Input: This study investigated the effects of ozone microbubble (OMCB) treatment on the removal of residual fenitrothion (FT) and benomyl pesticides from red and green persimmon leaves, and also the treatment effect on the leaf colours, physical properties and flavour.

ozone

fenitrothion

benomyl


Input: The continuous bubbling OMCB treatment was more effective than the non-bubbling OMCB treatments at reducing the FT and benomyl agricultural pesticide residues from both the red and green persimmon leaves.

benomyl


Input: Moreover, the bubbling OMCB treatment had no effect on the colour and pulling strength of the leaves.


Input: These results indicate that the treatment by bubbling OMCB is an extremely effective method for removing the residues of FT and benomyl in persimmon leaves and has relatively little effect on leaf quality characteristics.

benomyl


Input: The influence of pectolytic enzyme addition and prefermentative mash heating during the winemaking process on the phenolic composition of Okuzgozu red wine.

phenolic


Input: The effects of pectolytic enzyme addition and mash heating prior to fermentation on the phenolic component of Okuzgozu red wine during the winemaking and ageing processes were investigated.

phenolic


Input: In general, the highest concentration of total phenolics was found in the mash-heated wines, whereas the total flavan-3-ol and total anthocyanin contents in all of the wines, decreased notably during the winemaking and ageing processes.

phenolics

anthocyanin


Input: As determined by HPLC, hydroxycinnamic acids were the major phenolic acids in the red wines.

hydroxycinnamic acids

phenolic acids


Input: After 6 months in the bottle, the enzyme-treated wines had lower phenolic acid concentrations than had the control and mash-heated wines, but no significant (p < 0. 05) differences were found in the concentration of total phenolic acids between the control and mash-heated wines.

phenolic acid

phenolic acids


Input: All of the phenolic acid levels decreased with the winemaking and ageing processes whereas only gallic acid increased.

phenolic acid

gallic acid


Input: The wines treated by the pectolytic enzyme addition had a lower monomeric flavan-3-ol content than had the other wines, and the amount of monomeric anthocyanins extracted did not increase with the addition of enzymes.

anthocyanins


Input: Identification of xyloglucan endotransglucosylase/hydrolase genes (XTHs) and their expression in persimmon fruit as influenced by 1-methylcyclopropene and gibberellic acid during storage at ambient temperature.

gibberellic acid


Input: Xyloglucan endotransglucosylase/hydrolase (XTH) is thought to contribute to fruit softening by degrading xyloglucan that is a predominant hemicellulose in the cell wall.


Input: In this study, two full-length XTH genes (DKXTH1 and DKXTH2) were identified from' Fupingjianshi' persimmon fruit, and the expression level of both XTH genes was investigated during softening for 18-24 d using RT-qPCR.


Input: Sequence analysis showed that DKXTH1 and DKXTH2 contained a putative open reading frame of 861 and 876 bp encoding polypeptides of 287 and 292 amino acid residues, respectively, which contained the conserved DEIDFEFLG motif of XTH, a potential N-linked glycosylation signal site.

amino acid


Input: RT-qPCR analysis showed that DKXTH1 and DKXTH2 in untreated fruit had different expression patterns during fruit softening, in which maximum expression occurred on days 3 and 12 of ripening, respectively.


Input: 1-Methylcyclopropene (1-MCP) and gibberellic acid (GA (3)) treatments delayed the softening and ethylene peak of persimmon fruit, as well as suppressed the expression of both XTH genes, especially DKXTH1.

gibberellic acid

GA (3)

ethylene


Input: These results indicated that the expression of both XTH genes might be ethylene dependent action, and closely related to softening of persimmon in the early (DKXTH1) and later (DKXTH2) ripening stages.

ethylene


Input: Production of the alpha-glycosidase inhibitor 1-deoxynojirimycin from Bacillus species.


Input: 1-Deoxynojirimycin (DNJ), a potent alpha-glycosidase inhibitor, has therapeutic applications in treatments of HIV, Gaucher' s disease, and diabetes.

DNJ


Input: DNJ has been extracted from natural sources (mulberry leaves) for therapeutic purposes; however, DNJ ingredients are in limited supply and are costly to obtain on a large scale.

DNJ

DNJ


Input: Since certain strains of Bacillus and Streptomyces species reportedly produce DNJ, they may serve as potential sources for high-yield DNJ production.

DNJ

DNJ


Input: In this study, we obtained evidence for a DNJ production in Bacillus subtilis DSM704 by hydrophilic interaction chromatography-tandem mass spectrometry.

DNJ


Input: In addition, from a screen of 750 microorganisms, we identified additional Bacillus strains (Bacillus amyloliquefaciens AS385 and Bacillus subtilis B4) that produce DNJ in large quantities.

DNJ


Input: Investigation of the effect of various culture conditions, using Bacillus subtilis DSM704 and the DNJ high-production Bacillus strains, provided evidence for the importance of sorbitol supplementation on the yield of the DNJ precursor, 2-amino-2-deoxy-D-mannitol, thereby increasing DNJ production.

DNJ

sorbitol

DNJ

DNJ


Input: The role of sorbitol in increased DNJ production was supported by an observed increase in mRNA expression of the biosynthetic gene, gabT1.

sorbitol

DNJ


Input: When Bacillus amyloliquefaciens AS385 was cultured in medium supplemented with sorbitol, extracellular DNJ concentration reached a maximum of 460 mg/l of medium (equivalent to 9. 20mg/g of freeze-dried medium), indicating that this strain can serve as a source for food-and drug-grade products.

sorbitol

DNJ


Input: These findings not only lead to a further understanding of the DNJ biosynthetic pathway, but also suggest a method for microbial mass production of DNJ for therapeutic applications.

DNJ

DNJ


Input: Grape seed procyanidin extract modulates proliferation and apoptosis of pancreatic beta-cells.

procyanidin


Input: Grape seed procyanidin extract (GSPE) modulates glucose homeostasis and insulinemia in several animal models.

procyanidin

glucose


Input: Under pathological conditions, insulin levels are dependent on pancreatic beta-cell functionality, as well as on the beta-cell mass expansion or apoptosis in the pancreas.


Input: In this study, we analysed the effects of GSPE on modulating apoptosis and proliferation in beta-cells.


Input: We tested the effects of GSPE in the INS-1E pancreatic beta-cell line, either under basal or altered conditions with high glucose, insulin or palmitate levels.

glucose

palmitate


Input: GSPE enhanced the pro-apoptotic effect of high glucose and showed clear antiproliferative effects under high glucose, insulin and palmitate conditions.

glucose

glucose

palmitate


Input: These antiproliferative effects are likely due to high molecular weight compounds contained in the extract.


Input: GSPE also modulated pro-and anti-apoptotic markers in the pancreas of rats fed a cafeteria diet, with the effect depending on the dose of GSPE and duration of treatment.


Input: Thus, GSPE is able to modulate apoptosis and proliferation of beta-cells under altered, but not basal, conditions.


Input: Physicochemical properties of lard-based diacylglycerols in blends with lard.

diacylglycerols


Input: The objective of the study was to investigate how blending of triacylglycerols and diacylglycerols affected the melting and crystallisation properties in a solid fat system.

triacylglycerols

diacylglycerols


Input: Lard-based diacylglycerols (DAGs) were blended with lard in various concentrations (0%, 1%, 5%, 10%, 20%, 50%, 60%, 70%, 80%, 90%, and 100%).

diacylglycerols

DAGs


Input: The melting and crystallisation properties were investigated by the determination of dropping point (DP), solid fat content (SFC), differential scanning calorimetry (DSC) and X-ray diffraction (XRD).


Input: In general, the effects of DAGs were found to be dependent on concentration.

DAGs


Input: The DP was significantly (P < 0. 0001) decreased when DAGs were added to the lard from 5-50%, whereas the DP was increased (P < 0. 0001) when the blends contained more than 60% DAGs.

DAGs

DAGs


Input: The DSC thermograms showed that DAGs changed the melting and crystallisation profiles of lard.

DAGs


Input: The crystallisation onset point increased (P < 0. 05) with increasing the DAG concentrations (10-100%).

DAG


Input: The melting peaks and off-set points generally shifted slightly towards higher temperatures as the content of DAGs increased above 50%.

DAGs


Input: DAG content of 5% and 10% resulted in lowering of the off-set point.

DAG


Input: The lard contained both beta and beta' crystals.


Input: The beta form was more pronounced in the blends with high concentrations of DAGs.

DAGs


Input: Blending of TAGs and DAGs may serve as a solution to achieve specific functional properties in products containing solid fats.

TAGs

DAGs


Input: Reduction of acrylamide formation by vanadium salt in potato French fries and chips.

acrylamide

vanadium


Input: The effects of vanadyl sulphate on the formation of acrylamide have been studied in fried potato products, such as French fries and chips.

vanadyl sulphate

acrylamide


Input: Acrylamide formation was inhibited by 30. 3%, 53. 3% and 89. 3% when the sliced potato strips were soaked in 0. 001, 0. 01 and 0. 1 M vanadyl sulphate (VOSO (4)) solutions, respectively, for 60 min before frying.

Acrylamide

vanadyl sulphate

VOSO (4)


Input: Moreover, 57. 7%, 71. 4% and 92. 5% inhibition of acrylamide formation was observed when chips were soaked in the respective vanadyl sulphate solution before frying.

acrylamide

vanadyl sulphate


Input: In a separate model reaction, a solution containing an equimolar concentration of L-asparagine and D-glucose showed a significant inhibition of acrylamide formation when heated at 150 degrees C for 30 min in the presence of vanadyl sulphate (VOSO (4)).

L-asparagine

D-glucose

acrylamide

vanadyl sulphate

VOSO (4)


Input: The results indicate that the binding of VO (2 +) to asparagine and the decrease in the pH of the potato samples resulted in a significant reduction of acrylamide formation in fried potato products.

VO (2 +)

asparagine

acrylamide


Input: Determination of fluorine in milk samples via calcium-monofluoride by electrothermal molecular absorption spectrometry.

fluorine

calcium-monofluoride


Input: The determination of fluorine in milk samples via the molecular absorption of calcium mono-fluoride (CaF) was performed using a HR-CS-ETAAS.

fluorine

calcium mono-fluoride

CaF


Input: For this purpose, calcium was pipetted to graphite furnace together with samples.

calcium

graphite


Input: The amount of Ca and the graphite furnace program were optimised.

Ca

graphite


Input: Fluorine was determined in pyrolytically coated platforms at 606. 440 nm applying a pyrolysis temperature of 700 degrees C and a molecule forming temperature of 2250 degrees C.

Fluorine


Input: Finally, applying standard addition technique, F contents of several milk samples were determined.

Finally


Input: The results obtained by linear calibration and standard addition techniques were significantly different which can be attributed to non-spectral interferences in milk due to matrix concomitants.


Input: Therefore, in order to tolerate the errors, the F contents of several milk samples were determined applying standard addition technique.

F


Input: However, since the ingredients of milk samples change for different kinds, the F in each sample was determined from its own standard addition curve.

F


Input: The range of F content for the milk samples were 0. 027-0. 543 mu g mL (-1).

F


Input: The limit of detection and characteristic mass of the method were 0. 26 and 0. 13 ng of F, respectively.

F


Input: Characterising protein, salt and water interactions with combined vibrational spectroscopic techniques.


Input: In this paper a combination of NIR spectroscopy and FTIR and Raman microspectroscopy was used to elucidate the effects of different salts (NaCl, KCl and MgSO (4)) on structural proteins and their hydration in muscle tissue.

NaCl

KCl

MgSO (4)


Input: Multivariate multi-block technique Consensus Principal Component Analysis enabled integration of different vibrational spectroscopic techniques: macroscopic information obtained by NIR spectroscopy is directly related to microscopic information obtained by FTIR and Raman microspectroscopy.


Input: Changes in protein secondary structure observed at different concentrations of salts were linked to changes in protein hydration affinity.


Input: The evidence for this was given by connecting the underlying FTIR bands of the amide I region (1700-1600 cm (-1)) and the water region (3500-3000 cm (-1)) with water vibrations obtained by NIR spectroscopy.

amide


Input: In addition, Raman microspectroscopy demonstrated that different cations affected structures of aromatic amino acid residues differently, which indicates that cation-pi interactions play an important role in determination of the final structure of protein molecules.

aromatic amino acid


Input: Influence of nitrogen supply on the production of higher alcohols/esters and expression of flavour-related genes in cacha c a fermentation.

nitrogen

alcohols

esters


Input: This study provides the first attempt to analyse the influence of ammonium supplements on sugar-cane juice fermentation and the flavour profile in a cacha c a industrial process.

ammonium

sugar


Input: The objective was to find a relationship between higher alcohol/ester content and the transcription levels of the main genes involved in production of these compounds under cacha c a fermentation.

alcohol

ester


Input: Sugar-cane juice with a low amount of assimilable nitrogen (81 mg N/L), was further supplemented with mid-range or high concentrations of ammonium sulfate.

Sugar

nitrogen

ammonium sulfate


Input: Overall, higher alcohol production was reduced by ammonium supplementation, and this can be correlated with a general downregulation of genes encoding decarboxylases and dehydrogenases of the Ehrlich pathway.

alcohol

ammonium


Input: The production of acetate esters was enhanced by mid-range ammonium supplementation and the production of acyl esters by high ammonium supplementation.

acetate esters

ammonium

acyl esters

ammonium


Input: The acyl esters could be correlated with expression of alcohol acyl-transferase EEB1 and the acyl esterase IAH1.

acyl esters

alcohol acyl

acyl


Input: Near native binding of a fluorescent serotonin conjugate to serotonin type 3 receptors.

serotonin

serotonin


Input: Described is the synthesis of 5-hydroxytryptamine-tetramethylrhodamine (5HT *); an indole nitrogen linked fluorescent conjugate of serotonin.

5-hydroxytryptamine-tetramethylrhodamine

indole nitrogen

serotonin


Input: Through a series fluorescence quenching experiments and experiments in the presence of a known competitive antagonist (Granisetron), it was shown that 5HT * specifically binds to purified homo-pentameric type-3 human serotonin receptors (5HT (3A)).

Granisetron

serotonin


Input: The measured dissociation constant and Hill coefficient are K (d) = 83 +/- 3 nM and n = 3. 1 +/- 0. 3, respectively which is indicative of multi-ligand binding and cooperativity similar to that of unconjugated serotonin.


Input: Design and synthesis of tricyclic cores for kinase inhibition.


Input: Interest in therapeutic kinase inhibitors continues to grow beyond success in oncology.


Input: To date, ATP-mimetic kinase inhibitors have focused primarily on monocyclic and bicyclic heterocyclic cores.

ATP


Input: We sought to expand on the repertoire of potential cores for kinase inhibition by exploring tricyclic variants of classical bicyclic hinge binding motifs such as pyrrolopyridine and pyrrolopyrazine.

pyrrolopyridine

pyrrolopyrazine


Input: Herein we describe the syntheses of eight alternative tricyclic cores as well as in vitro screening results for representative kinases of potential therapeutic interest.


Input: 3'-Modified oligodeoxyribonucleotides for the study of 2-deoxyribose damage in DNA.


Input: Well-defined substrates for the study of oxidative processes are important for the elucidation of the role of DNA damage in the etiology of diseases such as cancer.


Input: We have synthesized 3'-modified oligodeoxyribonucleotides (ODNs) using 5' --> 3'' reverse' DNA synthesis for the study of 2-deoxyribose oxidative damage to DNA.


Input: The modified monomers designed for these studies all share a common feature, they lack the naturally occurring 3'-hydroxyl group found in 2-deoxyribonucleosides.


Input: Modified H-phosphonates containing 3'-phenyl selenides as well as saturated and unsaturated sugars were obtained and incorporated in ODNs.

H-phosphonates

3'-phenyl selenides

saturated and unsaturated sugars

ODNs


Input: These ODNs were used to investigate the fate of C3'-dideoxyribonucleotide radicals in DNA.

ODNs


Input: Discovery of nosokophic acid, a predicted intermediate of moenomycins, from nosokomycin-producing Streptomyces sp.

nosokophic acid

moenomycins

nosokomycin


Input: A new actinomycete metabolite designated nosokophic acid was isolated from the culture broth of nosokomycin-producing Streptomyces sp.

nosokophic acid

nosokomycin


Input: K04-0144, and the structure was elucidated by various NMR experiments.


Input: Nosokophic acid was found to be 3-phosphoglycosyl-2-sesquiterpenyl dihydroxypropionic acid, a predicted biosynthetic intermediate of nosokomycin-related moenomycins.

Nosokophic acid

3-phosphoglycosyl-2-sesquiterpenyl dihydroxypropionic acid

nosokomycin

moenomycins


Input: The compound showed no activity against MRSA, but potentiated imipenem activity against MRSA by 512-fold.


Input: Synthesis of new N-(arylcyclopropyl) acetamides and N-(arylvinyl) acetamides as conformationally-restricted ligands for melatonin receptors.

N-(arylcyclopropyl) acetamides

N-(arylvinyl) acetamides

melatonin


Input: N-(Arylcyclopropyl) acetamides and N-(arylvinyl) acetamides or methyl ureas have been prepared as constrained analogues of melatonin.

N-(Arylcyclopropyl) acetamides

N-(arylvinyl) acetamides

methyl ureas

melatonin


Input: The affinity of these new compounds for chicken brain melatonin receptors and recombinant human MT (1) and MT (2) receptors was evaluated using 2-[(125) I]-iodomelatonin as radioligand.

melatonin

2-[(125) I]-iodomelatonin


Input: Strict ethylenic or cyclopropyl analogues of the commercialized agonist agomelatine (Valdoxan (R)) were equipotent to agomelatine in binding bioassays.

ethylenic

cyclopropyl

agomelatine

Valdoxan

agomelatine


Input: However, the ethylenic analogue was more effective than the cyclopropyl one in the melanophore aggregation bioassay, but was still less potent than the disubstituted 2, 7-dimethoxy-naphtalenic compounds.

ethylenic

cyclopropyl

2, 7-dimethoxy-naphtalenic


Input: Non-benzimidazole containing inhibitors of respiratory syncytial virus.

benzimidazole


Input: Several non-benzimidazole containing inhibitors of respiratory syncytial virus are described.

benzimidazole


Input: Core template modification, analysis of antiviral activity, physicochemistry and optimisation of properties led to the thiazole-imidazole 13, that showed a good potency and pharmacokinetic profile in the rat.

thiazole

imidazole


Input: Design and synthesis of novel 2-methyl-4, 5-substitutedbenzo [f]-3, 3a, 4, 5-tetrahydro-pyrazolo [1, 5-d] [1, 4] oxazepin-8 (7H)-one derivatives as telomerase inhibitors.

2-methyl-4, 5-substitutedbenzo [f]-3, 3a, 4, 5-tetrahydro-pyrazolo [1, 5-d] [1, 4] oxazepin-8 (7H)-one


Input: Eight novel 4, 5-tetrahydropyrazolo [1, 5-d] [1, 4] oxazepine derivatives have been synthesized and purified to be screened for anticancer activity.

4, 5-tetrahydropyrazolo [1, 5-d] [1, 4] oxazepine


Input: By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 4a showed the most potent inhibitory activity with IC (50) value at 0. 78 +/- 0. 22 mu M.


Input: Western blot assays showed that compounds 4a and 4b could inhibit expression of Cyclin D1, TERT, phospho-AKT and PI3K/AKT pathway.


Input: Triazole-based inhibitors of geranylgeranyltransferase II.

Triazole


Input: A small set of triazole bisphosphonates has been prepared and tested for the ability to inhibit geranylgeranyltransferase II (GGTase II).

triazole bisphosphonates


Input: The compounds were prepared through use of click chemistry to assemble a central triazole that links a polar head group to a hydrophobic tail.

triazole


Input: The resulting compounds were tested for their ability to inhibit GGTase II in an in vitro enzyme assay and also were tested for cytotoxic activity in an MTT assay with the human myeloma RPMI-8226 cell line.

MTT


Input: The most potent enzyme inhibitor was the triazole with a geranylgeranyl tail, which suggests that inhibitors that can access the enzyme region that holds the isoprenoid tail will display greater activity.

triazole

geranylgeranyl

isoprenoid


Input: Protective effect of ganodermanondiol isolated from the Lingzhi mushroom against tert-butyl hydroperoxide-induced hepatotoxicity through Nrf2-mediated antioxidant enzymes.

ganodermanondiol

tert-butyl hydroperoxide


Input: Ganodermanondiol, a biologically active compound, was isolated from the Lingzhi mushroom (Ganoderma lucidum).

Ganodermanondiol


Input: The present study examined the protective effects of ganodermanondiol against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity.

ganodermanondiol

tert-butyl hydroperoxide

t-BHP


Input: Ganodermanondiol protected human liver-derived HepG2 cells through nuclear factor-E2-related factor 2 (Nrf2) pathway-dependent heme oxygenase-1 expressions.

Ganodermanondiol

heme


Input: Moreover, ganodermanondiol increased cellular glutathione levels and the expression of the glutamine-cysteine ligase gene in a dose-dependent manner.

ganodermanondiol

glutathione

glutamine

cysteine


Input: Furthermore, ganodermanondiol exposure enhanced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its upstream kinase activators, LKB1 and Ca (2 +)/calmodulin-dependent protein kinase-II (CaMKII).

ganodermanondiol

adenosine monophosphate

Ca (2 +)


Input: This study indicates that ganodermanondiol exhibits potent cytoprotective effects on t-BHP-induced hepatotoxicity in human liver-derived HepG2 cells, presumably through Nrf2-mediated antioxidant enzymes and AMPK.

ganodermanondiol

t-BHP


Input: Anti-inflammatory effects of trans-1, 3-diphenyl-2, 3-epoxypropane-1-one mediated by suppression of inflammatory mediators in LPS-stimulated RAW 264. 7 macrophages.

trans-1, 3-diphenyl-2, 3-epoxypropane-1-one


Input: To assess the potential therapeutic properties of trans-1, 3-diphenyl-2, 3-epoxypropane-1-one (DPEP), its anti-inflammatory effects were investigated in lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW 264. 7) cells.

trans-1, 3-diphenyl-2, 3-epoxypropane-1-one

DPEP


Input: DPEP induced dose-dependent reduction of the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitant reduction in the production of NO and prostaglandin E (2) (PGE (2)).

DPEP

nitric oxide

prostaglandin E (2)

PGE (2)


Input: Additionally, DPEP suppressed the production of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6.

DPEP


Input: We investigated the mechanism by which DPEP inhibits NO and PGE (2) by examining the level of nuclear factor-kappa B (NF-kappa B) activation within the mitogen-activated protein kinase (MAPK) pathway, which is an inflammation-induced signaling pathway in RAW 264. 7 cells.

DPEP

NO

PGE (2)


Input: DPEP inhibited LPS-induced phosphorylation of ERK, JNK, and p38.

DPEP


Input: Furthermore, DPEP inhibited the LPS-induced phosphorylation of inhibitor kappa B (I kappa B)-alpha and NF-kappa B p50.

DPEP


Input: Taken together, the results of this study demonstrate that DPEP inhibits LPS-stimulated inflammation by blocking the NF-kappa B and MAPK pathways in macrophages.

DPEP


Input: Radioprotection by two phenolic compounds: chlorogenic and quinic acid, on X-ray induced DNA damage in human blood lymphocytes in vitro.

phenolic

chlorogenic and quinic acid


Input: The present study was designed to determine the radioprotective effect of two phytochemicals, namely, quinic acid and chlorogenic acid, against X-ray irradiation-induced genomic instability in non-tumorigenic human blood lymphocytes.

quinic acid

chlorogenic acid


Input: The protective ability of two phenolic acids against radiation-induced DNA damage was assessed using the alkaline comet assay in human blood lymphocytes isolated from two healthy human donors.

phenolic acids


Input: A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for irradiation.


Input: The results of the alkaline comet assay revealed that quinic acid and chlorogenic acid decreased the DNA damage induced by X-ray irradiation and provided a significant radioprotective effect.

quinic acid

chlorogenic acid


Input: Quinic acid decreased the presence of irradiation-induced DNA damage by 5. 99-53. 57% and chlorogenic acid by 4. 49-48. 15%, as determined by the alkaline comet assay.

Quinic acid

chlorogenic acid


Input: The results show that quinic acid and chlorogenic acid may act as radioprotective compounds.

quinic acid

chlorogenic acid


Input: Future studies should focus on determining the mechanism by which these phenolic acids provide radioprotection.

phenolic acids


Input: Additive inhibition of human alpha 1 beta 2 gamma 2 GABAA receptors by mixtures of commonly used drugs of abuse.


Input: Yearly, exposure to drugs of abuse results in ~ 1 million emergency department visits in the US.


Input: In ~ 50% of the visits, stimulant drugs like cocaine and amphetamine-like substances (e. g. 3, 4-methylenedioxymethamphetamine (MDMA, the main active ingredient of ecstasy)) are involved, whereas in ~ 60% multiple drugs are involved.

cocaine

amphetamine

3, 4-methylenedioxymethamphetamine

MDMA

ecstasy


Input: These drugs induce higher dopamine and serotonin levels resulting in drug-induced toxicity.

dopamine

serotonin


Input: Since GABA receptors (GABA-R) provide the main inhibitory input on dopaminergic and serotonergic neurons, drug-induced inhibition of GABA-R could contribute to higher neurotransmitter levels and thus toxicity.

GABA

GABA

GABA


Input: We therefore investigated the effects of combinations of commonly abused stimulant drugs (cocaine, MDMA, 3, 4-methylenedioxyamphetamine (MDA) and meta-chlorophenylpiperazine (mCPP)) on the function of the human alpha 1 beta 2 gamma 2 GABAA receptor (hGABAA-R), expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique.

cocaine

MDMA

3, 4-methylenedioxyamphetamine

MDA

meta-chlorophenylpiperazine

mCPP


Input: These drugs concentration-dependently inhibited the GABA-evoked current (mCPP > cocaine > MDMA > MDA).

GABA

mCPP

cocaine

MDMA

MDA


Input: Most drug combinations decreased the GABA-evoked current stronger than the single drug.

GABA


Input: Additivity was observed during combined exposure to low concentrations of cocaine and mCPP as well as during combined exposure to MDA with cocaine or mCPP.

cocaine

mCPP

MDA

cocaine

mCPP


Input: However, combinations containing MDMA mainly resulted in sub-additivity or no additivity.

MDMA


Input: At drug concentrations relevant for clinical toxicology, co-exposure to >= 2 drugs can decrease the GABA-evoked current in an additive manner.

GABA


Input: Thus, in patients exposed to multiple drugs, inhibitory GABA-ergic input is reduced more prominently, likely resulting in higher brain dopamine levels.

GABA

dopamine


Input: As this will increase the risk for drug-induced toxicity, treatment of drug-intoxicated patients with drugs that enhance GABA-ergic input should be further optimized.

GABA


Input: A self-assembled nanocarrier loading teniposide improves the oral delivery and drug concentration in tumor.

teniposide


Input: We attempted to improve the oral delivery of lipophilic teniposide to achieve higher drug concentration in tumor by self-assembled nanocarrier for further oral chemotherapy.

teniposide


Input: The teniposide loaded self-assembled nanocarrier (TSN) was spherical nanometric particles with narrow size distribution.

teniposide


Input: The intestinal absorption of teniposide from TSN was obviously improved 4. 09-and 6. 35-fold in duodenum and jejunum at 0. 5h after oral administration, then significantly decreased with the prolongation of time.

teniposide


Input: The cellular uptake of TSN in Caco-2 cell monolayer was significantly enhanced over 3 folds and increased with incubation time.


Input: Moreover, TSN could be internalized into Caco-2 cell monolayer through clathrin-mediated endocytosis pathway, and then mainly transported into the systemic circulation via portal vein and intestinal lymphatic pathway.


Input: The pharmacokinetic results indicated that the AUC (0-t) value of TSN in rats was significantly improved 5. 41-fold than that of teniposide solution, moreover, the teniposide concentration in tumor from TSN was obviously improved over 7-fold in tumor bearing mice.

teniposide

teniposide


Input: The captured image indicated that the oral administered TSN could specifically accumulate in tumor in the xenograft model.


Input: Therefore, the self-assembled nanocarrier was promising to enhance the oral delivery of lipophilic teniposide and its concentration in tumor for oral chemotherapy.

teniposide


Input: Combined delivery of BMP-2 and bFGF from nanostructured colloidal gelatin gels and its effect on bone regeneration in vivo.


Input: During the process of bone regeneration, a multitude of morphogenetic signaling factors regulate cellular behavior and ultimately tissue response.


Input: These factors are presented to cells under strong spatial and temporal control, which stresses the relevance of controlled delivery of multiple growth factors for bone tissue regeneration.


Input: This demand for biomimetic delivery has prompted the development of a novel generation of biomaterials that is capable of delivering multiple growth factors in a controlled manner.


Input: Therefore, the current study has exploited the strong capacity of colloidal gels solely made of oppositely charged gelatin nanospheres to obtain controlled release of angiogenic and osteogenic growth factors.


Input: The release kinetics of dual delivery of osteogenic bone morphogenetic protein-2 (BMP-2) and angiogenic basic fibroblast growth factor (bFGF) were investigated in vitro by radiolabeling the respective growth factors and monitoring their release in vitro.


Input: Furthermore, the effect of single or dual delivery of BMP-2 and bFGF on bone regeneration was evaluated in vivo using a rat femoral condyle defect model.


Input: The in vitro results confirmed that the delivery kinetics of BMP-2 and/or bFGF are more dependent on the degree of crosslinking than on the type of gelatin.


Input: Sequential release characterized by rapid release of angiogenic bFGF and more sustained release of BMP-2 was obtained by loading bFGF onto cationic nanospheres of low crosslinking density and BMP-2 onto anionic nanospheres of high crosslinking density.


Input: The in vivo study demonstrated the biocompatibility and biodegradability of bare colloidal gelatin gels, and did not show any adverse effects on the process of bone healing after 4 week of implantation since the volumes of new bone formation were comparable to empty control defects.


Input: An obvious stimulatory effect on bone regeneration was observed for the colloidal gels loaded with BMP-2, whereas bFGF-loaded colloidal gelatin gels did not influence the rate of bone regeneration.


Input: In contrast, the combined delivery of BMP-2 and bFGF resulted into an inhibitory effect on osteogenesis under the current experimental conditions.


Input: Summarizing, the current study proved that nanostructured colloidal gelatin gels are suitable carriers for programmed and sustained release of multiple therapeutic proteins for tissue regeneration.


Input: Influence of drying and cooking process on the phytochemical content, antioxidant and hypoglycaemic properties of two bell Capsicum annum L. cultivars.


Input: The present study evaluates the influence of drying and cooking processes on the health properties of two bell Capsicum annuum L. cultivars Roggiano and Senise compared with fresh peppers.


Input: The content of phytochemicals decreased in the order fresh > dried > dried frying processes.


Input: HPLC analysis was applied to quantify five flavonoids from peppers.

flavonoids


Input: Apigenin was identified as main constituent.

Apigenin


Input: Its content was affected by drying and dried frying processes.


Input: The antioxidant activity was evaluated by DPPH, ABTS, beta-carotene bleaching test and Fe-chelating activity assay.

DPPH

ABTS

beta-carotene

Fe


Input: A comparable radical scavenging activity was observed for both cultivars.


Input: Interestingly, frying process did not influenced this property.


Input: Roggiano peppers exhibited the highest antioxidant activity using beta-carotene bleaching test with IC (50) values of 38. 1 and 24. 9 mu g/mL for total extract and n-hexane fraction, respectively.

beta-carotene

n-hexane


Input: GC-MS analysis of lipophilic fraction revealed the presence of fatty acids and vitamin E as major components.

fatty acids

vitamin E


Input: In the inhibition of the carbohydrate-hydrolyzing enzymes fresh Senise peppers exerted the strongest activity against alpha-amylase with an IC (50) value of 55. 3 mu g/mL.

carbohydrate


Input: Our results indicate that C. annuum cultivars Roggiano and Senise have an interestingly potential health benefits not influenced by processes that are used before consumption.


Input: Activation of an apoptotic signal transduction pathway involved in the upregulation of calpain and apoptosis-inducing factor in aldosterone-induced primary cultured cardiomyocytes.

aldosterone


Input: In this study, aldosterone (ALD)-induced apoptosis of cardiomyocyte was evaluated based on the previous studies, and the roles of calpain signaling were clarified.

aldosterone

ALD


Input: Primary cultured rat cardiomyocytes were injured by ALD (0. 01-10 mu M) for varying time periods.

ALD


Input: Then, the effects of ethylene glycol tetraacetic acid (EGTA) (0. 5 mM), calpeptin (2. 5 mu M), and spironoclactone (10 mu M) were evaluated on cardiomyocytes activated by ALD.

ethylene glycol tetraacetic acid

EGTA

calpeptin

spironoclactone

ALD


Input: Cardiomyocytes that were injured by ALD were assayed by the MTT and LDH leakage ratio.

ALD

MTT


Input: Apoptosis was evaluated by a TUNEL assay, annexin V/PI staining, and caspase-3 activity.


Input: The expression of cleavage of Bid (tBid), calpain and apoptosis-inducing factor (AIF) was evaluated by western blot analysis.


Input: ALD increased calpain expression and caspase-3 activity and promoted Bid cleavage.

ALD


Input: It also induced the release of AIF from mitochondria into the cytosol.


Input: The upregulation of calpain, tBid and caspase-3 activity were further inhibited by treatment with EGTA in the presence of ALD.

EGTA

ALD


Input: Additionally, AIF levels in the cytosol decreased due to EGTA but not due to calpeptin.

EGTA

calpeptin


Input: This was also accompanied by a significant decrease in apoptosis.


Input: Furthermore, treatment with spironoclactone not only attenuated the pro-apoptotic effect of ALD but reversed the ALD-induced increase of calpain and AIF levels.

spironoclactone

ALD

ALD


Input: DHA supplementation: current implications in pregnancy and childhood.

DHA


Input: Dietary supplementation with omega-3 long chain fatty acids including docosahexaenoic acid (DHA) has increased in popularity in recent years and adequate DHA supplementation during pregnancy and early childhood is of clinical importance.

omega-3 long chain fatty acids

docosahexaenoic acid

DHA

DHA


Input: Some evidence has been built for the neuro-cognitive benefits of supplementation with long chain polyunsaturated fatty acids (LCPUFA) such as DHA during pregnancy; however, recent data indicate that the anti-inflammatory properties may be of at least equal significance.

long chain polyunsaturated fatty acids

LCPUFA

DHA


Input: Adequate DHA availability in the fetus/infant optimizes brain and retinal maturation in part by influencing neurotransmitter pathways.

DHA


Input: The anti-inflammatory properties of LCPUFA are largely mediated through modulation of signaling either directly through binding to receptors or through changes in lipid raft formation and receptor presentation.

LCPUFA


Input: Our goal is to review the current findings on DHA supplementation, specifically in pregnancy and infant neurodevelopment, as a pharmacologic agent with both preventative and therapeutic value.

DHA


Input: Given the overall benefits of DHA, maternal and infant supplementation may improve neurological outcomes especially in vulernable populations.

DHA


Input: However, optimal composition of the supplement and dosing and treatment strategies still need to be determined to lend support for routine supplementation.


Input: Expression profiles of hippocampal regenerative sprouting-related genes and their regulation by E-64d in a developmental rat model of penicillin-induced recurrent epilepticus.

penicillin


Input: E-64d (a calpain and autophagy inhibitor) has previously been shown safe for the treatment of Alzheimer' s disease in humans.


Input: In the present study, the potential protective mechanism of E-64d on hippocampal aberrant mossy fiber sprouting was examined in a developmental rat model of penicillin-induced recurrent epilepticus.

penicillin


Input: A seizure was induced by penicillin every other day in Sprague-Dawley rats from postnatal day 21 (P21).

penicillin


Input: The rats were randomly assigned into the control group (CONT1), the control plus E-64d (CONT2), the seizure group (EXP1) and the seizure plus E-64d (EXP2).


Input: On P51, mossy fiber sprouting and related gene expression in hippocampus were assessed by Timm staining and real-time RT-PCR methods, respectively.


Input: To validate the RT-PCR results, western blot analysis was performed on selected genes.


Input: E-64d obviously suppressed the aberrant mossy fiber sprouting in the supragranular region of dentate gyrus and CA3 subfield of hippocampus.


Input: Among the total twelve genes, six genes were strongly up-(MT-3, ACAT1, clusterin and ApoE) or down-(ZnT-1 and PRG-3) regulated by developmental seizures (EXP1) compared with that in the CONT1.


Input: Up-regulation of ApoE and Clusterin was blocked by pretreatment with E-64d both in mRNA and protein levels.


Input: Further, E-64d-pretreated seizure rats (EXP2) showed a significant downregulation of mRNA expression of PRG-1, PRG-3 and PRG-5, cathepsin B and ApoE, as well as up-regulated nSMase and ANX7 in hippocampus when compared with EXP1 rats.


Input: The results of the present study suggest that E-64d, an elective inhibitor of calpain and autophagy, is potentially useful in the treatment of developmental seizure-induced brain damage both by regulating abnormal zinc signal transduction and through the modulation of altered lipid metabolism via ApoE/clusterin pathway in hippocampus.

zinc


Input: Studies on a rhein-producing endophytic fungus isolated from Rheum palmatum L.

rhein


Input: Rheum palmatum L.


Input: (Chinese rhubarb) is a highly regarded medicinal plant.


Input: Its dominant active constituents are anthraquinones including emodin, aloe-emodin, rhein, etc.

anthraquinones

emodin

aloe-emodin

rhein


Input: Rhein naturally occurs in anthraquinone (1, 3, 8-trihydroxy-6-methyl anthraquinone), which is found in R. palmatum L. and related plants such as rhubarb.

Rhein

anthraquinone

1, 3, 8-trihydroxy-6-methyl anthraquinone


Input: It has good antitumor, anti-inflammatory, anticancer, antimicrobial and hemostatic properties.


Input: In this study, a total of 14 strains of endophytic fungi were isolated from R. palmatum L.


Input: All fungal isolates were fermented in liquid PDA medium and their extracts were preliminarily analyzed by antibacterial reactions, magnesium acetate-methanol reagent and Borntraiger' s reaction, and the strain reselection was made by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and LC-MS to identify the fermentation products of the selected strains and confirmed through a comparison with authentic standards.

magnesium acetate

methanol


Input: Extract from one strain, R13, showed positive reactions with both reagents.


Input: The strain R13 had a component with the same TLC (Rf) value and HPLC, LC-MS retention time as authentic rhein standards.

rhein


Input: The yield of rhein in R13 can reach 5. 672mgl (-1).

rhein


Input: The fungi were identified as Fusarium solani by using both ITS rDNA sequencing and spore morphology.


Input: Phytochemical analysis of the triterpenoids with cytotoxicity and QR inducing properties from the total tea seed saponin of Camellia sinensis.

triterpenoids

saponin


Input: The tea seed triterpene saponin (TS) from Camellia sinensis was found to exhibit better antitumor activity in vivo in S180 implanted ICR mice and QR inducing activity for hepa lclc7 cells respectively compared with the total tea seed saponin (TTS), hydrolysate of the TTS and tea seed flavonoid glycosides (TF).

triterpene saponin

saponin

flavonoid glycosides


Input: By bioassay-guided isolation, the TS fraction was separated and seven major components were purified and identified as theasaponin E1 (1), theasaponin E2 (2), theasaponin C1 (3), assamsaponin C (4), theasaponin H1 (5), theasaponin A9 (6), and theasaponin A8 (7), among which compounds 4 and 5 were isolated from this genus for the first time.

theasaponin E1

theasaponin E2

theasaponin C1

assamsaponin C

theasaponin H1

theasaponin A9

theasaponin A8


Input: The antitumor bioassay of the isolated compounds showed that compounds 1, 2 and 3 exhibited potential activities against the human tumor cell lines K562 and HL60.


Input: Furthermore, compound 1 (the major constituent with a mass content of over 1%) showed significant QR inducing activity with an IR value of 4. 2 at 4 mu g/ml.


Input: So it can be concluded that tea seed especially the compound 1 (theasaponin E1) could be used as an antitumor agent and a chemoprevention agent of cancer.

theasaponin E1


Input: The preliminary structure-activity relationship in the anti-tumor activity and QR inducing activity of tea saponins was discussed briefly.

saponins


Input: On the structure of aspongopusin recently isolated from Aspongopus chinensis.

aspongopusin


Input: The 2, 5-disubstituted oxazole recently proposed for aspongopusin, a natural product isolated from Aspongopus chinensis, was synthesized through an unambiguous route.

2, 5-disubstituted oxazole

aspongopusin


Input: The synthetic sample showed (1) H and (13) C NMR entirely different from those in the literature, revealing that the initially assigned structure was incorrect.

(1) H

(13) C


Input: The spectroscopic data for the given structure are thus made available for the first time.


Input: DNA polymerase minor groove interactions modulate mutagenic bypass of a templating 8-oxoguanine lesion.


Input: A major base lesion resulting from oxidative stress is 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxoG) that has ambiguous coding potential.

8-oxo-7, 8-dihydro-2'-deoxyguanosine


Input: Error-free DNA synthesis involves 8-oxoG adopting an anti-conformation to base pair with cytosine whereas mutagenic bypass involves 8-oxoG adopting a syn-conformation to base pair with adenine.

cytosine

adenine


Input: Left unrepaired the syn-8-oxoG/dAMP base pair results in a G-C to T-A transversion.

dAMP


Input: During base excision repair of this mispair, DNA polymerase (pol) beta is confronted with gap filling opposite 8-oxoG.


Input: To determine how pol beta discriminates between anti-and syn-8-oxoG, we introduced a point mutation (R283K) to alter insertion specificity.

anti-and syn-8-oxoG


Input: Kinetic studies demonstrate that this substitution results in an increased fidelity opposite 8-oxoG.


Input: Structural studies with R283K pol beta show that the binary DNA complex has 8-oxoG in equilibrium between anti-and syn-forms.


Input: Ternary complexes with incoming dCTP resemble the wild-type enzyme, with templating anti-8-oxoG base pairing with incoming cytosine.

dCTP

cytosine


Input: In contrast to wild-type pol beta, the ternary complex of the R283K mutant with an incoming dATP-analogue and templating 8-oxoG resembles a G-A mismatched structure with 8-oxoG adopting an anti-conformation.

dATP


Input: These results demonstrate that the incoming nucleotide is unable to induce a syn-8-oxoG conformation without minor groove DNA polymerase interactions that influence templating (anti-/syn-equilibrium) of 8-oxoG while modulating fidelity.

nucleotide


Input: Effect of long-term co-administration of Wuzhi tablet (Schisandra sphenanthera extract) and prednisone on the pharmacokinetics of tacrolimus.

prednisone

tacrolimus


Input: Tacrolimus (TAC) is an immunosuppressant that has been widely used alone or in combination with prednisone (PRED) to prevent acute rejection after organ transplantation.

Tacrolimus

TAC

prednisone

PRED


Input: Wuzhi tablet (WZ, Schisandra sphenanthera extract) is often prescribed with TAC to prevent drug-induced hepatitis.

TAC


Input: We recently reported that WZ could significantly increase TAC blood exposure by inhibiting P-gp-mediated efflux and CYP3A-mediated metabolism of TAC.

TAC

TAC


Input: PRED is also a substrate of P-gp and is a weak inducer of CYP3A, and drug-drug interactions within this combination therapy might occur.

PRED


Input: Therefore, the purpose of this study was to investigate the effect of long-term treatment of WZ and PRED on the pharmacokinetics of TAC in rats.

PRED

TAC


Input: After 14 days of co-administration of WZ and PRED, the AUC (0-24h) of oral TAC was increased (from 59. 6 +/- 37. 3 to 95. 3 +/- 39. 4 ng h/ml, p = 0. 18) and the clearance was decreased (from 38. 4 +/- 28. 4 to 17. 7 +/- 6. 4 l/h/kg, p = 0. 15).

PRED

TAC


Input: When only co-administered with WZ, AUC (0-24h) of TAC was demonstrated a significantly increase (from 59. 6 +/- 37. 3 to 135. 9 +/- 34. 8 ng h/ml, p < 0. 05).

TAC


Input: The concomitant administration of PRED resulted in a reduction in the systemic exposure of TAC and an increase in its clearance, though neither was statistically significant.

PRED

TAC


Input: Thus, our study suggested that the presence of WZ and PRED still could increase the systemic exposure of TAC in rats.

PRED

TAC


Input: The drug-drug interactions among this combination therapy should still be taken into consideration in clinical practice.


Input: Naturally occurring HCA1 missense mutations result in loss of function: potential impact on lipid deposition.


Input: The hydroxy-carboxylic acid receptor (HCA1) is a G protein-coupled receptor that is highly expressed on adipocytes and considered a potential target for the treatment of dyslipidemia.

hydroxy-carboxylic acid


Input: In the current study, we investigated the pharmacological properties of naturally occurring variants in this receptor (H43Q, A110V, S172L, and D253H).


Input: After transient expression of these receptors into human embryonic kidney 293 cells, basal and ligand-induced signaling were assessed using luciferase reporter gene assays.


Input: The A110V, S172L, and D253 variants showed reduced basal activity; the S172L mutant displayed a decrease in potency to the endogenous ligand L-lactate.

L-lactate


Input: Both the S172L and D253H variants also showed impaired cell surface expression, which may in part explain the reduced activity of these receptors.


Input: The impact of a loss in HCA1 function on lipid accumulation was investigated in the adipocyte cell line, OP9.


Input: In these cells, endogenous HCA1 transcript levels rapidly increased and reached maximal levels 3 days after the addition of differentiation media.


Input: Knockdown of HCA1 using siRNA resulted in an increase in lipid accumulation as assessed by quantification of Nile Red staining and TLC analysis.

Nile Red


Input: Our data suggest that lipid homeostasis may be altered in carriers of selected HCA1 missense variants.


Input: Anti-inflammatory sesquiterpene derivatives from the leaves of Tripterygium wilfordii.

sesquiterpene


Input: Twelve new dihydroagarofuran sesquiterpene polyol esters, triptersinines A-L (1-12), and eight known sesquiterpene pyridine alkaloids were isolated from the leaves of Tripterygium wilfordii.

dihydroagarofuran sesquiterpene polyol esters

triptersinines A-L

sesquiterpene pyridine alkaloids


Input: Their structures were elucidated on the basis of spectroscopic analyses, including UV, IR, and NMR experiments ((1) H-(1) H COSY, NOESY, HSQC, and HMBC).

(1) H

(1) H


Input: Furthermore, in an in vitro bioassay, compounds 1, 9, 11, 13, 14, and 18 showed moderate inhibitory effects on nitric oxide production in LPS-induced macrophages at 5 mu M; all compounds were inactive when tested against five human cancer cell lines (IC (50) values > 1 mu M).

nitric oxide


Input: Bioassay-guided isolation of proanthocyanidins with antiangiogenic activities.

proanthocyanidins


Input: The proangiogenic members of the vascular endothelial growth factor (VEGF) family and related receptors play a central role in the modulation of pathological angiogenesis.


Input: In order to identify plant compounds able to interfere in the VEGFs/VEGFR-1 (Flt-1) recognition by VEGF family members, the extracts of the aerial parts of Campsiandra guayanensis and Feretia apodanthera were screened by a competitive ELISA-based assay.


Input: By using this bioassay-oriented approach five proanthocyanindins, including the new natural compounds (2S)-4', 5, 7-trihydroxyflavan-(4 beta --> 8)-afzelechin (1) and (2S)-4', 5, 7-trihydroxyflavan-(4 beta --> 8)-epiafzelechin (2) and the known geranin B (3), proanthocyanidin A2 (4), and proanthocyanidin A1 (5), were isolated.

proanthocyanindins

(2S)-4', 5, 7-trihydroxyflavan-(4 beta --> 8)-afzelechin

(2S)-4', 5, 7-trihydroxyflavan-(4 beta --> 8)-epiafzelechin

geranin B

proanthocyanidin A2

proanthocyanidin A1


Input: The study of the antiangiogenic activities of compounds 1-5 using ELISA and SPR assays showed compound 1 as being the most active.


Input: The antiangiogenic activity of 1 was also confirmed in vivo by the chicken chorioallantoic membrane assay.


Input: Our results indicated 1 as a new antiangiogenic compound inhibiting the interaction between VEGF-A or PlGF and their receptor VEGRF-1.


Input: Highly ordered cobalt-phthalocyanine chains on fractional atomic steps: one-dimensionality and electron hybridization.

cobalt

phthalocyanine


Input: Precisely controlled fabrication of low-dimensional molecular structures with tailored morphologies and electronic properties is at the heart of the nanotechnology research.


Input: Especially, the formation of one-dimensional (1D) structures has been strongly desired due to their expected high performance for information processing in electronic/magnetic devices.


Input: So far, however, they have been obtained by tough and slow methods such as manipulation of individual molecules, which are totally unsuited for mass production.


Input: Here we show that highly ordered cobalt-phthalocyanine chains can be self-assembled on a metal surface using fractional atomic steps as a template.

cobalt

phthalocyanine


Input: We also demonstrate that the substrate surface electrons, which can be confined by cobalt-phthalocyanine molecules, can propagate along the step arrays and can hybridize with the molecular orbitals.

cobalt

phthalocyanine


Input: These findings provide a significant step toward readily realization of 1D charge/spin transport, which can be mediated either directly by the molecules or by the surface electrons.


Input: Discovery of small molecule vanin inhibitors: new tools to study metabolism and disease.


Input: Vanins are enzymes with pantetheinase activity and are presumed to play a role in the recycling of pantothenic acid (vitamin B5) from pantetheine.

pantothenic acid

vitamin B5

pantetheine


Input: Pantothenic acid is an essential nutrient required to synthesize coenzyme A, a cofactor involved in many biological processes such as fatty acid synthesis and oxidation of pyruvate to fuel the citric acid cycle.

Pantothenic acid

coenzyme A

fatty acid

pyruvate

citric acid


Input: Hydrolysis of pantetheine also liberates cysteamine, a known antioxidant.

pantetheine

cysteamine


Input: Vanin-1 is highly expressed in liver and is under transcriptional control of PPAR-alpha and nutritional status, suggesting a role in energy metabolism.


Input: The lack of potent and specific inhibitors of vanins has hampered detailed investigation of their function.


Input: We hereby report the design, synthesis, and characterization of a novel pantetheine analogue, RR6, that acts as a selective, reversible, and competitive vanin inhibitor at nanomolar concentration.

pantetheine


Input: Oral administration of RR6 in rats completely inhibited plasma vanin activity and caused alterations of plasma lipid concentrations upon fasting, thereby illustrating its potential use in chemical biology research.


Input: Theoretical characterization of X-ray absorption, emission, and photoelectron spectra of nitrogen doped along graphene edges.

nitrogen

graphene


Input: K-edge X-ray absorption (XAS), emission (XES), and photoelectron (XPS) spectra of nitrogen doped along graphene edges are systematically investigated by using first-principles methods.

nitrogen

graphene


Input: In this study we considered pyridinium-like, pyridine-like, cyanide-like, and amine-like nitrogens at armchair and zigzag edges and pyrrole-like nitrogen at armchair edge as well as graphite-like nitrogen at graphene interior site.

pyridinium

pyridine

cyanide

amine

nitrogens

pyrrole

nitrogen

graphite

nitrogen

graphene


Input: Our results indicate that nitrogen configuration and its location (armchair or zigzag edge) in nitrogen-doped graphene can be identified via the spectral analysis.

nitrogen

nitrogen-doped graphene


Input: Furthermore, some controversial spectral features observed in experiment for N-doped graphene-like materials are unambiguously assigned.

N-doped graphene


Input: The present analysis gives an explanation to the reason why the peak assignment is usually made differently between XPS and XAS.


Input: Study of the potential oxidative stress induced by six solvents in the rat brain.


Input: The mechanisms of action involved in the neurotoxicity of solvents are poorly understood.


Input: In vitro studies have suggested that the effects of some solvents might be due to the formation of reactive oxygen species (ROS).

oxygen


Input: This study assesses hydroxyl radical (OH) generation and measures malondialdehyde (MDA) levels in the cerebral tissue of rats exposed to six solvents (n-hexane, n-octane, toluene, n-butylbenzene, cyclohexane and 1, 2, 4-trimethylcyclohexane).

hydroxyl

OH

malondialdehyde

MDA

n-hexane

n-octane

toluene

n-butylbenzene

cyclohexane

1, 2, 4-trimethylcyclohexane


Input: Three of these solvents have been shown to generate ROS in studies carried out in vitro on granular cell cultures from rat cerebellum.


Input: We assessed OH production by quantifying the rate of formation of 3, 4-dihydroxybenzoic acid using a trapping agent, 4-hydroxybenzoic acid, infused via the microdialysis probe, into the prefrontal cortex of rats exposed intraperitoneally to the solvents.

OH

3, 4-dihydroxybenzoic acid

4-hydroxybenzoic acid


Input: Extracellular MDA was quantified in microdialysates collected from the prefrontal cortex of rats exposed, 6h/day for ten days, to 1000ppm of the solvents (except for n-butylbenzene, generated at 830ppm) in inhalation chambers.

MDA

n-butylbenzene


Input: Tissue levels of free and total MDA were measured in different brain structures for rats acutely (intraperitoneal route) and sub-acutely (inhalation) exposed to solvents.

MDA


Input: None of the six solvents studied increased the production of hydroxyl radicals in the prefrontal cortex after acute administration.

hydroxyl


Input: Nor did they increase extracellular or tissue levels of MDA after 10 days' inhalation exposure.

MDA


Input: On the other hand, a decrease in the concentrations of free MDA in brain structures was observed after acute administration of n-hexane, 1, 2, 4-trimethylcyclohexane, toluene and n-butylbenzene.

MDA

n-hexane

1, 2, 4-trimethylcyclohexane

toluene

n-butylbenzene


Input: Therefore, data of this study carried out in vivo did not confirm observations made in vitro on cell cultures.


Input: Antivirals: past, present and future.


Input: Vaccination is possible to prevent infections with some viruses: hepatitis B virus (HBV), varicella-zoster virus (VZV), influenza A and B viruses, Yellow fever virus and poliovirus; but not for others: human immunodeficiency virus (HIV), hepatitis C virus (HCV), herpes simplex virus (HSV), cytomegalovirus (CMV), and most hemorrhagic fever viruses (HFV) (except for Yellow fever virus).


Input: Antiviral therapy is obviously needed to control those infections that are not amenable to prophylaxis by vaccination, but is also highly desirable for those infections where vaccination has not been implemented or did not fulfill its premises for complete protection.


Input: The vasorelaxant effects of 1-nitro-2-phenylethane involve stimulation of the soluble guanylate cyclase-cGMP pathway.

guanylate

cGMP


Input: 1-Nitro-2-phenylethane is the first organic NO 2-containing molecule isolated from plants.

NO 2


Input: It possesses interesting hypotensive, bradycardic, and vasodilator properties, but the mode by which it induces vasorelaxation is still unknown.


Input: The underlying mechanism involved in the vasodilator effect of 1-nitro-2-phenylethane was investigated in rat aorta.


Input: The vasorelaxant effects of 1-nitro-2-phenylethane did not depend on endothelial layer integrity, and the effects were refractory to L-N (G)-nitroarginine methyl ester (L-NAME)-induced nitric oxide synthase inhibition.

L-N (G)-nitroarginine methyl ester

L-NAME

nitric oxide


Input: Vasorelaxation was similarly resistant to treatment with indomethacin, cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride (MDL-12330A), and KT5720, indicating that neither prostaglandin release nor adenylyl cyclase activation is involved.

indomethacin

cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride

prostaglandin

adenylyl


Input: Conversely, methylene blue-and ODQ-induced guanylate cyclase inhibition reduced the vasorelaxation induced by 1-nitro-2-phenylethane.

methylene blue

ODQ

guanylate


Input: The pharmacological blockade of K (+) channels with tetraethylammonium, glybenclamide, and 4-aminopyridine also blunted vasorelaxation induced by 1-nitro-2-phenylethane.

K (+)

tetraethylammonium

glybenclamide


Input: The effects of 1-nitro-2-phenylethane were reversed by 1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one (ODQ) and comparable to the effects induced by sodium nitroprusside.

1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one

ODQ

sodium nitroprusside


Input: In silico analysis using an Ns H-NOX subunit of guanylate cyclase revealed a pocket on the macromolecule surface where 1-nitro-2-phenylethane preferentially docked.

guanylate


Input: In vitro, 1-nitro-2-phenylethane increased cyclic guanosine 3', 5'-monophosphate (cGMP) levels in rat aortic rings, an effect also reversed by ODQ.

cyclic guanosine 3', 5'-monophosphate

cGMP

ODQ


Input: In conclusion, 1-nitro-2-phenylethane produces vasodilator effects by stimulating the soluble guanylate cyclase-cGMP pathway.

guanylate

cGMP


Input: Antidiabetic effect of secoisolariciresinol diglucoside in streptozotocin-induced diabetic rats.

secoisolariciresinol diglucoside

streptozotocin


Input: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia.


Input: Its complications such as neuropathy, cardiopathy, nephropathy, and micro and macro vascular diseases are believed to be due to the increase in oxidative stress and decrease in the level of antioxidants.


Input: The aim of this study was to determine the antihyperglycemic activity of synthetic Secoisolariciresinol diglucoside (SDG) in streptozotocin (STZ)-induced diabetic rats.

Secoisolariciresinol diglucoside

SDG

streptozotocin

STZ


Input: The synthetic SDG in a single-dose (20 mg/kg b. w.) two-day study showed dose-dependent reduction in glucose levels with maximum effect of 64. 62% at 48 h post drug treatment (p < 0. 05), which is comparable to that of the standard drug tolbutamide (20 mg/kg b. w.).

SDG

glucose

tolbutamide


Input: In a multi-dose fourteen-day study, lower doses of SDG (5 and 10 mg/kg b. w.) exhibited moderate reduction in glucose levels, lipid profile, restoration of antioxidant enzymes and improvement of the insulin and c-peptide levels which shows the regeneration of beta-cell which secretes insulin.

SDG

glucose


Input: Altered levels of lipids and enzymatic antioxidants were also restored by the SDG to the considerable levels in diabetic rats.

SDG


Input: Results of the present investigation suggest that diabetes is associated with an increase in oxidative stress as shown by increase in serum malondialdehyde (MDA), decreased levels of catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH).

malondialdehyde

MDA

superoxide

glutathione

GSH


Input: Also, diabetes is associated with an increase in serum total cholesterol as well as triglycerides levels and decrease in insulin and c-peptide levels.

cholesterol

triglycerides


Input: SDG is effective in retarding the development of diabetic complications.

SDG


Input: We propose that synthetic SDG exerts anti hyperglycemic effect by preventing the liver from peroxidation damage through inhibition of ROS level mediated increased level of enzymatic and non-enzymatic antioxidants.

SDG


Input: And, also maintaining tissue function which results in improving the sensitivity and response of target cells in STZ-induced diabetic rats to insulin.

STZ


Input: Feeding of selenium alone or in combination with glucoraphanin differentially affects intestinal and hepatic antioxidant and phase II enzymes in growing rats.

selenium

glucoraphanin


Input: The anti-carcinogenic effects of sulforaphane (SFN) are based on the up-regulation of antioxidant enzymes (AE) and phase II enzymes (PIIE) through the transcription factor Nrf2.

sulforaphane

SFN


Input: Current knowledge on the roles of the SFN precursor glucoraphanin (GRA) on these processes is limited.

SFN

glucoraphanin

GRA


Input: Anti-carcinogenic effects of Se depending on glutathione peroxidase (GPx) activity have also been reported.

Se

glutathione


Input: We studied effects and possible synergisms of Se and GRA on the expression and activity of a broad spectrum of AE and PIIE in jejunum, colon and the liver of rats fed diets differing in Se and GRA concentration.

Se

GRA

Se

GRA


Input: In all organs, GPx1 mRNA expression was 70% to 90% lower in Se deficiency than in Se sufficiency.

Se

Se


Input: GPx2 expression increased in jejunum and liver under Se deficiency and decreased in the colon.

Se


Input: Se deficiency increased most colonic AE and PIIE compared to Se adequacy.

Se

Se


Input: Adequate and in particular supranutritive Se combined with GRA increased colonic AE and PIIE expression up to 3. 72-fold.

Se

GRA


Input: In the liver Se deficiency raised the expression of AE and PIIE up to 4. 49-fold.

Se


Input: GRA attenuated liver AE and PIIE response in Se deficiency.

GRA

Se


Input: Expression-and correlation analyses revealed that Keap1 mRNA better reflects AE and PIIE gene expression than Nrf2 mRNA.


Input: We conclude that: (1) GPx1 sensitively indicates Se deficiency; (2) the influence of Se and Nrf2/Keap1 on GPx2 expression depends on the organ; (3) GRA combined with supranutritive Se may effectively protect against inflammation and colon cancer; (4) future investigations on AE and PIIE expression should consider the role of Keap1 to a higher extent.

Se

Se

GRA

Se


Input: Specific conserved C-terminal amino acids of Caenorhabditis elegans HMP-1/alpha-catenin modulate F-actin binding independently of vinculin.

C

amino acids


Input: Stable intercellular adhesions formed through the cadherin-catenin complex are important determinants of proper tissue architecture and help maintain tissue integrity during morphogenetic movements in developing embryos.


Input: A key regulator of this stability is alpha-catenin, which connects the cadherin-catenin complex to the actin cytoskeleton.


Input: Although the C-terminal F-actin-binding domain of alpha-catenin has been shown to be crucial for its function, a more detailed in vivo analysis of discrete regions and residues required for actin binding has not been performed.

C


Input: Using Caenorhabditis elegans as a model system, we have characterized mutations in hmp-1/alpha-catenin that identify HMP-1 residues 687-742 and 826-927, as well as amino acid 802, as critical to the localization of junctional proximal actin during epidermal morphogenesis.

amino acid


Input: We also find that the S823F transition in a hypomorphic allele, hmp-1 (fe4), decreases actin binding in vitro.


Input: Using hmp-1 (fe4) animals in a mutagenesis screen, we were then able to identify 11 intragenic suppressors of hmp-1 (fe4) that revert actin binding to wild-type levels.


Input: Using homology modeling, we show that these amino acids are positioned at key conserved sites within predicted alpha-helices in the C terminus.

amino acids

C


Input: Through the use of transgenic animals, we also demonstrate that HMP-1 residues 315-494, which correspond to a putative mechanotransduction domain that binds vinculin in vertebrate alpha E-catenin, are not required during epidermal morphogenesis but may aid efficient recruitment of HMP-1 to the junction.


Input: Our studies are the first to identify key conserved amino acids in the C terminus of alpha-catenin that modulate F-actin binding in living embryos of a simple metazoan.

amino acids

C


Input: Nanoscale stabilization of new phases in the PbTe-Sb2Te3 system: Pb (m) Sb (2n) Te (m + 3n) nanocrystals.

PbTe

Pb (m) Sb (2n) Te (m + 3n)


Input: A series of novel rock-salt-type Pb (m) Sb (2n) Te (m + 3n) nanocrystals (m = 2, 3, 4, 6, 8, and 10; n = 1 and 2) were successfully prepared using a colloidal synthesis route.

Pb (m) Sb (2n) Te (m + 3n)


Input: These materials are stable only on the nanoscale and have no bulk analogues.


Input: Elemental compositions were determined using scanning transmission electron microscopy/energy-dispersive X-ray spectroscopy (STEM/EDS) and inductively coupled plasma atomic emission spectroscopy (ICP-AES).


Input: The nanocrystals exhibit well-defined band energies in the mid-IR region that are nearly independent of their atomic compositions.


Input: Pb (m) Sb (2n) Te (m + 3n) nanocrystals behave as metastable homogeneous solid solutions at room temperature and tend to phase separate into the respective binary PbTe + Sb (2) Te (3) at 300 degrees C.

Pb (m) Sb (2n) Te (m + 3n)

PbTe

Sb (2) Te (3)


Input: Furthermore, pair distribution function (PDF) analysis suggests that the local structure of these Pb (m) Sb (2n) Te (m + 3n) nanocrystals is distorted with respect to the rock-salt structure.

Pb (m) Sb (2n) Te (m + 3n)


Input: N-cinnamoylated chloroquine analogues as dual-stage antimalarial leads.

N-cinnamoylated chloroquine


Input: The control of malaria is challenged by drug resistance, and new antimalarial drugs are needed.


Input: New drug discovery efforts include consideration of hybrid compounds as potential multitarget antimalarials.


Input: Previous work from our group has demonstrated that hybrid structures resulting from cinnamic acid conjugation with heterocyclic moieties from well-known antimalarials present improved antimalarial activity.

cinnamic acid


Input: Now, we report the synthesis and SAR analysis of an expanded series of cinnamic acid derivatives displaying remarkably high activities against both blood-and liver-stage malaria parasites.

cinnamic acid


Input: Two compounds judged most promising, based on their in vitro activity and druglikeness according to the Lipinski rules and Veber filter, were active in vivo against blood-stage rodent malaria parasites.


Input: Therefore, the compounds reported represent a new entry as promising dual-stage antimalarial leads.


Input: Bistable magnetoresistance switching in exchange-coupled CoFe 2 O 4--Fe 3 O 4 binary nanocrystal superlattices by self-assembly and thermal annealing.

CoFe 2 O 4

Fe 3 O 4


Input: Self-assembly of multicomponent nanocrystal superlattices provides a modular approach to the design of metamaterials by choosing constituent nanocrystal building blocks with desired physical properties and engineering the interparticle coupling.


Input: In this work, we report the self-assembly of binary nanocrystal superlattices composed of magnetically hard CoFe 2 O 4 nanocrystals and magnetically soft Fe 3 O 4 nanocrystals.

CoFe 2 O 4

Fe 3 O 4


Input: Both NaZn 1 3-and MgZn 2-type CoFe 2 O 4--Fe 3 O 4 binary nanocrystal superlattices have been formed by the liquid-air interfacial assembly approach.

NaZn 1 3

MgZn 2

CoFe 2 O 4

Fe 3 O 4


Input: Exchange coupling is achieved in both types of binary superlattices after thermal annealing under vacuum at 400 degrees C.


Input: The exchange-coupled CoFe 2 O 4--Fe 3 O 4 binary nanocrystal superlattices show single-phase magnetization switching behavior and magnetoresistance switching behavior below 200 K.

CoFe 2 O 4

Fe 3 O 4


Input: The NaZn 1 3-type CoFe 2 O 4--Fe 3 O 4 binary nanocrystal superlattices annealed at 500 degrees C even exhibit bistable magnetoresistance switching behavior at room temperature constituting a simple nonvolatile memory function.

NaZn 1 3

CoFe 2 O 4

Fe 3 O 4


Input: Synthesis, molecular modeling and evaluation of novel N'-2-(4-benzylpiperidin-/piperazin-1-yl) acylhydrazone derivatives as dual inhibitors for cholinesterases and A beta aggregation.

N'-2-(4-benzylpiperidin-/piperazin-1-yl) acylhydrazone


Input: To develop new drugs for treatment of Alzheimer' s disease, a group of N'-2-(4-Benzylpiperidin-/piperazin-1-yl) acylhydrazones was designed, synthesized and tested for their ability to inhibit acetylcholinesterase, butyrylcholinesterase and aggregation of amyloid beta peptides (1-40, 1-42 and 1-40 _ 1-42).

N'-2-(4-Benzylpiperidin-/piperazin-1-yl) acylhydrazones


Input: The enzyme inhibition assay results indicated that compounds moderately inhibit both acetylcholinesterase and butyrylcholinesterase.


Input: beta-Amyloid aggregation results showed that all compounds exhibited remarkable A beta fibril aggregation inhibition activity with a nearly similar potential as the reference compound rifampicin, which makes them promising anti-Alzheimer drug candidates.

rifampicin


Input: Docking experiments were carried out with the aim to understand the interactions of the most active compounds with the active site of the cholinesterase enzymes.


Input: Synthesis and biological evaluation of analogues of the kinase inhibitor nilotinib as Abl and Kit inhibitors.

nilotinib


Input: The importance of the trifluoromethyl group in the polypharmacological profile of nilotinib was investigated.

trifluoromethyl

nilotinib


Input: Molecular editing of nilotinib led to the design, synthesis and biological evaluation of analogues where the trifluoromethyl group was replaced by a proton, fluorine and a methyl group.

nilotinib

trifluoromethyl

fluorine

methyl


Input: While these analogues were less active than nilotinib toward Abl, their activity toward Kit was comparable, with the monofluorinated analogue being the most active.

nilotinib


Input: Docking of nilotinib and of analogues 2a-c to the binding pocket of Abl and of Kit showed that the lack of shape complementarity in Kit is compensated by the stabilizing effect from its juxtamembrane region.

nilotinib


Input: HCV NS5A replication complex inhibitors.


Input: Part 3: discovery of potent analogs with distinct core topologies.


Input: In a recent disclosure, we described the discovery of dimeric, prolinamide-based NS5A replication complex inhibitors exhibiting excellent potency towards an HCV genotype 1b replicon.

prolinamide


Input: That disclosure dealt with the SAR exploration of the peripheral region of our lead chemotype, and herein is described the SAR uncovered from a complementary effort that focused on the central core region.


Input: From this effort, the contribution of the core region to the overall topology of the pharmacophore, primarily vector orientation and planarity, was determined, with a set of analogs exhibiting < 10 nM EC (50) in a genotype 1b replicon assay.


Input: Endophytic fungi from Miquelia dentata Bedd., produce the anti-cancer alkaloid, camptothecine.

camptothecine


Input: Camptothecine (Campothecin, CPT), a quinoline alkaloid, is a potent inhibitor of eukaryotic topoisomerase I.

Camptothecine

Campothecin

CPT

quinoline alkaloid


Input: Several semi-synthetic derivatives of CPT are in clinical use against ovarian, small lung and refractory ovarian cancers.

CPT


Input: While CPT is produced by several plant species belonging to the Asterid clade, in recent years, efforts have been made to isolate endophytic fungi from some of these plants as possible alternative sources of CPT.

CPT

CPT


Input: In this study we report the isolation of three endophytic fungi from fruit and seed regions of Miquelia dentata (Icacinaceae), that produce CPT, 9-methoxy CPT (9-MeO-CPT) and 10-hydroxy CPT (10-OH-CPT).

CPT

9-methoxy CPT

10-hydroxy CPT


Input: All the three fungi identified as, Fomitopsis sp.


Input: P.


Input: Karst (MTCC 10177), Alternaria alternata (Fr.) Keissl (MTCC 5477) and Phomposis sp.


Input: (Sacc.) produced CPT, 9-MeO-CPT and 10-OH-CPT in mycelial mats in shake flasks containing potato dextrose broth.

CPT


Input: Methanolic and ethyl acetate extracts of these fungal species were cytotoxic to colon and breast cancer cell lines.

ethyl acetate


Input: We discuss these results in the context of the recent interest in endophytic fungi as possible alternative sources of plant secondary metabolites.


Input: A link between the cytoplasmic engulfment protein Elmo1 and the Mediator complex subunit Med31.


Input: The cytoplasmic Elmo1: Dock180 complex acts as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac and functions downstream of the phagocytic receptor BAI1 during apoptotic cell clearance, and in the entry of Salmonella and Shigella into cells.

guanine nucleotide


Input: We discovered an unexpected binding between Elmo1 and the Mediator complex subunit Med31.


Input: The Mediator complex is a regulatory hub for nearly all gene transcription via RNA polymerase II, bridging the general transcription machinery with gene-specific regulatory proteins.


Input: Med31 is the smallest and the most evolutionarily conserved Mediator subunit, and knockout of Med31 results in embryonic lethality in mice; however, Med31 function in specific biological contexts is poorly understood.


Input: We observed that in primary macrophages, during Salmonella infection, Elmo1 and Med31 specifically affected expression of the cytokine genes Il10 and Il33 among the > 25 genes monitored.


Input: Although endogenous Med31 is predominantly nuclear localized, Elmo1 increased the cytoplasmic localization of Med31.


Input: We identify ubiquitination as a novel posttranslational modification of Med31, with the cytoplasmic monoubiquitinated form of Med31 being enhanced by Elmo1.


Input: These data identify Elmo1 as a novel regulator of Med31, revealing a previously unrecognized link between cytoplasmic signaling proteins and the Mediator complex.


Input: Jaceosidin, isolated from dietary mugwort (Artemisia princeps), induces G2/M cell cycle arrest by inactivating cdc25C-cdc2 via ATM-Chk1/2 activation.

Jaceosidin


Input: Jaceosidin, a flavonoid derived from Artemisia princeps (Japanese mugwort), has been shown to inhibit the growth of several human cancer cells, However, the exact mechanism for the cytotoxic effect of jaceosidin is not completely understood.

Jaceosidin

flavonoid

jaceosidin


Input: In this study, we investigated the molecular mechanism involved in the antiproliferative effect of jaceosidin in human endometrial cancer cells.

jaceosidin


Input: We demonstrated that jaceosidin is a more potent inhibitor of cell growth than cisplatin in human endometrial cancer cells.

jaceosidin

cisplatin


Input: In contrast, jaceosidin-induced cytotoxicity in normal endometrial cells was lower than that observed for cisplatin.

jaceosidin

cisplatin


Input: Jaceosidin induced G2/M phase cell cycle arrest and modulated the levels of cyclin B and p-Cdc2 in Hec1A cells.

Jaceosidin


Input: Knockdown of p21 using specific siRNAs partially abrogated jaceosidin-induced cell growth inhibition.

jaceosidin


Input: Additional mechanistic studies revealed that jaceosidin treatment resulted in an increase in phosphorylation of Cdc25C and ATM-Chk1/2.

jaceosidin


Input: Ku55933, an ATM inhibitor, reversed jaceosidin-induced cell growth inhibition, in part.

jaceosidin


Input: Moreover, jaceosidin treatment resulted in phosphorylation of ERK, and pretreatment with the ERK inhibitor, PD98059, attenuated cell growth inhibition by jaceosidin.

jaceosidin

jaceosidin


Input: These data suggest that jaceosidin, isolated from Japanese mugwort, modulates the ERK/ATM/Chk1/2 pathway, leading to inactivation of the Cdc2-cyclin B1 complex, followed by G2/M cell cycle arrest in endometrial cancer cells.

jaceosidin


Input: AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo.


Input: AMPK is a metabolic sensor that helps maintain cellular energy homeostasis.


Input: Despite evidence linking AMPK with tumor suppressor functions, the role of AMPK in tumorigenesis and tumor metabolism is unknown.


Input: Here we show that AMPK negatively regulates aerobic glycolysis (the Warburg effect) in cancer cells and suppresses tumor growth in vivo.


Input: Genetic ablation of the alpha 1 catalytic subunit of AMPK accelerates Myc-induced lymphomagenesis.


Input: Inactivation of AMPK alpha in both transformed and nontransformed cells promotes a metabolic shift to aerobic glycolysis, increased allocation of glucose carbon into lipids, and biomass accumulation.

glucose carbon


Input: These metabolic effects require normoxic stabilization of the hypoxia-inducible factor-1 alpha (HIF-1 alpha), as silencing HIF-1 alpha reverses the shift to aerobic glycolysis and the biosynthetic and proliferative advantages conferred by reduced AMPK alpha signaling.


Input: Together our findings suggest that AMPK activity opposes tumor development and that its loss fosters tumor progression in part by regulating cellular metabolic pathways that support cell growth and proliferation.


Input: Ptaquiloside reduces NK cell activities by enhancing metallothionein expression, which is prevented by selenium.

Ptaquiloside

selenium


Input: Pteridium aquilinum, one of the most important poisonous plants in the world, is known to be carcinogenic to animals and humans.


Input: Moreover, our previous studies showed that the immunosuppressive effects of ptaquiloside, its main toxic agent, were prevented by selenium in mouse natural killer (NK) cells.

ptaquiloside

selenium


Input: We also verified that this immunosuppression facilitated development of cancer.


Input: Here, we performed gene expression microarray analysis in splenic NK cells from mice treated for 14 days with ptaquiloside (5. 3 mg/kg) and/or selenium (1. 3 mg/kg) to identify gene transcripts altered by ptaquiloside that could be linked to the immunosuppression and that would be prevented by selenium.

ptaquiloside

selenium

ptaquiloside

selenium


Input: Transcriptome analysis of ptaquiloside samples revealed that 872 transcripts were expressed differentially (fold change > 2 and p < 0. 05), including 77 up-regulated and 795 down-regulated transcripts.

ptaquiloside


Input: Gene ontology analysis mapped these up-regulated transcripts to three main biological processes (cellular ion homeostasis, negative regulation of apoptosis and regulation of transcription).


Input: Considering the immunosuppressive effect of ptaquiloside, we hypothesized that two genes involved in cellular ion homeostasis, metallothionein 1 (Mt1) and metallothionein 2 (Mt2), could be implicated because Mt1 and Mt2 are responsible for zinc homeostasis, and a reduction of free intracellular zinc impairs NK functions.

ptaquiloside

zinc

zinc


Input: We confirm these hypotheses and show increased expression of metallothionein in splenic NK cells and reduction in free intracellular zinc following treatment with ptaquiloside that were completely prevented by selenium co-treatment.

zinc

ptaquiloside

selenium


Input: These findings could help avoid the higher susceptibility to cancer that is induced by P. aquilinum-mediated immunosuppressive effects.


Input: Interference of a novel indolylmaleimide with microtubules induces mitotic arrest and apoptosis in human progenitor and cancer cells.

indolylmaleimide


Input: Indolylmaleimides display a broad spectrum of biological activity and offer great opportunity to influence several aspects of cell fate, as proliferation and differentiation.

Indolylmaleimides


Input: In this study we describe the effect of PDA-66, a newly synthesised indolylmaleimide, showing a strong dose dependent anti-proliferative effect on immortalised human progenitor and cancer cells.

indolylmaleimide


Input: We demonstrated a highly depolymerizing effect on in vitro tubulin assembly and conclude that PDA-66 acts as microtubule destabilising agent.


Input: In addition we found that PDA-66 induces mitotic arrest of cells in the G 2/M phase of the cell cycle.


Input: Subsequently cells undergo apoptosis, indicating the major mechanism of the anti-proliferative effect.


Input: To prove a potential anti-cancer activity of PDA-66 we examined the effect of PDA-66 on human SH-SY5Y neuroblastoma and A-459 lung cancer cells, showing a significant reduction in cancer cell proliferation in a dose dependent manner.


Input: Thus PDA-66 is a new anti-mitotic compound with an indole-core with the potential to be used for cancer therapy.

indole


Input: alpha-Terpineol induces fatty liver in mice mediated by the AMP-activated kinase and sterol response element binding protein pathway.

alpha-Terpineol

AMP

sterol


Input: The use of herbal medicines in disease prevention and treatment is growing rapidly worldwide, without careful consideration of safety issues.


Input: alpha-Terpineol is a monoterpene alcoholic component of Melaleuca alternifolia, Salvia officinalis and Carthamus tinctorius that is used widely as a flavor and essential oil in food.

alpha-Terpineol

monoterpene alcoholic


Input: The present study showed that alpha-terpineol induces fatty liver via the AMP-activated protein kinase (AMPK)-mTOR-sterol regulatory element-binding protein-1 (SREBP-1) pathway.

alpha-terpineol

AMP

sterol


Input: alpha-Terpineol-treated hepatocytes had significantly increased neutral lipid accumulation.

alpha-Terpineol


Input: alpha-Terpineol suppressed AMPK phosphorylation, and increased p70S6 kinase (p70S6K) phosphorylation and SREBP-1 activation.

alpha-Terpineol


Input: It also increased luciferase activity in cells transfected with LXRE-tk-Luc and SRE-tk-Luc.


Input: Inhibition of mTOR signaling by co-treatment with rapamycin or co-transfection with dominant negative p70S6K blocked completely the effects of alpha-terpineol.

rapamycin

alpha-terpineol


Input: alpha-Terpineol oral administration to mice for 2weeks led to decreased AMPK phosphorylation and increased SREBP-1 activation in the liver, followed by hepatic lipid accumulation.

alpha-Terpineol


Input: Conversely, rapamycin co-treatment reversed alpha-terpineol-induced SREBP-1 activation and fatty liver in mice.

rapamycin

alpha-terpineol


Input: These data provide evidence that alpha-terpineol causes fatty liver, an effect mediated by the AMPK/mTOR/SREBP-1 pathway.

alpha-terpineol


Input: Multi-walled carbon nanotube increases the excitability of hippocampal CA1 neurons through inhibition of potassium channels in rat' s brain slices.

carbon

potassium


Input: This study was to investigate the neurotoxicity of multi-walled carbon nanotube (MWCNT) by measuring neuronal excitability in rat hippocampal neurons and exploring the underlying mechanism.

carbon


Input: Whole cell patch-clamp technique was used.


Input: Action potential properties and the pattern of repetitive firing rate were assessed.


Input: Our data showed that spike half-width and repetitive firing rate were significantly increased in a concentration-dependent manner.


Input: Furthermore, voltage-activated potassium currents were recorded.

potassium


Input: It was found that MWCNT produced a concentration-dependent inhibition in amplitudes of I (A) and I (K).

K


Input: In addition, MWCNT had effect on the activation kinetics of I (A) and I (K) with V (h) being shifted to the negative potential at high concentration, while I (A) inactivation curve was considerably shifted to the hyperpolarize potential with V (h) being increased.

K


Input: However, no effect was found on the recovery from inactivation of I (A).


Input: The results suggest that MWCNT increases the excitability of hippocampal CA1 neurons by inhibiting voltage-gated potassium current.

potassium


Input: Bile acids in the colon, from healthy to cytotoxic molecules.

Bile acids


Input: Bile acids are natural detergents mainly involved in facilitating the absorption of dietary fat in the intestine.

Bile acids


Input: In addition to this absorptive function, bile acids are also essential in the maintenance of the intestinal epithelium homeostasis.

bile acids


Input: To accomplish this regulatory function, bile acids may induce programmed cell death fostering the renewal of the epithelium.

bile acids


Input: Here we first discuss on the different molecular pathways of cell death focusing on apoptosis in colon epithelial cells.


Input: Bile acids may induce apoptosis in colonocytes through different mechanisms.

Bile acids


Input: In contrast to hepatocytes, the extrinsic apoptotic pathway seems to have a low relevance regarding bile acid cytotoxicity in the colon.

bile acid


Input: On the contrary, these molecules mainly trigger apoptosis through direct or indirect mitochondrial perturbations, where oxidative stress plays a key role.


Input: In addition, bile acids may also act as regulatory molecules involved in different cell signaling pathways in colon cells.

bile acids


Input: On the other hand, there is increasing evidence that the continuous exposure to certain hydrophobic bile acids, due to a fat-rich diet or pathological conditions, may induce oxidative DNA damage that, in turn, may lead to colorectal carcinogenesis as a consequence of the appearance of cell populations resistant to bile acid-induced apoptosis.

bile acids

bile acid


Input: Finally, some bile acids, such as UDCA, or low concentrations of hydrophobic bile acids, can protect colon cells against apoptosis induced by high concentrations of cytotoxic bile acids, suggesting a dual behavior of these agents as pro-death or pro-survival molecules.

bile acids

UDCA

bile acids

bile acids


Input: In vitro evaluation of cytochrome P450 induction and the inhibition potential of mitragynine, a stimulant alkaloid.

mitragynine


Input: CYP450 enzymes are key determinants in drug toxicities, reduced pharmacological effect and adverse drug reactions.


Input: Mitragynine, an euphoric compound was evaluated for its effects on the expression of mRNAs encoding CYP1A2, CYP2D6 and CYP3A4 and protein expression and resultant enzymatic activity.

Mitragynine


Input: The mRNA and protein expression of CYP450 isoforms were carried out using an optimized multiplex qRT-PCR assay and Western blot analysis.


Input: CYP1A2 and CYP3A4 enzyme activities were evaluated using P450-Glo (TM) assays.


Input: The effects of mitragynine on human CYP3A4 protein expression were determined using an optimized hCYP3A4-HepG2 cell-based assay.

mitragynine


Input: An in silico computational method to predict the binding conformation of mitragynine to the active site of the CYP3A4 enzyme was performed and further validated using in vitro CYP3A4 inhibition assays.

mitragynine


Input: Mitragynine was found to induce mRNA and protein expression of CYP1A2.

Mitragynine


Input: For the highest concentration of 25 mu M, induction of mRNA was approximately 70% that of the positive control and was consistent with the increased CYP1A2 enzymatic activity.


Input: Thus, mitragynine is a significant in vitro CYP1A2 inducer.

mitragynine


Input: However, it appeared to be a weak CYP3A4 inducer at the transcriptional level and a weak CYP3A4 enzyme inhibitor.


Input: It is therefore, unlikely to have any significant clinical effects on CYP3A4 activity.


Input: NF-kappa B-associated mechanisms underlying the response of embryonic cells to Doxorubicin.

Doxorubicin


Input: The involvement of NF-kappa B in the regulation of teratogen-induced apoptosis has not been established yet.


Input: Therefore, we tried to assess the involvement of the p65 subunit of NF-kappa B in the embryonic response to the anti-cancer drug Doxorubicin (DOX).

Doxorubicin

DOX


Input: Thus, exposure of p65 knockout (p65 (-/-)) or wild type (WT) mouse embryonic fibroblasts (MEFs) to DOX resulted in a decrease in cell survival, culture density and cell proliferation, which was found to be more prominent in p65 (-/-) MEFs.

DOX


Input: Those phenomena were accompanied by a DOX-induced increase in the proportion of apoptotic cells, which was demonstrated only in p65 (-/-) cells and a G2/M arrest, which was found to be more prominent in WT cells.

DOX


Input: Furthermore, DOX-treated WT and p65 (-/-) MEFs differed in their expression of various apoptosis-associated molecules, when the former demonstrated a decrease in the percentage of p65-positive and a more prominent decrease in the percentage of p53-positive cells, while a decreased percentage of I kappa B alpha-positive and a more prominent decrease in the percentage of bcl-2-positive cells was detected among the latter.

DOX


Input: The fact that the response of the cells to the teratogen was clearly p65-dependent implicates this molecule to be involved in the response of the embryonic cells to DOX.

DOX


Input: Chemical constituents from the fibrous root of Ophiopogon japonicus, and their effect on tube formation in human myocardial microvascular endothelial cells.


Input: In an effort to identify novel active constituents on the cardiovascular system, a systematic study on macroporous resin adsorption of extracts from the fibrous root of Ophiopogon japonicus was performed in a human myocardial microvascular endothelial cell line (HMMEC) based assay.


Input: One novel spirostan, named ophiogenin (1), together with six known spirostans (4-8, 10), and one new sesquiterpene glycoside, named ophioside A (2), together with one known monoterpene glycoside (9) were isolated from the active fractions, and the aglycone of compound 2 that was a new natural compound was obtained from the acid hydrolysis of 2, named ophiopogonol (3).

spirostan

ophiogenin

spirostans

sesquiterpene glycoside

ophioside A

monoterpene glycoside

ophiopogonol


Input: Their structures were determined by spectral and chemical analyses.


Input: Furthermore, their effect on HMMEC tube formation was also determined.


Input: Our results indicated that compounds 4 and 8 could significantly improve the tube formation and 2 showed moderate increasing effect, while compound 5 exhibited potent inhibitory effect.


Input: Fetal PGC-1 alpha overexpression programs adult pancreatic beta-cell dysfunction.


Input: Adult beta-cell dysfunction, a hallmark of type 2 diabetes, can be programmed by adverse fetal environment.


Input: We have shown that fetal glucocorticoids (GCs) participate in this programming through inhibition of beta-cell development.


Input: Here we have investigated the molecular mechanisms underlying this regulation.


Input: We showed that GCs stimulate the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), a coregulator of the GCs receptor (GR), and that the overexpression of PGC-1 alpha represses genes important for beta-cell development and function.


Input: More precisely, PGC-1 alpha inhibited the expression of the key beta-cell transcription factor pancreatic duodenal homeobox 1 (Pdx1).


Input: This repression required the GR and was mediated through binding of a GR/PGC-1 alpha complex to the Pdx1 promoter.


Input: To explore PGC-1 alpha function, we generated mice with inducible beta-cell PGC-1 alpha overexpression.


Input: Mice overexpressing PGC-1 alpha exhibited at adult age impaired glucose tolerance associated with reduced insulin secretion, decreased beta-cell mass, and beta-cell hypotrophy.

glucose


Input: Interestingly, PGC-1 alpha expression in fetal life only was sufficient to impair adult beta-cell function whereas beta-cell PGC-1 alpha overexpression from adult age had no consequence on beta-cell function.


Input: Altogether, our results demonstrate that the GR and PGC-1 alpha participate in the fetal programming of adult beta-cell function through inhibition of Pdx1 expression.


Input: G6PC2: A Negative Regulator of Basal Glucose-Stimulated Insulin Secretion.

Glucose


Input: Elevated fasting blood glucose (FBG) is associated with increased risk for the development of type 2 diabetes and cardiovascular-associated mortality.

glucose


Input: Genome-wide association studies (GWAS) have linked polymorphisms in G6PC2 with variations in FBG and body fat, although not insulin sensitivity or glucose tolerance.

glucose


Input: G6PC2 encodes an islet-specific, endoplasmic reticulum-resident glucose-6-phosphatase catalytic subunit.

glucose


Input: A combination of in situ perfused pancreas, in vitro isolated islet, and in vivo analyses were used to explore the function of G6pc2 in mice.


Input: G6pc2 deletion had little effect on insulin sensitivity and glucose tolerance, whereas body fat was reduced in female G6pc2 knockout (KO) mice on both a chow and high-fat diet, observations that are all consistent with human GWAS data.

glucose


Input: G6pc2 deletion resulted in a leftward shift in the dose-response curve for glucose-stimulated insulin secretion (GSIS).

glucose


Input: As a consequence, under fasting conditions in which plasma insulin levels were identical, blood glucose levels were reduced in G6pc2 KO mice, again consistent with human GWAS data.

glucose


Input: Glucose-6-phosphatase activity was reduced, whereas basal cytoplasmic calcium levels were elevated in islets isolated from G6pc2 KO mice.

Glucose

calcium


Input: These data suggest that G6pc2 represents a novel, negative regulator of basal GSIS that acts by hydrolyzing glucose-6-phosphate, thereby reducing glycolytic flux.


Input: Congenital Hyperinsulinism Caused by Hexokinase I Expression or Glucokinase-Activating Mutation in a Subset of beta-Cells.


Input: Congenital hyperinsulinism causes persistent hypoglycemia in neonates and infants.


Input: Most often, uncontrolled insulin secretion (IS) results from a lack of functional KATP channels in all beta-cells or only in beta-cells within a resectable focal lesion.

KATP


Input: In more rare cases, without KATP channel mutations, hyperfunctional islets are confined within few lobules, whereas hypofunctional islets are present throughout the pancreas.

KATP


Input: They also can be cured by selective partial pancreatectomy; however, unlike those with a KATP focal lesion, they show clinical sensitivity to diazoxide.

KATP

diazoxide


Input: Here, we characterized in vitro IS by fragments of pathological and adjacent normal pancreas from six such cases.


Input: Responses of normal pancreas were unremarkable.


Input: In pathological region, IS was elevated at 1 mmol/L and was further increased by 15 mmol/L glucose.

glucose


Input: Diazoxide suppressed IS and tolbutamide antagonized the inhibition.

Diazoxide

tolbutamide


Input: The most conspicuous anomaly was a large stimulation of IS by 1 mmol/L glucose.

glucose


Input: In five of six cases, immunohistochemistry revealed undue presence of low-Km hexokinase-I in beta-cells of hyperfunctional islets only.


Input: In one case, an activating mutation of glucokinase (I211F) was found in pathological islets only.


Input: Both abnormalities, attributed to somatic genetic events, may account for inappropriate IS at low glucose levels by a subset of beta-cells.

glucose


Input: They represent a novel cause of focal congenital hyperinsulinism.


Input: The naphthoquinone diospyrin is an inhibitor of DNA gyrase with a novel mechanism of action.

diospyrin


Input: Tuberculosis and other bacterial diseases represent a significant threat to human health.


Input: The DNA topoisomerases are excellent targets for chemotherapy, and DNA gyrase in particular is a well-validated target for antibacterial agents.


Input: Naphthoquinones (e. g. diospyrin and 7-methyljuglone) have been shown to have therapeutic potential, particularly against Mycobacterium tuberculosis.

Naphthoquinones

diospyrin


Input: We have found that these compounds are inhibitors of the supercoiling reaction catalyzed by M. tuberculosis gyrase and other gyrases.


Input: Our evidence strongly suggests that the compounds bind to the N-terminal domain of GyrB, which contains the ATPase active site, but are not competitive inhibitors of the ATPase reaction.

N


Input: We propose that naphthoquinones bind to GyrB at a novel site close to the ATPase site.

naphthoquinones


Input: This novel mode of action could be exploited to develop new antibacterial agents.


Input: Structure, stability and function of 5-chlorouracil modified A: U and G: U base pairs.