Input: The origins of these metabolites are largely unknown, but many of them are thought to be made by symbiotic bacteria.


Input: In contrast, mollusks with thick shells and toxic venoms are thought to lack these secondary metabolites because of reduced defensive needs.


Input: Here, we show that heavily defended cone snails also occasionally contain abundant secondary metabolites, gamma-pyrones known as nocapyrones, which are synthesized by symbiotic bacteria.

gamma-pyrones

nocapyrones


Input: The bacteria, Nocardiopsis alba CR167, are related to widespread actinomycetes that we propose to be casual symbionts of invertebrates on land and in the sea.


Input: The natural roles of nocapyrones are unknown, but they are active in neurological assays, revealing that mollusks with external shells are an overlooked source of secondary metabolite diversity.

nocapyrones


Input: Identification of early replicating fragile sites that contribute to genome instability.


Input: DNA double-strand breaks (DSBs) in B lymphocytes arise stochastically during replication or as a result of targeted DNA damage by activation-induced cytidine deaminase (AID).

cytidine


Input: Here we identify recurrent, early replicating, and AID-independent DNA lesions, termed early replication fragile sites (ERFSs), by genome-wide localization of DNA repair proteins in B cells subjected to replication stress.


Input: ERFSs colocalize with highly expressed gene clusters and are enriched for repetitive elements and CpG dinucleotides.

CpG dinucleotides


Input: Although distinct from late-replicating common fragile sites (CFS), the stability of ERFSs and CFSs is similarly dependent on the replication-stress response kinase ATR.


Input: ERFSs break spontaneously during replication, but their fragility is increased by hydroxyurea, ATR inhibition, or deregulated c-Myc expression.

hydroxyurea


Input: Moreover, greater than 50% of recurrent amplifications/deletions in human diffuse large B cell lymphoma map to ERFSs.


Input: In summary, we have identified a source of spontaneous DNA lesions that drives instability at preferred genomic sites.


Input: Point-to-point ligand-receptor interactions across the subunit interface modulate the induction and stabilization of conformational states of alpha7 nAChR by benzylidene anabaseines.

benzylidene anabaseines


Input: The homomeric alpha 7 nicotinic acetylcholine receptor is a well-studied therapeutic target, though its characteristically rapid desensitization complicates the development of drugs with specific agonist effects.

acetylcholine


Input: Moreover, some experimental compounds such as GTS-21 (2, 4diMeOBA), a derivative of the alpha 7-selective partial agonist benzylidene anabaseine (BA), produce a prolonged residual desensitization (RD) in which the receptor remains non-activatable long after the drug has been removed from extracellular solution.

2, 4diMeOBA

benzylidene anabaseine


Input: In contrast, the desensitization caused by GTS-21' s dihydroxy metabolite (2, 4diOHBA) is relatively short-lived.

dihydroxy

2, 4diOHBA


Input: RD is hypothetically due to stable binding of the ligand to the receptor in its desensitized state.


Input: We can attribute the reduction in RD to a single BA hydroxyl group on the 4' benzylidene position.

hydroxyl

benzylidene


Input: Computational prediction derived from homology modeling showed the serine36 (S36) residue of alpha 7 as a reasonable candidate for point-to-point interaction between BA compounds and the receptor.


Input: Through evaluating the activity of BA and simple derivatives on wild-type and mutant alpha 7 receptors, it was observed that the drug-receptor pairs which were capable of hydrogen bonding at residue 36 exhibited significantly less stable desensitization.

hydrogen


Input: Further experiments involving the type II positive allosteric modulator (PAM) PNU-120596 showed that the various BA compounds' preference to induce either a PAM-sensitive (D (s)) or PAM-insensitive (D (i)) desensitized state is concentration dependent and suggested that both states are destabilized by S36 H-bonding.

H


Input: These results indicate that the fine-tuning of agonists for specific interaction with S36 can facilitate the development of therapeutics with targeted effects on ion channel desensitization properties and conformational state stability.


Input: Rhododendron tomentosum (Ledum palustre).


Input: A review of traditional use based on current research.


Input: Rhododendron tomentosum Harmaja (previously: Ledum palustre) is a fragrant evergreen shrub found in peaty soils in northern Europe, Asia and North America, commonly referred to as wild rosemary, marsh tea, marsh rosemary or northern Labrador tea.


Input: At least since the eighteenth century it has been used in ethnomedicine for the treatment of various ailments, such as rheumatism, cough, cold and insect bites, as well as a repellent.


Input: The essential oil of wild rosemary with the rich polyphenolic fraction possesses analgesic, anti-inflammatory, antimicrobial, antiviral, antifungal and insecticidal potential, demonstrated by in vivo and in vitro studies.


Input: In addition, recent scientific research reported the promising antidiabetic, antioxidant and anticancer properties.


Input: This review summarizes the information concerning taxonomy, botany, ecology, chemical composition, biological activities, toxicology and traditional and contemporary application of Rhododendron tomentosum plants.


Input: Cell penetrating peptide tethered bi-ligand liposomes for delivery to brain in vivo: Biodistribution and transfection.


Input: Targeted nano-particulate systems hold extraordinary potential for delivery of therapeutics across blood brain barrier (BBB).


Input: In this work, we investigated the potential of novel bi-ligand (transferrin-poly-l-arginine) liposomal vector for delivery of desired gene to brain, in vivo.

poly-l-arginine


Input: The in vivo evaluation of the delivery vectors is essential for clinical translation.


Input: We followed an innovative approach of combining transferrin receptor targeting with enhanced cell penetration to design liposomal vectors for improving the transport of molecules into brain.


Input: The biodistribution profile of 1, 1'-dioctadecyl-3, 3, 3', 3'-tetramethyl-indocarbocyanine iodide (DiR)-labeled liposomes was evaluated in adult rats after single intravenous injection at dose of 15. 2 mu moles of phospholipids/kg body weight.

1, 1'-dioctadecyl-3, 3, 3', 3'-tetramethyl-indocarbocyanine iodide

DiR


Input: We demonstrated that bi-ligand liposomes accumulated in rat brain at significantly (p < 0. 05) higher concentrations as compared to the single-ligand (transferrin) or plain liposomes.


Input: In addition, the bi-ligand liposomes resulted in increased expression of beta-galactosidase (beta-gal) plasmid in rat brain tissue in comparison to the single-ligand liposomes.


Input: Histological examination of the transfected tissues did not show any signs of tissue necrosis or inflammation.


Input: Hemolysis assay further authenticated the biocompatibility of bi-ligand liposomes in blood up to 600 nmoles of phospholipids/1. 4 x 10 (7) erythrocytes.


Input: The findings of this study provide important and detailed information regarding the distribution of bi-ligand liposomes in vivo and accentuate their ability to demonstrate improved brain penetration and transfection potential over single-ligand liposomes.


Input: Suppressive effects of Indigofera suffruticosa Mill extracts on lipopolysaccharide-induced inflammatory responses in murine RAW 264. 7 macrophages.


Input: Indigofera suffruticosa Mill is used as an herbal medicine for the treatment of inflammation.


Input: The aim of this study is to assess the anti-inflammatory potency of I. suffruticosa and its likely molecular mechanisms of action in lipopolysaccharide (LPS)-induced RAW 264. 7 macrophages.


Input: Both water and ethanolic extracts of I. suffruticosa significantly decreased LPS-induced nitric oxide (NO) as well as the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha, and pro-interleukin-1 beta.

nitric oxide

NO

nitric oxide


Input: Moreover, LPS-induced inhibitory factor-kappa B-alpha phosphorylation, nuclear factor-kappa B (NF-kappa B) nuclear protein-DNA binding affinity, and NF-kappa B reporter gene activity were dramatically inhibited by I. suffruticosa extracts.


Input: Exogenous addition of I. suffruticosa significantly induced heme oxygenase-1 (HO-1) expression, and the presence of HO-1 small interfering RNA partly reversed the inhibitory effects of I. suffruticosa on LPS-induced NO production and iNOS expression.

NO


Input: Furthermore, I. suffruticosa induced HO-1 expression may be through activation of the ERK/nuclear factor E2-related factor 2 pathway.


Input: Eight phenolic compounds were found in the I. suffruticosa extracts, but salicylic acid was the only one detected in the plasma of mice fed with I. suffruticosa extracts.

phenolic

salicylic acid


Input: In summary, I. suffruticosa have a strong anti-inflammatory property that diminishes pro-inflammatory mediator expressions by lessening LPS-induced NF-kappa B activation and inducing HO-1 expression in macrophages.


Input: Oxidative stress involvement in manganese-induced alpha-synuclein oligomerization in organotypic brain slice cultures.

manganese


Input: Overexposure to manganese (Mn) has been known to induce neuronal damage.

manganese

Mn


Input: However, little is known of the role that reactive oxygen species (ROS) play in protein aggregation resulting from Mn exposure.

oxygen

Mn


Input: The current study investigated whether oxidative stress is involved in manganese-induced alpha-synuclein oligomerization in organotypic brain slices.

manganese


Input: After application of Mn (0-400 mu M) for 24h, there was a dose-dependent increase in average percentage of propidium iodide positive (PI (+)) nuclei in slices and levels of lactate dehydrogenase (LDH) in the culture medium.

Mn

propidium iodide

lactate


Input: Moreover, the treatment with Mn resulted in a dose-dependent increase in neurocyte apoptosis, ROS level, and decrease in superoxide dismutase (SOD) activity.

Mn

superoxide


Input: Mn also caused oxidative damage in cell lipid and protein.

Mn


Input: At the same time, the exposure of Mn leaded to significantly increase in the expression of alpha-synuclein mRNA and protein.

Mn


Input: Alpha-synuclein oligomerization occurred in Mn-treated slices, especially on membrane-bound form.

Mn


Input: It indicated that alpha-synuclein oligomers were more likely to combination cell membranes and resulting in membrane damage.


Input: Mn-induced neurocyte damage and alpha-synuclein oligomerization were also partially alleviated by the pretreatment with GSH and aggravated by H2O2 pretreatment.

Mn

GSH


Input: The findings revealed Mn might exert its neurotoxic effects by oxidative stress-mediated alpha-synuclein oligomerization in organotypic brain slices.

Mn


Input: In vitro toxicological characterisation of the S-containing arsenic metabolites thio-dimethylarsinic acid and dimethylarsinic glutathione.

S

arsenic

thio-dimethylarsinic acid

dimethylarsinic glutathione


Input: Inorganic arsenic is a well-documented, exposure relevant human carcinogen.

arsenic


Input: A promising starting point to further understand the mechanisms behind inorganic arsenic carcinogenicity might be a formation of reactive, highly toxic metabolites during human arsenic metabolism.

arsenic

arsenic


Input: This study characterises the toxicity of recently identified S-containing arsenic metabolites in cultured human A549 lung adenocarcinoma epithelium cells.

S

arsenic


Input: In direct comparison to arsenite, thio-dimethylarsinic acid (thio-DMA (V)) and dimethylarsinic glutathione (DMAG) exerted a 5-to 20-fold stronger cytotoxicity and showed a 2-to 20-fold higher cellular bioavailability, respectively.

arsenite

thio-dimethylarsinic acid

thio-DMA

dimethylarsinic glutathione

DMAG


Input: All three arsenicals disturbed cell cycle progression at cytotoxic concentrations, but failed to increase the level of reactive oxygen and nitrogen species (RONS) in healthy A549 cells.

oxygen

nitrogen


Input: However, a strong disturbance of the oxidative defense system was observed after incubation with absolutely sub-cytotoxic, pico-to nanomolar concentrations of arsenite and thio-DMA (V), respectively.

arsenite

thio-DMA


Input: Thus, both GSH and GSSG levels were significantly decreased by up to 40%.

GSH

GSSG


Input: Accordingly, RONS levels of oxidatively (H2O2) stressed cells were strongly increased by the arsenicals.


Input: Since in vivo RONS are permanently endogenously and exogenously produced, this boost of the existing oxidative stress by arsenite and thio-DMA (V) might contribute to the process of inorganic arsenic induced carcinogenicity.

arsenite

thio-DMA

arsenic


Input: Occurrence of copper acclimation in the least killifish Heterandria formosa, and associated biochemical and physiological mechanisms.

copper


Input: We investigated the occurrence of copper acclimation in the least killifish, Heterandria formosa using both lethal and sublethal endpoints.

copper


Input: We also investigated potential mechanisms underlying the observed acclimation.


Input: To assess the occurrence of acclimation, fish were exposed to either a background Cu level or to 15 mu g/L Cu for seven days and subsequently exposed to a lethal Cu level (150 mu g/L Cu).

Cu

Cu

Cu

Cu


Input: During the latter exposure, fish were monitored for survival till all fish had died, and (during the first 8h of this exposure) for changes in whole-body Na levels and lipid peroxidation (LPO).


Input: During the high-level Cu exposure, fish pre-exposed to copper had a significantly longer time-to-death than did the control fish.

Cu

copper


Input: Similarly, neither whole-body Na nor LPO changed in the Cu-pre-exposed fish during the 8h of the exposure to 150 mu g/L Cu-while both decreased significantly in the control fish.

Cu

Cu


Input: Thus, acclimation was evident for both time-to-death and the sublethal endpoints.


Input: These results also indicate that Cu toxicity may involve both Na loss and LPO, and that Cu-acclimation may be brought about by prevention of these effects.

Cu

Cu


Input: Our follow-up study on potential mechanisms underlying this copper acclimation used a similar pre-exposure/exposure design.

copper


Input: Fish were subsampled at the end of the 7-day acclimation period-just before the commencement of high-level Cu exposure (T), after 4h of this Cu exposure (T), and again after 8h of this Cu exposure (T).

Cu

Cu

Cu


Input: Whole-body Cu accumulation, Na/K-ATPase activity, metallothionein levels, and catalase activity were quantified for these time points.

Cu

K


Input: While Cu levels were higher in the Cu-pre-exposed fish than in the control fish at T, net Cu accumulation was faster in the control fish than in the Cu-pre-exposed fish during the subsequent high-level Cu exposure.

Cu

Cu

Cu

Cu

Cu


Input: Consequently, changes in Cu accumulation dynamics may play a role in the resistance.

Cu


Input: Metallothionein induction may also play a role in the observed acclimation, as Cu-acclimated fish had a significantly higher metallothionein concentration compared to the control fish.

Cu


Input: There was no evidence of involvement of Na/K-ATPase in the acclimation, as the activity of this enzyme remained lower in the pre-exposed fish than in the control fish throughout both Cu exposure periods.

K

Cu


Input: There was limited evidence that a reduced loss of catalase activity plays a role in the acclimation; catalase activity did not differ after the pre-exposure period but was significantly higher in Cu-acclimated fish than in the control fish at T.

Cu


Input: MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted-cell viability.


Input: Biocompatible nanomaterials and hydrogels have become an important tool for improving cell-based therapies by promoting cell survival and protecting cell transplants from immune rejection.


Input: Although their potential benefit has been widely evaluated, at present it is not possible to determine, in vivo, if and how long cells remain viable following their administration without the use of a reporter gene.


Input: Here, we report a pH-nanosensor-based magnetic resonance imaging (MRI) technique that can monitor cell death in vivo non-invasively.


Input: We demonstrate that specific MRI parameters that change on cell death of microencapsulated hepatocytes are associated with the measured bioluminescence imaging radiance.


Input: Moreover, the readout from this pH-sensitive nanosensor can be directly co-registered with high-resolution anatomical images.


Input: All of the components of these nanosensors are clinical grade and hence this approach should be a translatable and universal modification of hydrogels.


Input: In vitro permeability analysis, pharmacokinetic and brain distribution study in mice of imperatorin, isoimperatorin and cnidilin in Radix Angelicae Dahuricae.

imperatorin

isoimperatorin

cnidilin


Input: Coumarins are important constituents of Radix Angelicae Dahuricae, a well-known traditional Chinese medicine possess several known bioactivities with potentials in the treatment of central nervous system diseases.

Coumarins


Input: By using an HPLC-MS/MS method, we analyzed the in vivo plasma and brain pharmacokinetics of three ingredients of coumarins, including imperatorin, isoimperatorin and cnidilin in mice after oral administration of Dahuricae extract at doses of 800mg/kg.

coumarins

imperatorin

isoimperatorin

cnidilin


Input: The biosamples were prepared using acetonitrile precipitation and the separation was achieved on an XDB-C18 column by gradient elution.

acetonitrile


Input: The BBB permeability and P-gp-mediated efflux were further examined in Madin Canine kidney cells transfected with full length cDNA for human multidrug resistance gene1 (MDCKII-MDR1).


Input: Our results demonstrate that the method has excellent and satisfactory selectivity, sensitivity, linearity, precision, and accuracy for simultaneous determination of imperatorin, isoimperatorin and cnidilin.

imperatorin

isoimperatorin

cnidilin


Input: The pharmacokinetics parameters were determined by using noncompartmental analyses, including the AUC (0-t) in plasma (1695. 22, 1326. 45 and 636. 98mg * h/L), the AUC (0-t) in brain (1812. 35, 2125. 17 and 1145. 83ng * h/g) as well as the T1/2 in plasma (0. 66, 0. 82, 0. 97h) and brain (0. 96, 1. 1, 0. 99h) for imperatorin, isoimperatorin and cnidilin, respectively, suggesting that the three coumarins could easily pass through the BBB in vivo.

imperatorin

isoimperatorin

cnidilin

coumarins


Input: In the in vitro model we observed high permeability of imperatorin and isoimperatorin with the P-gp-mediated efflux ratios of 0. 53 and 0. 06, as well as medium permeability of cnidilin with 0. 82.

imperatorin

isoimperatorin

cnidilin


Input: All data suggest that these three coumarins have high BBB permeability and have pharmacokinetic potentials for the treatment of central nervous system diseases.

coumarins


Input: Phenolic glycosides from Curculigo orchioides Gaertn.

Phenolic glycosides


Input: Five new chlorophenolic glucosides, curculigine E (1), curculigine F (2), curculigine G (3), curculigine H (5), curculigine I (6) and one new phenolic glycoside, orcinoside H (4), together with eight known phenolic glycosides (7-14) were isolated from the Curculigo orchioides Gaertn.

chlorophenolic glucosides

curculigine E

curculigine F

curculigine G

curculigine H

curculigine I

phenolic glycoside

orcinoside H

phenolic glycosides


Input: Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and 2D NMR).


Input: The isolated phenolic glycosides were evaluated for antiosteoporotic activity against MC3T3-E1 cell line using MTT assays.

phenolic glycosides

MTT


Input: Compounds 1, 2, 3, and 5 showed moderate antiosteoporotic activity with the proliferation rate of 10. 1-14. 1%.


Input: ABT-737 resistance in B-cells isolated from chronic lymphocytic leukemia patients and leukemia cell lines is overcome by the pleiotropic kinase inhibitor quercetin through Mcl-1 down-regulation.

quercetin


Input: Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in adult population and despite numerous studies, it is considered an incurable disease.


Input: Since CLL is characterized by overexpression of pro-survival Bcl-2 family members, treatments with their antagonists, such as ABT-737, represent a promising new therapeutic strategy.


Input: ABT-737 is a BH3 mimetic agent which binds Bcl-2, Bcl-XL and Bcl-w with high affinity, while weakly interacts with Mcl-1 and Bfl-1.


Input: Previous studies demonstrated that quercetin, a flavonoid naturally present in food and beverages, was able to sensitize B-cells isolated from CLL patients to apoptosis when associated with death ligands or fludarabine, through a mechanism involving Mcl-1 down-regulation.

quercetin

flavonoid


Input: Here, we report that the association between ABT-737 and quercetin synergistically induces apoptosis in B-cells and in five leukemic cell lines (Combination Index < 1).

quercetin


Input: Peripheral blood mononuclear cell from healthy donors were not affected by quercetin treatment.

quercetin


Input: The molecular pathways triggered by quercetin have been investigated in HPB-ALL cells, characterized by the highest resistance to both ABT-737 and quercetin when applied as single molecules, but highly sensitivity to the co-treatment.

quercetin

quercetin


Input: In this cell line, quercetin down-regulated Mcl-1 through the inhibition of PI3K/Akt signaling pathway, leading to Mcl-1 instability.

quercetin


Input: The same mechanism was confirmed in B-cells.


Input: These results may open new clinical perspectives based on a translational approach in CLL therapy.


Input: c-Src-dependent MAPKs/AP-1 activation is involved in TNF-alpha-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells.


Input: TNF-alpha plays a critical mediator in the pathogenesis of chronic heart failure contributing to cardiac remodeling and peripheral vascular disturbances.


Input: The implication of TNF-alpha in inflammatory responses has been shown to be mediated through up-regulation of inflammatory genes, including matrix metalloproteinase-9 (MMP-9).


Input: However, the detailed mechanisms of TNF-alpha-induced MMP-9 expression are largely unclear in the heart cells.


Input: Here, we demonstrated that in rat embryonic-heart derived H9c2 cells, TNF-alpha could induce MMP-9 mRNA expression associated with an increase in the secretion of MMP-9, determined by real-time PCR, zymography, and promoter activity assays.


Input: TNF-alpha-mediated responses were attenuated by pretreatment with the inhibitor of c-Src (PP1), EGFR (AG1478), PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), or AP-1 (Tanshinone IIA) and transfection with siRNA of c-Src, EGFR, PDGFR, p110, Akt, or c-Jun.

Tanshinone IIA


Input: TNF-alpha stimulated c-Src, PDGFR, and EGFR phosphorylation, which were reduced by PP1.


Input: In addition, TNF-alpha-stimulated Akt phosphorylation was inhibited by PP1, AG1478, AG1296, or LY294002.


Input: We further demonstrated that TNF-alpha markedly stimulated p38 MAPK, p42/p44 MAPK, and JNK1/2 phosphorylation via a c-Src/EGFR, PDGFR/PI3K/Akt pathway.


Input: Finally, we showed that, in H9c2 cells, TNF-alpha-stimulated AP-1 promoter activity, c-Jun mRNA expression, and c-Jun phosphorylation were attenuated by PP1, AG1478, AG1296, LY294002, SB202190, SP600125, or U0126.


Input: These results suggested that TNF-alpha-induced MMP-9 expression is mediated through a c-Src/EGFR, PDGFR/PI3K/Akt/MAPKs/AP-1 cascade in H9c2 cells.


Input: Consequently, MMP-9 induction may contribute to cell migration and cardiovascular inflammation.


Input: A flexible approach to 1, 4-di-substituted 2-aminoimidazoles that inhibit and disperse biofilms and potentiate the effects of beta-lactams against multi-drug resistant bacteria.

1, 4-di-substituted 2-aminoimidazoles

beta-lactams


Input: The pyrrole-imidazole alkaloids are a 2-aminoimidazoles containing family of natural products that possess anti-biofilm activity.

pyrrole-imidazole alkaloids


Input: A library of 1, 4-di-substituted 2-aminoimidazole/triazoles (2-AITs) was synthesized, and its anti-biofilm activity as well as oxacillin resensitization efficacy toward methicillin resistant Staphylococcus aureus (MRSA) was investigated.

1, 4-di-substituted 2-aminoimidazole

triazoles


Input: These 2-AITs were found to inhibit biofilm formation by MRSA with low micromolar IC50 values.


Input: Additionally, the most active compound acted synergistically with oxacillin against MRSA lowering the minimum inhibitory concentration (MIC) 4-fold.


Input: Synthesis and biological evaluation of some novel resveratrol amide derivatives as potential anti-tumor agents.

resveratrol amide


Input: Three series of novel resveratrol amide derivatives (1a-q, 2a-h, 3a-l) were synthesized and evaluated for their biological activities.

resveratrol amide


Input: All compounds were characterized by (1) H NMR, (13) C NMR, MS and elemental analysis.

(1) H

(13) C


Input: Furthermore, compound 3e was also characterized by X-ray crystallography.


Input: All the compounds were evaluated for their anti-tumor activity against MCF-7, A549 and B16-F10 tumor cell lines as well as cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) inhibitory activity of murine macrophage RAW 264. 7 cell line.

prostaglandin E2


Input: Among them, compounds 1c, 1g and 3e displayed the most potent COX-2 inhibitory activity with the IC50 values of 1. 02, 1. 27 and 1. 98 mu M, respectively.


Input: Molecular docking studies were performed to position compounds 1c and 3e into the active site of COX-2 to determine the probable binding modes.


Input: Design and synthesis of novel 1, 2, 3-triazole-dithiocarbamate hybrids as potential anticancer agents.

1, 2, 3-triazole-dithiocarbamate


Input: A series of novel 1, 2, 3-triazole-dithiocarbamate hybrids were designed, synthesized and evaluated for anticancer activity against four selected human tumor cell lines (MGC-803, MCF-7, PC-3, EC-109).

1, 2, 3-triazole-dithiocarbamate


Input: Majority of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7.


Input: Among them, compounds 3a and 3c showed excellent broad spectrum anticancer activity with IC50 values ranging from 0. 73 to 11. 61 mu M and 0. 49-12. 45 mu M, respectively.


Input: Particularly, compound 3a was more potent than 5-fluorouracil against all tested human cancer cell lines.


Input: Flow cytometry analysis demonstrated that treatment of MGC-803 with 3c led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death after 12 h.


Input: Involvement of the essential metal transporter Zip14 in hepatic Cd accumulation during inflammation.

Cd


Input: Upregulation of Zip14 contributes to hepatic zinc (Zn) and non-transferrin-bound iron (Fe) uptake during infection and inflammation.

zinc

Zn

iron

Fe


Input: We investigated whether this essential metal transporter is also involved in hepatic cadmium (Cd) uptake under these conditions.

cadmium

Cd


Input: An injection of lipopolysaccharide (LPS), turpentine oil (Tur) and n-hexane (Hex) resulted in an decrease in plasma Zn and Fe concentrations to 25-50% and an increase in hepatic concentrations of both metals to 150-200% of control mice.

n-hexane

Hex

Zn

Fe


Input: LPS significantly increased plasma interleukin (IL)-6 levels more rapidly than Tur or Hex.

Hex


Input: Tur or Hex significantly increased hepatic Zip14 mRNA expression and decreased ferroportin 1 mRNA expression following continuous increase of IL-6 level.

Hex


Input: Hepatic Cd and Zn concentrations increased significantly after repeated injections of Cd in Tur-or Hex-treated mice fed a control diet.

Cd

Zn

Cd

Hex


Input: Treatment with Tur or Hex additionally increased hepatic Cd accumulation in Zn-deficient mice, unlike in Fe-deficient mice.

Hex

Cd

Zn

Fe


Input: These results suggest that Zn transporters, such as Zip14, may be involved in hepatic Cd uptake during inflammation.

Zn

Cd


Input: Differential toxicity and gene expression in Caco-2 cells exposed to arsenic species.

arsenic


Input: Inorganic arsenic [As (V) + As (III)] and its metabolites, especially the trivalent forms [monomethylarsonous acid, MMA (III), and dimethylarsinous acid, DMA (III)], are considered the forms of arsenic with the highest degree of toxicity, linked to certain types of cancer and other pathologies.

arsenic

As (V)

As (III)

monomethylarsonous acid

MMA (III)

dimethylarsinous acid

DMA (III)

arsenic


Input: The gastrointestinal mucosa is exposed to these forms of arsenic, but it is not known what toxic effect these species may have on it.

arsenic


Input: The aim of the present work was to evaluate the toxicity and some mechanisms of action of inorganic arsenic and its metabolites [monomethylarsonic acid, MMA (V), dimethylarsinic acid, DMA (V), MMA (III) and DMA (III)] in intestinal epithelial cells, using the Caco-2 human cell line as a model.

monomethylarsonic acid

MMA (V)

dimethylarsinic acid

DMA (V)

MMA (III)

DMA (III)


Input: The results show that the pentavalent forms do not produce toxic effects on the intestinal monolayer, but the trivalent species have a different degree of toxicity.


Input: As (III) induces death mainly by necrosis, whereas only apoptotic cells are detected after exposure to MMA (III), and for DMA (III) the percentages of apoptosis and necrosis are similar.

As (III)

MMA (III)

DMA (III)


Input: The three forms produce reactive oxygen species, accompanied by a reduction in intracellular GSH and lipid peroxidation, the latter being especially notable in the dimethylated form.

oxygen

GSH


Input: They also alter the enzyme activity of glutathione peroxidase and catalase and induce expression of stress proteins and metallothioneins.

glutathione


Input: The results indicate that the trivalent forms of arsenic can affect cell viability of intestinal cells by mechanisms related to the induction of oxidative stress.

arsenic


Input: Further studies are needed to evaluate how the effects observed in this study affect the structure and functionality of the intestinal epithelium.


Input: Evidence for a new binding mode to GSK-3: allosteric regulation by the marine compound palinurin.

palinurin


Input: Glycogen synthase kinase 3 beta (GSK-3 beta) is widely recognised as a relevant player in the pathogenesis of several highly prevalent disorders such as Alzheimer' s disease, mood disorders, diabetes and cancer.


Input: Therefore, this enzyme constitutes a highly attractive therapeutic target for the development of selective inhibitors as new promising drugs for the treatment of these pathologies.


Input: We describe here the isolation and biochemical characterization of the marine natural sesquiterpene palinurin as a GSK-3 beta inhibitor.

sesquiterpene palinurin


Input: Experimental studies performed for characterizing the inhibitory mechanism indicate that GSK-3 beta inhibition by palinurin cannot be competed out by ATP nor peptide substrate.

palinurin

ATP


Input: Molecular modelling techniques have enabled us to propose an unconventional binding mode to GSK-3 beta.


Input: Moreover, molecular dynamics simulations have identified an allosteric mechanism by which binding of palinurin leads to GSK-3 beta inhibition.

palinurin


Input: The inhibitory activities determined for a series of structurally related analogues support the proposed binding mode of palinurin, which is the first compound described to target this allosteric site.

palinurin


Input: The results offer new opportunities for designing and developing selective inhibitors with novel mechanisms of action.


Input: Isolation and identification of beta-hematin inhibitors from Flacourtia indica as promising antiplasmodial agents.

beta-hematin


Input: An ethanolic extract (A001) of the leaves and twigs of Flacourtia indica (Burm. f.) Merr., was purified to give a new phenolic glycoside, 2-(2-benzoyl-beta-D-glucopyranosyloxy)-7-(1 alpha, 2 alpha, 6 alpha-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol (1) together with poliothrysoside (2), catechin-[5, 6-e]-4 beta-(3, 4-dihydroxyphenyl) dihydro-2 (3H)-pyranone (3), 2-(6-benzoyl-beta-D-glucopyranosyloxy)-7-(1 alpha, 2 alpha, 6 alpha-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol (4), chrysoeriol-7-O-beta-D-glucopyranoside (5), and mururin A (6).

phenolic glycoside

2-(2-benzoyl-beta-D-glucopyranosyloxy)-7-(1 alpha, 2 alpha, 6 alpha-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol

poliothrysoside

catechin-[5, 6-e]-4 beta-(3, 4-dihydroxyphenyl) dihydro-2 (3H)-pyranone

2-(6-benzoyl-beta-D-glucopyranosyloxy)-7-(1 alpha, 2 alpha, 6 alpha-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol

mururin A


Input: Compound 6 significantly inhibited the in vitro growth of both a chloroquine-sensitive (3D7) and a chloroquine-resistant (K1) strain of Plasmodium falciparum.

chloroquine

chloroquine


Input: It forms a complex with hematin and inhibits beta-hematin formation, suggesting that this compound act on a heme polymerization target.

hematin

beta-hematin

heme


Input: Safety evaluation of daidzein in laying hens: part II.

daidzein


Input: Effects on calcium-related metabolism.

calcium


Input: Daidzein, an estrogen-like product, has become increasingly popular as a dietary supplement, particularly for postpeak-estrus animals seeking a safe natural alternative to play a role of estrogen.

Daidzein

estrogen

estrogen


Input: However, there is little available safety data of it for raisers and consumers.


Input: A subchronic laying hensafety study has been conducted to examine if the high-dose daidzein could affect calcium-related metabolism (eggshell quality and bone mineralization).

daidzein

calcium


Input: Seven hundred and sixty-eight 56-week-old Hyline Brown were randomly assigned to 4 groups with 8 replicates of 24 birds each (192 laying hensper group) and 3weeks later fed diets supplemented with 0 (control), 10, 50 and 100mg of daidzein/kg for 12week.

daidzein


Input: Eggshell thickness, eggshell percentage, eggshell strength, eggshell Ca concentration was increased linearly with increasing dietary daidzein supplementation (P = 0. 001, P = 0. 007, P = 0. 002 and P = 0. 000, respectively).

Ca

daidzein


Input: Serum Ca increased linearly with increasing dietarydaidzein supplementation (P = 0. 042), and serum P showed a significant quadratic response to dietarydaidzein supplementation (P = 0. 036).

Ca

dietarydaidzein

dietarydaidzein


Input: Bone ash and bone Ca were significantly influenced by dietarydaidzein supplementation (P < 0. 05).

Ca

dietarydaidzein


Input: These findings indicate that daidzein hold no observed adverse effect on calcium metabolism, but also a safe and effective food additive for calcium metabolism in animals and humans.

daidzein

calcium

calcium


Input: Osteoporosis in men: recent progress.


Input: As osteoporosis in men has been recognized as an important clinical problem, new information is being accumulated on its scope, pathophysiology, evaluation, and treatment.


Input: Fracture risk calculators, such as FRAX, identify a large proportion of the older male population to be at heightened risk for fracture.


Input: The classification of osteoporosis into primary and secondary forms, while still useful, is affected by the fact that many men have multiple contributing factors to their fracture risk.


Input: The role of sex steroids is being better defined as other risk factors for fracture are delineated.

steroids


Input: As longevity continues to increase in men and until osteoporotic fracture is truly recognized as a potentially fatal disorder, many men will be undiagnosed and untreated.


Input: Two recent studies provide more evidence that treatments which decrease fracture risk in women do the same in men.


Input: With the publication of guidelines and increasing strength of evidence for treatment efficacy, it is hoped that more men will be evaluated and treated for this often neglected disorder.


Input: Impact assessment of dredging to remove coal fly ash at the Tennessee Valley Authority Kingston Fossil plant using fathead minnow elutriate exposures.

coal


Input: On December 22, 2008, failure of an earthen containment structure resulted in the release of approximately 4. 1 million m (3) of coal fly ash into the Emory River and the surrounding area from the Tennessee Valley Authority Kingston Fossil Plant near Kingston, Tennessee, USA.

coal


Input: The purpose of the present study was to assess the potential of dredging activities performed to remove the fly ash from the river to result in increased risk to pelagic fish, with special consideration of mobilization of metals.


Input: Elutriates were created using two sources of fly ash by bubbling with air over 10 d.


Input: This elutriate preparation method was designed to represent worst-case conditions for oxidation, metal release, and dissolution.


Input: Larval and juvenile Pimephales promelas underwent 10-d exposures to these elutriates.


Input: Larval end points included survival and biomass, and juvenile end points included survival, length, biomass, liver somatic index, and bioaccumulation.


Input: No significant toxicity was observed.


Input: Bioaccumulation of metals in juveniles was found to be primarily attributable to metals associated with particles in the gut.


Input: Results suggest little potential for toxicity to related fish species due to fly ash removal dredging activities given the extreme conditions represented by the elutriates in the present study.


Input: Electrospun TiO2 nanorods with carbon nanotubes for efficient electron collection in dye-sensitized solar cells.

carbon


Input: A high power conversion efficiency of 10. 24% can be obtained in a dye-sensitized solar cell by incorporating multiwall carbon nanotubes inside a TiO2 nanorod photoanode.

carbon


Input: The multiwall carbon nanotubes in the nanorod can effectively collect and transport photogenerated electrons reducing the recombination as well as improving efficiency of the device.


Input: Role of fat body lipogenesis in protection against the effects of caloric overload in Drosophila.


Input: The Drosophila fat body is a liver-and adipose-like tissue that stores fat and serves as a detoxifying and immune responsive organ.


Input: We have previously shown that a high sugar diet leads to elevated hemolymph glucose and systemic insulin resistance in developing larvae and adults.

sugar

glucose


Input: Here, we used stable isotope tracer feeding to demonstrate that rearing larvae on high sugar diets impaired the synthesis of esterified fatty acids from dietary glucose.

sugar

fatty acids

glucose


Input: Fat body lipid profiling revealed changes in both carbon chain length and degree of unsaturation of fatty acid substituents, particularly in stored triglycerides.

carbon

fatty acid

triglycerides


Input: We tested the role of the fat body in larval tolerance of caloric excess.


Input: Our experiments demonstrated that lipogenesis was necessary for animals to tolerate high sugar feeding as tissue-specific loss of orthologs of carbohydrate response element-binding protein or stearoyl-CoA desaturase 1 resulted in lethality on high sugar diets.

sugar

carbohydrate

stearoyl-CoA

sugar


Input: By contrast, increasing the fat content of the fat body by knockdown of king-tubby was associated with reduced hyperglycemia and improved growth and tolerance of high sugar diets.

sugar


Input: Our work supports a critical role for the fat body and the Drosophila carbohydrate response element-binding protein ortholog in metabolic homeostasis in Drosophila.

carbohydrate


Input: Polycyclic peptide therapeutics.


Input: Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics.


Input: Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide.

vancomycin

actinomycin D

romidepsin


Input: All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide.

vancomycin

actinomycin D

romidepsin


Input: Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets.


Input: For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches.

cystine


Input: More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display.


Input: In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures.


Input: Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed.


Input: Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases.


Input: Ataxia telangiectasia mutated (ATM) is dispensable for endonuclease I-SceI-induced homologous recombination in mouse embryonic stem cells.


Input: Ataxia telangiectasia mutated (ATM) is activated upon DNA double strand breaks (DSBs) and phosphorylates numerous DSB response proteins, including histone H2AX on serine 139 (Ser-139) to form gamma-H2AX.

serine

Ser


Input: Through interaction with MDC1, gamma-H2AX promotes DSB repair by homologous recombination (HR).


Input: H2AX Ser-139 can also be phosphorylated by DNA-dependent protein kinase catalytic subunit and ataxia telangiectasia-and Rad3-related kinase.

Ser


Input: Thus, we tested whether ATM functions in HR, particularly that controlled by gamma-H2AX, by comparing HR occurring at the euchromatic ROSA26 locus between mouse embryonic stem cells lacking either ATM, H2AX, or both.


Input: We show here that loss of ATM does not impair HR, including H2AX-dependent HR, but confers sensitivity to inhibition of poly (ADP-ribose) polymerases.

poly (ADP-ribose)


Input: Loss of ATM or H2AX has independent contributions to cellular sensitivity to ionizing radiation.


Input: The ATM-independent HR function of H2AX requires both Ser-139 phosphorylation and gamma-H2AX/MDC1 interaction.

Ser


Input: Our data suggest that ATM is dispensable for HR, including that controlled by H2AX, in the context of euchromatin, excluding the implication of such an HR function in genomic instability, hypersensitivity to DNA damage, and poly (ADP-ribose) polymerase inhibition associated with ATM deficiency.

poly (ADP-ribose)


Input: Occupational exposure to anaesthetic gases and high-frequency audiometry.


Input: Objectives: Occupational exposure to anaestethic gases has been suggested to induce auditory damages.


Input: The aim of this study is to investigate high-frequency audiometric responses in subjects exposed to anaesthetic gases, in order to highlight the possible effects on auditory system.


Input: METHODS: The study was performed on a sample of 30 medical specialists of Messina University Anaesthesia and Intensive care.


Input: We have used tonal audiometry as well as high-frequency one.


Input: We have compared the responses with those obtained in a similar control group not exposed to anaesthetic gases.


Input: Results were compared statistically.


Input: Results: Results show a strong correlation (p = 0. 000) between left and right ear responses to all the audiometric tests.


Input: The exposed and the control group run though the standard audiometry analysis plays different audiometric responses up only to higher frequencies (2000 HZ p = 0. 009 and 4000 Hz p = 0. 04); in high-frequency audiometry, as all other frequencies, the attention is drew to the fact that the sample groups distinguish themselves in a significantly statistic way (10, 000 Hz p = 0. 025, 12, 000 Hz p = 0. 008, 14, 000 Hz p = 0. 026, 16, 000 Hz p = 0. 08).


Input: The highest values are the ones related to exposed subjects both in standard (2000 Hz p = 0. 01, 4000 Hz p = 0. 02) and in high-frequency audiometry (10, 000 Hz p = 0. 011, 12, 000 Hz p = 0. 004, 14, 000 Hz p = 0. 012, 16, 000 Hz p = 0. 004).


Input: Conclusion: Results, even if preliminary and referred to a low-range sample, show an involvement of the anatomic structure responsible for the perception of high-frequency audiometric responses in subjects exposed to anaesthetic gases.


Input: Effects of DNA methylation on nucleosome stability.


Input: Methylation of DNA at CpG dinucleotides represents one of the most important epigenetic mechanisms involved in the control of gene expression in vertebrate cells.

CpG dinucleotides


Input: In this report, we conducted nucleosome reconstitution experiments in conjunction with high-throughput sequencing on 572 KB of human DNA and 668 KB of mouse DNA that was unmethylated or methylated in order to investigate the effects of this epigenetic modification on the positioning and stability of nucleosomes.


Input: The results demonstrated that a subset of nucleosomes positioned by nucleotide sequence was sensitive to methylation where the modification increased the affinity of these sequences for the histone octamer.

nucleotide


Input: The features that distinguished these nucleosomes from the bulk of the methylation-insensitive nucleosomes were an increase in the frequency of CpG dinucleotides and a unique rotational orientation of CpGs such that their minor grooves tended to face toward the histones in the nucleosome rather than away.

CpG dinucleotides

CpGs


Input: These methylation-sensitive nucleosomes were preferentially associated with exons as compared to introns while unmethylated CpG islands near transcription start sites became enriched in nucleosomes upon methylation.

CpG


Input: The results of this study suggest that the effects of DNA methylation on nucleosome stability in vitro can recapitulate what has been observed in the cell and provide a direct link between DNA methylation and the structure and function of chromatin.


Input: Quantitative purity-activity relationships of natural products: the case of anti-tuberculosis active triterpenes from Oplopanax horridus.

triterpenes


Input: The present study provides an extension of the previously developed concept of purity-activity relationships (PARs) and enables the quantitative evaluation of the effects of multiple minor components on the bioactivity of residually complex natural products.


Input: The anti-tuberculosis active triterpenes from the Alaskan ethnobotanical Oplopanax horridus were selected as a case for the development of the quantitative PAR (QPAR) concept.


Input: The residual complexity of the purified triterpenes was initially evaluated by 1D-and 2D-NMR and identified as a combination of structurally related and unrelated impurities.

triterpenes


Input: Using a biochemometric approach, the qHNMR purity and anti-TB activity of successive chromatographic fractions of O. horridus triterpenes were correlated by linear regression analysis to generate a mathematical QPAR model.

triterpenes


Input: The results demonstrate that impurities, such as widely occurring monoglycerides, can have a profound impact on the observed antimycobacterial activity of triterpene-enriched fractions.

monoglycerides

triterpene


Input: The QPAR concept is shown to be capable of providing a quantitative assessment in situations where residually complex constitution contributes toward the biological activity of natural products.


Input: A comparison of the signalling properties of two tyramine receptors from Drosophila.

tyramine


Input: In invertebrates, the phenolamines, tyramine and octopamine, mediate many functional roles usually associated with the catecholamines, noradrenaline and adrenaline, in vertebrates.

phenolamines

tyramine

octopamine

catecholamines

noradrenaline

adrenaline


Input: The alpha-and beta-adrenergic classes of insect octopamine receptor are better activated by octopamine than tyramine.

octopamine

octopamine

tyramine


Input: Similarly, the Tyramine 1 subgroup of receptors (or Octopamine/Tyramine receptors) are better activated by tyramine than octopamine.

Tyramine

Octopamine

Tyramine

tyramine

octopamine


Input: However, recently, a new Tyramine 2 subgroup of receptors was identified, which appears to be activated highly preferentially by tyramine.

Tyramine

tyramine


Input: We examined immunocytochemically the ability of CG7431, the founding member of this subgroup from Drosophila melanogaster, to be internalized in transfected Chinese hamster ovary (CHO) cells by different agonists.


Input: It was only internalized after activation by tyramine.

tyramine


Input: Conversely, the structurally related receptor, CG16766, was internalized by a number of biogenic amines, including octopamine, dopamine, noradrenaline, adrenaline, which also were able to elevate cyclic AMP levels.

amines

octopamine

dopamine

noradrenaline

adrenaline

cyclic AMP


Input: Studies with synthetic agonists and antagonists confirm that CG16766 has a different pharmacological profile to that of CG7431.


Input: Species orthologues of CG16766 were only found in Drosophila species, whereas orthologues of CG7431 could be identified in the genomes of a number of insect species.


Input: We propose that CG16766 represents a new group of tyramine receptors, which we have designated the Tyramine 3 receptors.

tyramine

Tyramine


Input: Formaldehyde metabolism and formaldehyde-induced stimulation of lactate production and glutathione export in cultured neurons.

Formaldehyde

formaldehyde

lactate

glutathione


Input: Formaldehyde is endogenously produced in the human body and brain levels of this compound are elevated in neurodegenerative conditions.

Formaldehyde


Input: Although the toxic potential of an excess of formaldehyde has been studied, little is known on the molecular mechanisms underlying its neurotoxicity as well as on the ability of neurons to metabolize formaldehyde.

formaldehyde

formaldehyde


Input: To address these topics, we have used cerebellar granule neuron cultures as model system.


Input: These cultures express mRNAs of various enzymes that are involved in formaldehyde metabolism and were remarkably resistant toward acute formaldehyde toxicity.

formaldehyde

formaldehyde


Input: Cerebellar granule neurons metabolized formaldehyde with a rate of around 200 nmol/(h x mg) which was accompanied by significant increases in the cellular and extracellular concentrations of formate.

formaldehyde

formate


Input: In addition, formaldehyde application significantly increased glucose consumption, almost doubled the rate of lactate release from viable neurons and strongly accelerated the export of the antioxidant glutathione.

formaldehyde

glucose

lactate

glutathione


Input: The latter process was completely prevented by inhibition of the known glutathione exporter multidrug resistance protein 1.

glutathione


Input: These data indicate that cerebellar granule neurons are capable of metabolizing formaldehyde and that the neuronal glycolysis and glutathione export are severely affected by the presence of formaldehyde.

formaldehyde

glutathione

formaldehyde


Input: Formulation and characterization of Brucea javanica oil microemulsion for improving safety.


Input: Abstract Objective: This study engaged in investigation of optimal formulation, characteristics analysis of Brucea javanica oil microemulsion (BJOM) in order to address safety concerns and make recommendations for improvements in BJOM safety during clinical use in vivo.


Input: Methods: Pseudo-ternary phase diagram techniques were used to determine the appropriate ratio of surfactant, cosurfactant and oil phases.


Input: Subsequent stability testing of BJOM was performed by dilution, centrifugation and accelerated stability testing.


Input: The results were expounded through additional assessment utilizing the classical thermostat method to establish the shelf life of the material.


Input: These results were utilized to evaluate the safety of BJOM by haemolytic, irritative and allergic testing in vitro.


Input: In addition, the cytotoxicity of BJOM was examined using the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), with particular emphasis given to potential uses in cancer treatment.

tetrazolium

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

MTT


Input: Results: The most suitable method of preparation for BJOM was found to be a one to one ratio (K (m) 1: 1) of Solutol HS15 surfactant matched with sorbitol cosurfactant in the ratio.


Input: The microemulsion droplets of BJOM possessed a spherical shape, uniform size and average diameter of 23. 8 nm.


Input: The expiration date of BJOM was found to be 568 d.


Input: The safety study demonstrated no hemolysis activity at the experimental BJOM concentrations; however, mild hemolysis was observed at higher concentrations of Brucea javanica oil emulsion (BJOE), a common commercially available product.


Input: Irritation observed upon BJOM treatment can be primarily attributed to Brucea javanica oil (BJO) with little influence of BJOM excipients.


Input: In addition, BJOM caused no observed hypersensitivity or other visible allergic reactions in guinea pigs.


Input: The anticancer activity curves of BJOM and BJOE demonstrate that both BJOM and BJOE inhibit Hela cells, with BJOM demonstrating significantly more dramatic anticancer activity.


Input: Conclusion: An optimal formulation of BJOM superior to commercially available products and safe for medical application such as intravenous injection has been outlined along with its anticancer activity rating.


Input: Solution structure, dynamics and binding studies of a family 11 carbohydrate-binding module from Clostridium thermocellum (CtCBM11).

carbohydrate


Input: Non-catalytic cellulosomal CBMs (carbohydrate-binding modules) are responsible for increasing the catalytic efficiency of cellulosic enzymes by selectively putting the substrate (a wide range of poly-and oligo-saccharides) and enzyme into close contact.

carbohydrate


Input: In the present study we carried out an atomistic rationalization of the molecular determinants of ligand specificity for a family 11 CBM from thermophilic Clostridium thermocellum [CtCBM11 (C. thermocellum CBM11)], based on a NMR and molecular modelling approach.


Input: We have determined the NMR solution structure of CtCBM11 at 25 degrees C and 50 degrees C and derived information on the residues of the protein that are involved in ligand recognition and on the influence of the length of the saccharide chain on binding.

saccharide


Input: We obtained models of the CtCBM11-cellohexaose and CtCBM11-cellotetraose complexes by docking in accordance with the NMR experimental data.

cellohexaose

cellotetraose


Input: Specific ligand-protein CH-pi and Van der Waals interactions were found to be determinant for the stability of the complexes and for defining specificity.


Input: Using the order parameters derived from backbone dynamics analysis in the presence and absence of ligand and at 25 degrees C and 50 degrees C, we determined that the protein' s backbone conformational entropy is slightly positive.


Input: This data in combination with the negative binding entropy calculated from ITC (isothermal titration calorimetry) studies supports a selection mechanism where a rigid protein selects a defined oligosaccharide conformation.


Input: Phthalocyanine-Peptide Conjugates: Receptor-Targeting Bifunctional Agents for Imaging and Photodynamic Therapy.

Phthalocyanine


Input: The synthesis of a series of new zinc phthalocyanine-peptide conjugates targeting the gastrin-releasing peptide (GRP) and integrin receptors is reported.

zinc phthalocyanine


Input: Two alternative synthetic methods based on Sonogashira cross-coupling of an iodinated zinc phthalocyanine with acetylenic bombesin or arginine-glycine-aspartic acid (RGD) derivatives, either in solution or on solid phase, are presented.

zinc phthalocyanine

acetylenic bombesin

arginine

glycine

aspartic acid


Input: The water-soluble conjugates were screened for their photodynamic efficacy against several cancer cell lines expressing different levels of GRP and integrin receptors, and their intracellular localization was evaluated via confocal fluorescence microscopy.


Input: Variations in photocytotoxicity between the conjugates correlate to differences in hydrophobicity as well as receptor-mediated cell uptake.


Input: In the case of the phthalocyanine-bombesin conjugate, competition experiments confirm the involvement of the GRP receptor in both the phototherapeutic activity as well as intracellular localization.

phthalocyanine

bombesin


Input: These findings warrant further in vivo studies to evaluate the potential of this conjugate as photosensitizer for photodynamic therapy (PDT) of cancers overexpressing the GRP receptor.


Input: Chemical synthesis and characterization of epicatechin glucuronides and sulfates: bioanalytical standards for epicatechin metabolite identification.

epicatechin glucuronides and sulfates


Input: The monoglucuronides and sulfates of epicatechin, 3'-O-methylepicatechin, and 4'-O-methylepicatechin, respectively, were synthesized as authentic bioanalytical standards.

monoglucuronides

sulfates


Input: Reversed-phase HPLC methods capable of baseline separation of the glucuronides and sulfates have been developed.

glucuronides

sulfates


Input: Both the epicatechin glucuronides and sulfates were stable in the solid state when stored under ambient conditions and in aqueous solution when stored refrigerated.

epicatechin glucuronides and sulfates


Input: These results should prove invaluable to the research community as analytical standards as well as in future studies of the biological and pharmacological effects of epicatechin in humans.

epicatechin


Input: Flavone tetraglycosides and benzyl alcohol glycosides from the Mongolian medicinal plant Dracocephalum ruyschiana.

Flavone tetraglycosides

benzyl alcohol glycosides


Input: From an extract of the aerial parts of Dracocephalum ruyschiana, five new flavone tetraglycosides, five new benzyl alcohol glycosides, and 19 known compounds were isolated.

flavone tetraglycosides

benzyl alcohol glycosides


Input: The tetraglycosides contain a 7-O-beta-d-glucopyranosyl-(1 --> 2)-beta-d-glucopyranosyl-(1 --> 2)-[alpha-l-rhamnopyranosyl-(1 --> 6)]-beta-d-glucopyranosyl moiety.

7-O-beta-d-glucopyranosyl-(1 --> 2)-beta-d-glucopyranosyl-(1 --> 2)-[alpha-l-rhamnopyranosyl-(1 --> 6)]-beta-d-glucopyranosyl


Input: The benzyl alcohol glycosides had acyl groups on their glycosyl or aglycone moieties.

benzyl alcohol glycosides

acyl

glycosyl


Input: The compounds were tested for antioxidant activity using DPPH.

DPPH


Input: Although the new compounds were not active, phenylpropanoylquinic acid derivatives were revealed as radical scavengers in D. ruyschiana.

phenylpropanoylquinic acid


Input: Inactivation of Lrp5 in osteocytes reduces young' s modulus and responsiveness to the mechanical loading.


Input: Low-density-lipoprotein receptor-related protein 5 (Lrp5) is a co-receptor in Wnt signaling, which plays a critical role in development and maintenance of bone.


Input: Osteoporosis-pseudoglioma syndrome, for instance, arises from loss-of-function mutations in Lrp5, and global deletion of Lrp5 in mice results in significantly lower bone mineral density.


Input: Since osteocytes are proposed to act as a mechanosensor in the bone, we addressed a question whether a conditional loss-of-function mutation of Lrp5 selective to osteocytes (Dmp1-Cre; Lrp5 (f/f)) would alter responses to ulna loading.


Input: Loading was applied to the right ulna for 3 min (360 cycles at 2Hz) at a peak force of 2. 65 N for 3 consecutive days, and the contralateral ulna was used as a non-loaded control.


Input: Young' s modulus was determined using a midshaft section of the femur.


Input: The results showed that compared to age-matched littermate controls, mice lacking Lrp5 in osteocytes exhibited smaller skeletal size with reduced bone mineral density and content.


Input: Compared to controls, Lrp5 deletion in osteocytes also led to a 4. 6-fold reduction in Young' s modulus.


Input: In response to ulna loading, mineralizing surface, mineral apposition rate, and bone formation rate were diminished in mice lacking Lrp5 in osteocytes by 52%, 85%, and 69%, respectively.


Input: Collectively, the results support the notion that the loss-of-function mutation of Lrp5 in osteocytes causes suppression of mechanoresponsiveness and reduces bone mass and Young' s modulus.


Input: In summary, Lrp5-mediated Wnt signaling significantly contributes to maintenance of mechanical properties and bone mass.


Input: Male mice housed in groups engage in frequent fighting and show a lower response to additional bone loading than females or individually housed males that do not fight.


Input: Experiments to investigate bone' s physiological adaptation to mechanical loading frequently employ models that apply dynamic loads to bones in vivo and assess the changes in mass and architecture that result.


Input: It is axiomatic that bones will only show an adaptive response if the applied artificial loading environment differs in a significant way from that to which the bones have been habituated by normal functional loading.


Input: It is generally assumed that this normal loading is similar between experimental groups.


Input: In the study reported here we found that this was not always the case.


Input: Male and female 17-week-old C57BL/6 mice were housed in groups of six, and a single episode (40 cycles) of non-invasive axial loading, engendering 2, 200 mu epsilon on the medial surface of the proximal tibiae in sample mice, was applied to right tibiae on alternate days for two weeks.


Input: This engendered an adaptive increase in bone mass in females, but not males.


Input: Observation revealed the main difference in behaviour between males and females was that males were involved in fights 1. 3 times per hour, whereas the females never fought.


Input: We therefore housed all mice individually.


Input: In females, there was a similar significant osteogenic response to loading in cortical and trabecular bone of both grouped and individual mice.


Input: In contrast, in males, adaptive increases in the loaded compared with non-loaded control bones was only apparent in animals housed individually.


Input: Our interpretation of these findings is that the frequent vigorous fighting that occurs between young adult males housed in groups could be sufficient to engender peak strains and strain rates that equal or exceed the stimulus derived from artificial loading.


Input: This indicates the importance of ensuring that physical activity is consistent between groups.


Input: Reducing the background level of the naturally engendered strain environment allows adaptive responses to artificial loading to be demonstrated at lower loads.


Input: Synthesis of some new 2-(3-pyridyl)-4, 5-disubstituted thiazoles as potent antimicrobial agents.

2-(3-pyridyl)-4, 5-disubstituted thiazoles


Input: As a part of ongoing studies in developing new potent antimicrobial agents, a series of novel 2-(3-pyridyl)-4, 5-disubstituted thiazoles was efficiently synthesized and characterized by spectral and elemental analyses.

2-(3-pyridyl)-4, 5-disubstituted thiazoles


Input: The newly synthesized compounds were evaluated for their in vitro antimicrobial activity against ten bacterial and five fungal human pathogenic strains using the disc diffusion assay.


Input: Among the synthesized compounds, 5-acetyl-4-methyl-2-(3-pyridyl) thiazole (5) exhibited twofold antibacterial activity of ampicillin in inhibiting the growth of Staphylococcus epidermidis (MIC 0. 24 mu g/mL) and also showed equipotent antifungal activity with amphotricin B against Geotricum candidum (MIC 0. 48 mu g/mL).

5-acetyl-4-methyl-2-(3-pyridyl) thiazole

ampicillin

amphotricin B


Input: From structure-activity relationship (SAR) point of view, increasing the size of the substitutions either at position 4 or 5 on the thiazole nucleus decreased the antimicrobial activity.

thiazole


Input: Introducing new dimensions in MIA-QSAR: A case for chemokine receptor inhibitors.


Input: Multivariate image analysis applied to quantitative structure-activity relationships (MIA-QSAR) is a very simple correlative method that uses pixels (binaries) of chemical structures built from 2D viewer programs as descriptors; structural changes correspond to different pixel coordinates, which explain the variance in the bioactivities block.


Input: The MIA-QSAR method has shown to be predictive and capable of encoding some chemical information, but introduction of more descriptive information, such as atom size and colors to differentiate atom types, would improve predictability and interpretability.


Input: The bioactivities of a series of chemokine receptor (CCR2) inhibitors have been modeled using both conventional and atom color/size-dependent MIA-QSAR (namely aug-MIA-QSAR); the latter showed to be better.


Input: Moreover, the results were comparable to those obtained by 3D methodologies, indicating that 2D shape and substituent size are more significant descriptors than the conformational profiles required by field fit techniques.


Input: Paeonol suppresses oxidized low-density lipoprotein induced endothelial cell apoptosis via activation of LOX-1/p38MAPK/NF-kappa B pathway.

Paeonol


Input: Paeonol is an active compound isolated from traditional Chinese medicine, and has been shown to have anti-atherosclerosis, anti-inflammatory, antioxidant effects.

Paeonol


Input: The present investigation was undertaken to determine the suppression effects of paeonol on oxidized low-density lipoprotein (ox-LDL) induced endothelial cell line HUVEC apoptosis and to uncover some of the underlying mechanisms of these effects.

paeonol


Input: Cell viability and lactate dehydrogenase (LDH) were measured to evaluate the cell injuries.

lactate


Input: Apoptosis was evaluated by Hoechst 33342 staining and flow cytometry.

Hoechst 33342


Input: Intracellular reactive oxygen species (ROS) generation was detected by 2', 7'-dichlorofluorescein diacetate (DCFH-DA).

oxygen

2', 7'-dichlorofluorescein diacetate

DCFH-DA


Input: Real-time PCR was used to confirm the expression of LOX-1 mRNA.


Input: Western blotting was used to evaluate the protein expression of LOX-1 and Bcl-2, as well as caspase-3 cleavage, p38-mitogen-activated protein kinase (p38MAPK) phosphorylation.


Input: NF-kappa B nuclear translocation was detected by Western blotting and immunofluorescence.


Input: Caspase-3 activity was measured using a colorimetric protease assay kit.


Input: The results showed that ox-LDL significantly decreased cell viability and increased the LDH release, as well as the apoptotic rate (P < 0. 01).


Input: Pre-treatment of paeonol resulted in remarkable increase of cell viability, decrease of LDH release and cell apoptosis in a concentration-dependent manner.

paeonol


Input: Besides, ox-LDL caused the up-regulation of LOX-1, the down-regulation of Bcl-2, the phosphorylation of p38MAPK, the translocation of NF-kappa B and the activation of caspase-3.


Input: Paeonol pre-treatment reversed these effects introduced by ox-LDL.

Paeonol


Input: Moreover, paeonol also showed its inhibition effects on ox-LDL induced ROS overproduction.

paeonol


Input: These results indicate the preventive effects of paeonol on ox-LDL induced endothelial cell apoptosis.

paeonol


Input: The effects might, at least partly, be obtained via inhibition of LOX-1-ROS-p38MAPK-NF-kappa B signaling pathway.


Input: Testing of Perilla frutescens extract and Vicenin 2 for their antispasmodic effect.

Vicenin 2


Input: Gastrointestinal discomfort is frequently observed.


Input: The effects of Perilla frutescens extract and Vicenin 2 (a compound in this extract) were assayed in rat ileum with or without stimulation with acetylcholine or Ba (2 +).

Vicenin 2

acetylcholine

Ba (2 +)


Input: Both had no direct spasmolytic effect, but both decreased acetylcholine-or Ba (2 +)-induced contraction of rat ileum indicating an antispasmodic effect.

acetylcholine

Ba (2 +)


Input: This is valuable because effects were only observed when spasms were induced and may disturb the patient.


Input: The extract and the compound may be used to maintain and improve gut health.


Input: Genetic risk factors for glucocorticoid-induced osteonecrosis: a meta-analysis.


Input: Glucocorticoid-induced osteonecrosis is a common and severe adverse event.


Input: We conducted a meta-analysis to investigate whether polymorphisms in target genes were associated with the risk of corticosteroid-induced osteonecrosis.


Input: Published literature from PubMed and EMBASE were searched for eligible publications.


Input: Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed-or random-effects model.


Input: There were 23 articles with 35 genes described the relationship between polymorphisms and glucocorticoid-induced osteonecrosis.


Input: Meta-analyses were carried out for those SNPs with three or more eligible studies, which included four SNPs located in three genes (PAI-1, MTHFR, ABCB1).


Input: The meta-analysis revealed that the PAI-1 4G allele was associated with an increased risk of osteonecrosis compared with the 5G allele (combined studies: OR = 1. 932, 95% CI = 1. 145-3. 261).


Input: The OR for the 4G/4G vs. 5G/5G genotype of PAI-1 was 3. 217 (95% CI 1. 667-6. 209 with combined studies), The relative risk of osteonecrosis was increased in the 4G allele vs. 5G/5G and 4G/4G genotype vs. 5G allele, with odds ratios of 2. 304 (95% CI = 1. 235-4. 299) and 2. 307 (95% CI = 1. 527-3. 485) in combined studies, respectively.


Input: The ABCB1 C3435T genotype distributions available confirmed that the C allele increased osteonecrosis risk compared with the T allele (OR 1. 668, 95% CI = 1. 214-2. 293) and TT genotype (OR 2. 946, 95% CI = 1. 422-6. 101).


Input: There was no evidence for significant association between MTHFR C677T and ABCB1 G2677T/A polymorphisms and risk of osteonecrosis.


Input: Results of this meta-analysis indicate that the PAI-1 4G/5G and ABCB1 C3435T polymorphisms may be risk factors for osteonecrosis.


Input: Protective effect of silymarin against ethanol-induced gastritis in rats: role of sulfhydryls, nitric oxide and gastric sensory afferents.

silymarin

ethanol

sulfhydryls

nitric oxide


Input: Silymarin has been known to exert antioxidant, anti-carcinogenic and anti-inflammatory effects.

Silymarin


Input: In this study, we examined the effect of silymarin on gastritis in rats.

silymarin


Input: Oral administration of silymarin dose-dependently decreased gastric lesions in ethanol-induced gastritis model.

silymarin

ethanol


Input: Silymarin also significantly suppressed the development of gastric lesions in aspirin-or water immersion-restraint stress-induced gastritis models.

Silymarin

aspirin


Input: Further study demonstrated that the gastroprotective effect of silymarin was blocked by nitric oxide (NO) synthase inhibitor l-NAME, SH blocker N-ethylmaleimide or TRPV1 antagonist capsazepine in ethanol-induced gastritis model.

silymarin

nitric oxide

NO

l-NAME

SH

N-ethylmaleimide

capsazepine

ethanol


Input: In addition, ex vivo analysis revealed that ethanol-induced decrease in gastric mucus and non-protein sulfhydryl (NPSH) groups was significantly reversed by silymarin treatment and lipid peroxidation was also suppressed by silymarin in ethanol-induced gastritis model.

ethanol

sulfhydryl

silymarin

silymarin

ethanol


Input: Taken together, these results suggest that silymarin exerts gastroprotective effects and the gastroprotective effects of silymarin might be related to the protection of gastric mucosal NO and NP-SH and the modulation of capsaicin-sensitive gastric sensory afferents.

silymarin

silymarin

NO

SH

capsaicin


Input: Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives.

aplyronine A


Input: Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S (3) cells.

Aplyronine A

mycalolide B


Input: Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells.


Input: Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells.

aplyronine A


Input: The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells.


Input: These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity.


Input: Phosphonic analogues of glutamic acid as irreversible inhibitors of Staphylococcus aureus endoproteinase GluC: an efficient synthesis and inhibition of the human IgG degradation.

Phosphonic

glutamic acid


Input: Endoproteinase GluC (V8 protease) is one of many virulence factors released by the Staphylococcus aureus species in vivo.


Input: The V8 protease is able to hydrolyze some serpins and all classes of mammalian immunoglobulins.


Input: The application of specific and potent inhibitors of V8 protease may lead to the development of new antibacterial agents.


Input: Herein, we present the synthesis and the inhibitory properties of novel peptidyl derivatives of a phosphonic glutamic acid analogue.

phosphonic glutamic acid


Input: One of the compounds Boc-Phe-Leu-Glu (P) (OC (6) H (4)) (2) displayed an apparent second-order inhibition rate value of 8540 M (-1) s (-1).

Boc-Phe-Leu-Glu (P) (OC (6) H (4)) (2)


Input: The Boc-Phe-Leu-Glu (P) (OC (6) H (4)) (2) compound with the highest inhibitory potency showed the ability to prevent V8-mediated human IgG proteolysis in vitro.

Boc-Phe-Leu-Glu (P) (OC (6) H (4)) (2)


Input: Design and synthesis of dimethylaminomethyl-substituted curcumin derivatives/analogues: potent antitumor and antioxidant activity, improved stability and aqueous solubility compared with curcumin.

dimethylaminomethyl-substituted curcumin

curcumin


Input: A series of dimethylaminomethyl-substituted curcumin derivatives/analogues were designed and synthesized.

dimethylaminomethyl-substituted curcumin


Input: All compounds effectively inhibited HepG2, SGC-7901, A549 and HCT-116 tumor cell lines proliferation in MTT assay.

MTT


Input: Particularly, compounds 2a and 3d showed much better activity than curcumin against all of the four tumor cell lines.

curcumin


Input: Antioxidant test revealed that these compounds had higher free radical scavenging activity than curcumin towards both DPPH and galvinoxyl radicals.

DPPH

galvinoxyl


Input: Furthermore, the aqueous solubility and stability of the target compounds were also significantly improved compared with curcumin.

curcumin


Input: Design, synthesis, characterization and anti-inflammatory evaluation of novel pyrazole amalgamated flavones.

pyrazole

flavones


Input: A series of novel pyrazole amalgamated flavones has been designed and synthesized from 1-methyl-5-(2, 4, 6-trimethoxy-phenyl)-1H-pyrazole 6.

pyrazole

flavones

1-methyl-5-(2, 4, 6-trimethoxy-phenyl)-1H-pyrazole


Input: The structures of regioisomers 6 and 7 were resolved by 2D (1) H-(1) H COSY, (1) H-(13) C HSQC and (1) H-(13) C HMBC experiments.

(1) H

(1) H

(1) H

(13) C

(1) H

(13) C


Input: The newly synthesized compounds were tested for their in vitro COX inhibition and in vivo carrageenan induced hind paw edema in rats and acetic acid induced vascular permeability in mice.

acetic acid


Input: Although the compounds have inhibitory profile against both COX-1 and COX-2, some of the compounds are found to be selective against COX-2, supported by inhibition of paw edema and vascular permeability.


Input: Docking studies were also carried out to determine the structural features which sway the anti-inflammatory activity of the tested compounds.


Input: The keto and phenolic-OH are major factors that are prominently involved in interaction with COX-2 active site.

keto

phenolic

OH


Input: Antimycobacterial activity evaluation, time-kill kinetic and 3D-QSAR study of C-(3-aminomethyl-cyclohexyl)-methylamine derivatives.

C-(3-aminomethyl-cyclohexyl)-methylamine


Input: A series of C-(3-aminomethyl-cyclohexyl)-methylamine derivatives were synthesized and evaluated for their antitubercular activity.

C-(3-aminomethyl-cyclohexyl)-methylamine


Input: Some of the compounds exhibited potent activity against Mycobacterium tuberculosis H37Rv.


Input: One of the compound having t-butyl at para position of the benzene ring showed excellent activity even better than the standard drug ethambutol with MIC value 1. 1 +/- 0. 2 mu M.

t-butyl

benzene

ethambutol


Input: The time-kill kinetics study of two most active compounds showed rapid killing of the M. tuberculosis within 4 days.


Input: Additionally atom-based quantitative structure-activity relationship (QSAR) model was developed that gave a statistically satisfying result (R (2)) = 0. 92, Q (2) = 0. 75, Pearson-R = 0. 96 and effectively predicts the anti-tuberculosis activity of training and test set compounds.


Input: Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes.

glucose


Input: Type 2 11 beta-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.

11 beta-hydroxysteroid

cortisol

cortisone

glucose


Input: We investigated the association of HSD11B2 variant with glucose homeostasis.

glucose


Input: Subjects with normal glucose tolerance (n = 585), impaired glucose tolerance (n = 202) and type 2 diabetes (n = 355) were genotyped for a highly polymorphic CA-repeat polymorphism in the first intron of HSD11B2.

glucose

glucose


Input: Allele and genotype frequencies differed between normal and impaired glucose tolerance (P = 0. 0014 and 0. 0407, respectively; 4DF) or type 2 diabetes (P = 0. 0053 and 0. 0078), with significant linear trends between the repeat length and the phenotype fraction.

glucose


Input: In normal subjects, total CA-repeat length was negatively correlated with fasting insulin and HOMA-beta.


Input: Thus, subjects having more CA repeats are susceptible to developing abnormal glucose tolerance, whereas normal subjects carrying more CA repeats appeared to have frugal characteristics in insulin secretion.

glucose


Input: Crosslinking using rapid thermal processing for the fabrication of efficient solution-processed phosphorescent organic light-emitting diodes.


Input: Copolymers with a triscarbazole hole-transport group and an oxetane or benzocyclobutene crosslinkable group can be readily thermally crosslinked on timescales of 30 min or less, with rapid thermal processing (RTP) being highly effective for this purpose.

triscarbazole

oxetane

benzocyclobutene


Input: Devices with RTP-crosslinked hole-transport layers and spin-coated emissive layers exhibit high external quantum efficiencies of up to 15%.


Input: Pycnogenol (R) Supplementation Improves Health Risk Factors in Subjects with Metabolic Syndrome.


Input: This open, controlled study evaluated the effects of 6 month supplementation with Pycnogenol (R) maritime pine bark extract on health risk factors in subjects with metabolic syndrome.


Input: Pycnogenol (R) was used with the aim of improving risk factors associated with metabolic syndrome, central obesity, elevated triglycerides (TG), low HDL cholesterol, high blood pressure and fasting blood glucose.

triglycerides

cholesterol

glucose


Input: Sixty-four subjects (range 45-55 years) presenting with all five risk factors of metabolic syndrome were included, and Pycnogenol (R) was administered for 6 months.


Input: A group of 66 equivalent subjects were followed up as controls.


Input: In the 6-month study Pycnogenol (R) supplementation 150 mg/day decreased waist circumference, TG levels, blood pressure and increased the HDL cholesterol levels in subjects.

cholesterol


Input: Pycnogenol lowered fasting glucose from baseline 123 +/- 8. 6 mg/dl to 106. 4 +/- 5. 3 after 3 months and to 105. 3 +/- 2. 5 at the end of the study (p < 0. 05 vs controls).

glucose


Input: Men' s waist circumference decreased with Pycnogenol from 106. 2 +/- 2. 2 cm to 98. 8 +/- 2. 3 cm and to 98. 3 +/- 2. 1 after 3 and 6 months.


Input: Women' s waist decreased from 90. 9 +/- 1. 6 cm to 84. 6 +/- 2. 1 cm and to 83. 6 +/- 2. 2 cm after 3 and 6 months.


Input: Both genders waist circumference reduction was significant as compared to controls at both time points.


Input: In addition, plasma free radicals decrease in the Pycnogenol group was more effective than in the control group (-34. 6%; p < 0. 05).


Input: In conclusion, this study indicates a role for Pycnogenol (R) for improving health risk factors in subjects with metabolic syndrome.


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


Input: Tailor-Made Micro-Object Optical Sensor Based on Mesoporous Pellets for Visual Monitoring and Removal of Toxic Metal Ions from Aqueous Media.


Input: Methods for the continuous monitoring and removal of ultra-trace levels of toxic inorganic species (e. g., mercury, copper, and cadmium ions) from aqueous media such as drinking water and biological fluids are essential.

mercury

copper

cadmium


Input: In this paper, the design and engineering of a simple, pH-dependent, micro-object optical sensor is described based on mesoporous aluminosilica pellets with an adsorbed dressing receptor (a porphyrinic chelating ligand).

aluminosilica


Input: This tailor-made optical sensor permits ultra-fast (<= 60 s), specific, pH-dependent visualization and removal of Cu (2 +), Cd (2 +), and Hg (2 +) at sub-picomolar concentrations (~ 10 (-11) mol dm (-3)) from aqueous media, including drinking water and a suspension of red blood cells.

Cu (2 +)

Cd (2 +)

Hg (2 +)


Input: The acidic active acid sites of the pellets consist of heteroatoms arranged around uniformly shaped pores in 3D nanoscale gyroidal mesostructures densely coated with the chelating ligand.


Input: The sensor can be used in batch mode, as well as in a flow-through system in which sampling, target ion recognition and removal, and analysis are integrated in a highly automated and efficient manner.


Input: Because the pellets exhibit long-term stability, reproducibility, and versatility over a number of analysis/regeneration cycles, they can be expected to be useful for the fabrication of inexpensive sensor devices for naked-eye detection of toxic pollutants.


Input: Electrochemical Synthesis of Transparent, Amorphous, C (60)-Rich, Photoactive, and Low-Doped Film with an Interconnected Structure.

C (60)


Input: An electrochemical synthesis is developed through quantitative electrochemical reaction of N-alkylcarbazole leading to a novel class of structurally interconnected high-C (60) content (60 wt%) polymer films with negligible doping and intrinsic physicochemical properties of pure C (60).

N-alkylcarbazole

C (60)

C (60)


Input: This strategy allows preparation of previously unavailable low-doped fullerene-containing non-conjugated polymers and broadens the potential applications of electrochemical synthesis for controlled polymer film structures.

fullerene


Input: In vivo biological responses to silk proteins functionalized with bone sialoprotein.


Input: Recombinant 6mer + BSP protein, combining six repeats of the consensus sequence for Nephila clavipes dragline (6mer) and bone sialoprotein sequence (BSP), shows good support for cell viability and induces the nucleation of hydroxyapatite and tricalcium phosphate during osteoblast in vitro culture.

hydroxyapatite

tricalcium phosphate


Input: The present study is conducted to characterize this bioengineered protein-based biomaterial further for in vivo behavior related to biocompatibility.


Input: 6mer + BSP protein films are implanted in subcutaneous pouches in the back of mice and responses are evaluated by flow cytometry and histology.


Input: The results show no major differences between the inflammatory responses induced by 6mer + BSP films and the responses observed for the controls.


Input: Thus, this new chimeric protein could represent an alternative for bone regeneration applications.


Input: CO and CO-releasing molecules in medicinal chemistry.

CO

CO


Input: Since the discovery that CO acts as a cytoprotective and homeostatic molecule, increasing research efforts have been devoted to the exploitation of its therapeutic effects.

CO


Input: Both endogenous and exogenous CO improves experimental lung, vascular and cardiac injuries and protects against several inflammatory states.

CO


Input: The technology is now in place to bring CO to clinical applications, but the use of the gaseous molecule poses several problems.

CO


Input: The challenges associated with the clinical implementation of the gas have in part been answered by the development of CO-releasing molecules (CO-RMs).

CO

CO


Input: As stable solid forms of CO, these molecules represent an alternative to the administration of carbon monoxide (orally or by injection).

CO

carbon monoxide


Input: In this article, we present insights into the biochemical action of CO and discuss the efficacy of CO and CO-RMs in preclinical disease models.

CO

CO

CO


Input: Recent advances in the CO-RMs field are critically addressed.

CO


Input: Combined effects of Ag nanoparticles and oxygen plasma treatment on PLGA morphological, chemical, and antibacterial properties.

Ag

oxygen


Input: The purpose of this study is to investigate the combined effects of oxygen plasma treatments and silver nanoparticles (Ag) on PLGA in order to modulate the surface antimicrobial properties through tunable bacteria adhesion mechanisms.

oxygen

silver

Ag

PLGA


Input: PLGA nanocomposite films, produced by solvent casting with 1 wt% and 7 wt% of Ag nanoparticles were investigated.

PLGA

Ag


Input: The PLGA and PLGA/Ag nanocomposite surfaces were treated with oxygen plasma.

PLGA

PLGA

Ag

oxygen


Input: Surface properties of PLGA were investigated by field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), static contact angle (CA), and high resolution X-ray photoelectron spectroscopy (XPS).

PLGA


Input: Antibacterial tests were performed using an Escherichia coli RB (a Gram negative) and Staphylococcus aureus 8325-4 (a Gram positive).


Input: The PLGA surface becomes hydrophilic after the oxygen treatment and its roughness increases with the treatment time.

PLGA

oxygen


Input: The surface treatment and the Ag nanoparticle introduction have a dominant influence on the bacteria adhesion and growth.

Ag


Input: Oxygen-treated PLGA/Ag systems promote higher reduction of the bacteria viability in comparison to the untreated samples and neat PLGA.

Oxygen

PLGA

Ag

PLGA


Input: The combination of Ag nanoparticles with the oxygen plasma treatment opens new perspectives for the studied biodegradable systems in biomedical applications.

Ag

oxygen


Input: Surface-enhanced Raman scattering dye-labeled Au nanoparticles for triplexed detection of leukemia and lymphoma cells and SERS flow cytometry.

Au


Input: The labeling of cell surface receptors by fluorescent markers is an established method for the identification of cell phenotype in both research and clinical settings.


Input: Fluorescence dye labeling has inherent constraints, most notably the upper limit of labels per cell that may be probed using a single excitation source, in addition to a physical limit to the number of broad emission spectra that can be distinctly collected within the visible wavelength region.


Input: SERS labeling has the potential to mitigate these shortfalls.


Input: Herein, antibody-targeted, PEG-coated surface-enhanced Raman scattering (SERS) Au nanoparticles are used simultaneously to label three cell surface markers of interest on malignant B cells from the LY10 lymphoma cell line.

PEG

Au


Input: The SERS probes were characterized by multiple methods to confirm their monodispersity and functionalization with both PEG and monoclonal antibodies.

PEG


Input: The specificity of the particles' cell labeling was demonstrated on both primary chronic lymphocytic leukemia and LY10 cells using SERS from cell suspensions and confocal Raman mapping, respectively.


Input: Fluorescence flow cytometry was employed to confirm the binding of SERS probes to LY10 over large cell populations, and the particles' SERS was collected directly from labeled cells using a commercial flow cytometer.


Input: To the best of our knowledge, this is the first demonstration of SERS flow cytometry from cells tagged with targeted SERS probes.


Input: Surface-modified HK: siRNA nanoplexes with enhanced pharmacokinetics and tumor growth inhibition.


Input: We characterized in this study the pharmacokinetics and antitumor efficacy of histidine-lysine (HK): siRNA nanoplexes modified with PEG and a cyclic RGD (cRGD) ligand targeting alpha v beta 3 and alpha v beta 5 integrins.

histidine

lysine

PEG


Input: With noninvasive imaging, systemically administered surface-modified HK: siRNA nanoplexes showed nearly 4-fold greater blood levels, 40% higher accumulation in tumor tissue, and 60% lower luciferase activity than unmodified HK: siRNA nanoplexes.


Input: We then determined whether the surface-modified HK: siRNA nanoplex carrier was more effective in reducing MDA-MB-435 tumor growth with an siRNA targeting Raf-1.


Input: Repeated systemic administration of the selected surface modified HK: siRNA nanoplexes targeting Raf-1 showed 35% greater inhibition of tumor growth than unmodified HK: siRNA nanoplexes and 60% greater inhibition of tumor growth than untreated mice.


Input: The improved blood pharmacokinetic results and tumor localization observed with the integrin-targeting surface modification of HK: siRNA nanoplexes correlated with greater tumor growth inhibition.


Input: This investigation reveals that through control of targeting ligand surface display in association with a steric PEG layer, modified HK: siRNA nanoplexes show promise to advance RNAi therapeutics in oncology and potentially other critical diseases.

PEG


Input: Vesicles composed of fatty acid and N-[3-(dimethylamino) propyl]-octadecanamide: effect of fatty acid chain length on physicochemical properties of vesicles.

fatty acid

N-[3-(dimethylamino) propyl]-octadecanamide

fatty acid


Input: Abstract Background and objectives: Vesicles, recently claimed as drug delivery carriers, were prepared by taking advantage of an electrostatic interaction between the carboxylic groups of fatty acids (FAs) and the amino groups of N-[3-(Dimethylamino) propyl]-Octadecanamide (DMAPODA).

carboxylic

fatty acids

amino

N-[3-(Dimethylamino) propyl]-Octadecanamide

DMAPODA


Input: The study is to find out the effect of FAs' chain length on physicochemical properties of vesicles.


Input: Methods: Decanoic acid (DA), myristic acid (MA), stearic acid (SA) and behenic acid (BA) were used as FAs.

Decanoic acid

myristic acid

stearic acid

behenic acid


Input: Vesicles composed of them and DMAPODA were studied about formation on microscope, calorimetric analysis, size and zeta potential.

DMAPODA


Input: Results: On microphotographs, all of FAs could form vesicles when mixed with DMAPODA in an equi-molar ratio.

DMAPODA


Input: However, DA/DMAPODA vesicles were disintegrated during the homogenization.

DMAPODA


Input: Due to the asymmetry of DA/DMAPODA associate, it seems to hardly form a stable and well-packed bilayer.

DMAPODA


Input: On thermograms, the vesicles exhibited one strong peak, indicating that FAs can be homogeneously mixed with the cationic amphiphile.


Input: The sizes of the four kinds of vesicles suspended in an aqueous solution (final pH 7. 5) were in the same order (hundreds of nanometer) on microphotographs.


Input: But, on a light scattering machine, the mean size of MA/DMAPODA vesicle was measured to be much greater than those of the other vesicles, possibly because of the low absolute value of the zeta potential.

DMAPODA


Input: In addition, the medium pH value had a significant effect on the size of BA/DMAPODA vesicle possibly because the zeta potential was strongly dependent on the pH value.

DMAPODA


Input: Conclusion: FAs' chain length would affect the physicochemical properties of vesicles composed of them and DMAPODA.

DMAPODA


Input: Elucidation of the Molecular Interaction between Cisplatin and Flavonol (s) and their Effect on DNA Binding.

Cisplatin

Flavonol


Input: Combination therapy of cisplatin with flavonols is a promising treatment for increasing the efficacy of cisplatin when combating cancer.

cisplatin

flavonols

cisplatin


Input: However, little is known about the molecular interactions between cisplatin and flavonols.

cisplatin

flavonols


Input: The data herein helps to elucidate this interaction.


Input: Spectrophotometric data in the UV-visible range indicates that hydroxyl groups on the B-ring of flavonols are essential for reactivity with cisplatin.

hydroxyl

flavonols

cisplatin


Input: The use of a quartz crystal microbalance with dissipation monitoring approach clearly supports the critical role played by B-ring hydroxyls in their interactions with a cisplatin-bound double-stranded DNA surface; an increase in the number of hydroxyl groups on the B-ring of flavonols parallels the increase in their reaction rates with cisplatin and correlates well with their reported effects on leukemia cell apoptosis efficacy.

quartz

hydroxyls

cisplatin

hydroxyl

flavonols

cisplatin


Input: This study underscores the importance of B-ring hydroxyls in cisplatin' s toxicity and may be used to better understand and improve combination therapies of flavonols with cisplatin.

hydroxyls

cisplatin

flavonols

cisplatin


Input: Bioactivation of the nasal toxicant 2, 6-dichlorobenzonitrile: an assessment of metabolic activity in human nasal mucosa and identification of indicators of exposure and potential toxicity.

2, 6-dichlorobenzonitrile


Input: The herbicide 2, 6-dichlorobenzonitrile (DCBN) is a potent nasal toxicant in rodents; however, it is not known whether DCBN causes similar nasal toxicity in humans.

2, 6-dichlorobenzonitrile

DCBN

DCBN


Input: The tissue-selective toxicity of DCBN in mouse nasal mucosa is largely dependent on target tissue bioactivation by CYP2A5.

DCBN


Input: The human orthologues of CYP2A5, CYP2A6 and CYP2A13, are both expressed in nasal mucosa and are capable of activating DCBN.

DCBN


Input: In this study, we directly determined the ability of human nasal mucosa to bioactivate DCBN.

DCBN


Input: We also tested the suitability of a glutathione conjugate of DCBN (GS-DCBN) or its derivatives as biomarkers of DCBN exposure and nasal toxicity in mouse models.

glutathione

DCBN

DCBN

DCBN


Input: We found that human fetal nasal mucosa microsomes catalyze the formation of GS-DCBN, with a Km value comparable to that of adult mouse nasal mucosa microsomes.

DCBN


Input: The activity of the human nasal mucosa microsomes was inhibited by 8-methoxypsoralen, a known CYP2A inhibitor.


Input: GS-DCBN and its metabolites were detected in the nasal mucosa and nasal-wash fluid obtained from DCBN-treated mice, in amounts that increased with escalations in DCBN dose, and they were all still detectable at 24 h after a DCBN treatment (at 10 mg/kg).

DCBN

DCBN

DCBN

DCBN


Input: Further studies in Cyp2a5-null mice indicated that GS-DCBN and its metabolites in nasal-wash fluid were generated in the nasal mucosa, rather than in other organs.

DCBN


Input: Thus, our data indicate for the first time that the human nasal mucosa is capable of bioactivating DCBN and that GS-DCBN and its metabolites in nasal-wash fluid may collectively serve as indicators of DCBN exposure and potential nasal toxicity in humans.

DCBN

DCBN

DCBN


Input: Toward large-scale energy harvesting by a nanoparticle-enhanced triboelectric nanogenerator.


Input: This article describes a simple, cost-effective, and scalable approach to fabricate a triboelectric nanogenerator (NG) with ultrahigh electric output.


Input: Triggered by commonly available ambient mechanical energy such as human footfalls, a NG with size smaller than a human palm can generate maximum short-circuit current of 2 mA, delivering instantaneous power output of 1. 2 W to external load.


Input: The power output corresponds to an area power density of 313 W/m (2) and a volume power density of 54, 268 W/m (3) at an open-circuit voltage of ~ 1200 V.


Input: An energy conversion efficiency of 14. 9% has been achieved.


Input: The power was capable of instantaneously lighting up as many as 600 multicolor commercial LED bulbs.


Input: The record high power output for the NG is attributed to optimized structure, proper materials selection and nanoscale surface modification.


Input: This work demonstrated the practicability of using NG to harvest large-scale mechanical energy, such as footsteps, rolling wheels, wind power, and ocean waves.


Input: The relative protein abundance of UGT1A alternative splice variants as a key determinant of glucuronidation activity in vitro.