Input: Additionally, it was observed that cadmium induced vacuolization, the presence of electron dense deposits in vacuoles, cytoplasm and cell membranes, as well as the distinct behavior of polyphosphate fractions.

cadmium


Input: The results obtained with C. elegans suggest that precipitation, vacuolization and polyphosphate fractions were associated to cadmium tolerance, and this species demonstrated a higher potential for bioremediation of heavy metals.

cadmium


Input: Chemical Stability of the Lipid Phase in Concentrated Beverage Emulsions Colored with Natural beta-Carotene.

beta-Carotene


Input: The aim of this study was to examine the oxidation of selected plant oils in concentrated beverage emulsions colored with natural beta-carotene.

beta-carotene


Input: Carotenoid preparations obtained from carrots were dissolved in cold-pressed linseed oil, refined canola oil, and refined palm olein.


Input: Oxidative stability of the lipids was examined with and without addition of the pigment to the oil/water (O/W) emulsion.


Input: Carotenoid/lipid hydro peroxide (LOOH) concentration was evaluated using two different methods: LOOH + Fe (2 +) reaction connected with a colored complex of ammonium thiocyanate determined with the help of a spectrophotometer, and LOOH determined with the help of a chemiluminometer.

hydro peroxide

Fe (2 +)

ammonium thiocyanate


Input: It was shown that oxidation rate of lipids in the O/W emulsions strongly depended on chemical composition of the lipid fraction (type of oil used).


Input: Presence of the carotenoid pigment increased the rate.


Input: Therefore, if a carotenoid-containing emulsion is to be stable, it should be based on oils of a high oxidative stability.


Input: The Relationship Between Serum Calcium Level, Blood Lipids, and Blood Pressure in Hypertensive and Normotensive Subjects who Come from a Normal University in East of China.

Calcium


Input: Previous studies revealed that low calcium intake is related to high prevalence of cardiovascular diseases such as hypertension.

calcium


Input: However, the relationship between serum calcium and blood pressure was unclear.

calcium


Input: The prevalence of hypertension is high in China.


Input: Thus, the aim of this study was to evaluate the serum calcium level between hypertensive and normotensive groups and to investigate the correlation between serum calcium, blood pressure, and blood lipid parameters.

calcium

calcium


Input: A total of 1, 135 adult subjects participated in this study and were divide into two study groups: a hypertensive group (n = 316) who had 140 mmHg or higher in systolic blood pressure (SBP) or 90 mmHg or higher in diastolic blood pressure (DBP) and an age-and sex-matched normotensive group (n = 819, 120 mmHg or less SBP and 80 mmHg or less DBP).


Input: Our results indicate a significant trend for men (60 years old or older) in the direction of decreasing blood pressure with increasing serum calcium level, but no trend for women was indicated.

calcium


Input: In the normotensive group, a significant positive correlation was found between DBP and total cholesterol (P < 0. 01) and triglyceride (P < 0. 01), Likewise, triglyceride was positively correlated with SBP (P < 0. 01).

cholesterol

triglyceride

triglyceride


Input: Overall, these data suggest that serum calcium may have an influence in the blood pressure of older male subjects with hypertension and in blood lipid profiles of normotensive subjects.

calcium


Input: Inhibitors of bacterial tubulin target bacterial membranes in vivo.


Input: FtsZ is a homolog of eukaryotic tubulin that is widely conserved among bacteria and coordinates the assembly of the cell division machinery.


Input: FtsZ plays a central role in cell replication and is a target of interest for antibiotic development.


Input: Several FtsZ inhibitors have been reported.


Input: We characterized the mechanism of these compounds in bacteria and found that many of them disrupt the localization of membrane-associated proteins, including FtsZ, by reducing the transmembrane potential or perturbing membrane permeability.


Input: We tested whether the reported phenotypes of a broad collection of FtsZ inhibitors disrupt the transmembrane potential in Bacillus subtilis strain 168.


Input: Using a combination of flow cytometry and microscopy, we found that zantrin Z1, cinnamaldehyde, totarol, sanguinarine, and viriditoxin decreased the B. subtilis transmembrane potential or perturbed membrane permeability, and influenced the localization of the membrane-associated, division protein MinD.

zantrin Z1

cinnamaldehyde

totarol

sanguinarine

viriditoxin


Input: These studies demonstrate that small molecules that disrupt membrane function in bacterial cells produce phenotypes that are similar to the inhibition of proteins associated with membranes in vivo, including bacterial cytoskeleton homologs, such as FtsZ.


Input: The results provide a new dimension for consideration in the design and testing of inhibitors of bacterial targets that are membrane-associated and provide additional insight into the structural characteristics of antibiotics that disrupt the membrane.


Input: Transfer of lipids to high-density lipoprotein (HDL) is altered in patients with familial hypercholesterolemia.


Input: OBJECTIVE: In familial hypercholesterolemia (FH), the metabolism and anti-atherogenic functions of HDL can be affected by the continuous interactions with excess LDL amounts.


Input: Here, lipid transfers to HDL, an important step for HDL intravascular metabolism and for HDL role in reverse cholesterol transport (RCT) were investigated in FH patients.

cholesterol


Input: METHODS: Seventy-one FH patients (39 +/- 15years, LDL-cholesterol = 274 +/- 101; HDL-cholesterol = 50 +/- 14mg/dl) and 66 normolipidemic subjects (NL) (38 +/- 11years, LDL-cholesterol = 105 +/- 27; HDL-cholesterol = 52 +/- 12mg/dl) were studied.

cholesterol

cholesterol

cholesterol

cholesterol


Input: In vitro, lipid transfers were evaluated by incubation of plasma samples (37 degrees C, 1h) with a donor lipid nanoemulsion labeled with 3H-triglycerides (TG) and 14C-unesterified cholesterol (UC) or with 3H-cholesteryl ester (EC) and 14C-phospholipids (PL).

cholesterol

3H-cholesteryl ester


Input: Radioactivity was counted at the HDL fraction after chemical precipitation of apolipoprotein (apo) B-containing lipoproteins and the nanoemulsion.


Input: Data are% of total radioactivity measured in the HDL fraction.


Input: RESULTS: Transfer of UC to HDL was lower in FH than in NL (5. 6 +/- 2. 1 vs 6. 7 +/- 2. 0%, p = 0. 0005) whereas TG (5. 5 +/- 3. 1 vs 3. 7 +/- 0. 9%, p = 0. 018) and PL (20. 9 +/- 4. 6 vs 18. 2 +/- 3. 7%, p = 0. 023) transfers were higher in FH.


Input: EC transfer was equal.


Input: By multivariate analysis, transfers of all four lipids correlated with HDL-cholesterol and with apo A-I.

cholesterol


Input: CONCLUSION: FH elicited marked changes in three of the four tested lipid transfers to HDL.


Input: The entry of UC into HDL for subsequent esterification is an important driving force for RCT and reduction of UC transfer to HDL was previously associated to precocious coronary heart disease.


Input: Therefore, in FH, HDL functions can be lessened, which can also contribute to atherogenesis.


Input: Design, synthesis and biological activity of multifunctional alpha, beta-unsaturated carbonyl scaffolds for Alzheimer' s disease.

alpha, beta-unsaturated carbonyl


Input: A series of compounds containing an alpha, beta-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer' s disease (AD) agents.

alpha, beta-unsaturated carbonyl

chalcones

coumarins


Input: The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (A beta) self-assembly and the disassembly of preformed A beta oligomers.


Input: Several compounds showed excellent potential as multifunctional compounds for AD.


Input: Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE.


Input: Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.

coumarin


Input: Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth.


Input: Glioblastomas (GBMs) are highly vascular and lethal brain tumors that display cellular hierarchies containing self-renewing tumorigenic glioma stem cells (GSCs).


Input: Because GSCs often reside in perivascular niches and may undergo mesenchymal differentiation, we interrogated GSC potential to generate vascular pericytes.


Input: Here, we show that GSCs give rise to pericytes to support vessel function and tumor growth.


Input: In vivo cell lineage tracing with constitutive and lineage-specific fluorescent reporters demonstrated that GSCs generate the majority of vascular pericytes.


Input: Selective elimination of GSC-derived pericytes disrupts the neovasculature and potently inhibits tumor growth.


Input: Analysis of human GBM specimens showed that most pericytes are derived from neoplastic cells.


Input: GSCs are recruited toward endothelial cells via the SDF-1/CXCR4 axis and are induced to become pericytes predominantly by transforming growth factor beta.


Input: Thus, GSCs contribute to vascular pericytes that may actively remodel perivascular niches.


Input: Therapeutic targeting of GSC-derived pericytes may effectively block tumor progression and improve antiangiogenic therapy.


Input: Novel Pyridinone Derivatives As Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) with High Potency against NNRTI-Resistant HIV-1 Strains.

Pyridinone

Nucleoside


Input: Novel 6-substituted-4-cycloalkyloxy-pyridin-2 (1H)-ones were synthesized as non-nucleoside reverse transcriptase inhibitors (NNRTIs), and their biological activity was evaluated.

6-substituted-4-cycloalkyloxy-pyridin-2 (1H)-ones

nucleoside


Input: Most of the compounds, especially 26 and 22, bearing a 3-isopropyl and 3-iodine group, respectively, exhibited highly potent activity against wild-type HIV-1 strains and those resistant to reverse transcriptase inhibitors (RTIs).


Input: The diastereoisomers of 26-trans and 26-cis were synthesized separately and confirmed with HPLC and NOESY spectra.


Input: The 26-trans isomers had an activity about 400-fold more potent than that of 26-cis.


Input: The pair of 26-trans enantiomers, one of the most potent inhibitors with EC50 of 4 nM and selectivity index (SI) of 75000, was highly effective against a panel of RTIs-resistant strains with single (Y181C and K103N) or double (A17) mutations in reverse transcriptase.


Input: The results suggest that these novel pyridinone derivatives have the potential to be further developed as new antiretroviral drugs with improved antiviral efficacy and drug resistance profile.

pyridinone


Input: Antiallodynic and Analgesic Effects of Maslinic Acid, a Pentacyclic Triterpenoid from Olea europaea.

Maslinic Acid

Pentacyclic Triterpenoid


Input: The effects of maslinic acid (1), a pentacyclic triterpenoid obtained from Olea europaea, were studied in several tests for nociception in mice.

maslinic acid

pentacyclic triterpenoid


Input: Systemic administration of 1 reduced acetic acid-induced writhing, the inflammatory phase of formalin-induced pain, and capsaicin-induced mechanical allodynia.

acetic acid

formalin

capsaicin


Input: However, it did not induce motor incoordination in the rotarod test.


Input: The topical administration of 1 also reduced the inflammatory phase of the formalin test, indicating that at least some of its effects are mediated peripherally.

formalin


Input: The present results demonstrate for the first time that maslinic acid induces antinociceptive and antiallodynic effects.

maslinic acid


Input: Emergence of Glass-like Behavior in Markov State Models of Protein Folding Dynamics.


Input: The extent to which glass-like kinetics govern dynamics in protein folding has been heavily debated.


Input: Here, we address the subject with an application of space-time perturbation theory to the dynamics of protein folding Markov state models.


Input: Borrowing techniques from the s-ensemble method, we argue that distinct active and inactive phases exist for protein folding dynamics, and that kinetics for specific systems can fall into either dynamical regime.


Input: We do not, however, observe a true glass transition in any system studied.


Input: We go on to discuss how these inactive and active phases might relate to general protein folding properties.


Input: T-Cells from HLA-B * 57: 01 + Human Subjects Are Activated with Abacavir through Two Independent Pathways and Induce Cell Death by Multiple Mechanisms.

Abacavir


Input: Susceptibility to abacavir hypersensitivity has been attributed to possession of the specific human leukocyte antigen allele HLA-B * 57: 01.


Input: HLA-B * 57: 01-restricted activation of CD8 + T-cells provides a link between the genetic association and the iatrogenic disease.


Input: The objectives of this study were to characterize the functionality of drug-responsive CD8 + T-cell clones generated from HLA-B * 57: 01 + drug-naive subjects and to explore the relationship between abacavir accumulation in antigen presenting cells and the T-cell response.

abacavir


Input: Seventy-four CD8 + clones expressing different V beta receptors were shown to proliferate and kill target cells via different mechanisms when exposed to abacavir.

abacavir


Input: Certain clones were activated with abacavir in the absence of antigen presenting cells.

abacavir


Input: Analysis of the remaining clones revealed two pathways of drug-dependent T-cell activation.


Input: Overnight incubation of antigen presenting cells with abacavir, followed by repeated washing to remove soluble drug, activated approximately 50% of the clones, and the response was blocked by glutaraldehyde fixation.

abacavir

glutaraldehyde


Input: In contrast, a 1 h antigen presenting cell pulse did not activate any of the clones.


Input: Accumulation of abacavir in antigen presenting cells was rapid (less than 1 h), and the intracellular concentrations were maintained for 16 h.

abacavir


Input: However, intracellular abacavir was not detectable by mass spectrometry after pulsing.

abacavir


Input: These data suggest that T-cells can be activated by abacavir through a direct interaction with surface and intracellular major histocompatibility complex (MHC) molecules.

abacavir


Input: With the former, abacavir seemingly participates in the MHC T-cell receptor binding interaction.

abacavir


Input: In contrast, the latter pathway likely involves MHC binding peptides displayed as a consequence of abacavir exposure, but not abacavir itself.

abacavir

abacavir


Input: Activation of Transient Receptor Potential Ankyrin-1 (TRPA1) in Lung Cells by Wood Smoke Particulate Material.


Input: Cigarette smoke, diesel exhaust, and other combustion-derived particles activate the calcium channel transient receptor potential ankyrin-1 (TRPA1), causing irritation and inflammation in the respiratory tract.

calcium


Input: It was hypothesized that wood smoke particulate and select chemical constituents thereof would also activate TRPA1 in lung cells, potentially explaining the adverse effects of wood and other forms of biomass smoke on the respiratory system.


Input: TRPA1 activation was assessed using calcium imaging assays in TRPA1-overexpressing HEK-293 cells, mouse primary trigeminal neurons, and human adenocarcinoma (A549) lung cells.

calcium


Input: Particles from pine and mesquite smoke were less potent agonists of TRPA1 than an equivalent mass concentration of an ethanol extract of diesel exhaust particles; pine particles were comparable in potency to cigarette smoke condensate, and mesquite particles were the least potent.

ethanol


Input: The fine particulate (PM < 2. 5 mu m) of wood smoke were the most potent TRPA1 agonists and several chemical constituents of wood smoke particulate, 3, 5-ditert-butylphenol, coniferaldehyde, formaldehyde, perinaphthenone, agathic acid, and isocupressic acid, were TRPA1 agonists.

3, 5-ditert-butylphenol

coniferaldehyde

formaldehyde

perinaphthenone

agathic acid

isocupressic acid


Input: Pine particulate activated TRPA1 in mouse trigeminal neurons and A549 cells in a concentration-dependent manner, which was inhibited by the TRPA1 antagonist HC-030031.


Input: TRPA1 activation by wood smoke particles occurred through the electrophile/oxidant-sensing domain (i. e., C621/C641/C665/K710), based on the inhibition of cellular responses when the particles were pretreated with glutathione; a role for the menthol-binding site of TRPA1 (S873/T874) was demonstrated for 3, 5-ditert-butylphenol.

glutathione

menthol

3, 5-ditert-butylphenol


Input: This study demonstrated that TRPA1 is a molecular sensor for wood smoke particulate and several chemical constituents thereof, in sensory neurons and A549 cells, suggesting that TRPA1 may mediate some of the adverse effects of wood smoke in humans.


Input: Effects of exposure to amitraz on noradrenaline, serotonin and dopamine levels in brain regions of 30 and 60 days old male rats.

amitraz

noradrenaline

serotonin

dopamine


Input: The effects of amitraz oral exposure (20, 50 and 80mg/kg bw, 5 days) on brain region monoamine levels of male rats at 30 and 60 days of age were examined.

amitraz

monoamine


Input: The amitraz-treated rats at the oral doses of 20 and 50mg/kg bw had no visible injury, i. e., any clinical signs of dysfunction observed in any of the animals.

amitraz


Input: However, rats treated with amitraz at the highest dose (80mg/kg bw, 5 days) showed a slight motor incoordination after 1-2h of treatment.

amitraz


Input: These signs were reversible approximately at 6h after dose.


Input: After the last dose of amitraz, NE, DA and 5-HT and its metabolites levels were determined in the brain regions hypothalamus, midbrain, prefrontal cortex, striatum and hippocampus by HPLC.

amitraz


Input: Amitraz caused changes in the NE, DA and 5-HT and their metabolite levels in a brain regional-, dose-and age-related manner.


Input: In the brain regions studied, amitraz induced a statistically significant increase in 5-HT, NE and DA content with age interaction, but the NE increases in prefrontal cortex and hippocampus was without age interaction.


Input: Moreover, in the brain regions studied, amitraz induced a statistically significant decrease in the metabolite 5-HIAA, MHPG, DOPAC and HVA levels displaying an age interaction, excepting the 5-HIAA decrease in midbrain and the DOPAC decrease in hypothalamus and striatum which were without age interaction.

amitraz

MHPG

DOPAC

HVA

DOPAC


Input: Furthermore, amitraz evoked a statistically significant decrease in 5-HT, NE and DA turnover in the brain regions studied.

amitraz


Input: The present findings indicate that amitraz significantly altered CNS monoaminergic neurotransmitters in a brain regional-, dose-and age-related manner.

amitraz


Input: Development of PVP/PEG mixtures as appropriate carriers for the preparation of drug solid dispersions by melt mixing technique and optimization of dissolution using artificial neural networks.

PVP

PEG


Input: The effect of plasticizer' s (PEG) molecular weight (MW) on PVP based solid dispersions (SDs), prepared by melt mixing, was evaluated in the present study using Tibolone as a poorly water soluble model drug.

PEG

PVP

Tibolone


Input: PEGs with MW of 400, 600, and 2000g/mol were tested, and the effect of drug content, time and temperature of melt mixing on the physical state of Tibolone, and the dissolution characteristics from SDs was investigated.

PEGs

Tibolone


Input: PVP blends with PEG400 and PEG600 were completely miscible, while blends were heterogeneous.

PVP


Input: Furthermore, a single Tg recorded in all samples, indicating that Tibolone was dispersed in a molecular lever (or in the form of nanodispersions), varied with varying PEG' s molecular weight, melt mixing temperature, and drug content, while FTIR analysis indicated significant interactions between Tibolone and PVP/PEG matrices.

Tibolone

PEG

Tibolone

PVP

PEG


Input: All prepared solid dispersion showed long-term physical stability (18months in room temperature).


Input: The extent of interaction between mixture components was verified using Fox and Gordon-Taylor equations.


Input: Artificial neural networks, used to correlate the studied factors with selected dissolution characteristics, showed good prediction ability.


Input: Targeting miRNAs to treat Hepatitis C Virus infections and liver pathology: Inhibiting the virus and altering the host.


Input: Hepatitis C Virus (HCV) infection-induced liver disease is a growing problem worldwide, and is the primary cause of liver failure requiring liver transplantation in North America.


Input: Improved therapeutic strategies are required to control and possibly eradicate HCV infections, and to modulate HCV-induced liver disease.


Input: Cellular microRNAs anneal to and regulate mRNA translation and stability and form a regulatory network that modulates virtually every cellular process.


Input: Thus, miRNAs are promising cellular targets for therapeutic intervention for an array of diseases including cancer, metabolic diseases, and virus infections.


Input: In this review we outline the features of miRNA regulation and how miRNAs may be targeted in strategies to modulate HCV replication and pathogenesis.


Input: In particular, we highlight miR-122, a miRNA that directly modulates the HCV life cycle using an unusual mechanism.


Input: This miRNA is very important since miR-122 antagonists dramatically reduced HCV titres in HCV-infected chimpanzees and humans and currently represents the most likely candidate to be the first miRNA-based therapy licensed for use.


Input: However, we also discuss other miRNAs that directly or indirectly alter HCV replication efficiency, liver cirrhosis, fibrosis and the development of hepatocellular carcinoma (HCC).


Input: We also discuss a few miRNAs that might be targets to treat HCV in cases of HCV/HIV co-infection.


Input: Finally, we review methods to deliver miRNA antagonists and mimics to the liver.


Input: In the future, it may be possible to design and deliver specific combinations of miRNA antagonists and mimics to cure HCV infection or to limit liver pathogenesis.


Input: Synthesis and biological evaluation of Foscan ((R)) bile acid conjugates to target esophageal cancer cells.

Foscan

bile acid


Input: Porphyrins and chlorins such as Foscan (R) have a natural proclivity to accumulate in cancer cells.

Porphyrins

chlorins

Foscan


Input: This trait has made them good candidates for photosensitizers and as imaging agents in phototherapy.


Input: In order to improve on cellular selectivity to lower post-treatment photosensitivity bile acid porphyrin bioconjugates have been prepared and investigated in esophageal cancer cells.

bile acid porphyrin


Input: Bile acids which are known to selectively bind to, or be readily taken up by cancer cells were chosen as targeting moieties.

Bile acids


Input: Synthesis of the conjugates was achieved via selective nucleophilic monofunctionalization of 5, 10, 15, 20-tetrahydroxyphenylporphyrins with propargyl bromide followed by Cu (I) mediated cycloaddition with bile acid azides in good yields.

5, 10, 15, 20-tetrahydroxyphenylporphyrins

propargyl bromide

Cu (I)

bile acid azides


Input: The compounds were readily taken up by esophageal cancer cells but showed no PDT activity.


Input: A diazen-1-ium-1, 2-diolate analog of 7-azabenzobicyclo [2. 2. 1] heptane: Synthesis, nitric oxide and nitroxyl release, in vitro hemodynamic, and anti-hypertensive studies.

diazen-1-ium-1, 2-diolate

7-azabenzobicyclo [2. 2. 1] heptane

nitric oxide

nitroxyl


Input: 1-(7-Azabenzobicyclo [2. 2. 1] heptane) diazen-1-ium-1, 2-diolate (16) was designed with the expectation that it would act as a dual nitric oxide (NO) and nitroxyl (HNO) donor that is not carcinogenic or genotoxic.

1-(7-Azabenzobicyclo [2. 2. 1] heptane) diazen-1-ium-1, 2-diolate

nitric oxide

NO

nitroxyl

HNO


Input: Compound 16, with a suitable half-life (17. 8min) in PBS at pH 7, released NO (19%) and HNO (22%) during a 2h incubation in PBS at pH 7.

NO

HNO


Input: In addition, compound 16 exhibited a significant in vitro positive inotropic effect, increased the rates of contraction and relaxation, and increased coronary flow rate, but did not induce a chronotropic effect.


Input: Furthermore, compound 16 (13. 7mgkg (-1), po dose) provided a significant reduction in the blood pressure of mice up to 3h post-drug administration.


Input: All these data suggest that compound 16 constitutes an attractive' lead-compound' that could have potential applications to treat cardiovascular disease (s) such as congestive heart failure.


Input: Synthetic oligoureas of metaphenylenediamine mimic host defence peptides in their antimicrobial behaviour.

metaphenylenediamine


Input: Oligomeric ureas of m-phenylenediamine target anionic DMPG (dimyristoylphosphatidylglycerol) and possess promise as antimicrobial agents.

ureas

m-phenylenediamine

DMPG

dimyristoylphosphatidylglycerol


Input: Their similar size, shape and hydrophobicity to helical antimicrobial peptides (AMPs) may be important for activity to exist and the ability of these compounds to insert into a well ordered lipid environment.


Input: PEG mediated synthesis and pharmacological evaluation of some fluoro substituted pyrazoline derivatives as antiinflammatory and analgesic agents.

PEG

fluoro substituted pyrazoline


Input: A new series of fluoro substituted pyrazoline derivatives 5a-g and 6a-g were synthesized in good to excellent yield from the corresponding pyrazole chalcones, 4a-g, by using polyethylene glycol-400 (PEG-400) as an alternative reaction medium.

fluoro substituted pyrazoline

pyrazole chalcones

polyethylene glycol-400


Input: The newly synthesized compounds were characterized and screened for their in vivo antiinflammatory and analgesic activity.


Input: Compounds 5g and 6g were found to be more potent than standard drug Diclofenac and six other compounds 5b, 5c, 5f, 6b, 6c and 6f showed significant antiinflammatory activity as compared to standard drug.

Diclofenac


Input: Compounds 5c, 5d, 5e, 5f, 6c, 6d, 6e and 6f showed significant analgesic activity as compared to standard drug Aspirin.


Input: Identification of metal ion binding peptides containing unnatural amino acids by phage display.

amino acids


Input: The bidentate metal binding amino acid bipyridylalanine (BpyAla) was incorporated into a disulfide linked cyclic peptide phage displayed library to identify metal ion binding peptides.

amino acid bipyridylalanine

BpyAla

disulfide


Input: Selection against Ni (2 +)-nitrilotriacetic acid (NTA) enriched for sequences containing histidine and BpyAla.

Ni (2 +)

nitrilotriacetic acid

NTA

histidine

BpyAla


Input: BpyAla predominated when selections were carried out at lower pH, consistent with the differential pKa' s of histidine and BpyAla.

BpyAla

histidine

BpyAla


Input: Two peptides containing BpyAla were synthesized and found to bind Ni (2 +) with low micromolar dissociation constants.

BpyAla

Ni (2 +)


Input: Incorporation of BpyAla and other metal binding amino acids into peptide and protein libraries should enable the evolution of novel binding and catalytic activities.

BpyAla

amino acids


Input: Tuning into diversity of homeostatic synaptic plasticity.


Input: Neurons are endowed with the remarkable ability to integrate activity levels over time and tune their excitability such that action potential firing is maintained within a computationally optimal range.


Input: These feedback mechanisms, collectively referred to as " homeostatic plasticity ", enable neurons to respond and adapt to prolonged alterations in neuronal activity by regulating several determinants of cellular excitability.


Input: Perhaps the best-characterized of these homeostatic responses involves the regulation of excitatory glutamatergic transmission.


Input: This homeostatic synaptic plasticity (HSP) operates bidirectionally, thus providing a means for neurons to tune cellular excitability in response to either elevations or reductions in net activity.


Input: The last decade has seen rapid growth in interest and efforts to understand the mechanistic underpinnings of HSP in part because of the theoretical stabilization that HSP confers to neural network function.


Input: Since the initial reports describing HSP in central neurons, innovations in experimental approaches have permitted the mechanistic dissection of this cellular adaptive response and, as a result, key advances have been made in our understanding of the cellular and molecular basis of HSP.


Input: Here, we review recent evidence that outline the presence of distinct forms of HSP at excitatory glutamatergic synapses which operate at different sub-cellular levels.


Input: We further present theoretical considerations on the potential computational roles afforded by local, synapse-specific homeostatic regulation.


Input: This article is part of a Special Issue entitled' Homeostatic Plasticity'.


Input: Impact of flow pulsatility on arterial drug distribution in stent-based therapy.


Input: Drug-eluting stents reside in a dynamic fluid environment where the extent to which drugs are distributed within the arterial wall is critically modulated by the blood flowing through the arterial lumen.


Input: Yet several factors associated with the pulsatile nature of blood flow and their impact on arterial drug deposition have not been fully investigated.


Input: We employed an integrated framework comprising bench-top and computational models to explore the factors governing the time-varying fluid dynamic environment within the vasculature and their effects on arterial drug distribution patterns.


Input: A custom-designed bench-top framework comprising a model of a single drug-eluting stent strut and a poly-vinyl alcohol-based hydrogel as a model tissue bed simulated fluid flow and drug transport under fully apposed strut settings.

poly-vinyl alcohol


Input: Bench-top experiments revealed a relative independence between drug distribution and the factors governing pulsatile flow and these findings were validated with the in silico model.


Input: Interestingly, computational models simulating suboptimal deployment settings revealed a complex interplay between arterial drug distribution, Womersley number and the extent of malapposition.


Input: In particular, for a stent strut offset from the wall, total drug deposition was sensitive to changes in the pulsatile flow environment, with this dependence increasing with greater wall displacement.


Input: Our results indicate that factors governing pulsatile luminal flow on arterial drug deposition should be carefully considered in conjunction with device deployment settings for better utilization of drug-eluting stent therapy.


Input: Antagonists reversibly reverse chemical LTD induced by group I, group II and group III metabotropic glutamate receptors.

glutamate


Input: Metabotropic glutamate (mGlu) receptors are implicated in many neurological and psychiatric diseases and are the targets of therapeutic agents currently in clinical development.

glutamate


Input: Their activation has diverse effects in the central nervous system (CNS) that includes an involvement in synaptic plasticity.


Input: We previously reported that the brief exposure of hippocampal slices to dihydroxyphenylglycine (DHPG) can result in a long-term depression (LTD) of excitatory synaptic transmission.

dihydroxyphenylglycine

DHPG


Input: Surprisingly, this LTD could be fully reversed by mGlu receptor antagonists in a manner that was itself fully reversible upon washout of the antagonist.


Input: Here, 15 years after the discovery of DHPG-LTD and its reversible reversibility, we summarise these initial findings.

DHPG


Input: We then present new data on DHPG-LTD, which demonstrates that evoked epileptiform activity triggered by activation of group I mGlu receptors can also be reversibly reversed by mGlu receptor antagonists.

DHPG


Input: Furthermore, we show that the phenomenon of reversible reversibility is not specific to group I mGlu receptors.


Input: We report that activation of group II mGlu receptors in the temporo-ammonic pathway (TAP) and mossy fibre pathway within the hippocampus and in the cortical input to neurons of the lateral amygdala induces an LTD that is reversed by LY341495, a group II mGlu receptor antagonist.


Input: We also show that activation of group III mGlu8 receptors induces an LTD at lateral perforant path inputs to the dentate gyrus and that this LTD is reversed by MDCPG, an mGlu8 receptor antagonist.


Input: In conclusion, we have shown that activation of representative members of each of the three groups of mGlu receptors can induce forms of LTD than can be reversed by antagonists, and that in each case washout of the antagonist is associated with the re-establishment of the LTD.


Input: This article is part of a Special Issue entitled' GluR-dep synaptic plasticity'.


Input: Arsenic trioxide depletes cancer stem-like cells and inhibits repopulation of neurosphere derived from glioblastoma by downregulation of Notch pathway.

Arsenic trioxide


Input: Notch signaling has been demonstrated to have a central role in cancer stem-like cells (CSLCs) in glioblastoma multiforme (GBM).


Input: We have recently demonstrated the inhibitory effect of arsenic trioxide (ATO) on CSLCs in glioblastoma cell lines.

arsenic trioxide

ATO


Input: In this study we used neurosphere recovery assay that measured neurosphere formation at three time points to assess the capacity of the culture to repopulate after ATO treatment.

ATO


Input: Our results provided strong evidence that ATO depleted CSLCs in GBM, and inhibited neurosphere recovery and secondary neurosphere formation.

ATO


Input: ATO inhibited the phosphorylation and activation of AKT and STAT3 through Notch signaling blockade.

ATO


Input: These data show that the ATO is a promising new approach to decrease glioblastoma proliferation and recurrence by downregulation of Notch pathway.

ATO


Input: Structure-activity relationship of 5-chloro-2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indole analogues as 5-HT6 receptor agonists.

5-chloro-2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indole


Input: To further investigate the structure-activity relationship (SAR) of the 5-hydroxytryptamine type 6 (5-HT6) receptor agonist 5-chloro-2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indole (EMD386088, 6), a series of 2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indoles were synthesized, and in vitro affinity to, and functional activity at 5-HT6 receptors was tested.

5-chloro-2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indole

2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indoles


Input: We focused on substituents made at the indole N (1)-, 2-and 5-positions and these were found to not only influence the affinity at 5-HT6 receptors but also the intrinsic activity leading to antagonists, partial agonists and full agonists.

indole


Input: In order for a compound to demonstrate potent 5-HT6 receptor agonist properties, the indole N (1) should be unsubstituted, an alkyl group such as 2-methyl is needed and finally halogen substituents in the indole 5-position (fluoro, chloro or, bromo) were essential requirements.

indole

alkyl

halogen

indole

fluoro

chloro

bromo


Input: However, the introduction of a benzenesulfonyl group at N (1)-position switched the full agonist 6 to be a 5-HT6 receptor antagonist (30).

benzenesulfonyl


Input: A few compounds within the 2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indoles were also screened for off-targets and generally they displayed low affinity for other 5-HT subtypes and serotonin transporter protein (SERT).

2-methyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indoles

serotonin


Input: Induction of G2/M arrest, caspase activation and apoptosis by alpha-santonin derivatives in HL-60 cells.

alpha-santonin


Input: Sesquiterpene lactones (SLs) are natural products with a variety of biological activities.

Sesquiterpene lactones

SLs


Input: Previously, we demonstrated the cytotoxic effects of three new alpha-santonin derivatives on different tumor cell lines with low toxic effects upon peripheral human leukocytes.

alpha-santonin


Input: Here, we evaluated the mechanism of action triggered by these derivatives.


Input: HL-60 cell cycle determined after 24h treatment revealed a significant inhibition on cell-cycle progression and leading to an increasing of cells in G2/M [7. 6% and 9. 0% for compound 3% and 9. 0% and 8. 6% for compound 4 (1 and 2 mu M, respectively)].


Input: However, after 48h exposure, all compounds caused G2/M reduction and a significant DNA fragmentation.


Input: Compounds 2, 3 and 4 were able to induce apoptosis on leukemia cells, which was corroborated by phosphatidyserine externalization and activation of caspases-3 and-7 after 24h exposure.


Input: None of the derivatives analyzed caused depolarization of mitochondrial membrane within 24h of incubation, suggesting the involvement of the extrinsic apoptotic pathway in the death process.


Input: The antiproliferative action of these compounds is related to the DNA synthesis inhibition and cell cycle arrest, which probably lead to apoptosis activation.


Input: Therefore, these santonin derivatives are promising lead candidates for development of new cytotoxic agents.

santonin


Input: Systematic review of the effects of maternal hypertension in pregnancy and antihypertensive therapies on child neurocognitive development.


Input: As many as 15% of women experience hypertension during pregnancy.


Input: Large proportions of them are receiving antihypertensive medications.


Input: This review investigated whether hypertension itself, or the antihypertensive medications, adversely affect long term child neurocognitive development.


Input: The existing evidence suggests that methyldopa and labetalol probably do not adversely affect neurobehavioral development.

methyldopa

labetalol


Input: Although an increasing body of evidence suggests adverse neurocognitive effects of the hypertension itself, none of the existing studies examined simultaneously the effects of both hypertension and the drugs used therapeutically.


Input: The confounding effects by indication must be addressed in future studies.


Input: Tail Tip Proteins Related to Bacteriophage lambda gpL Coordinate an Iron-Sulfur Cluster.

Iron-Sulfur


Input: The assembly of long non-contractile phage tails begins with the formation of the tail tip complex (TTC).


Input: TTCs are multi-functional protein structures that mediate host cell adsorption and genome injection.


Input: The TTC of phage lambda is assembled from multiple copies of eight different proteins, including gpL.


Input: Purified preparations of gpL and several homologues all displayed a distinct reddish color, suggesting the binding of iron by these proteins.

iron


Input: Further characterization of the gpL homologue from phage N15, which was most amenable to in vitro analyses, showed that it contains two domains.


Input: The C-terminal domain was demonstrated to coordinate an iron-sulfur cluster, providing the first example of a viral structural protein binding to this type of metal group.

C

iron-sulfur


Input: We characterized the iron-sulfur cluster using inductively coupled plasma-atomic emission spectroscopy, absorbance spectroscopy, and electron paramagnetic resonance spectroscopy and found that it is an oxygen-sensitive [4Fe-4S] (2 +) cluster.

iron-sulfur

oxygen

[4Fe-4S] (2 +)


Input: Four highly conserved cysteine residues were shown to be required for coordinating the iron-sulfur cluster, and substitution of any of these Cys residues with Ser or Ala within the context of lambda gpL abolished biological activity.

cysteine

iron-sulfur

Cys

Ser

Ala


Input: These data imply that the intact iron-sulfur cluster is required for function.

iron-sulfur


Input: The presence of four conserved Cys residues in the C-terminal regions of very diverse gpL homologues suggest that utilization of an iron-sulfur cluster is a widespread feature of non-contractile tailed phages that infect Gram-negative bacteria.

Cys

C

iron-sulfur


Input: In addition, this is the first example of a viral structural protein that binds an iron-sulfur cluster.

iron-sulfur


Input: Cell adhesion and homeostatic synaptic plasticity.


Input: At synapses, pre-and post-synaptic cells get in direct contact with each other via cell adhesion molecules (CAMs).


Input: Several CAMs have been identified at the neuromuscular junction and at central synapses, where they regulate synaptic strength, by recruiting scaffolding proteins, neurotransmitter receptors and synaptic vesicles in response to the binding of counter-receptors across the synaptic cleft.


Input: Many synapses are also surrounded by astrocytic processes and embedded in conspicuous extracellular matrix (ECM).


Input: It is now widely recognized that astrocytes play a central role in regulating the synaptic machinery by exchanging information with the neuronal elements via diffusible molecules and direct physical interactions; this has lead to the concept of the' tri-partite synapse'.


Input: More recently, the term' tetra-partite synapse' has been introduced to underlie the importance of ECM in shaping synaptic function by mediating interaction and signaling between neurons and astrocytes.


Input: Here, we will review how this integrated view of the synapse can help us understand homeostatic synaptic plasticity at the neuromuscular junction and in the central nervous system.


Input: We will explore how synaptic CAMs regulate two forms of homeostatic plasticity: (i) postsynaptic scaling of synaptic currents to counteract changes in neuronal network activity and (ii) the compensatory modulation of presynaptic neurotransmitter release in response to changes in postsynaptic efficacy.


Input: We will discuss recent findings on activity-dependent trans-synaptic signaling events and the role of cell adhesion in the feedback control of network activity.


Input: This article is part of a Special Issue entitled' Homeostatic Plasticity'.


Input: Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: Preparation, characterization and in vivo evaluation.

curcumin didecanoate


Input: The objective of this study was to prepare the nanocrystals of curcumin didecanoate (CurDD) by wet ball milling and to investigate the comparative pharmacokinetics of oily nano-and micro-suspensions after intramuscular (i. m.) administration to rats.

curcumin didecanoate

CurDD


Input: Upon optimizing the wet ball milling parameters, CurDD nanocrystals were produced with median particle size of ~ 500nm and the freeze-dried nanocrystals were readily dispersed in peanut oil to form stable nanosuspensions.

CurDD


Input: Although the nanosuspension appeared to exhibit slower clearance from the injection site after i. m. injection, compared to microsuspension (~ 5 mu m), a significantly higher maximum plasma curcumin concentration (69. 0ng/ml) was observed for the former than that for the latter (18. 5ng/ml).

curcumin


Input: In addition, the nanosuspension provided significant higher plasma curcumin concentrations and brain CurDD contents for at least 15days than the microsuspension, except for the initial times.

curcumin

CurDD


Input: A single i. m. injection of nanosuspension appeared to achieve reversal effect on reserpine-induced hypothermia for at least 13days.

reserpine


Input: This study demonstrates that CurDD nanosuspension may act as a long-acting i. m. injectable for sustained delivery of curcumin, potentially applicable to elicit a long-lasting antidepressant effect.

CurDD

curcumin


Input: Chloroaluminium phthalocyanine polymeric nanoparticles as photosensitisers: Photophysical and physicochemical characterisation, release and phototoxicity in vitro.

Chloroaluminium phthalocyanine


Input: Nanoparticles of poly (d, l-lactide-co-glycolide), poly (d, l-lactide) and polyethylene glycol-block-poly (d, l-lactide) were developed to encapsulate chloroaluminium phthalocyanine (AlClPc), a new hydrophobic photosensitiser used in photodynamic therapy (PDT).

poly (d, l-lactide-co-glycolide)

poly (d, l-lactide)

polyethylene glycol-block-poly (d, l-lactide)

chloroaluminium phthalocyanine

AlClPc


Input: The mean nanoparticle size varied from 115 to 274nm, and the encapsulation efficiency ranged from 57% to 96% due to drug precipitation induced by different types of polymer.


Input: All nanoparticle formulations presented negative zeta potential values (-37mV to-59mV), explaining their colloidal stability.


Input: The characteristic photophysical parameters were analysed: the absorption spectrum profile, fluorescence quantum yield and transient absorbance decay, with similar values for free and nanoparticles of AlClPc.

AlClPc


Input: The time-resolved spectroscopy measurements for AlClPc triplet excited state lifetimes indicate that encapsulation in nanocapsules increases triplet lifetime, which is advantageous for PDT efficiency.

AlClPc


Input: A sustained release profile over 168h was obtained using external sink method.


Input: An in vitro phototoxic effect higher than 80% was observed in human fibroblasts at low laser light doses (3J/cm (2)) with 10 mu M of AlClPc.

AlClPc


Input: The AlClPc loaded within polymeric nanocapsules presented suitable physical stability, improved photophysical properties, sustained released profile and suitable activity in vitro to be considered a promising formulation for PDT.

AlClPc


Input: A global toxicogenomic analysis investigating the mechanistic differences between tobacco and marijuana smoke condensates in vitro.


Input: Like tobacco smoking, habitual marijuana smoking causes numerous adverse pulmonary effects.


Input: However, the mechanisms of action involved, especially as compared to tobacco smoke, are still unclear.


Input: To uncover putative modes of action, this study employed a toxicogenomics approach to compare the toxicological pathways perturbed following exposure to marijuana and tobacco smoke condensate in vitro.


Input: Condensates of mainstream smoke from hand-rolled tobacco and marijuana cigarettes were similarly prepared using identical smoking conditions.


Input: Murine lung epithelial cells were exposed to low, medium and high concentrations of the smoke condensates for 6h.


Input: RNA was extracted immediately or after a 4h recovery period and hybridized to mouse whole genome microarrays.


Input: Tobacco smoke condensate (TSC) exposure was associated with changes in xenobiotic metabolism, oxidative stress, inflammation, and DNA damage response.


Input: These same pathways were also significantly affected following marijuana smoke condensate (MSC) exposure.


Input: Although the effects of the condensates were largely similar, dose-response analysis indicates that the MSC is substantially more potent than TSC.


Input: In addition, steroid biosynthesis, apoptosis, and inflammation pathways were more significantly affected following MSC exposure, whereas M phase cell cycle pathways were more significantly affected following TSC exposure.


Input: MSC exposure also appeared to elicit more severe oxidative stress than TSC exposure, which may account for the greater cytotoxicity of MSC.


Input: This study shows that in general MSC impacts many of the same molecular processes as TSC.


Input: However, subtle pathway differences can provide insight into the differential toxicities of the two complex mixtures.


Input: Statins decrease all-cause mortality only in CKD patients not requiring dialysis therapy-A meta-analysis of 11 randomized controlled trials involving 21, 295 participants.


Input: The available studies have reported the benefits of statins on all-cause and cardiovascular mortality in chronic kidney disease (CKD) patients.


Input: However studies in end-stage renal disease patients on dialysis yielded conflicting results.


Input: Therefore, we performed a meta-analysis and provide the most reliable trial data to date on the impact of statin therapy on cardiovascular events and death from all causes in CKD patients.


Input: Data from PubMed, Web of Science, Cochrane Library, and Scopus for the years 1966 to October 2012 were searched.


Input: The final meta-analysis included 11 randomized controlled trials involving 21, 295 participants with CKD.


Input: Among them 6857 were on dialysis.


Input: The use of statins in subjects with non-dialysis-dependent CKD resulted in a marked reduction in death from all causes (relative risk [RR]: 0. 66; 95% confidence interval [CI]: 0. 55-0. 79; p < 0. 0001), cardiac causes (RR: 0. 69; 95% CI: 0. 55-0. 68; p = 0. 0012), cardiovascular events (RR: 0. 55; 95% CI: 0. 4-0. 75; p = 0. 0001) and stroke (RR: 0. 66; 95% CI: 0. 5-0. 88; p = 0. 0022).


Input: The use of statins in dialysis-dependent CKD patients resulted in a non-significant effect on death from all causes (RR: 0. 99; 95% CI: 0. 88-1. 11; p = 0. 85) and stroke (RR: 1. 31; 95% CI: 0. 9-1. 89; p > 0. 05), but had the effect of reducing death from cardiac causes (RR: 0. 79; 95% CI: 0. 64-0. 98; p < 0. 05) and cardiovascular events (RR: 0. 81; 95% CI: 0. 7-0. 94; p < 0. 05).


Input: In conclusion, the use of statins should be indicated in cardiovascular disease prevention especially in patients with non-dialysis-dependent CKD.


Input: According to the very limited data the obtained results suggest caution in expecting a reduction in cardiovascular events in patients on dialysis.


Input: Arsenic trioxide induces cardiac fibroblast apoptosis in vitro and in vivo by up-regulating TGF-beta 1 expression.

Arsenic trioxide


Input: Arsenic trioxide (As2O3; ATO) is clinically effective in treating acute promyelocytic leukemia (APL); however, it frequently causes cardiotoxic effects.

Arsenic trioxide

ATO


Input: This study was designed to investigate whether ATO could induce apoptosis of cardiac fibroblasts (CFs) that play very important roles in maintaining the structure integrity and function of the heart.

ATO


Input: Cardiac fibroblasts from guinea pigs administered with ATO (1mg/kgbw) were used to test the pro-apoptotic role of ATO in vivo.

ATO

ATO


Input: The current study demonstrated that ATO induced morphological characteristics of apoptosis and Caspase-3 activation in CFs of guinea pigs along with a significant up-regulation in TGF-beta 1 protein expression, Bax/Bcl-2 ratio and ERK1/2 phosphorylation.

ATO


Input: In vitro MTT assay showed that ATO remarkably reduced the viability of cultured cardiac fibroblasts (NRCFs) from neonatal rat in a concentration-and time-dependent manner.

MTT

ATO


Input: Consistent with the notions in vivo, ATO significantly induced the apoptosis in NRCFs, dramatically up-regulated TGF-beta 1 protein level and Bax/Bcl-2 ratio in a time-dependent fashion and activated Caspase-3 and ERK1/2.

ATO


Input: Finally, pretreatment with LY364947, an inhibitor of TGF-beta signaling could apparently reverse these changes.


Input: We therefore conclude that TGF-beta is functionally linked to ERK1/2 and that TGF-beta signaling is responsible for ATO-induced CFs apoptosis, which provides a novel mechanism of ATO related cardiac toxicology.

ATO

ATO


Input: In utero phthalate effects in the female rat: A model for MRKH syndrome.

phthalate


Input: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly defined etiology.


Input: Reproductive toxicity of phthalate esters (PEs) occurs in rat offspring exposed in utero, a phenomenon that is better studied in male offspring than females.

phthalate esters

PEs


Input: The current study reports female reproductive tract malformations in the Sprague-Dawley rat similar to those characteristic of MRKH syndrome, following in utero exposure to a mixture of 5 PEs.

PEs


Input: We determined that females are ~ 2-fold less sensitive to the effects of the 5-PE mixture than males for reproductive tract malformations.


Input: We were not fully successful in defining the critical exposure period for females; however, incidence of malformations was 88% following dosing from GD8 to 19 versus 22% and 0% for GD8-13 and GD14-19, respectively.


Input: Overall, this study provides valuable information regarding female vulnerability to in utero phthalate exposure and further characterizes a potential model for the human MRKH syndrome.

phthalate


Input: Disruption of the integrity and function of brain microvascular endothelial cells in culture by exposure to diesel engine exhaust particles.


Input: Diesel exhaust particles (DEPs), a by-product of diesel engine exhaust (DEE), are known to produce pro-oxidative and pro-inflammatory effects, thereby leading to oxidative stress-induced damage.


Input: Given the key role of DEPs in inducing oxidative stress, we investigated the role of DEPs in disrupting the integrity and function of immortalized human brain microvascular endothelial cells (HBMVEC).


Input: To study this, HBMVEC cells were exposed to media containing three different concentrations of DEPs or plain media for 24h.


Input: Those exposed to DEPs showed significantly higher oxidative stress than the untreated group, as indicated by the glutathione (GSH) and malondialdehyde (MDA) levels, and the glutathione peroxidase and glutathione reductase activities.

glutathione

GSH

malondialdehyde

MDA

glutathione

glutathione


Input: DEPs also induced oxidative stress-related disruption of the HBMVEC cells monolayer, as measured by trans-epithelial electrical resistance.


Input: Taken together, these data suggest that DEPs induce cell death and disrupt the function and integrity of HBMVEC cells, indicating a potential role of DEPs in neurotoxicities.


Input: The ethylene bis-dithiocarbamate fungicide Mancozeb activates voltage-gated KCNQ2 potassium channel.

ethylene bis-dithiocarbamate

Mancozeb

potassium


Input: Mancozeb (manganese/zinc ethylene bis-dithiocarbamate) is an organometallic fungicide that has been associated with human neurotoxicity and neurodegeneration.

Mancozeb

manganese/zinc ethylene bis-dithiocarbamate


Input: In a high-throughput screen for modulators of KCNQ2 channel, a fundamental player modulating neuronal excitability, Mancozeb, was found to significantly potentiate KCNQ2 activity.

Mancozeb


Input: Mancozeb was validated electrophysiologically as a KCNQ2 activator with an EC50 value of 0. 92 +/- 0. 23 mu M.

Mancozeb


Input: Further examination showed that manganese but not zinc ethylene bis-dithiocarbamate is the active component for the positive modulation effects.

manganese

zinc ethylene bis-dithiocarbamate


Input: In addition, the compounds are effective when the metal ions are substituted by iron but lack potentiation activity when the metal ions are substituted by sodium, signifying the importance of the metal ion.

iron

sodium


Input: However, the iron (Fe (3 +)) alone, organic ligands alone or the mixture of iron with the organic ligand did not show any potentiation effect, suggesting as the active ingredient is a specific complex rather than two separate additive or synergistic components.

iron

Fe (3 +)

iron


Input: Our study suggests that potentiation on KCNQ2 potassium channels might be the possible mechanism of Mancozeb toxicity in the nervous system.

potassium

Mancozeb


Input: Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis.


Input: Oxidative stress basically defines a condition in which prooxidant-antioxidant balance in the cell is disturbed; cellular biomolecules undergo severe oxidative damage, ultimately compromising cells viability.


Input: In recent years, a number of studies have shown that oxidative stress could cause cellular apoptosis via both the mitochondria-dependent and mitochondria-independent pathways.


Input: Since these pathways are directly related to the survival or death of various cell types in normal as well as pathophysiological situations, a clear picture of these pathways for various active molecules in their biological functions would help designing novel therapeutic strategy.


Input: This review highlights the basic mechanisms of ROS production and their sites of formation; detail mechanism of both mitochondria-dependent and mitochondria-independent pathways of apoptosis as well as their regulation by ROS.


Input: Emphasis has been given on the redox-sensitive ASK1 signalosome and its downstream JNK pathway.


Input: This review also describes the involvement of oxidative stress under various environmental toxin-and drug-induced organ pathophysiology and diabetes-mediated apoptosis.


Input: We believe that this review would provide useful information about the most recent progress in understanding the mechanism of oxidative stress-mediated regulation of apoptotic pathways.


Input: It will also help to figure out the complex cross-talks between these pathways and their modulations by oxidative stress.


Input: The literature will also shed a light on the blind alleys of this field to be explored.


Input: Finally, readers would know about the ROS-regulated and apoptosis-mediated organ pathophysiology which might help to find their probable remedies in future.


Input: Global and MGMT promoter hypomethylation independently associated with genomic instability of lymphocytes in subjects exposed to high-dose polycyclic aromatic hydrocarbon.

polycyclic aromatic hydrocarbon


Input: Global hypomethylation, gene-specific methylation, and genome instability are common events in tumorigenesis.


Input: To date, few studies have examined the aberrant DNA methylation patterns in coke oven workers, who are highly at risk of lung cancer by occupational exposure to polycyclic aromatic hydrocarbons (PAHs).

polycyclic aromatic hydrocarbons

PAHs


Input: We recruited 82 PAH-exposed workers and 62 unexposed controls, assessed exposure levels by urinary 1-hydroxypyrene, and measured genetic damages by comet assay, bleomycin sensitivity, and micronucleus assay.

PAH

bleomycin


Input: The PAHs in coke oven emissions (COE) were estimated based on toxic equivalency factors.

PAHs


Input: We used bisulfite-PCR pyrosequencing to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and O (6)-methylguanine-DNA methyltransferase (MGMT).

bisulfite

O (6)-methylguanine


Input: Further, the methylation alteration was also investigated in COE-treated human bronchial epithelial (16HBE) cells.


Input: We found there are higher levels of PAHs in COE.

PAHs


Input: Among PAH-exposed workers, LINE-1 and MGMT methylation levels (with CpG site specificity) were significantly lowered.

PAH

CpG


Input: LINE-1, MGMT, and its hot CpG site-specific methylation were negatively correlated with urinary 1-hydroxypyrene levels (r =-0. 329, p < 0. 001; r =-0. 164, p = 0. 049 and r =-0. 176, p = 0. 034, respectively).

CpG


Input: In addition, LINE-1 methylation was inversely associated with comet tail moment and micronucleus frequency, and a significant increase of micronucleus in low MGMT methylation group.


Input: In vitro study revealed that treatment of COE in 16HBE cells resulted in higher production of BPDE-DNA adducts, LINE-1 hypomethylation, hypomethylation, and suppression of MGMT expression.

BPDE


Input: These findings suggest hypomethylation of LINE-1 and MGMT promoter could be used as markers for PAHs exposure and merit further investigation.

PAHs


Input: Comparison of the Therapeutic Effectiveness of Sustained Low-Efficiency Dialysis (SLED) with Continuous Blood Purification (CBP) in Critically Ill Patients.


Input: The differences in therapeutic effectiveness between sustained low-efficiency dialysis (SLED) and continuous blood purification (CBP) were investigated.


Input: In order to assess the different treatment methods, 56 critically ill patients were divided into two groups, the CBP group and the SLED group.


Input: A comparison was made between all the biochemical indicators, in-hospital duration, hemodynamic parameters, acute physiology and chronic health evaluation (APACHE-II), the survival, and the mortality rates.


Input: After treatment, the levels of serum creatine kinase isozyme MB (CK-MB), creatine kinase, creatinine, glutamate-oxalacetate transaminase (AST), glutamate-pyruvate transaminase (ALT), APACHE II score on the 1st, 2nd, and 7th day in both the treatment groups were lower than that before the treatment (P < 0. 05).

creatine

creatine

creatinine

glutamate

oxalacetate

glutamate

pyruvate


Input: There are no statistical differences in in-hospital duration, biochemical indicators, APACHE II score, hemodynamic parameters, the survival rate and the mortality rate between the two groups (P > 0. 05).


Input: It was concluded that SLED has similar hemodynamic stability with CBP and the two methods have similar treatment effects in critically ill patients.


Input: However, we noticed that SLED can be relatively economical and convenient for critically ill patients in clinical practice.


Input: The ameliorating effects of 5, 7-dihydroxy-6-methoxy-2 (4-phenoxyphenyl)-4H-chromene-4-one, an oroxylin A derivative, against memory impairment and sensorimotor gating deficit in mice.

5, 7-dihydroxy-6-methoxy-2 (4-phenoxyphenyl)-4H-chromene-4-one

oroxylin A


Input: We previously reported that oroxylin A, a gamma-aminobutyric acid A (GABAA) receptor antagonist, ameliorates drugs-induced memory impairments.

oroxylin A

gamma-aminobutyric acid


Input: We synthesized several oroxylin A derivatives in efforts to find a substance that has pro-cognitive effects as well as improves sensorimotor gating.

oroxylin A


Input: The aim of the present study is to investigate the effect of a novel oroxylin A derivative, 5, 7-dihydroxy-6-methoxy-2 (4-phenoxyphenyl)-4H-chromene-4-one (DMPC), on pharmacological models of schizophrenia, which exhibit memory impairment and sensorimotor gating deficit.

oroxylin A

5, 7-dihydroxy-6-methoxy-2 (4-phenoxyphenyl)-4H-chromene-4-one

DMPC


Input: Memory impairment was induced by scopolamine, a muscarinic receptor antagonist, or MK-801, an N-methyl-D-aspartate receptor antagonist.

scopolamine

N-methyl-D-aspartate


Input: Sensorimotor gating deficits were induced by MK-801 and measured by prepulse inhibition (PPI) of the acoustic startle response task.


Input: DMPC treatment (20 mg/kg) significantly attenuated scopolamine-or MK-801-induced memory impairment and it even enhanced cognitive performance of normal animals.

DMPC

scopolamine


Input: Furthermore, DMPC significantly ameliorated MK-801-induced PPI deficits in the acoustic startle response task.

DMPC


Input: In an in vitro study, DMPC (20 mu M) inhibited intracellular Cl (-) influx induced by muscimol, a selective GABAA receptor agonist.

DMPC

Cl (-)

muscimol


Input: These results suggest that DMPC would be a potential candidate for alleviating cognitive dysfunction and sensorimotor gating deficits in schizophrenia, and that its effects may be mediated, in part, via blockade of the GABAergic neurotransmitter system.

DMPC


Input: Progress in the studies on tryptanthrin, an alkaloid of history.

tryptanthrin


Input: Tryptanthrin, an indoloquinazoline alkaloid, was first obtained by sublimation of natural indigo and later isolated from the culture of fungus Candida lipolytica and a variety of other natural sources.

Tryptanthrin

indoloquinazoline alkaloid


Input: Tryptanthrin showed a variety of intriguing biological properties such as antibacterial, antifungal, antiprotozoal, and antiparasitic activities, inhibitory activities against COX-2, 5-LOX, NO synthase and PGE (2) expression, as well as cytotoxic and antitumor activities.

Tryptanthrin

NO

PGE (2)


Input: Present review covers recent studies on the natural sources, biological activities and mechanisms of their actions, synthesis, structure-activity relationship, and metabolism of tryptanthrin.

tryptanthrin


Input: Design, synthesis, in vitro cytotoxicity evaluation and structure-activity relationship of Goniothalamin analogs.

Goniothalamin


Input: A series of six/five member (E/Z)-Goniothalamin analogs were synthesized from commercially available (3, 4-dihydro-2H-pyran-2-yl) methanol/5-(hydroxymethyl) dihydrofuran-2 (3H)-one in three steps with good to moderate overall yields and their cytotoxicity against lymphoblastic leukemic T cell line (Jurkat E6. 1) have been evaluated.

(E/Z)-Goniothalamin

(3, 4-dihydro-2H-pyran-2-yl) methanol

5-(hydroxymethyl) dihydrofuran-2 (3H)-one


Input: Among the synthesized analogs, (Z)-Goniothalamin appeared to be the most active in cytotoxicity (IC50 = 12 mu M).

(Z)-Goniothalamin


Input: Structure-activity relationship study indicates that introducing substituent in phenyl ring or replacing phenyl ring by pyridine/naphthalene, or decreasing the ring size of lactones (from six to five member) do not increase the cytotoxicity.

phenyl

pyridine

naphthalene

lactones


Input: Loss of Calcium/Calmodulin-Dependent Protein Kinase II Activity in Cortical Astrocytes Decreases Glutamate Uptake and Induces Neurotoxic Release of ATP.

Calcium

Glutamate

ATP


Input: The extent of calcium/calmodulin-dependent protein kinase II (CaMKII) inactivation in the brain following ischemia correlates with the extent of damage.

calcium


Input: We have previously shown that a loss of CaMKII activity in neurons is detrimental to neuronal viability by inducing excitotoxic glutamate release.

glutamate


Input: In the current study, we extend these findings to show that the ability of astrocytes to buffer extracellular glutamate is reduced when CaMKII is inhibited.

glutamate


Input: Furthermore, CaMKII inhibition in astrocytes is associated with the rapid onset of intracellular calcium oscillations.

calcium


Input: Surprisingly, this rapid calcium influx is blocked by the N-type calcium channel antagonist, omega-conotoxin.

calcium

N

calcium


Input: While the function of N-type calcium channels within astrocytes is controversial, these voltage-gated calcium channels have been linked to calcium-dependent vesicular gliotransmitter release.

N

calcium

calcium

calcium


Input: When extracellular glutamate and ATP levels are measured following CaMKII inhibition within our enriched astrocyte cultures, no alterations in glutamate levels are observed, whereas ATP levels in the extracellular environment significantly increase.

glutamate

ATP

glutamate

ATP


Input: Extracellular ATP accumulation associated with CaMKII inhibition contributes both to calcium oscillations within astrocytes and ultimately cortical neuron toxicity.

ATP

calcium


Input: Thus, a loss of CaMKII signaling within astrocytes dysregulates glutamate uptake and supports ATP release, two processes that would compromise neuronal survival following ischemic/excitotoxic insults.

glutamate

ATP


Input: Mass and Ion Transport in Ketones and Ketone Electrolytes: Comparison with Acetate Systems.

Ketones

Ketone

Acetate


Input: Self-diffusion coefficient measurements were performed for pure n-alkyl ketone liquids using the pulsed field gradient NMR spin-echo technique.

n-alkyl ketone


Input: Ionic conductivities and dielectric constants of 0. 0055 mol. L (-1) tetrabutylammonium trifluoromethanesulfonate in 2-pentanone, 2-hexanone, 2-heptanone, 2-octanone, 2-nonanone, and 2-decanone were also measured.

tetrabutylammonium trifluoromethanesulfonate


Input: The temperature-dependent conductivities and diffusion coefficients over the range 5-80 degrees C can be described using the compensated Arrhenius formalism.


Input: Compensated Arrhenius equation plots were used to calculate the average activation energy for both sets of data.


Input: The average activation energy from conductivity data is approximately equal to that from diffusion data.


Input: The data for the pure ketones and ketone-based electrolytes are compared with analogous data for pure n-alkyl acetates and n-alkyl acetate-based electrolytes.

ketones

ketone

n-alkyl acetates

n-alkyl acetate


Input: Synthesis and Pharmacological Characterization of 2-(Acylamino) thiophene Derivatives as Metabolically Stable, Orally Effective, Positive Allosteric Modulators of the GABAB Receptor.

2-(Acylamino) thiophene


Input: Two recently reported hit compounds, COR627 and COR628, underpinned the development of a series of 2-(acylamino) thiophene derivatives.

2-(acylamino) thiophene


Input: Some of these compounds displayed significant activity in vitro as positive allosteric modulators of the GABAB receptor by potentiating GTP gamma S stimulation induced by GABA at 2. 5 and 25 mu M while failing to exhibit intrinsic agonist activity.

GABAB


Input: Compounds were also found to be effective in vivo, potentiating baclofen-induced sedation/hypnosis in DBA mice when administered either intraperitoneally or intragastrically.

baclofen


Input: Although displaying a lower potency in vitro than the reference compound GS39783, the new compounds 6, 10, and 11 exhibited a higher efficacy in vivo: combination of these compounds with a per se nonsedative dose of baclofen resulted in shorter onset and longer duration of the loss of righting reflex in mice.

baclofen


Input: Test compounds showed cytotoxic effects at concentrations comparable to or higher than those of GS39783 or BHF177.


Input: Catalytic Asymmetric Synthesis of gamma-Butenolides by Direct Vinylogous Reactions.

gamma-Butenolides


Input: The gamma-butenolide structural motif is a prominent feature in many bioactive natural products and drugs.

gamma-butenolide


Input: This short review summarizes catalytic asymmetric synthesis of gamma-butenolides through direct vinylogous reactions by metal complexes and organocatalysts.

gamma-butenolides


Input: In light of building chiral gamma-tertiary and quaternary carbon centers of butenolides, three synthetic strategies are included: 1) the reactions with furanone derivatives as nucleophiles, 2) olefination of gamma, gamma-disubstituted butenolides and 3) the reactions by using gamma, gamma-disubstituted butenolides as nucleophiles.

gamma-tertiary and quaternary carbon

butenolides

gamma, gamma-disubstituted butenolides

gamma, gamma-disubstituted butenolides


Input: Transition metal-catalyzed efficient and green transformations of p (o)-h compounds to functional organophosphorus compounds.

Transition metal

organophosphorus


Input: Organophosphorus compounds are of high importance in organic synthesis, catalysis, biochemistry, pharmaceuticals, and material science.

Organophosphorus


Input: In this mini review, we summarize our recent studies on transition metal-catalyzed green and atom efficient transformations of P (O)-H bonds to various versatile organophosphorus compounds, including the highly regio-and stereoselective P (O)-H additions to carbon-carbon unsaturated compounds, asymmetric hydrophosphorylation reactions, and dehydrogenative coupling reactions of P (O)-H compounds with carbon-H and heteroatom-H compounds.

transition metal

P (O)-H

organophosphorus

P (O)-H

carbon

carbon

P (O)-H

carbon

H

H


Input: These new reactions provide efficient, general and practical ways for the preparation of a variety of well-defined functional organophosphorus compounds.

organophosphorus


Input: Mechanistic aspects related to the catalytic processes are also discussed.


Input: Organic selenium resin in solid phase synthesis and its application in constructing medicinally relevant small organic molecules.

selenium


Input: Heterocyclic compounds are of high importance in constructing active drug intermediates library.


Input: The emergence of solid-phase and combinatorial chemistry has led to renewed interest in using organoselenium resins to library drug-like production.

organoselenium


Input: In this mini review, we summarize the construction of heterocyclic compounds libraries such as isoxazoles, oxadiazoles, triazoles, pyrimidines, pyrrolines, indolines, benzopyrans, furans etc. using organoselenium resins.

isoxazoles

oxadiazoles

triazoles

pyrimidines

pyrrolines

indolines

benzopyrans

furans

organoselenium


Input: And it provided efficient and practical ways for the preparation of a variety of well-defined functional heterocyclic compounds with the advantages of good yields, high purity, straightforward operations, broad range and high diversity of the products, lack of odor, and good stability of the resins, all of these give expression to green chemistry.


Input: Enzyme-Catalyzed Synthesis of Aliphatic-Aromatic Oligoamides.


Input: Enzymatically catalyzed polycondensation of p-xylylenediamine and diethyl sebacate resulted in oligo (p-xylylene sebacamide) with high melting temperatures (223-230 degrees C) and the enzymatic polycondensation of dimethyl terephthalate and 1, 8-diaminooctane leads to oligo (octamethylene terephthalamide) with two melting temperatures at 186 and 218 degrees C.

p-xylylenediamine

diethyl sebacate

oligo (p-xylylene sebacamide)

dimethyl terephthalate

1, 8-diaminooctane

oligo (octamethylene terephthalamide)


Input: No oligoamides, but products 1 and 2, were formed from the enzymatic reaction of dimethyl terephthalate and p-xylylenediamine.

dimethyl terephthalate

p-xylylenediamine


Input: All reactions were catalyzed by CAL-B, icutinase, or CLEA cutinase.


Input: All reactions catalyzed by CAL-B show higher conversion than reactions catalyzed by icutinase or CLEA cutinase.


Input: The highest DPmax of 15 was achieved in a one-step and two-step synthesis of oligo (p-xylylene sebacamide) catalyzed by CLEA cutinase.

oligo (p-xylylene sebacamide)


Input: Impurity partitioning during colloidal crystallization.


Input: We have found that an impurity partitioning takes place during growth of colloidal crystals, which was recognized by the fact that the impurity concentration in the solid (CS) was different from that in the initial solution (C0).


Input: The effective partition coefficient keff (= CS/C0) was investigated for pure polystyrene and polystyrene dyed with fluorescent particles by changing the ratio of particle diameters dimp/dcryst and growth rate V.

polystyrene

polystyrene


Input: At each size ratio for the polystyrene impurity, keff was less than unity and increased to unity with increasing V, whereas at a given growth rate, keff increased to unity as dimp/dcryst approached unity.

polystyrene


Input: These results were consistent with the solute behavior analyzed using the Burton, Prim, and Slichter (BPS) model.


Input: The obtained k0, equilibrium partition coefficient, from a BPS plot increased as dimp/dcryst approached unity.


Input: In contrast, while the fluorescent particles also followed the BPS model, they showed higher k0 values than those of the same size of polystyrene particles.

polystyrene


Input: A k0 value greater than unity was obtained for impurities that were similar in size to the host particle.


Input: This behavior is attributed to the positive free energy of fusion associated with the incorporation of the fluorescent particles into the host matrix.


Input: Such positive free energy of fusion implies the presence of the enthalpy associated with interaction between particles.


Input: Virtual medicinal chemistry: In silico pre-docking functional group transformation for discovery of novel inhibitors of botulinum toxin serotype A light chain.


Input: A novel method for applying high-throughput docking to challenging metalloenzyme targets is described.


Input: The method utilizes information-based virtual transformation of library carboxylates to hydroxamic acids prior to docking, followed by compound acquisition, one-pot (two steps) chemical synthesis and in vitro screening.

carboxylates

hydroxamic acids


Input: In two experiments targeting the botulinum neurotoxin serotype A metalloprotease light chain, hit rates of 32% and 18% were observed.


Input: Antimicrobial activity of southern African medicinal plants with dermatological relevance: From an ethnopharmacological screening approach, to combination studies and the isolation of a bioactive compound.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical reports on more than 100 southern African medicinal plants with dermatological relevance have been highlighted, yet there is still limited scientific data to support claims for their antimicrobial effectiveness against skin pathogens.


Input: Guided by ethnobotanical data, this paper explores the antimicrobial efficacies of southern African medicinal plants used to treat skin ailments.


Input: AIM OF THE STUDY: To investigate the antimicrobial properties of southern African medicinal plants against dermatologically relevant pathogens.


Input: The study also aimed at providing a scientific rationale for the traditional use of plant combinations to treat skin diseases and the isolation of the bioactive compound from the most active species, Aristea ecklonii (Iridaceae).


Input: MATERIALS AND METHODS: Organic and aqueous extracts (132) were prepared from 47 plant species and screened for antimicrobial properties against dermatologically relevant pathogens using the micro-titre plate dilution method.


Input: Four different plant combinations were investigated for interactive properties and the sum of the fractional inhibitory concentration (Esh FIC) calculated.


Input: Isobolograms were used to further investigate the antimicrobial interactive properties of Pentanisia prunelloides combined with Elephantorrhiza elephantina at varied ratios.


Input: A bioactivity-guided fractionation process was adopted to fractionate the organic leaf extract of Aristea ecklonii.


Input: RESULTS: Plants demonstrating notable broad-spectrum activities (MIC values <= 1. 00mg/ml) against the tested pathogens included extracts from Aristea ecklonii, Chenopodium ambrosioides, Diospyros mespiliformis, Elephantorrhiza elephantina, Eucalyptus camaldulensis, Gunnera perpensa, Harpephyllum caffrum, Hypericum perforatum, Melianthus comosus, Terminalia sericea and Warburgia salutaris.


Input: The organic extract of Elephantorrhiza elephantina, a plant reportedly used to treat acne vulgaris, demonstrated noteworthy antimicrobial activity (MIC value of 0. 05mg/ml) against Propionibacterium acnes.


Input: Similarly, Diospyros mespiliformis reported for its traditional use to treat ringworm, also displayed noteworthy antimicrobial activity against Trichophyton mentagrophytes (MIC 0. 10mg/ml) and Microsporum canis (MIC 0. 50mg/ml).


Input: The aqueous root extracts of Pentanisia prunelloides combined (1: 1) with Elephantorrhiza elephantina displayed synergistic interactions (Esh FIC values 0. 31-0. 38) against Staphylococcus aureus, gentamycin-methicillin resistant Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans.

gentamycin

methicillin


Input: Fractionation of Aristea ecklonii resulted in the isolation of the known bioactive compound, plumbagin, displaying noteworthy antimicrobial activity (MIC range between 2. 00 mu g/ml and 16. 00 mu g/ml).

plumbagin


Input: CONCLUSION: Most of the plant extracts demonstrated pathogen specific antimicrobial effects with a few exhibiting broad-spectrum activities.


Input: Positive antimicrobial effects noted for plants such as Elephantorrhiza elephantina and Diospyros mespiliformis used for acne vulgaris and ringworm infections, respectively, give some validation to their reported traditiona l uses.


Input: Synergistic interactions noted for Pentanisia prunelloides combined with Elephantorrhiza elephantina validate an enhanced antimicrobial effect when used in combination.


Input: Noteworthy antimicrobial activities (MIC range between 2. 00 mu g/ml and 16. 00 mu g/ml) were observed for plumbagin isolated from Aristea ecklonii.

plumbagin


Input: Stable and high-rate overcharge protection for rechargeable lithium batteries.

lithium


Input: Rechargeable lithium or lithium-ion cells can be overcharge-protected by an electroactive polymer composite separator.

lithium

lithium


Input: The use of non-woven fibrous membranes instead of conventional microporous membranes as the composite substrates allowed better distribution of the electroactive polymer, which led to improved utilization and a 40-fold increase in sustainable current density.


Input: For the first time, stable overcharge protection for hundreds of cycles was demonstrated in several cell chemistries, including LiNi1/3Co1/3Mn1/3O2, LiFePO4, and spinel Li1. 05Mn1. 95O4 half-cells.

Li1. 05Mn1. 95O4


Input: Protection at a charging rate as high as 5 C was achieved at a steady state cell potential below 4. 85 V.


Input: PD-1, but not PD-L1, expressed by islet-reactive CD4 + T cells suppresses infiltration of the pancreas during Type 1 Diabetes.


Input: The inhibitory receptor PD-1 constrains Type 1 Diabetes (T1D) in the non-obese diabetic (NOD) mouse.


Input: However, how PD-1 influences diabetogenic CD4 (+) T cells during natural diabetes is not fully understood.


Input: To address this question we developed a novel model to investigate antigen-specific CD4 (+) T cells under physiological conditions in vivo.


Input: We transferred a low number of na i ve CD4 (+) T cells from the BDC2. 5 mouse into prediabetic NOD mice to mimic a physiological precursor frequency and allowed the cells to become primed by endogenous autoantigen.


Input: Transferred BDC2. 5 T cells became activated, differentiated into T-bet (+) IFN gamma-producing cells, and infiltrated the pancreas.


Input: In this model, loss of PD-1, but not PD-L1, on the antigen-specific CD4 (+) T cell resulted in increased cell numbers in the spleen, pancreas-draining lymph node and pancreas.


Input: PD-1-deficiency also increased expression of the chemokine receptor CXCR3.


Input: Lastly, histological data showed that a loss of PD-1 caused BDC2. 5 cells to penetrate deep into the islet core, resulting in conversion from peri-insulitis to destructive insulitis.


Input: These data support a model by which PD-1 regulates islet-reactive CD4 (+) T cells in a cell intrinsic manner by suppressing proliferation, inhibiting infiltration of the pancreas, and limiting diabetes.


Input: The metabolic profile of mitoxantrone and its relation with mitoxantrone-induced cardiotoxicity.

mitoxantrone

mitoxantrone


Input: Mitoxantrone (MTX) is an antitumor agent that causes cardiotoxicity in 18% patients.

Mitoxantrone

MTX


Input: The metabolic profile of MTX was assessed after incubation of 100 mu M MTX with hepatic S9 fraction isolated from rats.

MTX

MTX


Input: The presence of MTX and its metabolites was also assessed in vivo through the analysis of liver and heart extracts of MTX-treated rats.

MTX

MTX


Input: The cytotoxic effects of MTX and MTX metabolites were evaluated in the H9c2 cells after 24-h incubation with MTX alone and MTX + metabolites.

MTX

MTX

MTX

MTX


Input: The influence of CYP450-and CYP2E1-mediated metabolism for the cytotoxicity of MTX was assessed after 96-h incubation with MTX (100 nM and 1 mu M) in the presence/absence of CYP450 or CYP2E1 inhibitors.

MTX

MTX


Input: After 4-h incubation in supplemented S9 fraction, the MTX content was 35% lower and 5 metabolites were identified: an acetoxy ester derivative (never described before), two glutathione conjugates, a monocarboxylic acid derivative, and the naphtoquinoxaline, the later commonly related to MTX pharmacological effects.

MTX

glutathione

monocarboxylic acid

naphtoquinoxaline

MTX


Input: The presence of MTX and naphtoquinoxaline metabolite was evidenced in vivo in liver and heart of MTX-treated rats.

MTX

naphtoquinoxaline

MTX


Input: The cytotoxicity caused by MTX + metabolites was higher than that observed in the H9c2 cells incubated with non-metabolized MTX group.

MTX

MTX


Input: The co-incubation of MTX with CYP450 and CYP2E1 inhibitors partially prevented the cytotoxicity observed in the MTX groups incubated with H9c2 cells, highlighting that the metabolism of MTX is relevant for its undesirable effects.

MTX

MTX

MTX


Input: The naphtoquinoxaline metabolite is described in heart and liver in vivo, highlighting that this metabolite accumulates in these tissues.

naphtoquinoxaline


Input: It was demonstrated that MTX P450-mediated metabolism contributed to MTX toxicity.

MTX

MTX


Input: Six New Cyclic Peptides from the Roots of Gypsophila oldhamiana.


Input: Six new cyclic peptides, gypsophin A-F (1-6), were isolated from Gypsophila oldhamiana.

gypsophin A-F


Input: Their structures were elucidated by extensive NMR and chemical degradation.


Input: Compound 3 exhibited moderate activity of antiplatelet aggregation in vitro.


Input: Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.

ethanol


Input: The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells.

petroleum ether

chloroform

ethyl acetate

ethanol


Input: Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 mu g/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h.

ethanol


Input: After the exposure, cell viability using (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied.

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

neutral red


Input: Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol.

ethanol


Input: Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated.

oxygen

glutathione

GSH

ethanol


Input: Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol.

GSH

ethanol


Input: The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells.

ethanol


Input: However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective.


Input: The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia.


Input: Differential propensity of citrate-and polyethylene glycol-coated silver nanoparticles to bovine hemoglobin.

citrate

polyethylene glycol

silver


Input: Propensity of two different silver nanoparticles (Ag-NPs) to bovine hemoglobin (BHb) was investigated by means of spectroscopic methods.

silver

Ag


Input: We have combined spectrophotometric and calorimetric methods to show that there is no significant interaction between citrate-coated Ag-NPs and BHb at physiological pH and 20 degrees C.

citrate

Ag


Input: However, our previous results show that polyethylene glycol-coated Ag-NPs strongly bind to Hb and effect on the secondary and tertiary structures of BHb.

polyethylene glycol

Ag


Input: Thus, a suitable surface coating and modification of surface charge would increase the NPs safety and reduce adverse biological responses.


Input: Excess androgens in utero alters fetal testis development.

androgens


Input: Prenatal androgenization induces a polycystic ovary syndrome-like phenotype in adult female offspring, which is associated with alterations that can be detected in the fetal ovary, suggesting gestational origins of this condition.


Input: We therefore investigated whether increased prenatal androgen exposure also altered testicular development using ovine animal models.

androgen


Input: Biweekly maternal testosterone propionate (TP; 100 mg) from day 62 to day 70/day 90 of gestation altered male developmental trajectory.

testosterone propionate


Input: In male fetuses serum LH was decreased (P <. 01), and testicular STAR, CYP11, and CYP17 abundance were reduced.


Input: Coincident with this, basal testicular T synthesis was decreased in vitro (P <. 001).


Input: Leydig cell distribution was severely perturbed in all testes prenatally exposed to TP (P <. 001).


Input: To examine the contribution of estrogens, fetuses were injected with TP (20 mg), the potent estrogen agonist, diethylstilbestrol (DES; 20 mg), or vehicle control at day 62 and day 82 and assessed at day 90.

estrogens

estrogen

diethylstilbestrol

DES


Input: The effects of fetal (direct) TP treatment, but not DES, paralleled maternal (indirect) TP exposure, supporting a direct androgen effect.

DES

androgen


Input: Cessation of maternal androgenization at day 102 returned Leydig cell distribution to normal but increased basal T output, at day 112, demonstrating Leydig cell developmental plasticity.


Input: Earlier maternal androgen exposure from day 30 similarly influenced Leydig cell development at day 90 but additionally affected the expression of Sertoli and germ cell markers.

androgen


Input: We show in this study that increased prenatal androgen exposure alters development and function of Leydig cells at a time when androgen production is paramount for male development.

androgen


Input: This supports the concept that gestational antecedents associated with polycystic ovary syndrome may have effects on the male fetus.


Input: Budesonide/cyclodextrin complex-loaded lyophilized microparticles for intranasal application.

Budesonide


Input: Abstract Objective: Lyophilized microparticles composed of budesonide (BDS), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and hydroxypropylmethylcellulose (HPMC) or sodium carboxymethylcellulose (CMC-Na) were developed for intranasal delivery and their characteristics were evaluated.

budesonide

BDS

hydroxypropyl-beta-cyclodextrin

HP-beta-CD

sodium


Input: Materials and methods: The particle size and morphology were assessed by mean diameter measurement and scanning electron microscopy (SEM) image, respectively.


Input: The solid-state of products was tested by X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC).


Input: In vitro drug release and cytotoxicity to the primary human nasal epithelial (HNE) cells were also evaluated.


Input: Results and discussion: Lyophilized microparticles exhibited vanishment of crystallinity of drug in XRPD analysis, the enfeeblement of carbonyl (C = O) stretching bands of carboxyl group in BDS in FT-IR spectra and the disappearance of endothermic peak of drug in the results of DSC study.

carbonyl

C = O

carboxyl

BDS


Input: Based on the results of solid-state studies, BDS was existed as an amorphous form in the lyophilized microparticles.

BDS


Input: CD complexation enhanced drug solubility and release rate, and HPMC or CMC-Na also improved drug dissolution rates.


Input: Cytotoxicity of developed microparticles to the HNE cells was measured and their safety to HNE cell was identified.


Input: Conclusion: Developed microparticles can efficiently deliver insoluble drug, such as BDS, to the nasal epithelium and thus it may improve therapeutic efficacy in the respiratory tract.

BDS


Input: Serotonin (5-HT) in the Regulation of Depression-Related Emotionality: Insight from 5-HT Transporter and Tryptophan Hydroxylase-2 Knockout Mouse Models.

Serotonin

Tryptophan


Input: Disorders of emotion regulation such as anxiety disorders and depression are common and yet debilitating.


Input: Accumulating evidence suggests involvement of serotonin (5-HT) in the regulation of emotion.

serotonin


Input: Mice with targeted deletion of genes encoding mediators of the serotonergic transmission have proven to be a powerful tool for understanding contributions of such mediators of emotion regulation.


Input: Over the last decade, research on mice with a targeted inactivation of the 5-HT transporter (5-Htt, Sert, Slc6a4) has considerably advanced our knowledge about functions that the 5-HTT plays in the context of emotion related to depression.


Input: Moreover, the recent advent of knockout (KO) mice for tryptophan hydroxylase 2 (Tph2 KO), which lacks the rate-limiting enzyme for 5-HT synthesis in the brain, has further provided insight to the brain serotonergic system and its role in emotion dysregulation.

tryptophan


Input: Here, we first highlight basic characteristics of the serotonergic system including the biosynthesis of 5-HT as well as the anatomy and firing activity of serotonergic neurons.


Input: Furthermore, characteristics of 5-Htt and Tph2 KO mice are covered together with association studies on human variants of 5-HTT and TPH2 in emotional regulation.


Input: Among various targets of serotonergic projections, which originate from the raphe nuclei in the brain stem, particular focus is placed on the hippocampus due to its unique dual role in memory and emotion.


Input: Finally, effects of therapeutic drugs and psychoactive drugs on KO mouse models as well as on synaptic plasticity will be discussed.


Input: Controllable Hydrogen Sulfide Donors and Their Activity against Myocardial Ischemia-Reperfusion Injury.

Hydrogen Sulfide


Input: Hydrogen sulfide (H2S), known as an important cellular signaling molecule, plays critical roles in many physiological and/or pathological processes.

Hydrogen sulfide


Input: Modulation of H2S levels could have tremendous therapeutic value.


Input: However, the study on H2S has been hindered due to the lack of controllable H2S releasing agents that could mimic the slow and moderate H2S release in vivo.


Input: In this work we report the design, synthesis, and biological evaluation of a new class of controllable H2S donors.


Input: Twenty-five donors were prepared and tested.


Input: Their structures were based on a perthiol template, which was suggested to be involved in H2S biosynthesis.

perthiol


Input: H2S release mechanism from these donors was studied and proved to be thiol-dependent.

thiol


Input: We also developed a series of cell-based assays to access their H2S-related activities.


Input: H9c2 cardiac myocytes were used in these experiments.


Input: We tested lead donors' cytotoxicity and confirmed their H2S production in cells.


Input: Finally we demonstrated that selected donors showed potent protective effects in an in vivo murine model of myocardial ischemia-reperfusion injury, through a H2S-related mechanism.


Input: Interfacial Nanoarchitectonics: Lateral and Vertical, Static and Dynamic.


Input: The exploration of nanostructures and nanomaterials is essential to the development of advanced functions.


Input: For such innovations, nanoarchitectonics has been proposed as a novel paradigm of nanotechnology aimed at assembling nanoscale structural units into predesigned configurations or arrangements.


Input: In this Feature Article, we provide an overview of several recent research works from the viewpoint of interfacial nanoarchitectonics with features developed in lateral directions or grown in vertical directions with construction on solid, static, or flexible dynamic surfaces.


Input: Lateral nanoarchitectonics at a static interface provides molecular organization by bottom-up nanoarchitectonics and can also be used to realize device integration by top-down nanoarchitectonics.


Input: In particular, in the latter case, the fabrication of novel devices, so-called atomic switches, are introduced as a demonstration of atomic-level electronics.


Input: Lateral nanoarchitectonics at dynamic interfaces is exemplified by 2D molecular patterning and molecular machine operation induced by macroscopic motion.


Input: The dynamic nature of interfaces enables us to operate molecular-sized machines by macroscopic mechanical stimuli such as our hand motion, which we refer to as hand-operated nanotechnology.


Input: Vertical nanoarchitectonics is mainly discussed in relation to layer-by-layer (LbL) assembly.


Input: By using this technique, we can assemble a variety of functional materials in ultrathin film structures of defined thickness and layer sequence.


Input: The organization of biomolecules (or even living cells) within thin films and their integration with device structures is exemplified.


Input: Finally, the anticipated research directions of interfacial nanoarchitectonics are described.


Input: Polycyclic Hybrid Isoprenoids from a Reed Rhizosphere Soil Derived Streptomyces sp.

Isoprenoids


Input: Two new hybrid isoprenoids, named indotertine B (2) and drimentine H (3), along with the known analogue drimentine C (4), were isolated from the reed rhizosphere soil derived actinomycete Streptomyces sp.

isoprenoids

indotertine B

drimentine H

drimentine C


Input: The structures of these compounds, including absolute configurations, were elucidated by extensive NMR, MS, and CD analyses.


Input: Indotertine B (2) exists as a pair of rotamers about the N-C (O) bond with a 2: 1 ratio and displays activities against HCT-8 and A549 tumor cell lines with IC50 values of 6. 96 and 4. 88 mu M, respectively.

Indotertine B

N-C (O)


Input: A mass-tagging approach for enhanced sensitivity of dynamic cytokine detection using a label-free biosensor.


Input: Monitoring cytokine release by cells allows the investigation of cellular response to specific external stimuli, such as pathogens or candidate drugs.


Input: Unlike conventional colorimetric techniques, label-free detection of cytokines enables studying cellular secretions in real time by eliminating additional wash and labeling steps after the binding step.


Input: However, label-free techniques that are based on measuring mass accumulation on a sensor surface are challenging for measuring small cytokines binding to much larger capture agents (usually antibodies) because the relative signal change is small.


Input: This problem is exacerbated when the capturing antibodies desorb from the surface, a phenomenon that almost inevitably occurs in immunoassays but is rarely accounted for.