite different molecular pharmacology.

quinoline


Input: This paper reviews the molecular diversity and highlights important implications for understanding quinoline antimalarial drug resistance and for future drug design.

quinoline


Input: Interactions between oral antineoplastic agents and concomitant medication: a systematic review.


Input: Introduction: In recent years, the number of oral antitumoral agents has considerably increased.


Input: Oral administration increases the risk of interactions, because most oral anticancer drugs are taken on a daily basis.


Input: Interactions can increase exposure to antitumoral agents or cause treatment failure.


Input: Many antitumoral drugs undergo enzymatic metabolism by cytochrome P450.


Input: As some act as inducers or inhibitors of one or more isoenzymes, they can lead to decreases or increases in plasma concentrations of concomitant drugs.


Input: Hence, cytostatic drugs can act not only as victims but also as perpetrators.


Input: P-glycoprotein, an efflux transporter, can also be involved in pharmacokinetic interactions.


Input: Areas covered: A Medline search was performed to summarize the available evidence of the most clinically relevant interactions between oral chemotherapy agents and other drugs.


Input: The search covered the period from 1966 until August 2012 for each antitumoral drug using the medical subject headings' Drug Interactions' OR' Pharmacokinetics'.


Input: While the present review is not exhaustive, it aims to increase clinicians' awareness of potential drug-drug interactions.


Input: Expert opinion: As cancer patients are often polymedicated and treated by different physicians, the risk of drug interactions between antitumoral agents and other medications is high.


Input: More clinical interaction studies are encouraged to ensure appropriate antineoplastic pharmacokinetics in clinical practice.


Input: Structure and Absolute Configuration of Fumiquinazoline L, an Alkaloid from a Gorgonian-Derived Scopulariopsis sp.

Fumiquinazoline L


Input: Fungus.


Input: Fumiquinazoline L (1), an alkaloid with a heptacyclic skeleton formed via a bridging hemiaminal linkage, was isolated from a gorgonian-derived Scopulariopsis sp. fungus.

Fumiquinazoline L


Input: The structure and absolute configuration of the new compound were identified by comprehensive spectroscopic data and X-ray diffraction analysis.


Input: During acid hydrolysis of 1, the isomerization of the valine residue was observed and also studied in different conditions.

valine


Input: Fumiquinazoline L (1) showed no cytotoxic or antibacterial activities.

Fumiquinazoline L


Input: Identification of the Post-Polyketide Synthase Modification Enzymes for Fostriecin Biosynthesis in Streptomyces pulveraceus.

Fostriecin


Input: Fostriecin (FST, 1) is a natural product with promising antitumor activity produced by Streptomyces pulveraceus.

Fostriecin

FST


Input: Its antitumor activity is associated with the selective inhibition of protein phosphatase activities.


Input: The biosynthetic gene cluster for FST has recently been cloned and sequenced.


Input: To better understand the post-polyketide synthase (PKS) modification steps in the biosynthetic pathway of FST, we constructed and characterized three post-PKS modification gene mutants of fosG, fosK, and fosM by knockout inactivation in S. pulveraceus.


Input: As a result, we determined that a fosK-encoded cytochrome P450 monooxygenase is responsible for C-18 hydroxylation, formation of an unsaturated lactone is dependent upon FosM, and the fosG gene product is involved in hydroxylation at C-4 after the action of FosM to yield PD 113, 271 from FST.

unsaturated lactone

PD 113, 271

FST


Input: The accumulated analogues from the Delta fosK and Delta fosM mutant strains possessed a malonyl ester moiety that suggested that all the post-PKS modification steps in FST biosynthesis occur with the polyketide chain bearing a malonyl ester at the C-3 position, with formation of the unsaturated six-membered lactone as the last step in FST biosynthesis.

malonyl ester

malonyl ester

lactone

FST


Input: Does Colloid Shape Affect Detachment of Colloids by a Moving Air-Water Interface?


Input: Air-water interfaces interact strongly with colloidal particles by capillary forces.


Input: The magnitude of the interaction force depends on, among other things, the particle shape.


Input: Here, we investigate the effects of particle shape on colloid detachment by a moving air-water interface.


Input: We used hydrophilic polystyrene colloids with four different shapes (spheres, barrels, rods, and oblong disks), but otherwise identical surface properties.

polystyrene


Input: The nonspherical shapes were created by stretching spherical microspheres on a film of polyvinyl alcohol (PVA).

polyvinyl alcohol

PVA


Input: The colloids were then deposited onto the inner surface of a glass channel.


Input: An air bubble was introduced into the channel and passed through, thereby generating a receding followed by an advancing air-water interface.


Input: The detachment of colloids by the air-water interfaces was visualized with a confocal microscope, quantified by image analysis, and analyzed statistically to determine significant differences.


Input: For all colloid shapes, the advancing air-water interface caused pronounced colloid detachment (> 63%), whereas the receding interface was ineffective in colloid detachment (< 1. 5%).


Input: Among the different colloid shapes, the barrels were most readily removed (94%) by the advancing interface, followed by the spheres and oblong disks (80%) and the rods (63%).


Input: Colloid detachment was significantly affected by colloid shape.


Input: The presence of an edge, as it occurs in a barrel-shaped colloid, promoted colloid detachment because the air-water interface is being pinned at the edge of the colloid.


Input: This suggests that the magnitude of colloid mobilization and transport in porous media is underestimated for edged particles and overestimated for rodlike particles when a sphere is used as a model colloid.


Input: Biomimetic Silicification of Demineralized Hierarchical Collagenous Tissues.


Input: Unlike man-made composite materials, natural biominerals containing composites usually demonstrate different levels of sophisticated hierarchical structures which are responsible for their mechanical properties and other metabolic functions.


Input: However, the complex spatial organizations of the organic-inorganic phases are far beyond what they achieved by contemporary engineering techniques.


Input: Here, we demonstrate that carbonated apatite present in collagen matrices derived from fish scale and bovine bone may be replaced by amorphous silica, using an approach that simulates what is utilized by phylogenetically ancient glass sponges.

silica


Input: The structural hierarchy of these collagen-based biomaterials is replicated by the infiltration and condensation of fluidic polymer-stabilized silicic acid precursors within the intrafibrillar milieu of type I collagen fibrils.

silicic acid


Input: This facile biomimetic silicification strategy may be used for fabricating silica-based, three-dimensional functional materials with specific morphological and hierarchical requirements.

silica


Input: Nocardiamides A and B, Two Cyclohexapeptides from the Marine-Derived Actinomycete Nocardiopsis sp.

Nocardiamides A and B

Cyclohexapeptides


Input: Two new cyclic hexapeptides, nocardiamides A (1) and B (2), were isolated from the culture broth of marine-derived actinomycete CNX037 strain that was identified as a Nocardiopsis species.

cyclic hexapeptides

nocardiamides


Input: The planar structures of nocardiamides A (1) and B (2) were assigned on the basis of 1D and 2D NMR and HRESIMS spectroscopic analyses.

nocardiamides


Input: Their absolute configurations were deduced by the advanced Marfey' s method and chiral-phase HPLC analysis.


Input: The challenge of locating two d-and one l-valine residue in 1 and 2 was accomplished by total synthesis using solid-phase peptide synthetic methods.

d-and one l-valine


Input: Both 1 and 2 showed negligible antimicrobial activities against seven indicator strains and exhibited no cytotoxicity against HCT-116.


Input: Potency switch between CHK1 and MK2: Discovery of imidazo [1, 2-a] pyrazine-and imidazo [1, 2-c] pyrimidine-based kinase inhibitors.

imidazo [1, 2-a] pyrazine

imidazo [1, 2-c] pyrimidine


Input: Chemistry has been developed to access both imidazo [1, 2-a] pyrazines and imidazo [1, 2-c] pyrimidines.

imidazo [1, 2-a] pyrazines

imidazo [1, 2-c] pyrimidines


Input: Small structural modifications in both series led to a switch of potency between two kinases involved in mediating cell cycle checkpoint control, CHK1 and MK2.


Input: The in vitro effect of duroquinone on functional competence, genomic integrity, and oxidative stress indices of sterlet (Acipenser ruthenus) spermatozoa.

duroquinone


Input: The sturgeon is a highly endangered fish species mostly due to over-fishing, habitat destruction, and water pollution.


Input: Duroquinone (derivative of 1, 4-benzoquinone) is a xenobiotic compound widespread in the environment.

Duroquinone

1, 4-benzoquinone


Input: The effect of duroquinone on motility, DNA integrity, and oxidative stress indices in sterlet, Acispenser ruthenus, spermatozoa was investigated.

duroquinone


Input: Sterlet sperm was exposed for 2h to duroquinone at concentrations of 25, 50, 100, and 150 mu M.

duroquinone


Input: Spermatozoa motility, velocity, and ATP content were significantly decreased with exposure to duroquinone.

ATP

duroquinone


Input: The level of DNA damage significantly increased at concentrations of 50 mu M and above.


Input: Oxidative stress indices (lipid peroxidation and content of carbonyl proteins) and superoxide dismutase (SOD) activity increased significantly with increasing concentrations of duroquinone.

carbonyl

superoxide

duroquinone


Input: Oxidative stress in sterlet spermatozoa induced by duroquinone was shown to impair spermatozoa DNA integrity, motility parameters, and the antioxidant defense system.

duroquinone


Input: Spermatozoa motility, content of carbonyl proteins, and SOD activity were shown to be sensitive biomarkers, exhibiting strong responses to low concentrations of the xenobiotic.

carbonyl


Input: Results also suggested that fish spermatozoa in vitro assays may provide a simple and efficient means of monitoring residual pollutants in the aquatic environment.


Input: Kappa opioid receptors in the central amygdala regulate ethanol actions at presynaptic GABAergic sites.

ethanol


Input: Human and animal studies indicate that kappa opioid receptor (KOR) systems are involved in ethanol drinking and dependence (Xuei et al., 2006; Walker and Koob, 2008; Walker et al., 2011).

ethanol


Input: The central amygdala (CeA) is a critical brain region mediating anxiety-related behavior and drug reward and is a likely site for the interaction of the KOR system and ethanol, although few studies have explored this interaction.

ethanol