Input: Although the genotoxicity of mercury has been well demonstrated in mussels, little is known about its toxic effects on the translational machinery at the molecular level.

mercury


Input: To investigate possible effects, we exposed the common mussel Mytilus galloprovincialis in seawater supplemented by 30 mu g/L Hg (2 +) for 15 days.

Hg (2 +)


Input: We observed that Hg (2 +) was significantly accumulated in the digestive glands of mussels, reaching a level around 80 mu g/g tissue (dry weight) at the 15th day of exposure.

Hg (2 +)


Input: Exposure of mussels to Hg (2 +) resulted in failure of redox homeostasis, as reflected on lipid peroxidation levels and superoxide dismutase activity in glands, and micronucleus frequency in gills.

Hg (2 +)

superoxide


Input: Extracts from digestive glands after 15-day exposure to Hg (2 +) exhibited decreased tRNA aminoacylation ability and, moreover, a 70% reduction in the ability of 40S ribosomal subunits to form the 48S initiation ribosomal complex.

Hg (2 +)


Input: A similar reduction was detected in the ability of ribosomes to translocate peptidyl-tRNA from the A-site to the P-site, an observation coinciding with the notion that regulation of protein synthesis by Hg (2 +) mainly occurs at the initiation and elongation stages of translation.

Hg (2 +)


Input: A-site binding, peptidyl transferase activity, and termination of peptide chain synthesis underwent less pronounced but measurable reductions, a finding which explains why poly (Phe)-synthesis in ribosomes isolated from exposed mussels is reduced by 70%.

poly (Phe)


Input: In conclusion, Hg (2 +) apart from being a genotoxic ion acts as a modulator of protein synthesis in mussels, an observation probably related with its ability to induce oxidative stress.

Hg (2 +)


Input: Analysis of MC-LR and MC-RR in tissue from freshwater fish (Tinca tinca) and crayfish (Procambarus clarkii) in tench ponds (C a ceres, Spain) by liquid chromatography-mass spectrometry (LC-MS).


Input: In the present study a new method has been developed and validated for detecting free microcystins (MCs) (MC-RR, MC-LR and MC-YR) by liquid chromatography-mass spectrometry (LC-MS) in the cyprinid Tinca tinca and in the crayfish Procambarus clarkii collected from three ponds in Extremadura (Spain) where the presence of the cyanobacteria species Microcystis aeruginosa and Anabaena spiroides has been confirmed.

microcystins

MC-RR

MC-LR

MC-YR


Input: Once the method had been validated, free MCs were determined in fish (tench, T. tinca) and crayfish from different ponds in order to understand how they are bioaccumulated through the food web.


Input: MCs were not detected in any of the fish samples analyzed.


Input: It was confirmed that P. clarkii accumulated MCs in their tissues without losing their organoleptic characteristics, with MC-LR (2. 3-18. 1 mu g MC-LR/g body weight) being the predominant MC variant detected in all the crayfish samples.

MC-LR

MC-LR


Input: MC-RR was measured in 50% of the samples analyzed, ranging between 1. 4 and 7. 8 mu g MC-RR/g body weight and no MC-YR was detected.

MC-RR

MC-RR

MC-YR


Input: The results indicated that crayfish can accumulate free MCs in higher quantities than tench that live in ponds contaminated by toxic cyanobacteria species, and emphasized the need for regular monitoring if the health risks associated with their consumption are to be avoided.


Input: Lead, mercury, and cadmium in blood and their relation to diet among Swedish adults.

mercury

cadmium


Input: The aim of the present study was to examine the body burden of lead (Pb), mercury (Hg), and cadmium (Cd) in blood among Swedish adults and the association between blood levels, diet and other lifestyle factors.

Pb

mercury

Hg

cadmium

Cd


Input: The study was based on a subgroup (n = 273) of the national survey Riksmaten 2010-2011 (4-day food records and questionnaire).


Input: Lead, Hg, and Cd were measured in whole blood, and Cd additionally in urine, by mass or fluorescence spectrometry methods.

Hg

Cd

Cd


Input: The median values (5-95th percentiles) of the metals in blood were as follows; Pb: 13. 4 (5. 8-28. 6) mu g/L, Hg: 1. 13 (0. 31-3. 45) mu g/L, and Cd: 0. 19 (0. 09-1. 08) mu g/L.

Pb

Hg

Cd


Input: All three metals increased with increasing age.


Input: Lead levels in blood were positively associated with intakes of game and alcohol, Hg was related to fish intake, and blood Cd related to smoking and low iron stores and to a low meat intake.

alcohol

Hg

Cd

iron


Input: Body burdens of the studied metals were generally below health based reference values, but several individuals had blood Pb levels above the reference point for possible nephrotoxic and developmental neurotoxic effects.

Pb


Input: As health effects cannot be excluded, individuals with high Pb exposure should aim at decreasing their body burden, both from food and from other exposure routes.

Pb


Input: The involvement of heme oxygenase 1 but not nitric oxide synthase 2 in a hepatoprotective action of quercetin in lipopolysaccharide-induced hepatotoxicity of d-galactosamine sensitized rats.

heme

nitric oxide

quercetin

d-galactosamine


Input: The objective of this study was to evaluate potential hepatoprotective capabilities of quercetin in relation to its modulation of the HO-1 and NOS-2 activities in an experimental model of fulminant liver failure.

quercetin


Input: Liver insult was induced by in vivo administration of d-galactosamine (d-GalN, 400mg/kg, i. p.) and lipopolysaccharide (LPS, 10 mu g/kg, i. p.).

d-galactosamine

d-GalN


Input: The effects of quercetin (50mg/kg, i. p) on d-GalN toxicity was evaluated by standard biochemical, RT-PCR and Western blot methods.

quercetin

d-GalN


Input: Administration of d-GalN/LPS combination resulted in significantly higher plasma levels of aminotransferases, as well as increased mRNA and protein expressions of both HO-1 and NOS-2 enzymes.

d-GalN


Input: Quercetin exhibited cytoprotective effects on the liver, as evidenced by decreased aminotransferase plasma levels.

Quercetin


Input: Additionally, quercetin treatment in d-GalN/LPS treated rats significantly increased HO-1 mRNA and its protein expressions.

quercetin

d-GalN


Input: On the contrary, quercetin did not exhibit any significant effects on the levels of nitrites, and NOS-2 mRNA and protein expressions in d-GalN/LPS treated rats.

quercetin

nitrites

d-GalN


Input: Quercetin when given alone did not have any significant changes on liver enzymes nor HO-1 and NOS-2 mRNA and protein expressions.

Quercetin


Input: It can be concluded that the quercetin' s induction of HO-1 and its byproducts, without concomitant NOS-2 activity reduction, is among mechanisms contributing to the hepatoprotective effect in d-GalN/LPS hepatotoxicity.

quercetin

d-GalN


Input: Apoptotic and proinflammatory effect of combustion-generated organic nanoparticles in endothelial cells.


Input: Air pollution exposure in industrialized cities is associated with an increased risk of morbidity and mortality attributed to cardiovascular diseases.


Input: Combustion exhausts emitted from motor vehicles and industries represent a major source of nanoparticles in the atmosphere.


Input: Flame-generated organic carbon nanoparticles (OC NPs) provide interesting model nanoparticles that simulate fresh combustion emissions near roadways or combustion sources.

carbon


Input: These model nanoparticles can be produced by controlling flame operating conditions and used to test possible toxicological mechanisms responsible for the observed health effects.


Input: OC NPs were used to investigate their possible effect on endothelial cells (EC) growth and production of proinflammatory lipid mediators.


Input: Results indicated a dose and time-dependent reduction in cell viability following incubation of EC with OC NPs for 24 and 48h.


Input: Fluorescence-activated cell sorting revealed that EC treated with OC NPs showed a cell proliferation index significantly lower than that of control cells and an increased apoptotic cell death.


Input: The annexin assay confirmed the increased apoptotic cell death.


Input: Moreover, OC NPs also induced a time-dependent increase of proinflammatory lysophospholipid production.


Input: These results, establishing that OC NPs induce EC proinflammatory lysophosholipid production and apoptotic cell death, provide the first evidence of the detrimental effect of OC NPs on EC.


Input: Discovery of adamantane based highly potent HDAC inhibitors.

adamantane


Input: Herein, we report the development of highly potent HDAC inhibitors for the treatment of cancer.


Input: A series of adamantane and nor-adamantane based HDAC inhibitors were designed, synthesized and screened for the inhibitory activity of HDAC.

adamantane

adamantane


Input: A number of compounds exhibited GI50 of 10-100 nM in human HCT116, NCI-H460 and U251 cancer cells, in vitro.


Input: Compound 32 displays efficacy in human tumour animal xenograft model.


Input: EZETIMIBE INCREASES HEPATIC IRON LEVELS IN MICE FED A HIGH-FAT DIET.

EZETIMIBE

IRON


Input: Accumulating evidence suggests that ezetimibe may be a promising agent for treatment of non-alcoholic fatty liver disease and steatohepatitis (NAFLD/NASH).

ezetimibe


Input: Phlebotomy and dietary iron restriction reduces serum transaminase in NAFLD/NASH patients.

iron


Input: Recent studies showed that mutual effects exist between lipid metabolism and iron metabolism.

iron


Input: Accordingly, the effects of ezetimibe on iron metabolism were examined in mice fed a high-fat diet with or without iron.

ezetimibe

iron

iron


Input: C57BL/6 mice were fed the following diets for 12 weeks.


Input: Experiment 1: 1) a control diet; C 2) C plus ezetimibe (0. 3mg/day; 4 weeks); CE 3) a high-fat diet; H 4) H plus ezetimibe; HE.

ezetimibe

ezetimibe


Input: Experiment 2: 1) C containing carbonyl iron (average; 22. 4mg/day; 6 weeks); CI 2) CI plus ezetimibe; CIE 3) H containing carbonyl iron; HI 4) HI plus ezetimibe; HIE.

carbonyl iron

ezetimibe

carbonyl iron

ezetimibe


Input: Blood, livers, and duodenum were removed after 12 weeks.


Input: In Experiment 1, hepatic iron levels were higher in HE than H, whereas there was no difference between C and CE.

iron


Input: Hepatic mRNA expression of transferrin receptor 1 and 2, ferritins, and hepcidin were increased more in CE than C, and in HE than H.


Input: In duodenum, DMT1, ferritinH, and hephaestin mRNA levels were increased in CE compared to C.


Input: In Experiment 2, hepatic iron concentrations were higher in HIE than HI.

iron


Input: Hepatic mRNA expression of ferritinL and hepcidin were increased in HIE compared to HI.


Input: In duodenum, ferritinL mRNA was increased in HIE compared to CIE.


Input: Ezetimibe induced hepatic iron uptake transporter expression in mice fed a high-fat diet, causing increased hepatic iron concentrations.

Ezetimibe

iron

iron


Input: Astaxanthin Suppresses MPP +-Induced Oxidative Damage in PC12 Cells through a Sp1/NR1 Signaling Pathway.

Astaxanthin

MPP +


Input: Objective: To investigate astaxanthin (ATX) neuroprotection, and its mechanism, on a 1-methyl-4-phenyl-pyridine ion (MPP +)-induced cell model of Parkinson' s disease.

astaxanthin

ATX

MPP +


Input: Methods: Mature, differentiated PC12 cells treated with MPP + were used as an in vitro cell model.

MPP +


Input: The MTT assay was used to investigate cell viability after ATX treatment, and western blot analysis was used to observe Sp1 (activated transcription factor 1) and NR1 (NMDA receptor subunit 1) protein expression, real-time PCR was used to monitor Sp1 and NR1 mRNA, and cell immunofluorescence was used to determine the location of Sp1 and NR1 protein and the nuclear translocation of Sp1.

MTT

ATX

NMDA


Input: Results: PC12 cell viability was significantly reduced by MPP + treatment.

MPP +


Input: The expression of Sp1 and NR1 mRNA and protein were increased compared with the control (p < 0. 01).


Input: Following co-treatment with ATX and MPP +, cell viability was significantly increased, and Sp1 and NR1 mRNA and protein were decreased, compared with the MPP + groups (p < 0. 01).

ATX

MPP +

MPP +


Input: In addition, mithracycin A protected PC12 cells from oxidative stress caused by MPP + by specifically inhibiting the expression of Sp1.

mithracycin A

MPP +


Input: Moreover, cell immunofluorescence revealed that ATX could suppress Sp1 nuclear transfer.

ATX


Input: Conclusion: ATX inhibited oxidative stress induced by MPP + in PC12 cells, via the SP1/NR1 signaling pathway.

ATX

MPP +


Input: p38 Mitogen Activated Protein Kinase Regulates the Nuclear Receptor CAR to Activate the CYP2B6 Gene.


Input: The constitutive active/androstane receptor (CAR) regulates hepatic drug metabolism by activating genes such as cytochrome P450 (CYP) and certain transferases.

androstane


Input: p38 mitogen activated protein kinase (MAPK) is highly activated in human primary hepatocytes but barely in human hepatoma cell-lines including HepG2 cells.


Input: Liganded-CAR induced CYP2B6 mRNA in human primary hepatocytes far more effectively than in HepG2 cells ectopically expressing CAR.


Input: Here, we have now found that activation of p38 MAPK by anisomycin potentiated induction of CYP2B6 mRNA by CAR ligand in HepG2 cells to levels observed in ligand-treated human primary hepatocytes.

anisomycin


Input: siRNA knockdown of p38 MAPK abrogated the ability of anisomycin to synergistically induce CYP2B6 mRNA.

anisomycin


Input: In addition to CYP2B6, anisomycin co-treatment potentiated an increase in CYP2A7 and CYP2C9 mRNAs but not CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs.

anisomycin

UDP


Input: Thus, activated p38 MAPK is required for liganded-CAR to selectively activate a set of genes that encode drug metabolizing enzymes.


Input: Our present results suggest that CAR-mediated induction of these enzymes can not be understood by ligand binding alone because the specificity and magnitude of induction are co-determined by a given cell signaling such as p38 MAPK; both physiological and pathophysiological states of cell signaling may have a strong impact in hepatic drug metabolizing capability during therapeutic treatments.


Input: Insulin-like Factor 3 promotes wound healing at the ocular surface.


Input: Tear fluid is known to contain many different hormones with relevance for ocular surface homeostasis.


Input: We studied the presence and functional role of insulin-like factor 3 (INSL3) and its cognate receptor RXFP2 at the ocular surface and in tears.


Input: Expression of human INSL3 and RXFP2 was determined in tissues of the ocular surface, lacrimal apparatus, in human corneal (HCE), conjunctival (HCjE), sebaceous (SC) epithelial cell lines and in human tears by RT-PCR and ELISA.


Input: We investigated effects of human recombinant (hr) INSL3 on cell proliferation and cell migration and the influence of hrINSL3 on the expression of MMP2,-9,-13 and TIMP1 and-2 was quantified by real-time PCR and ELISA in HCE, HCjE and SC cells.


Input: We used a C57BL/6 mouse corneal defect model to elucidate the effect of topical application of hrINSL3 on corneal wound healing.


Input: INSL3 and RXFP2 transcripts and INSL3 protein were detected in all tissues and cell lines investigated.


Input: Significantly higher concentrations of INSL3 were detected in tears from male vs. female volunteers.


Input: Stimulation of HCE, HCjE and SC with hrINSL3 significantly increased cell proliferation in HCjE and SC and migration of HCjE.


Input: Treatment with hrINSL3 for 24 h regulated MMP2, TIMP1 and TIMP2 expression.


Input: The local application of hrINSL3 onto denuded corneal surface resulted in significantly accelerated corneal wound healing in mice.


Input: These findings suggest a novel and gender specific role for INSL3 and cognate receptor RXFP2 signaling in ocular surface homeostasis and determined a novel role for hrINSL3 in corneal wound healing.


Input: Amphetamine, past and present-a pharmacological and clinical perspective.

Amphetamine


Input: Amphetamine was discovered over 100 years ago.

Amphetamine


Input: Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy.


Input: This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners.

amphetamine


Input: Amphetamine' s diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse.

Amphetamine


Input: Accordingly, the balance of benefit/risk is the key challenge for its clinical use.


Input: The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults.

amphetamine

lisdexamfetamine

d-amphetamine


Input: The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology.

lisdexamfetamine

d-amphetamine


Input: How lisdexamfetamine' s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.

lisdexamfetamine


Input: Strategic use of conformational bias and structure based design to identify potent JAK3 inhibitors with improved selectivity against the JAK family and the kinome.


Input: Using a structure based design approach we have identified a series of indazole substituted pyrrolopyrazines, which are potent inhibitors of JAK3.

indazole

pyrrolopyrazines


Input: Intramolecular electronic repulsion was used as a strategy to induce a strong conformational bias within the ligand.


Input: Compounds bearing this conformation participated in a favorable hydrophobic interaction with a cysteine residue in the JAK3 binding pocket, which imparted high selectivity versus the kinome and improved selectivity within the JAK family.

cysteine


Input: Copper-catalyzed diastereoselective arylation of tryptophan derivatives: total synthesis of (+)-naseseazines a and B.

Copper

tryptophan

(+)-naseseazines a and B


Input: A copper-catalyzed arylation of tryptophan derivatives is reported.

copper

tryptophan


Input: The reaction proceeds with high site-and diastereoselectivity to provide aryl pyrroloindoline products in one step from simple starting materials.

aryl pyrroloindoline


Input: The utility of this transformation is highlighted in the five-step syntheses of the natural products (+)-naseseazine A and B.

(+)-naseseazine A and B


Input: Surface Engineering of Ultrafine Cellulose Nanofibrils toward Polymer Nanocomposite Materials.


Input: Surface grafting of crystalline and ultrafine cellulose nanofibrils with poly (ethylene glycol) (PEG) chains via ionic bonds was achieved by a simple ion-exchange treatment.

poly (ethylene glycol)

PEG


Input: The PEG-grafted cellulose nanofibrils exhibited nanodispersibility in organic solvents such as chloroform, toluene, and tetrahydrofuran.

PEG

chloroform

toluene

tetrahydrofuran


Input: Then, the PEG-grafted cellulose nanofibril/chloroform dispersion and poly (l-lactide) (PLLA)/chloroform solution were mixed, and the PEG-grafted cellulose nanofibril/PLLA composite films with various blend ratios were prepared by casting the mixtures on a plate and drying.

PEG

chloroform

poly (l-lactide)

PLLA

chloroform

PEG

PLLA


Input: The tensile strength, Young' s modulus, and work of fracture of the composite films were remarkably improved, despite low cellulose addition levels (< 1 wt%).


Input: The highly efficient nanocomposite effect was explained in terms of achievement of nanodispersion states of the PEG-grafted cellulose nanofibrils in the PLLA matrix.

PEG

PLLA


Input: Moreover, some attractive interactions mediated by the PEG chains were likely to be formed between the cellulose nanofibrils and PLLA molecules in the composites, additionally enhancing the efficient nanocomposite effect.

PEG

PLLA


Input: Small Molecule Regulation of Protein Conformation by Binding in the Flap of HIV Protease.


Input: The fragment indole-6-carboxylic acid (1F1), previously identified as a flap site binder in a fragment-based screen against HIV protease (PR), has been cocrystallized with pepstatin-inhibited PR and with apo-PR.

indole-6-carboxylic acid

pepstatin


Input: Another fragment, 3-indolepropionic acid (1F1-N), predicted by AutoDock calculations and confirmed in a novel inhibition of nucleation crystallization assay, exploits the same interactions in the flap site in two crystal structures.

3-indolepropionic acid


Input: Both 1F1 and 1F1-N bind to the closed form of apo-PR and to pepstatin: PR.

pepstatin


Input: In solution, 1F1 and 1F1-N raise the Tm of apo-PR by 3. 5-5 degrees C as assayed by differential scanning fluorimetry (DSF) and show equivalent low-micromolar binding constants to both apo-PR and pepstatin: PR, assayed by backscattering interferometry (BSI).

pepstatin


Input: The observed signal intensities in BSI are greater for each fragment upon binding to apo-PR than to pepstatin-bound PR, consistent with greater conformational change in the former binding event.

pepstatin


Input: Together, these data indicate that fragment binding in the flap site favors a closed conformation of HIV PR.


Input: Improving the Catalytic Activity of Semiconductor Nanocrystals through Selective Domain Etching.


Input: Colloidal chemistry offers an assortment of synthetic tools for tuning the shape of semiconductor nanocrystals.


Input: While many nanocrystal architectures can be obtained directly via colloidal growth, other nanoparticle morphologies require alternative processing strategies.


Input: Here, we show that chemical etching of colloidal nanoparticles can facilitate the realization of nanocrystal shapes that are topologically inaccessible by hot-injection techniques alone.


Input: The present methodology is demonstrated by synthesizing a two-component CdSe/CdS nanoparticle dimer, constructed in a way that both CdSe and CdS semiconductor domains are exposed to the external environment.

CdSe

CdS

CdSe

CdS


Input: This structural morphology is highly desirable for catalytic applications as it enables both reductive and oxidative reactions to occur simultaneously on dissimilar nanoparticle surfaces.


Input: Hydrogen production tests confirmed the improved catalytic activity of CdSe/CdS dimers, which was enhanced 3-4 times upon etching treatment.

Hydrogen

CdSe

CdS


Input: We expect that the demonstrated application of etching to shaping of colloidal heteronanocrystals can become a common methodology in the synthesis of charge-separating nanocrystals, leading to advanced nanoparticles architectures for applications in areas of photocatalysis, photovoltaics, and light detection.


Input: Synergistic effects of diosmetin with erythromycin against ABC transporter over-expressed methicillin-resistant Staphylococcus aureus (MRSA) RN4220/pUL5054 and inhibition of MRSA pyruvate kinase.

diosmetin

erythromycin

methicillin

pyruvate


Input: Increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) worldwide with limited therapeutic options is a growing public health concern.

methicillin


Input: Natural products have been shown to possess antibacterial actions against MRSA.


Input: Flavonoids from natural products have been shown to possess antibacterial actions against MRSA by antagonizing its resistance mechanisms.

Flavonoids


Input: Diosmin and diosmetin are natural flavonoids found in a variety of citrus fruits.

Diosmin

diosmetin

flavonoids


Input: The aim of this study was to investigate whether diosmin and diosmetin could inhibit the growth of MRSA and the in vitro enzymatic activity of a newly discovered MRSA drug target, pyruvate kinase (PK).

diosmin

diosmetin

pyruvate


Input: By using a panel of MRSA strains with known resistant mechanisms, neither diosmin nor diosmetin was shown to possess direct antibacterial activities against all tested MRSA strains.

diosmin

diosmetin


Input: However, in checkerboard assay, we found that diosmetin together with erythromycin, could synergistically inhibit the growth of ABC-pump overexpressed MRSA-RN4220/pUL5054, and time kill assay also showed that the antibacterial activities of diosmetin with erythromycin were bactericidal.

diosmetin

erythromycin

diosmetin

erythromycin


Input: Diosmetin was further shown to significantly suppress the MRSA PK activities in a dose dependent manner.

Diosmetin


Input: In conclusion, the inhibition of MRSA PK by diosmetin could lead to a deficiency of ATP and affect the bacterial efflux pump which might contribute to the antibacterial actions of diosmetin against MRSA.

diosmetin

ATP

diosmetin


Input: Endothelin-3 Expression in the Subfornical Organ Enhances the Sensitivity of Nax, the Brain Sodium-Level Sensor, to Suppress Salt Intake.

Sodium


Input: Salt homeostasis is essential to survival, but brain mechanisms for salt-intake control have not been fully elucidated.


Input: Here, we found that the sensitivity of Nax channels to [Na (+)] o is dose-dependently enhanced by endothelin-3 (ET-3).

Na (+)


Input: Nax channels began to open when [Na (+)] o exceeded ~ 150 mM without ET-3, but opened fully at a physiological [Na (+)] o (135-145 mM) with 1 nM ET-3.

Na (+)

Na (+)


Input: Importantly, ET-3 was expressed in the subfornical organ (SFO) along with Nax, and the level was robustly increased by dehydration.


Input: Pharmacological experiments revealed that endothelin receptor B (ETBR) signaling is involved in this modulation of Nax gating through protein kinase C and ERK1/2 activation. ETBR agonists increased the firing rate of GABAergic neurons via lactate in the SFO, and an ETBR antagonist attenuated salt aversion during dehydration.

lactate


Input: These results indicate that ET-3 expression in the SFO is tightly coupled with body-fluid homeostasis through modulation of the [Na (+)] o sensitivity of Nax.

Na (+)


Input: Pharmacological study of a new Asp49 phospholipase A2 (Bbil-TX) isolated from Bothriopsis bilineata smargadina (forest viper) venom in vertebrate neuromuscular preparations.


Input: The neuromuscular activity of Bbil-TX, a PLA2 with catalytic activity isolated from Bothriopsis bilineata smargadina venom, was examined in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations.


Input: In BC preparations, Bbil-TX (0. 5-10 mu g/ml) caused time-and concentration-dependent blockade that was not reversed by washing; the times for 50% blockade were 87 +/- 7, 41 +/- 7 and 19 +/- 2 min (mean +/- SEM; n = 4-6) for 1, 5 and 10 mu g/ml, respectively.


Input: Muscle contractures to exogenous ACh and KCl were unaffected.

ACh

KCl


Input: The toxin (10 mu g/ml) also did not affect the twitch-tension of directly-stimulated, curarized (10 mu g/ml) BC preparations.


Input: However, Bbil-TX (10 mu g/ml) produced mild morphological alterations (edematous and/or hyperchromic fibers) in BC; there was also a progressive release of CK (from 116 +/- 17 IU/ml (basal) to 710 +/- 91 IU/ml after 45 min).


Input: Bbil-TX (5 mu g/ml)-induced blockade was markedly inhibited at 22-24 degrees C and pretreatment with p-bromophenacyl bromide (p-BPB) abolished the neuromuscular blockade.

p-bromophenacyl bromide

p-BPB


Input: Bbil-TX (3-30 mu g/ml, n = 4-6) caused partial time-and concentration-dependent blockade in PND preparations (52 +/- 2% at the highest concentration).


Input: Bbil-TX (30 mu g/ml) also markedly reduced the MEPPs frequency [from 26 +/- 2. 5 (basal) to 10 +/- 1 after 60 min; n = 5; p < 0. 05] and the quantal content [from 94 +/- 14 (basal) to 24 +/- 3 after 60 min; n = 5; p < 0. 05] of PND preparations, but caused only minor depolarization of the membrane resting potential [from-80 +/- 1 mV (basal) to-66 +/- 2 mV after 120 min; n = 5; p < 0. 05], with no significant change in the depolarizing response to exogenous carbachol.

carbachol


Input: These results show that Bbil-TX is a presynaptic PLA2 that contributes to the neuromuscular blockade caused by B.


Input: b. smargadina venom.


Input: Selenium and mercury molar ratios in commercial fish from New Jersey and Illinois: Variation within species and relevance to risk communication.

Selenium

mercury


Input: There is an emerging consensus that people consuming large amounts of fish with selenium: mercury ratios below 1 are at higher risk from mercury toxicity.

selenium

mercury

mercury


Input: As the relative amount of selenium increases compared to mercury, risk may be lowered, but it is unclear how much excess selenium is required.

selenium

mercury

selenium


Input: It would be useful if the selenium: mercury ratio was relatively consistent within a species, but this has not been the case in our studies of wild-caught fish.

selenium

mercury


Input: Since most people in developed countries and urban areas obtain their fish and other seafood commercially, we examined selenium: mercury molar ratios in commercial fish purchased in stores and fish markets in central New Jersey and Chicago.

selenium

mercury


Input: There was substantial interspecific and intraspecific variation in molar ratios.


Input: Across species the selenium: mercury molar ratio decreased with increasing mean mercury levels, but selenium variation also contributed to the ratio.

selenium

mercury

mercury

selenium


Input: Few samples had selenium: mercury molar ratios below 1, but there was a wide range in ratios, complicating the interpretation for use in risk management and communication.

selenium

mercury


Input: Before ratios can be used in risk management, more information is needed on mercury: selenium interactions and mutual bioavailability, and on the relationship between molar ratios and health outcomes.

mercury

selenium


Input: Further, people who are selenium deficient may be more at risk from mercury toxicity than others.

selenium

mercury


Input: Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2, 2-difluoro-2-deoxyribose-1-phosphate.

2, 2-difluoro-2-deoxyribose-1-phosphate


Input: We report in this Letter the synthesis of prodrugs of 2-fluoro-2-deoxyarabinose-1-phosphate and 2, 2-difluoro-2-deoxyribose-1-phosphate.

2, 2-difluoro-2-deoxyribose-1-phosphate


Input: We demonstrate the difficulty of realising a phosphorylation step on the anomeric position of 2-deoxyribose, and we discover that introduction of fluorine atoms on the 2 position of 2-deoxyribose enables the phosphorylation step: in fact, the stability of the prodrugs increases with the degree of 2-fluorination.

fluorine


Input: Stability studies of produgs of 2-fluoro-2-deoxyribose-1-phosphate and 2, 2-difluoro-2-deoxyribose-1-phosphate in acidic and neutral conditions were conducted to confirm our observation.

2, 2-difluoro-2-deoxyribose-1-phosphate


Input: Biological evaluation of prodrugs of 2, 2-difluoro-2-deoxyribose-1-phosphate for antiviral and cytotoxic activity is reported.

2, 2-difluoro-2-deoxyribose-1-phosphate


Input: Oxidation-specific epitopes and immunological responses: Translational biotheranostic implications for atherosclerosis.


Input: Oxidation-specific epitopes (OSE), present on oxidized LDL (OxLDL), apoptotic cells, cell debris and modified proteins in the vessel wall, accumulate in response to hypercholesterolemia, and generate potent pro-inflammatory, disease-specific antigens.


Input: They represent an important class of' danger associated molecular patterns' (DAMPs), against which a concerted innate immune response is directed.


Input: OSE are recognized by innate' pattern recognition receptors', such as scavenger receptors present on dendritic cells and monocyte/macrophages, as well as by innate proteins, such as IgM natural antibodies and soluble proteins, such as C-reactive protein and complement factor H.


Input: These innate immune responses provide a first line of defense against atherosclerosis-specific DAMPs, and engage adaptive immune responses, provided by T and B-2 cells, which provide a more specific and definitive response.


Input: Such immune responses are ordinarily directed to remove foreign pathogens, such as those found on microbial pathogens, but when persistent or maladaptive, lead to host damage.


Input: In this context, atherosclerosis can be considered as a systemic chronic inflammatory disease initiated by the accumulation of OSE type DAMPs and perpetuated by maladaptive response of the innate and adaptive immune system.


Input: Understanding this paradigm leads to new approaches to defining cardiovascular risk and suggests new modes of therapy.


Input: Therefore, OSE have become potential targets of diagnostic and therapeutic agents.


Input: Human and murine OSE-targeting antibodies have been developed and are now being used as biomarkers in human studies and experimentally in translational applications of non-invasive molecular imaging of oxidation-rich plaques and immunotherapeutics.


Input: Posttranslational mechanisms modulating the expression of the cytochrome P450 1A1 gene by methylmercury in HepG2 cells: A role of heme oxygenase-1.

methylmercury

heme


Input: Recently we demonstrated the ability of mercuric chloride (Hg (2 +)) in human hepatoma HepG2 cells to significantly decrease the TCDD-mediated induction of Cytochrome P450 1A1 (CYP1A1) mRNA, protein, and catalytic activity levels.

mercuric chloride

Hg (2 +)

TCDD


Input: In this study we investigated the effect of methylmercury (MeHg) on CYP1A1 in HepG2 cells.

methylmercury

MeHg


Input: For this purpose, cells were co-exposed to MeHg and TCDD and the expression of CYP1A1 mRNA, protein, and catalytic activity levels were determined.

MeHg

TCDD


Input: Our results showed that MeHg did not alter the TCDD-mediated induction of CYP1A1 mRNA, or protein levels; however it was able to significantly decrease CYP1A1 catalytic activity levels in a concentration-dependent manner.

MeHg

TCDD


Input: Importantly, this inhibition was specific to CYP1A1and was not radiated to other aryl hydrocarbon receptor (AhR)-regulated genes, as MeHg induced NAD (P) H: quinone oxidoreductase 1 mRNA and protein levels.

aryl hydrocarbon

MeHg

NAD (P) H

quinone


Input: Mechanistically, the inhibitory effect of MeHg on the induction of CYP1A1 coincided with an increase in heme oxygenase-1 (HO-1) mRNA levels.

MeHg

heme


Input: Furthermore, the inhibition of HO-1 activity, by tin mesoporphyrin, caused a complete restoration of MeHg-mediated inhibition of CYP1A1 activity, induced by TCDD.

tin mesoporphyrin

MeHg

TCDD


Input: In addition, transfection of HepG2 cells with siRNA targeting the human HO-1 gene reversed the MeHg-mediated inhibition of TCDD-induced CYP1A1.

MeHg

TCDD


Input: In conclusion, this study demonstrated that MeHg inhibited the TCDD-mediated induction of CYP1A1 through a posttranslational mechanism and confirms the role of HO-1 in a MeHg-mediated effect.

MeHg

TCDD

MeHg


Input: Molecular Basis of SMC ATPase Activation: Role of Internal Structural Changes of the Regulatory Subcomplex ScpAB.


Input: In many bacteria, a homodimer of structural-maintenance-of-chromosomes proteins associates with two regulatory subunits (known as ScpA and ScpB), assembling a protein complex that plays a crucial role in chromosome organization and segregation.


Input: It remains poorly understood, however, how this complex might work at the mechanistic level.


Input: Here, we report crystal structures of the ScpAB core complex that display a highly unusual structure in which the central segment of ScpA winds around an asymmetrically oriented ScpB dimer.


Input: The two C-terminal domains of the ScpB dimer primarily interact with different regions of ScpA with different affinities.

C


Input: Moreover, flexible interdomain regions of ScpB contribute to a dynamic folding process of the ScpAB subcomplex.


Input: Together with other genetic and biochemical assays, we provide evidence that internal structural changes of the ScpAB subcomplex are tightly coupled with activation of the structural-maintenance-of-chromosomes ATPase.


Input: Osteochondral tissue regeneration using a bilayered composite hydrogel with modulating dual growth factor release kinetics in a rabbit model.


Input: Biodegradable oligo (poly (ethylene glycol) fumarate) (OPF) composite hydrogels have been investigated for the delivery of growth factors (GFs) with the aid of gelatin microparticles (GMPs) and stem cell populations for osteochondral tissue regeneration.

oligo (poly (ethylene glycol) fumarate)

OPF


Input: In this study, a bilayered OPF composite hydrogel that mimics the distinctive hierarchical structure of native osteochondral tissue was utilized to investigate the effect of transforming growth factor-beta 3 (TGF-beta 3) with varying release kinetics and/or insulin-like growth factor-1 (IGF-1) on osteochondral tissue regeneration in a rabbit full-thickness osteochondral defect model.

OPF


Input: The four groups investigated included (i) a blank control (no GFs), (ii) GMP-loaded IGF-1 alone, (iii) GMP-loaded IGF-1 and gel-loaded TGF-beta 3, and (iv) GMP-loaded IGF-1 and GMP-loaded TGF-beta 3 in OPF composite hydrogels.

OPF


Input: The results of an in vitro release study demonstrated that TGF-beta 3 release kinetics could be modulated by the GF incorporation method.


Input: At 12weeks post-implantation, the quality of tissue repair in both chondral and subchondral layers was analyzed based on quantitative histological scoring.


Input: All groups incorporating GFs resulted in a significant improvement in cartilage morphology compared to the control.


Input: Single delivery of IGF-1 showed higher scores in subchondral bone morphology as well as chondrocyte and glycosaminoglycan amount in adjacent cartilage tissue when compared to a dual delivery of IGF-1 and TGF-beta 3, independent of the TGF-beta 3 release kinetics.


Input: The results suggest that although the dual delivery of TGF-beta 3 and IGF-1 may not synergistically enhance the quality of engineered tissue, the delivery of IGF-1 alone from bilayered composite hydrogels positively affects osteochondral tissue repair and holds promise for osteochondral tissue engineering applications.


Input: Fishing and knockout of bioactive compounds using a combination of high-speed counter-current chromatography (HSCCC) and preparative HPLC for evaluating the holistic efficacy and interaction of the components of Herba Epimedii.


Input: Due to the complex chemical compositions and pharmacological effects of traditional Chinese medicines, we developed a strategy based on fishing and knockout of bioactive compounds using a combination of high-speed counter-current chromatography (HSCCC) and preparative HPLC for evaluating the holistic activity and interaction of the components of Herba Epimedii.


Input: First, osteoblast target cell extraction was used for preliminary screening of the potential bioactive compounds of Herba Epimedii.


Input: Second, the bioactive compounds identified (epimedin A, epimedin B, epimedin C and icariin) were fished and knocked out using high-speed counter-current chromatography and preparative HPLC.

epimedin A

epimedin B

epimedin C

icariin


Input: Third, the bioactivity of resulting fractions was assessed by determining their influence on cell proliferation and differentiation, thereby allowing for an evaluation of their interaction. The pharmacodynamic contribution ratio of each bioactive compound to the efficacy of the herbal medicine could then be comprehensively and intuitively determined based on the spectra-activity correlations (VIP values) of the tested compositions using partial least-squares regression (PLS-R), through which the reliability of the screening and isolation of bioactive compounds by the target cell extraction technique were verified.


Input: The proposed strategy is a useful approach with potential application in other traditional Chinese medicines.


Input: Potential diagnostic applications of side chain oxysterols analysis in plasma and cerebrospinal fluid.

oxysterols


Input: The neurospecific cholesterol 24-hydroxylase converts excess brain cholesterol into 24S-hydroxycholesterol (24OHC) which, via the liver X receptor (LXR), can increase the expression and synthesis of astrocyte ApoE.

cholesterol

cholesterol


Input: 24OHC effluxes directly from brain into plasma where it is considered an indicator of brain cholesterol turnover.

cholesterol


Input: It is reduced in neurodegenerative disease states proportionally to the severity of disease and the degree of brain atrophy.


Input: In the early phases of active disease, a higher rate of turnover may result in transitory increases in plasma 24OHC.


Input: Less than 1% of the total brain excretion of 24OHC occurs via the cerebrospinal fluid (CSF) whereas almost all 27-hydroxycholesterol (27OHC) excretion is dependent on the function of the blood-cerebrospinal fluid barrier.


Input: Iincreased CSF oxysterols were found in patients with neurodegenerative and neuroinflammatory diseases in the presence of barrier dysfunction.

oxysterols


Input: In neurodegeneration, free cholesterol released from dying cells may engulf neurons.

cholesterol


Input: Cholesterol also increases Amyloid beta (A beta) deposition and tau pathology.

Cholesterol


Input: ApoE, 24OHC, tau and soluble APP were correlated in Alzheimer disease (AD) samples.


Input: Excess of cholesterol converted into 24OHC may up-regulate ApoE synthesis which is a scavenger for A beta and Tau.

cholesterol


Input: In AD this protective mechanism seems to be inefficient, probably due to the presence of high concentrations of 27OHC, microvascular dysfunction and the decreased efficiency of ApoE4 as lipid transporter and A beta scavenger.


Input: 24OHC itself was cytotoxic.


Input: Analysis of side chain oxysterols in the CSF is likely to provided useful information about cholesterol metabolism and ApoE function in the pathogenesis of AD.

oxysterols

cholesterol


Input: Anti-inflammatory and antioxidant properties of hydroalcoholic crude extract from Casearia sylvestris Sw.


Input: (Salicaceae).


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris Sw.


Input: is widely used in popular medicine to treat inflammatory conditions.


Input: AIM OF THE STUDY: To investigate the anti-inflammatory and antioxidant properties of hydroalcoholic crude extract (HCE) taken from Casearia sylvestris Sw.


Input: (Salicaceae).


Input: METHODS AND RESULTS: The effect of the HCE from this plant (3-300mg/kg) on the reduction of inflammatory response to carrageenan was investigated in pleurisy in rats (intrapleural, 2% in 0. 2mL) or paw edema in mice (intraplantar, 300 mu g/20 mu L, right hind paw).


Input: The plant anti-inflammatory action was assessed by its capability in inhibiting cell migration, enzymatic activity of myeloperoxidase (MPO) and production of nitrite/nitrate or edema.

nitrite

nitrate


Input: The in vitro antioxidant activity of this extract against lipid peroxidation and damage to proteins was assessed as possible pathways to contribute as anti-inflammatory mechanisms.


Input: Carrageenan-induced hind paw edema (739. 3 +/- 11. 9 mu m) was reduced by HCE (30mg/kg: 462. 8 +/- 28. 38 mu m) to similar extents as dexametasone (365. 1 +/- 16. 7).

dexametasone


Input: In pleurisy, treatment of the animals with HCE (100mg/kg: 0. 010 +/- 0. 001mU/mg of protein) also reduced MPO activity augmented by carrageenan (0. 020 +/- 0. 001mU/mg of protein) as well as leukocytes migration (carrageenan: 17. 8890 +/- 2. 3900leukocytes/mL, HCE 100mg/kg: 7. 0880 +/- 9631leukocytes/mL).


Input: Significant effects were also observed in animals treated with different doses of HCE in biochemical tests for oxidative stress analysis.


Input: CONCLUSION: The anti-inflammatory and antioxidant effects of HCE from Casearia sylvestris Sw. suggests a potential therapeutic benefit of this plant in treatment of inflammatory conditions.


Input: Ethanol extract of Adiantum capillus-veneris L. suppresses the production of inflammatory mediators by inhibiting NF-kappa B activation.

Ethanol


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Adiantum capillus-veneris L.


Input: is a wildly distributed plant species and has been extensively used in south of China as traditional folk medicine for the treatment of inflammatory diseases.


Input: AIM OF THE STUDY: To investigate the anti-inflammatory effect of ethanolic extracts of Adiantum capillus-veneris L. and the involvement of NF-kappa B signaling in the regulation of inflammation.


Input: MATERIALS AND METHODS: The plant ethanolic extracts were initially tested against lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) production in RAW264. 7 mouse macrophages, and interleukin 6 (IL-6) and tumor necrosis factor (TNF) production in human U937 monocytes.

prostaglandin E2


Input: The effect of the plant extracts on the transcription factor nuclear factor kappa B (NF-kappa B) pathway was evaluated in TNF-alpha stimulated HepG2 cells by luciferase gene reporter assay and Western blotting at the transcriptional and translational levels.


Input: Subsequently, the inhibition of NF-kappa B downstream gene expression (IL-8 and ICAM-1) by the plant extracts was assessed via quantitative real time polymerase chain reaction (qPCR).


Input: Lastly, the anti-inflammatory activities of the plant extracts in vivo were evaluated by testing spleen index and NF-kappa B related protein expression in LPS-stimulated CD1 mice.


Input: RESULTS: The plant ethanolic extracts effectively suppressed PGE2, IL-6 and TNF release with an IC50 less than 50 mu g/ml.


Input: Moreover, luciferase expression could be specifically blocked in HepG2 cells, not in HEK293 cells, showing that the plant extracts displayed a cell-specific pattern on NF-kappa B gene transcription.


Input: The assayed biological activity also depended on the order of adding TNF-alpha and the plant extracts because the plant extracts could only block the NF-kappa B activation if added earlier but were unable to stop the signal when added after TNF-alpha.


Input: However, the plant extracts did not exert any effect on ubiquitination which regulates several steps in the NF-kappa B pathway.


Input: Additionally, the plant extracts down-regulated phosphorylation of IKK alpha/beta at S176/180, p38 at T180/Y182 and p65 at S536, but not p65 at S276.


Input: This was confirmed by their ability to selectively abrogate the induction of IL-8 transcription, whereas the ICAM-1 gene, which is not transcribed selectively by an NF-kappa B complex containing a form of p65 phosphorylated on Ser536, did not change.


Input: Finally, the plant extracts at 200 mu g/mg could normalize the LPS-induced elevation of spleen index as well as NF-kappa B and p38 activations in CD1 mice.


Input: CONCLUSION: The present studies presents the potential utilization of this plant extracts, as a natural resources for the development of an anti-inflammatory medicine.


Input: Neuroprotection by steroids after neurotrauma in organotypic spinal cord cultures: A key role for progesterone receptors and steroidal modulators of GABAA receptors.

steroids

progesterone


Input: Progesterone is neuroprotective after spinal cord injury, however its mechanism of action remains unexplored.

Progesterone


Input: Here we used organotypic spinal cord slice cultures from 3 weeks-old mice to evaluate the mechanisms of neuroprotection by progesterone and its 5 alpha-reduced metabolites.

progesterone


Input: In vitro spinal cord injury, using a weight drop model, induced a decrease in the number of motoneurons.


Input: This was correlated with an increase in the number of dying cells (PI (+) cells) and in LDH release.


Input: Addition of 10 mu M of progesterone, 5 alpha-dihydroprogesterone (5 alpha-DHP) or allopregnanolone (3 alpha, 5 alpha-tetrahydroprogesterone) to the medium at the time of injury rescued the spinal cord slices from the effects of damage.

progesterone

5 alpha-dihydroprogesterone

5 alpha-DHP

allopregnanolone

3 alpha, 5 alpha-tetrahydroprogesterone


Input: Progesterone prevented membrane cell damage, motoneuron loss and cell death.

Progesterone


Input: These effects were not due to its bioconversion to 5 alpha-DHP nor to allopregnanolone, as supported by the finasteride, an inhibitor of 5 alpha-reductase enzymes, and by the absence of 5 alpha-reduced progesterone metabolites in the slices analyzed by gas chromatography-mass spectrometry.

5 alpha-DHP

allopregnanolone

finasteride

progesterone


Input: The neuroprotective effects of progesterone required PR as they could not be observed in slices from homozygous knockout PR (-/-) mice.

progesterone


Input: Allopregnanolone treatment was also neuroprotective.

Allopregnanolone


Input: Its effects were not due to its bioconversion back to 5 alpha-DHP, which can activate gene transcription via PR, because they were still observed in slices from knockout PR (-/-) mice.

5 alpha-DHP


Input: Allopregnanolone effects involved GABAA receptors, as they were inhibited by the selective GABAA receptor antagonist Gabazine, in both PR (+/+) and PR (-/-) mice.

Allopregnanolone

Gabazine


Input: Altogether, these findings identify both PR and GABAA receptors as important targets for neuroprotection by progestagens after spinal cord injury.

progestagens


Input: Central functional response to the novel peptide cannabinoid, hemopressin.

hemopressin


Input: Hemopressin is the first peptide ligand to be described for the CB1 cannabinoid receptor.

Hemopressin


Input: Hemopressin acts as an inverse agonist in vivo and can cross the blood-brain barrier to both inhibit appetite and induce antinociception.

Hemopressin


Input: Despite being highly effective, synthetic CB1 inverse agonists are limited therapeutically due to unwanted, over dampening of central reward pathways.


Input: However, hemopressin appears to have its effect on appetite by affecting satiety rather than reward, suggesting an alternative mode of action which might avoid adverse side effects.

hemopressin


Input: Here, to resolve the neuronal circuitry mediating hemopressin' s actions, we have combined blood-oxygen-level-dependent, pharmacological-challenge magnetic resonance imaging with c-Fos functional activity mapping to compare brain regions responsive to systemic administration of hemopressin and the synthetic CB1 inverse agonist, AM251.

hemopressin

oxygen

hemopressin


Input: Using these complementary methods, we demonstrate that hemopressin activates distinct neuronal substrates within the brain, focused mainly on the feeding-related circuits of the mediobasal hypothalamus and in nociceptive regions of the periaqueductal grey (PAG) and dorsal raphe (DR).

hemopressin


Input: In contrast to AM251, there is a distinct lack of activation of the brain reward centres, such as the ventral tegmental area, nucleus accumbens and orbitofrontal cortex, which normally form a functional activity signature for the central action of synthetic CB1 receptor inverse agonists.


Input: Thus, hemopressin modulates the function of key feeding-related brain nuclei of the mediobasal hypothalamus, and descending pain pathways of the PAG and DR, and not higher limbic structures.

hemopressin


Input: Thus, hemopressin may offer behaviourally selective effects on nociception and appetite, without engaging reward pathways.

hemopressin


Input: A novel method for preparing complete antigens of gonyautoxin 2, 3 and their feature of immunogenicity.

gonyautoxin 2, 3


Input: In this paper, a novel method was proposed to prepare artificial antigens of gonyaulax parlaytic shellfish toxin 2 and 3 (GTX2, 3).

GTX2, 3


Input: An intermediate GTX2, 3-aldehyde was first synthesized by activating the NH2 group of the 2nd and 8th amino acid residues with three different aldehydes and two artificial complete antigens GTX2, 3-aldehyde-bovine serum albumin (BSA) and GTX2, 3-aldehyde-keyhole limpet hemocyanin (KLH) were then prepared by cross-linking the intermediate with BSA or KLH.

GTX2, 3-aldehyde

amino acid

aldehydes

GTX2, 3-aldehyde

GTX2, 3-aldehyde


Input: The successful preparation of the two complete antigens was confirmed by UV spectral scanning, HPLC, production of antibodies with titer of 1. 28 x 10 (4) from mice immunized with the two complete antigens, indirect ELISA and Western-blot.


Input: In conclusion, the synthesized complete antigens have strong immunogenicity, which provides a solid foundation for preparing GTX2, 3 monoclonal antibody and rapid detection kit.

GTX2, 3


Input: A GLUE uncertainty analysis of a drying model of pharmaceutical granules.


Input: A shift from batch processing towards continuous processing is of interest in the pharmaceutical industry.


Input: However, this transition requires detailed knowledge and process understanding of all consecutive unit operations in a continuous manufacturing line to design adequate control strategies.


Input: This can be facilitated by developing mechanistic models of the multi-phase systems in the process.


Input: Since modelling efforts only started recently in this field, uncertainties about the model predictions are generally neglected.


Input: However, model predictions have an inherent uncertainty (i. e. prediction uncertainty) originating from uncertainty in input data, model parameters, model structure, boundary conditions and software.


Input: In this paper, the model prediction uncertainty is evaluated for a model describing the continuous drying of single pharmaceutical wet granules in a six-segmented fluidized bed drying unit, which is part of the full continuous from-powder-to-tablet manufacturing line (Consigma (TM), GEA Pharma Systems).


Input: A validated model describing the drying behaviour of a single pharmaceutical granule in two consecutive phases is used.


Input: First of all, the effect of the assumptions at the particle level on the prediction uncertainty is assessed.


Input: Secondly, the paper focuses on the influence of the most sensitive parameters in the model.


Input: Finally, a combined analysis (particle level plus most sensitive parameters) is performed and discussed.


Input: To propagate the uncertainty originating from the parameter uncertainty to the model output, the Generalized Likelihood Uncertainty Estimation (GLUE) method is used.


Input: This method enables a modeller to incorporate the information obtained from the experimental data in the assessment of the uncertain model predictions and to find a balance between model performance and data precision.


Input: A detailed evaluation of the obtained uncertainty analysis results is made with respect to the model structure, interactions between parameters and uncertainty boundaries.


Input: Liver X receptors: Emerging therapeutic targets for Alzheimer' s disease.


Input: Alzheimer' s disease (AD) is a complex neurodegenerative disorder, typified by the pathological accumulation of beta-amyloid peptides (A beta) and neurofibrillary tangles within the brain, culminating to cognitive impairment.


Input: Epidemiological and biochemical data have suggested a link between cholesterol content, APP (amyloid precursor protein) processing, A beta, inflammation and AD.

cholesterol


Input: The intricacy of the disease presents considerable challenges for the development of newer therapeutic agents.


Input: Liver X receptors (LXRa and LXR beta) are oxysterol activated nuclear receptors that play essential role in lipid and glucose homeostasis, steroidogenesis and inflammatory responses.

oxysterol

glucose


Input: LXR signalling impacts the development of AD pathology through multiple pathways.


Input: Reports indicate that genetic loss of either lxra or lxr beta in APP/PS1 transgenic mice results in increased amyloid plaque load.


Input: Studies also suggest that ligand activation of LXRs in Tg2576 mice enhanced, the expression of genes linked with cholesterol efflux e. g. apoe, abca-1, down regulated APP processing and A beta production with significant improvement in memory functions.

cholesterol


Input: LXR agonists have also depicted to inhibit neuroinflammation through modulation of microglial phagocytosis and by repressing the expression of cox2, mcp1 and iNos in glial cells.


Input: This review summarizes in brief the biology of LXRs, with an emphasis on their probable pathophysiological mechanisms that may elicit the defending role of these receptors in brains of AD patients.


Input: Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria.

cocaine

cocaine

morphine


Input: Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers.

cocaine


Input: Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented.

Cocaine


Input: Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction.

cocaine


Input: In this work, we compared the effects of cocaine and/or morphine on the bioenergetics of isolated brain and liver mitochondria, to understand their specific effects in each tissue.

cocaine

morphine


Input: Upon energization with complex I substrates, cocaine decreased state-3 respiration in brain (but not in liver) mitochondria and decreased uncoupled respiration and mitochondrial potential in both tissues, through a direct effect on complex I.

cocaine


Input: Morphine presented only slight effects on brain and liver mitochondria, and the combination cocaine + morphine had similar effects to cocaine alone, except for a greater decrease in state-3 respiration.

Morphine

cocaine

morphine

cocaine


Input: Brain and liver mitochondrial respirations were differentially affected, and liver mitochondria were more prone to proton leak caused by the drugs or their combination.


Input: This was possibly related with a different dependence on complex I in mitochondrial populations from these tissues.


Input: In summary, cocaine and cocaine + morphine induce mitochondrial complex I dysfunction in isolated brain and liver mitochondria, with specific effects in each tissue.

cocaine

cocaine

morphine


Input: In vitro characterisation of the anti-intravasative properties of the marine product heteronemin.

heteronemin


Input: Metastases destroy the function of infested organs and are the main reason of cancer-related mortality.


Input: Heteronemin, a natural product derived from a marine sponge, was tested in vitro regarding its properties to prevent tumour cell intravasation through the lymph-endothelial barrier.

Heteronemin


Input: In three-dimensional (3D) cell cultures consisting of MCF-7 breast cancer cell spheroids that were placed on lymph-endothelial cell (LEC) monolayers, tumour cell spheroids induce " circular chemorepellent-induced defects " (CCIDs) in the LEC monolayer; 12 (S)-Hydroxyeicosatetraenoic acid (12 (S)-HETE) and NF-kappa B activity are major factors inducing CCIDs, which are entry gates for tumour emboli intravasating the vasculature.

12 (S)-Hydroxyeicosatetraenoic acid

12 (S)-HETE


Input: This 3D co-culture is a validated model for the investigation of intravasation mechanisms and of drugs preventing CCID formation and hence lymph node metastasis.


Input: Furthermore, Western blot analyses, NF-kappa B reporter, EROD, SELE, 12 (S)-HETE, and adhesion assays were performed to investigate the properties of heteronemin.

12 (S)-HETE

heteronemin


Input: Five micromolar heteronemin inhibited the directional movement of LECs and, therefore, the formation of CCIDs, which were induced by MCF-7 spheroids.

heteronemin


Input: Furthermore, heteronemin reduced the adhesion of MCF-7 cells to LECs and suppressed 12 (S)-HETE-induced expression of the EMT marker paxillin, which is a regulator of directional cell migration.

heteronemin

12 (S)-HETE


Input: The activity of CYP1A1, which contributed to CCID formation, was also inhibited by heteronemin.

heteronemin


Input: Hence, heteronemin inhibits important mechanisms contributing to tumour intravasation in vitro and should be tested in vivo.

heteronemin


Input: Nicotine-Induced Structural Plasticity in Mesencephalic Dopaminergic Neurons Is Mediated by Dopamine D3 Receptors and Akt-mTORC1 Signalling.

Nicotine

Dopaminergic


Input: Though long-term exposure to nicotine is highly addictive, one " beneficial " consequence of chronic tobacco use is a reduced risk for Parkinson' s disease.

nicotine


Input: Interestingly, these effects both reflect structural and functional plasticity of brain circuits controlling reward and motor behavior, and specifically recruitment of nicotinic acetylcholine receptors (nAChR) in mesencephalic dopaminergic neurons.

acetylcholine


Input: Since the underlying cellular mechanisms are poorly understood, we addressed this issue employing primary cultures of mouse mesencephalic dopaminergic neurons.


Input: Exposure to nicotine (1-10 mu M) for 72 hr in vitro increased dendritic arborization and soma size in primary cultures.

nicotine


Input: These effects were blocked by mecamylamine and dihydro-beta-erythroidine, but not methyllycaconitine.

mecamylamine

dihydro-beta-erythroidine

methyllycaconitine


Input: The involvement of alpha 4 beta 2 nAChR was supported by the lack of nicotine-induced structural remodeling in neurons from alpha 4 null mutant mice (KO).

nicotine


Input: Challenge with nicotine triggered phosphorylation of the extracellular signal-regulated kinase (ERK) and the thymoma viral proto-oncogene (Akt) followed by activation of the mTORC1-dependent p70 ribosomal S6 protein kinase.

nicotine


Input: Upstream pathway blockade using the phosphatidylinositol 3-kinase inhibitor LY294002 resulted in suppression of nicotine-induced phosphorylations and structural plasticity.

phosphatidylinositol

nicotine


Input: These effects were dependent upon functional DA D3 receptor (D3R) since nicotine was inactive both in cultures from D3R KO mice and following pharmacologic blockade with D3R antagonist SB-277011-A (50 nM).

nicotine


Input: Finally, exposure to nicotine in utero (5 mg/kg/day for 5 days) resulted in increased soma area of DAergic neurons of newborn mice, effects not observed in D3KO mice.

nicotine


Input: These findings indicate that nicotine-induced structural plasticity in mesencephalic dopaminergic neurons involves alpha 4 beta 2 nAChRs together with dopamine D3R-mediated recruitment of ERK/Akt-mTORC1 signaling.

nicotine

dopaminergic


Input: Macroprolactinemia in hyperprolactinemic infertile women.


Input: Hyperprolactinemia occurs in 15-20% of women with menstrual disturbances and 30-40% of infertile women and it can adversely affect the fertility.


Input: High molecular weight prolactin (macroprolactin) has long been known in hyperprolactinemic fertile women.


Input: However, the prevalence of macroprolactinemia in hyperprolactinemic infertile women is not known.


Input: This cross-sectional study was carried out during the period of June 2010 and June 2011 at a single tertiary care centre.


Input: All women who attended the infertility clinic during this period were screened for hyperprolactinemia and only women with hyperprolactinemia and infertility were further studied for the presence of macroprolactin by polyethylene glycol precipitation assay.

polyethylene glycol


Input: We compared the clinical, hormonal profile and fertility outcome of infertile women with true hyperprolactinemia and macroprolacinemia using appropriate statistical tests.


Input: Of 1, 163 infertile women, 183 (15. 7%) had hyperprolactinemia [134 (73%) had primary infertility and 49 (27%) had secondary infertility].


Input: Out of these 183 women with hyperprolactinemia, one had microadenoma, 161 had true idiopathic hyperprolactinemia and 21 (11. 5%) women had macroprolactinemia.


Input: The prevalence of oligomenorrhea and galactorrhea were significantly higher in patients with true hyperprolactinemia than macroprolactinemia (46 vs. 14%, p < 0. 008 and 30 vs. 5%, p = 0. 01 respectively).


Input: Twenty-two patients (13. 5%) of true hyperprolactinemia and two (9%) in macroprolactinemia became pregnant during the study period.


Input: Prolactin measurement should be a part of routine evaluation of couples referred to infertility clinics.


Input: Macroprolactin screening is mandatory when clinical features and serum PRL assay results are conflicting.


Input: Patients with macroprolactinemia should be investigated for causes of infertility other than hyperprolactinemia.


Input: Theoretical Considerations and Practical Approaches to Address the Effect of Anti-drug Antibody (ADA) on Quantification of Biotherapeutics in Circulation.


Input: Continuous improvement in bioanalytical method development is desired in order to ensure the quality of the data and to better support pharmacokinetic (PK) and safety studies of biotherapeutics.


Input: One area that has been getting increasing attention recently is in the assessment of " free " and " total " analyte and the impact of the assay format on those assessments.


Input: To compliment these considerations, the authors provide a critical review of available literature and prospectively explore methods to mitigate the potential impact of anti-drug antibody on PK assay measurement.


Input: This challenge is of particular interest and importance since biotherapeutic drugs often elicit an immune response, and thus may have a direct impact on quantification of the drug for its PK and safety evaluations.


Input: Pharmacokinetic characterization of CK2 inhibitor CX-4945.


Input: Over-expression of protein kinase CK2 is highly linked to the survival of cancer cells and the poor prognosis of patients with cancers.


Input: CX-4945, a potent and selective orally bioavailable ATP-competitive inhibitor of CK2, inhibits the oncogenic cellular events such as proliferation and angiogenesis, and the increase of tumor growth in mouse xenograft model.

ATP


Input: In this study, the pharmacokinetic information about CX-4945 was provided; at 10 mu M, CX-4945 with high stability in human and rat liver microsome exhibited low percentage of inhibition (< 10%) in CYP450 isoforms (1A2, 2C19, 3A4), but considerable inhibition (~ 70%) in CYP450 2C9 and 2D6.


Input: In hERG potassium channel inhibition assay, CX-4945 exhibited relatively low inhibition rate.

potassium


Input: Additionally, CX-4945 showed high MDCK cell permeability (> 10 x 10 (-6) cm/s) and above 98% of plasma protein binding in the rat.


Input: After intravenous administration, Vss (1. 39 l/kg) and extremely low CL (0. 08 l/kg/h) were observed.


Input: Moreover, orally administrated CX-4945 showed high bioavailability (> 70%) and these data might be related to the MDCK cell permeability results.


Input: Novel 4-substituted-2 (1H)-phthalazinone derivatives: synthesis, molecular modeling study and their effects on alpha-receptors.

4-substituted-2 (1H)-phthalazinone


Input: Novel 4-(4-bromophenyl) phthalazine derivatives connected via an alkyl spacer to amine or N-substituted piperazine were designed and synthesized as promising alpha-adrenoceptor antagonists.

4-(4-bromophenyl) phthalazine

alkyl

amine

N-substituted piperazine


Input: The structures of the phthalazine derivatives were established using elemental and spectral analyses.

phthalazine


Input: Twelve of the tested compounds displayed significant alpha-blocking activity.


Input: Molecular modeling studies were performed to rationalize the biological results.


Input: Among the tested compounds, 7j displayed the best-fitting score and the highest in vitro activity.


Input: Nickel and Cobalt-Catalyzed Coupling of Alkyl Halides with Alkenes via Heck Reactions and Radical Conjugate Addition.

Nickel

Cobalt

Alkyl Halides

Alkenes


Input: Cross-coupling of alkyl halides with alkenes leading to Heck-type and addition products is summarized.

alkyl halides

alkenes


Input: The development of Heck reaction with aliphatic halides although has made significant progress in the past decade and particularly recently, it was much less explored in comparison with the aryl halides.

aliphatic halides

aryl halides


Input: The use of Ni-and Co-catalyzed protocols allowed efficient Heck coupling of activated and unactivated alkenes with 1 (o), 2 (o) and 3 (o) alkyl halides.

Ni

Co

alkenes

alkyl halides


Input: In addition, radical conjugate addition to activated alkenes has become a well-established method that has led to efficient construction of many natural products.

alkenes


Input: The utilization of Ni-and Co-catalyzed strategies would avoid toxic tin reagents, and therefore worth exploring.

Ni

Co


Input: The recent development of Ni-and Co-catalyzed addition of alkyl halides to alkenes displays much improved reactivity and functional group tolerance.

Ni

Co

alkyl halides

alkenes


Input: In this mini-review, we also attempt to overview the mechanisms that are proposed in the reactions, aiming at providing insight into the nickel and cobalt-catalyzed coupling of alkyl halides with alkenes.

nickel

cobalt

alkyl halides

alkenes


Input: Pyrazolines: a biological review.

Pyrazolines


Input: Pyrazoline is an important five membered nitrogen heterocycle, which has been extensively researched upon.

Pyrazoline

nitrogen


Input: The ring is quite stable and has inspired chemists to carry out various structural variations in the ring.


Input: This has propelled the development of distinct pyrazolines with an array of pharmacological activities viz. anti-inflammatory, analgesic, antimicrobial, anticancer, antidepressant etc.

pyrazolines


Input: The review aims at highlighting this pharmacological diversity of pyrazolines.

pyrazolines


Input: The review is a gist of latest work done describing the pharmacological aspects and potential of pyrazoline ring.

pyrazoline


Input: Nanoscale Imaging of Neutral Atoms with a Pulsed Magnetic Lens.


Input: We present a scheme for imaging of neutral atoms to the nanoscale with a pulsed magnetic lens and show its viability through numerical calculations.


Input: This scheme achieves focal lengths on the order of several centimeters and focal spots of less than 10 nm.


Input: With these results, it is possible to create sub-10 nm structures on surfaces in a parallel and time-efficient manner.


Input: When used with metastable noble gas atoms, and in combination with electron spectroscopy, this scheme can create a chemically sensitive microscope which can probe surfaces on the nanometer scale.


Input: In Vitro Fertilization outcomes in treated hypothyroidism.


Input: Background: Levothyroxine has been shown to enhance pregnancy outcomes in women with hypothyroidism requiring In Vitro Fertilization (IVF).

Levothyroxine


Input: However, the precise magnitude of these benefits remains to be determined.


Input: In particular, it has yet to be clarified whether levothyroxine may fully overcome the detrimental effects of hypothyroidism or, conversely, whether affected women remain at reduced prognosis for pregnancy outcomes.

levothyroxine


Input: Methods: Patients who underwent IVF-ICSI (IVF-intracytoplasmic sperm injection) over a three-year period were reviewed.


Input: Cases were deemed eligible if they were diagnosed with clinical or subclinical hypothyroidism and were receiving levothyroxine.

levothyroxine


Input: Controls were two subsequently age-matched euthyroid women for every case.


Input: Both cases and controls were selected only if serum TSH was <= 2. 5 mIU/L.


Input: Results: One hundred thirty-seven women with treated hypothyroidism and 274 controls were included.


Input: Baseline characteristics of the two study groups were similar with the exception of BMI, which was slightly higher among the cases (22. 9 +/- 3. 9 versus 21. 9 +/- 3. 3 Kg/m2, p = 0. 013).


Input: Most IVF-ICSI cycle outcome variables were also similar with the exception of a higher rate of cancellation for poor response (3. 6% versus 0. 7%, p = 0. 04), a longer duration of stimulation (10. 9 +/- 2. 2 versus 10. 1 +/- 2. 0 days, p = 0. 001), a higher proportion of women failing to obtain viable embryos (17% versus 7%, p = 0. 006), and a lower fertilization rate (75% versus 86%, p = 0. 017) among cases.


Input: Conversely, the clinical pregnancy rate per started cycle, the implantation rate and the live birth rate per started cycle did not differ; they were 36% and 34% (p = 0. 93), 28% and 22% (p = 0. 11) and 30% and 27% (p = 0. 50) in cases and controls, respectively.


Input: Subgroup analyses comparing women with (n = 79) and without (n = 58) thyroid autoimmunity and comparing women who were diagnosed with overt hypothyroidism (n = 70) or subclinical hypothyroidism (n = 67) failed to identify relevant differences.


Input: Conclusions: In our population, IVF-ICSI outcome was not significantly hampered in women with adequately treated hypothyroidism.


Input: The magnitude of the detected differences in cycle outcome was mild and we failed to document any differences for the most relevant outcomes, i. e. pregnancy rate, implantation rate and delivery rate.


Input: In conclusion, adequate levothyroxine treatment maintaining TSH serum levels below 2. 5 mIU/L may overcome the detrimental effects of hypothyroidism.

levothyroxine


Input: Chronic dietary exposure to chlorpyrifos causes behavioral impairments, low activity of brain membrane-bound acetylcholinesterase, and increased brain acetylcholinesterase-R mRNA.

chlorpyrifos


Input: Chlorpyrifos (CPF) is an organophosphate (OP) insecticide that is metabolically activated to the highly toxic chlorpyrifos oxon.

Chlorpyrifos

CPF

organophosphate

chlorpyrifos oxon


Input: Dietary exposure is the main route of intoxication for non-occupational exposures.


Input: However, only limited behavioral effects of chronic dietary exposure have been investigated.


Input: Therefore, male Wistar rats were fed a dose of 5mg/kg/day of CPF for thirty-one weeks.

CPF


Input: Animals were evaluated in spatial learning and impulsivity tasks after 21 weeks of CPF dietary exposure and one week after exposure ended, respectively.

CPF


Input: In addition, the degree of inhibition of brain acetylcholinesterase (AChE) was evaluated for both the soluble and particulate forms of the enzyme, as well as AChE gene expression.


Input: Also, brain acylpeptide hydrolase (APH) was investigated as an alternative target for OP-mediated effects.


Input: All variables were evaluated at various time points in response to CPF diet and after exposure ended.

CPF


Input: Results from behavioral procedures suggest cognitive and emotional disorders.


Input: Moreover, low levels of activity representing membrane-bound oligomeric forms (tetramers) were also observed.


Input: In addition, increased brain AChE-R mRNA levels were detected after four weeks of CPF dietary exposure.

CPF


Input: However, no changes in levels of brain APH were observed among groups.


Input: In conclusion, our data point to a relationship between cognitive impairments and changes in AChE forms, specifically to a high inhibition of the particulate form and a modification of alternative splicing of mRNA during CPF dietary exposure.

CPF


Input: In vitro intestinal and hepatic metabolism of Di (2-ethylhexyl) phthalate (DEHP) in human and rat.

Di (2-ethylhexyl) phthalate

DEHP


Input: Species and organ differences in the intrinsic clearance and the enzymes involved in the metabolism of DEHP were examined in subcellular fractions of the intestine and liver as well as by recombinant cytochrome P450 (CYP) isoforms of human and rat.

DEHP


Input: Estimated clearance (CLint) of DEHP via esterase-mediated pathway in human intestine was 2. 4-fold greater than that in human liver while its value in rat intestine was 1. 7-fold less than that in rat liver.

DEHP


Input: Ranks of CLint for CYP-mediated oxidation/dealkylation of MEHP were human liver > rat liver > human intestine > rat intestine.

MEHP


Input: Estimates of CLint for the production of mono (2-ethyl-5-hydroxyhexyl) phthalate and mono (2-ethyl-5-oxohexyl) phthalate by human CYP2C9 (*) 1 were 4. 2-and 2. 6-fold greater than those by rat CYP2C6, respectively.

mono (2-ethyl-5-hydroxyhexyl) phthalate

mono (2-ethyl-5-oxohexyl) phthalate


Input: Total CLint via hCYP2C9 (*) 3-mediated oxidation was 1. 9-and 2. 6-fold less than those by hCYP2C9 (*) 2 and 2C9 (*) 1, respectively.


Input: Estimated CLint for phthalic acid production by hCYP3A4 was 24. 5 mu LnmolCYP (-1) min (-1) while it was continuously produced by rCYP2C6 and 3A2 via passive mechanism.

phthalic acid


Input: These species/organ differences in major metabolic pathway and CYP isoforms should be considered for appraisal of the potential adverse health effects of DEHP.

DEHP


Input: Electroactive nanoparticle directed assembly of functionalized graphene nanosheets into hierarchical structures with hybrid compositions for flexible supercapacitors.

graphene


Input: Hierarchical structures of hybrid materials with the controlled compositions have been shown to offer a breakthrough for energy storage and conversion.


Input: Here, we report the integrative assembly of chemically modified graphene (CMG) building blocks into hierarchical complex structures with the hybrid composition for high performance flexible pseudocapacitors.

graphene


Input: The formation mechanism of hierarchical CMG/Nafion/RuO2 (CMGNR) microspheres, which is triggered by the cooperative interplay during the in situ synthesis of RuO2 nanoparticles (NPs), was extensively investigated.

Nafion


Input: In particular, the hierarchical CMGNR microspheres consisting of the aggregates of CMG/Nafion (CMGN) nanosheets and RuO2 NPs provided large surface area and facile ion accessibility to storage sites, while the interconnected nanosheets offered continuous electron pathways and mechanical integrity.

Nafion


Input: The synergistic effect of CMGNR hybrids on the supercapacitor (SC) performance was derived from the hybrid composition of pseudocapacitive RuO2 NPs with the conductive CMGNs as well as from structural features.


Input: Consequently, the CMGNR-SCs showed a specific capacitance as high as 160 F g (-1), three-fold higher than that of conventional graphene SCs, and a capacitance retention of > 95% of the maximum value even after severe bending and 1000 charge-discharge tests due to the structural and compositional features.

graphene


Input: Beneficial influence of topical extra virgin olive oil application on an experimental model of penile fracture in rats.


Input: Penile fracture (PF) is known as a traumatic rupture of the tunica albuginea of corpus cavernosum.


Input: In this study, we aimed to investigate the healing influence of topical extra virgin olive oil (EVOO) on PF through evaluating levels of some oxidative stress biomarkers for the first time.


Input: Histopathological evaluation was also realized.


Input: A total of 18 male Sprague-Dawley albino rats were divided into three groups of six rats each as control group, in PF (alone) group, and PF + EVOO group.


Input: Experimental PF was formed via incising from the proximal dorsal side of the penis in the rats of all groups except control.


Input: While in PF (alone) group, fracture was formed and the incision was primarily closed, in PF + EVOO group in addition to foregoing processes, EVOO was also administrated topically twice a day for 3 weeks.


Input: At the end of the experiment, all rats were killed and penectomy was carried out.


Input: While malondialdehyde, myeloperoxidase, lipid hyroperoxide, and total oxidant status significantly (p < 0. 05) increased, reduced glutathione and total free sulfhydryl groups markedly (p < 0. 05) decreased in PF (alone) group when compared with PF + EVOO group.

malondialdehyde

hyroperoxide

glutathione

sulfhydryl


Input: Levels of these parameters were reversed to nearly normal values by topical EVOO application.


Input: Protection by EVOO is further substantiated via the improved histological findings in PF + EVOO group as against degenerative changes in the rats of PF (alone) group.


Input: Our data revealed that EVOO has protective effect in penile cavernosal tissue through probably its antioxidant, free radical defusing, anti-inflammatory, and antimicrobial effects.


Input: Design, Synthesis and Antiviral Activity of 2-(3-Amino-4-piperazinylphenyl) chromone Derivatives.

2-(3-Amino-4-piperazinylphenyl) chromone


Input: Previously, we have confirmed that the antiviral activities of the chromone derivatives were controlled by the type as well as the position of the substituents attached to the chromone core structure.

chromone

chromone


Input: In the course of our ongoing efforts to optimize the antiviral activity of the chromone derivatives, we have been attempting to derivatize the chromone scaffold via introduction of various substituents.

chromone

chromone


Input: In this proof-of-concept study, we introduced a 3-amino-4-piperazinylphenyl functionality to the chromone scaffold and evaluated the antiviral activities of the resulting chromone derivatives.

chromone

chromone


Input: The synthesized 2-(3-amino-4-piperazinylphenyl)-chromones showed severe acute respiratory syndrome-corona virus (SARS-CoV)-specific antiviral activity.

2-(3-amino-4-piperazinylphenyl)-chromones


Input: In particular, the 2-pyridinylpiperazinylphenyl substituents provided the resulting chromone derivatives with selective antiviral activity.

chromone


Input: Taken together, this result indicates the possible pharmacophoric role of the 2-pyridinylpiperazine functionality attached to the chromone scaffold, which warrants further in-depth structure-activity relationship study.

chromone


Input: Randomly amplified polymorphic-DNA analysis for detecting genotoxic effects of Boron on maize (Zea mays L.).

Boron


Input: This study was carried out to investigate the genotoxic effect of boron (B) on maize using randomly amplified polymorphic DNA (RAPD) method.

boron

B


Input: Experimental design was conducted under 0, 5, 10, 25, 50, 100, 125, and 150 ppm B exposures, and physiological changes have revealed a sharp decrease in root growth rates from 28% to 85%, starting from 25 ppm to 150 ppm, respectively.

B


Input: RAPD-polymerase chain reaction (PCR) analysis shows that DNA alterations are clearly observed from beginning to 100 ppm.


Input: B-induced inhibition in root growth had a positive correlation with DNA alterations.

B


Input: Total soluble protein, root and stem lengths, and B content analysis in root and leaves encourage these results as a consequence.

B


Input: These preliminary findings reveal that B causes chromosomal aberration and genotoxic effects on maize.

B


Input: Meanwhile, usage of RAPD-PCR technique is a suitable biomarker to detect genotoxic effect of B on maize and other crops for the future.

B


Input: PTHrP is endogenous relaxant for spontaneous smooth muscle contraction in urinary bladder of female rat.


Input: Acute bladder distension causes various morphological and functional changes, in part through altered gene expression.


Input: We aimed to investigate the physiological role of PTHrP, which is upregulated in an acute bladder distension model in female rats.


Input: In the control Empty group, bladders were kept empty for 6 h, and in the Distension group, bladders were kept distended for 3 h after an artificial storing-voiding cycle for 3 h.


Input: In the Distention group bladder, upregulation of transcripts was noted for three genes reported to be upregulated by stretch in the cultured bladder smooth muscle cells (BSMC) in vitro.


Input: Further transcriptome analysis by microarray identified PTHrP as the 2second highest gene upregulated in Distension group bladder, among more than 27, 000 genes.


Input: Localization of PTHrP and its functional receptor, PTH/PTHrP receptor 1 (PTH1R), were analyzed in the untreated rat bladders and cultured bladder cells using real-time RT-PCR and immunoblotting, which revealed that PTH1R and PTHrP were more predominantly expressed in smooth muscle than in urothelium.


Input: Exogenous PTHrP peptide (1-34) increased intracellular cAMP level in cultured BSMC.

cAMP


Input: In organ bath study using bladder strips, the PTHrP peptide caused a marked reduction in the amplitude of spontaneous contraction, but caused only modest suppression for carbachol-induced contraction.

carbachol


Input: In in vivo functional study by cystometrogram, the PTHrP peptide decreased voiding pressure and increased bladder compliance.


Input: Thus, PTHrP is a potent endogenous relaxant of bladder contraction, and autocrine or paracrine mechanism of PTHrP-PTH1R axis is a physiologically relevant pathway functioning in the bladder.


Input: 17 beta-estradiol activates glucose uptake via GLUT4 translocation and PI3K/Akt signaling pathway in MCF-7 cells.

17 beta-estradiol

glucose


Input: The relationship between estrogen and some types of breast cancer has been clearly established.

estrogen


Input: However, although several studies have demonstrated the relationship between estrogen and glucose uptake via PI3K/Akt in other tissues, not too much is known about the possible cross talk between them for development and maintenance of breast cancer.

estrogen

glucose


Input: This study was designed to test the rapid effects of 17 beta-estradiol (E2) or its membrane-impermeable form conjugated with bovine serum albumin (E2BSA) on glucose uptake in a positive estrogen receptor (ER) breast cancer cell line, through the possible relationship between key components of the PI3K/Akt signaling pathway and acute steroid treatment.

17 beta-estradiol

glucose

estrogen

steroid


Input: MCF-7 human breast cancer cells were cultured in standard conditions.


Input: Then 10nM of 17 beta-estradiol or estradiol BSA conjugated were administrated before obtaining the cell lysates.

17 beta-estradiol

estradiol


Input: To study the glucose uptake, the glucose fluorescent analogue 2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-d-glucose was used.

glucose

glucose

2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-d-glucose


Input: We report an ER-dependent activation of some of the key steps of the PI3K/Akt signaling pathway cascade that leads cells to improve some mechanisms that finally increase glucose uptake capacity.

glucose


Input: Our data suggest that both E2 and E2BSA enhance the entrance of the fluorescent glucose analogue 2-NBDG, and also activates s PI3K/Akt signaling pathway, leading to translocation of GLUT4 to the plasma membrane in an ER alpha dependent manner.

glucose


Input: E2 enhances ER-dependent rapid signaling triggered, partially in the plasma membrane, allowing ER alpha-positive MCF-7 breast cancer cells to increase glucose uptake, which could be essential to meet the energy demands of the high rate of proliferation.

glucose


Input: The consumption of n-3 polyunsaturated fatty acids differentially modulates gene expression of peroxisome proliferator-activated receptor alpha and gamma and hypoxia-inducible factor 1 alpha in subcutaneous adipose tissue of obese adolescents.

n-3 polyunsaturated fatty acids


Input: The aim of this study was to evaluate the effect of long-chain omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on metabolic state and gene expression in subcutaneous adipose tissues of obese adolescents.

omega-3 polyunsaturated fatty acid

n-3 PUFA


Input: Obese adolescents (n = 26, 10 girls and 16 boys) aged 12. 4 +/- 2. 1 years were assigned to a 12-week regimen of n-3 PUFA intake.

n-3 PUFA


Input: Five times per day, subjects received a food supplement consisting of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (3 g per day, 944 mg EPA, and 2, 088 mg DHA).

eicosapentaenoic acid

EPA

docosahexaenoic acid

DHA

EPA

DHA


Input: Blood parameters were measured, and subcutaneous adipose tissue biopsies were analyzed to determine gene expression at baseline and after 12 weeks.


Input: Student' s t test and the Wilcoxon signed-rank test were used to estimate differences in arithmetic means of pre-and post-dietary supplementation for various anthropometric, biochemical, clinical, and gene expression parameters.


Input: After 12 weeks, n-3 PUFA consumption was associated with decreased body mass index (29. 7 +/- 4. 6 vs. 27. 8 +/- 4. 4 kg/m (2); P < 0. 001), waist circumference (93. 2 +/- 9. 9 vs. 90. 5 +/- 10. 0 cm; P < 0. 003), hip circumference (102. 9 +/- 10. 9 vs. 101. 1 +/- 10. 9 cm; P < 0. 014), and blood triglyceride levels (220. 8 +/- 27. 4 vs. 99. 7 +/- 32. 7 mg/dL; P < 0. 001).

n-3 PUFA

triglyceride


Input: Fatty acid supplementation/n3 PUFA supplementation was associated with a downregulated expression of the genes encoding PPAR gamma and PGC-1 alpha (P < 0. 001), and an upregulated expression of the genes encoding PPAR alpha (P < 0. 007) and SREBP1 (P < 0. 021).

Fatty acid

n3 PUFA


Input: The expressions of SOD2 (P < 0. 04), CAT (P < 0. 001), GPX3 (P < 0. 032) and HIF-1 alpha protein also decreased.


Input: Our study demonstrated that n-3 PUFA consumption and dietary restriction improved the anthropometric parameters and decreased the triglycerides levels of the adolescents, suggesting a reduction in hypoxia in subcutaneous adipose tissue.

n-3 PUFA

triglycerides


Input: Structure of Bradyrhizobium japonicum transcription factor FixK2 unveils sites of DNA binding and oxidation.


Input: FixK2 is an important regulatory protein that helps activating a large number of genes for the anoxic and microoxic, endosymbiotic and nitrogen-fixing life styles of the alpha-proteobacterium Bradyrhizobium japonicum.

nitrogen


Input: FixK2 belongs to the cyclic AMP receptor protein (CRP) superfamily.

cyclic AMP


Input: While most CRP-family members are co-regulated by effector molecules, the activity of FixK2 is negatively controlled by oxidation of its single cysteine (C183) located next to the DNA binding domain, and possibly also by proteolysis.

cysteine


Input: Here we report the three-dimensional X-ray structure of FixK2, a representative of the FixK subgroup of the CRP superfamily.


Input: Crystallization succeeded only (i) when an oxidation-and protease-insensitive protein variant (C183S-FixK2His6) was used, in which C183 was replaced by serine and the C-terminus fused with a hexa-histidine tag, and (ii) when this protein was allowed to form a complex with a 30mer double-strand target DNA.

serine

C

hexa-histidine


Input: The structure of the FixK2-DNA complex was solved at a resolution of 1. 77 A in which the protein formed a homodimer.


Input: The precise protein-DNA contacts were identified which led to an affirmation of the canonical target sequence, the so-called FixK2 box.


Input: The C-terminus is surface-exposed which might explain its sensitivity to specific cleavage and degradation.

C


Input: The oxidation-sensitive C183 is also surface-exposed and in close proximity to DNA.


Input: Therefore, we propose a mechanism whereby the oxo-acids generated after oxidation of the cysteine thiol cause an electrostatic repulsion, thus preventing specific DNA binding.

oxo-acids

cysteine thiol


Input: Nanostructured potential of optical trapping using a plasmonic nanoblock pair.


Input: We performed two-dimensional mapping of optical trapping potentials experienced by a 100 nm dielectric particle above a plasmon-resonant gold nanoblock pair with a gap of several nanometers.


Input: Our results demonstrate that the potentials have nanoscale spatial structures that reflect the near-field landscape of the nanoblock pair.


Input: When an incident polarization parallel to the pair axis is rotated by 90 degrees, a single potential well turns into multiple potential wells separated by a distance smaller than the diffraction limit; this is associated with super-resolution optical trapping.


Input: In addition, we show that the trap stiffness can be enhanced by approximately 3 orders of magnitude compared to that with conventional far-field trapping.


Input: Photoinduced and Thermal Denitrogenation of Bulky Triazoline Crystals: Insights into Solid-to-Solid Transformation.

Triazoline


Input: The photoinduced and thermal denitrogenation of crystalline triazolines with bulky substituents leads to the quantitative formation of aziridines in clean solid-to-solid reactions despite very large structural changes in the transition from reactant to product.

triazolines

aziridines


Input: Analysis of the reaction progress by powder X-ray diffraction, solid-state (13) C CPMAS NMR, solid-state FTIR spectroscopy, and thermal analysis has revealed that solid-to-solid reactions proceed either through metastable phases susceptible to amorphization or by mechanisms that involve a reconstructive phase transition that culminates in the formation of the stable phase of the product.

(13) C


Input: While the key for a solid-to-solid transformation is that the reaction occurs below the eutectic temperature of the reactant and product two-component system, experimental evidence suggests that those reactions will undergo a reconstructive phase transition when they take place above the glass transition temperature.


Input: Genetics of serotonin receptors and depression: state of the art.

serotonin


Input: Major depression (MD) is a major health problem, partly due to the incomplete understanding of the pathogenic mechanisms of the disease.


Input: Research efforts have mainly focused on alterations in monoaminergic neurotransmission, especially in relation to the serotonergic system, due to its key role in the regulation of mood and related biological functions.


Input: Given the high heritability of MD (estimated between 31% and 42% for unipolar depression), genes coding for key regulators of the serotonergic neurotransmission have been considered as optimal candidates.


Input: The present review is focused on the role of genes coding for serotonin receptors in MD pathogenesis, since the serotonin transporter and enzymes involved in serotonin metabolism have been reviewed elsewhere.

serotonin

serotonin

serotonin


Input: Despite the large number of candidate gene studies focusing on genes coding for serotonin receptors, results have been inconsistent.

serotonin


Input: The most replicated findings are the associations between rs6295 (HTR1A gene) G allele or G/G genotype and rs6311 (HTR2A gene) A allele or A/A genotype and MD or depressive symptoms.


Input: Preclinical and imaging/post-mortem studies in humans provide strong support for the involvement of HTR1A and HTR2A genes in MD.


Input: Nevertheless, the inconsistency across previous studies clearly suggests that innovative approaches should be designed in order to overcome the limitations of candidate gene studies.


Input: To date, the most appealing methodologies seem to be full exome or genome sequencing, genome-wide pathway analyses, endophenotypes, and epigenetic biomarkers.


Input: The reported tools may assist in the detection of multiple-loci models, which could potentially explain the high percentage of MD susceptibility ascribed to genetic factors.


Input: Key targets and relevant inhibitors for the drug discovery of tuberculosis.


Input: Tuberculosis (TB) is an infectious disease caused by the pathogen Mycobacterium tuberculosis (M. tuberculosis), killing about two million people worldwide each year.


Input: An increase in the prevalence of drug-resistant strains of M. tuberculosis in the past decades has renewed focus on the development of new drugs that can treat both drug-sensitive and resistant TB infections.


Input: M. tuberculosis evades the host immune system and drug regimes by entering dormant phase within macrophage.


Input: As a consequence, there is a pressing need for new vaccines and antimicrobials to treat persistent infections.


Input: As clinically used antibiotics target very few essential functions of mycobacterium, it is rational that identification of new targets that are essential for bacterial growth and survival can serve as starting point for designing of novel drugs to cure both drug-sensitive and resistant TB infections.


Input: With the development of molecular biology and structural biology and the availability of the genome sequence of M. tuberculosis, some success has been achieved in the identification of new targets in M. tuberculosis and their relevant inhibitors.


Input: This review summarizes about ninety important targets that participate in a range of diverse physiological processes in M. tuberculosis and seven new drugs currently in clinical phase 2 or 3 trials.


Input: In addition, promising inhibitors with novel mechanisms of action and clinical vaccine candidates are highlighted.


Input: Discovery of the First C-Nucleoside HCV Polymerase Inhibitor (GS-6620) with Demonstrated Antiviral Response in HCV Infected Patients.

C-Nucleoside


Input: Hepatitis C virus (HCV) infection presents an unmet medical need requiring more effective treatment options.


Input: Nucleoside inhibitors (NI) of HCV polymerase (NS5B) have demonstrated pan-genotypic activity and durable antiviral response in the clinic, and they are likely to become a key component of future treatment regimens.

Nucleoside


Input: NI candidates that have entered clinical development thus far have all been N-nucleoside derivatives.

N-nucleoside


Input: Herein, we report the discovery of a C-nucleoside class of NS5B inhibitors.

C-nucleoside


Input: Exploration of adenosine analogs in this class identified 1'-cyano-2'-C-methyl 4-aza-7, 9-dideaza adenosine as a potent and selective inhibitor of NS5B.

adenosine

1'-cyano-2'-C-methyl 4-aza-7, 9-dideaza adenosine


Input: A monophosphate prodrug approach afforded a series of compounds showing submicromolar activity in HCV replicon assays.

monophosphate


Input: Further pharmacokinetic optimization for sufficient oral absorption and liver triphosphate loading led to identification of a clinical development candidate GS-6620.

triphosphate


Input: In a phase I clinical study, the potential for potent activity was demonstrated but with high intra-and interpatient pharmacokinetic and pharmacodynamic variability.


Input: Cytotoxicity and Modulation of Cancer-Related Signaling by (Z)-and (E)-3, 4, 3', 5'-Tetramethoxystilbene Isolated from Eugenia rigida.

(Z)-and (E)-3, 4, 3', 5'-Tetramethoxystilbene