Input: The enzyme generates a biocompatible, biodegradable biopolyester coat on the fibers with applicablity in medical engineering.


Input: This approach provides a template for generation of functional bionanomaterials.


Input: Solid-state NMR study reveals collagen I structural modifications of amino acid side chains upon fibrillogenesis.

amino acid


Input: In vivo, collagen I, the major structural protein in human body, is found assembled into fibrils.


Input: In the present work, we study a high concentrated collagen sample in its soluble, fibrillar, and denatured states using one and two dimensional {(1) H}-(13) C solid-state NMR spectroscopy.

(1) H

(13) C


Input: We interpret (13) C chemical shift variations in terms of dihedral angle conformation changes.

(13) C


Input: Our data show that fibrillogenesis increases the side chain and backbone structural complexity.


Input: Nevertheless, only three to five rotameric equilibria are found for each amino acid residue, indicating a relatively low structural heterogeneity of collagen upon fibrillogenesis.

amino acid


Input: Using side chain statistical data, we calculate equilibrium constants for a great number of amino acid residues.

amino acid


Input: Moreover, based on a (13) C quantitative spectrum, we estimate the percentage of residues implicated in each equilibrium.

(13) C


Input: Our data indicate that fibril formation greatly affects hydroxyproline and proline prolyl pucker ring conformation.

hydroxyproline

proline prolyl


Input: Finally, we discuss the implication of these structural data and propose a model in which the attractive force of fibrillogenesis comes from a structural reorganization of 10 to 15% of the amino acids.

amino acids


Input: These results allow us to further understand the self-assembling process and fibrillar structure of collagen.


Input: Detecting Allosteric Sites of HIV-1 Reverse Transcriptase by X-ray Crystallographic Fragment Screening.


Input: HIV-1 reverse transcriptase (RT) undergoes a series of conformational changes during viral replication and is a central target for antiretroviral therapy.


Input: The intrinsic flexibility of RT can provide novel allosteric sites for inhibition.


Input: Crystals of RT that diffract X-rays to better than 2 A resolution facilitated the probing of RT for new druggable sites using fragment screening by X-ray crystallography.


Input: A total of 775 fragments were grouped into 143 cocktails, which were soaked into crystals of RT in complex with the non-nucleoside drug rilpivirine (TMC278).

nucleoside

rilpivirine


Input: Seven new sites were discovered, including the Incoming Nucleotide Binding, Knuckles, NNRTI Adjacent, and 399 sites, located in the polymerase region of RT, and the 428, RNase H Primer Grip Adjacent, and 507 sites, located in the RNase H region.

Nucleotide


Input: Three of these sites (Knuckles, NNRTI Adjacent, and Incoming Nucleotide Binding) are inhibitory and provide opportunities for discovery of new anti-AIDS drugs.

Nucleotide


Input: Cluster phases of decorated micellar solutions with macrocyclic ligands.


Input: An aqueous self-assembled micellar system (sodium dodecyl sulfate, SDS, decorated with various adhesive sites, cryptand Kryptofix 222 and crown ether 18-Crown-6 molecules) has been investigated by dynamic light scattering (DLS) and small angle x-ray scattering (SAXS) to have insights into the micellar structure, the micellar interactions, and the aggregation properties of the system.

sodium dodecyl sulfate

SDS

cryptand Kryptofix 222

crown ether 18-Crown-6


Input: DLS demonstrates the existence of populations of aggregates in the submicrometer/micrometer range, while the Guinier analysis of the SAXS curves helps in detailing objects smaller than 30 nm.


Input: The aggregates of micelles are here named cluster phases of micelles (CPMs).


Input: Considering that SDS micelles in water do not aggregate at low concentration, it is shown that macrocyclic ligands induce the SDS micelle aggregation as a function of the concentration (i. e., investigated ligand/SDS molar ratios are 5. 0, 1. 5, 1. 0, and 0. 5) and hydrophobicity of the adhesive sites.

SDS

SDS

SDS


Input: The sizes and the percentages of the micelles and the CPMs have been monitored to test the stability and reversibility of the system.


Input: DLS results clearly show that the aggregation processes of the decorated micelles are reproducible at time intervals of the order of 1 month, while the stability may not be entirely maintained after a year.


Input: As an issue of particular relevance, the higher the ligand/surfactant molar ratio, the larger are the CPMs induced.


Input: The K222 ligand results in being more effective in promoting the micellar aggregation than 18C6 as a consequence of the different hydrophobicity.


Input: Personality and the acute subjective effects of d-amphetamine in humans.

d-amphetamine


Input: There is evidence that subjective responses to psychoactive drugs are related to personality traits.


Input: Here, we extend previous findings by examining personality measures in relation to acute responses to d-amphetamine (AMPH) in a large sample of healthy volunteers.

d-amphetamine

AMPH


Input: Healthy adults (n = 286) completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF) and participated in four sessions during which they received oral AMPH (0, 5, 10, 20 mg), under double-blind conditions.

AMPH


Input: Subjective responses to the drug were measured using the Profile of Mood States, Addiction Research Center Inventory, and Drug Effects Questionnaire.


Input: Drug responses were reduced via principal components analysis to three higher-order factors (' Euphoria',' Arousal',' Dysphoria').


Input: Participants were rank ordered on selected MPQ-BF scales; the top and bottom third on each trait were compared on the drug response factors.


Input: High trait physical fearlessness was significantly associated with greater amphetamine-related Arousal, and high trait reward sensitivity was significantly associated with greater Euphoria.

amphetamine


Input: In addition, high trait impulsivity was significantly associated with greater Arousal and Euphoria.


Input: These results provide further evidence that individual differences in the subjective effects of AMPH are partially explained by differences in personality, and are consistent with the idea that both personality and responses to stimulants depend upon shared neurochemical systems.

AMPH


Input: In-plane coassembly route to atomically thick inorganic-organic hybrid nanosheets.


Input: Control over the anisotropic assembly of small building blocks into organized structures is considered an effective way to design organic nanosheets and atomically thick inorganic nanosheets with nonlayered structure.


Input: However, there is still no available route so far to control the assembly of inorganic and organic building blocks into a flattened hybrid nanosheet with atomic thickness.


Input: Herein, we highlight for the first time a universal in-plane coassembly process for the design and synthesis of transition-metal chalcogenide-alkylamine inorganic-organic hybrid nanosheets with atomic thickness.

transition-metal chalcogenide-alkylamine


Input: The structure, formation mechanism, and stability of the hybrid nanosheets were investigated in detail by taking the Co 9 S 8-oleylamine (Co 9 S 8-OA) hybrid nanosheets as an example.

Co 9 S 8

oleylamine

Co 9 S 8


Input: Both experimental data and theoretical simulations demonstrate that the hybrid nanosheets were formed by in-plane connection of small two-dimensional (2D) Co 9 S 8 nanoplates via oleylamine molecules adsorbed at the side surface and corner sites of the nanoplates.

Co 9 S 8

oleylamine


Input: X-ray absorption fine structure spectroscopy study reveals the structure distortion of the small 2D Co 9 S 8 nanoplates that endows structural stability of the atomically thick Co 9 S 8-OA hybrid nanosheets.

Co 9 S 8

Co 9 S 8


Input: The brand new atomically thick nanosheets with inorganic-organic hybrid network nanostructure will not only enrich the family of atomically thick 2D nanosheets but also inspire more interest in their potential applications.


Input: Targeted drug delivery to treat pain and cerebral hypoxia.


Input: Limited drug penetration is an obstacle that is often encountered in treatment of central nervous system (CNS) diseases including pain and cerebral hypoxia.


Input: Over the past several years, biochemical characteristics of the brain (i. e., tight junction protein complexes at brain barrier sites, expression of influx and efflux transporters) have been shown to be directly involved in determining CNS permeation of therapeutic agents; however, the vast majority of these studies have focused on understanding those mechanisms that prevent drugs from entering the CNS.


Input: Recently, this paradigm has shifted toward identifying and characterizing brain targets that facilitate CNS drug delivery.


Input: Such targets include the organic anion-transporting polypeptides (OATPs in humans; Oatps in rodents), a family of sodium-independent transporters that are endogenously expressed in the brain and are involved in drug uptake.

sodium


Input: OATP/Oatp substrates include drugs that are efficacious in treatment of pain and/or cerebral hypoxia (i. e., opioid analgesic peptides, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors).

3-hydroxy-3-methylglutaryl coenzyme A


Input: This clearly suggests that OATP/Oatp isoforms are viable transporter targets that can be exploited for optimization of drug delivery to the brain and, therefore, improved treatment of CNS diseases.


Input: This review summarizes recent knowledge in this area and emphasizes the potential that therapeutic targeting of OATP/Oatp isoforms may have in facilitating CNS drug delivery and distribution.


Input: Additionally, information presented in this review will point to novel strategies that can be used for treatment of pain and cerebral hypoxia.


Input: A Molecular-Modeling Toolbox Aimed at Bridging the Gap between Medicinal Chemistry and Computational Sciences.


Input: In the current era of high-throughput drug discovery and development, molecular modeling has become an indispensable tool for identifying, optimizing and prioritizing small-molecule drug candidates.


Input: The required background in computational chemistry and the knowledge of how to handle the complex underlying protocols, however, might keep medicinal chemists from routinely using in silico technologies.


Input: Our objective is to encourage those researchers to exploit existing modeling technologies more frequently through easy-to-use graphical user interfaces.


Input: In this account, we present two innovative tools (which we are prepared to share with academic institutions) facilitating computational tasks commonly utilized in drug discovery and development: (1) the VirtualDesignLab estimates the binding affinity of small molecules by simulating and quantifying their binding to the three-dimensional structure of a target protein; and (2) the MD Client launches molecular dynamics simulations aimed at exploring the time-dependent stability of ligand-protein complexes and provides residue-based interaction energies.


Input: This allows medicinal chemists to identify sites of potential improvement in their candidate molecule.


Input: As a case study, we present the application of our tools towards the design of novel antagonists for the FimH adhesin.


Input: Bioactivity and applications of sulphated polysaccharides from marine microalgae.


Input: Marine microalgae have been used for a long time as food for humans, such as Arthrospira (formerly, Spirulina), and for animals in aquaculture.


Input: The biomass of these microalgae and the compounds they produce have been shown to possess several biological applications with numerous health benefits.


Input: The present review puts up-to-date the research on the biological activities and applications of polysaccharides, active biocompounds synthesized by marine unicellular algae, which are, most of the times, released into the surrounding medium (exo-or extracellular polysaccharides, EPS).


Input: It goes through the most studied activities of sulphated polysaccharides (sPS) or their derivatives, but also highlights lesser known applications as hypolipidaemic or hypoglycaemic, or as biolubricant agents and drag-reducers.


Input: Therefore, the great potentials of sPS from marine microalgae to be used as nutraceuticals, therapeutic agents, cosmetics, or in other areas, such as engineering, are approached in this review.


Input: Catalytic transformation of alcohols to carboxylic acid salts and H2 using water as the oxygen atom source.

alcohols

carboxylic acid

oxygen


Input: The oxidation of alcohols to carboxylic acids is an important industrial reaction used in the synthesis of bulk and fine chemicals.

alcohols

carboxylic acids


Input: Most current processes are performed by making use of either stoichiometric amounts of toxic oxidizing agents or the use of pressurized dioxygen.

dioxygen


Input: Here, we describe an alternative dehydrogenative pathway effected by water and base with the concomitant generation of hydrogen gas.


Input: A homogeneous ruthenium complex catalyses the transformation of primary alcohols to carboxylic acid salts at low catalyst loadings (0. 2 mol%) in basic aqueous solution.

ruthenium

alcohols

carboxylic acid


Input: A consequence of this finding could be a safer and cleaner process for the synthesis of carboxylic acids and their derivatives at both laboratory and industrial scales.

carboxylic acids


Input: Increased impulsive choice for saccharin during PCP withdrawal in female monkeys: influence of menstrual cycle phase.

saccharin

PCP


Input: BACKGROUND: In previous studies with male and female rhesus monkeys, withdrawal of access to oral phencyclidine (PCP) self-administration reduced responding for food under a high fixed-ratio (FR) schedule more in males than females, and with a delay discounting (DD) task with saccharin (SACC) as the reinforcer impulsive choice for SACC increased during PCP withdrawal more in males than females.

phencyclidine

PCP

saccharin

SACC

SACC

PCP


Input: OBJECTIVES: The goal of the present study was to examine the effect of PCP (0. 25 or 0. 5 mg/ml) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle.

PCP

SACC


Input: MATERIALS AND METHODS: In component 1, PCP and water were available from two drinking spouts for 1. 5 h sessions under concurrent FR 16 schedules.

PCP


Input: In component 2, a SACC solution was available for 45 min under a DD schedule.

SACC


Input: Monkeys had a choice of one immediate SACC delivery (0. 6 ml) or six delayed SACC deliveries, and the delay was increased by 1 s after a response on the delayed lever and decreased by 1 s after a response on the immediate lever.

SACC

SACC


Input: There was then a 10-day water substitution phase, or PCP withdrawal, that occurred during the mid-follicular phase (days 7-11) or the late luteal phase (days 24-28) of the menstrual cycle.

PCP


Input: Access to PCP and concurrent water was then restored, and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases.

PCP

PCP


Input: RESULTS: PCP deliveries were higher during the luteal (vs follicular) phase.

PCP


Input: Impulsive choice was greater during the luteal (vs follicular) phase during withdrawal of the higher PCP concentration.

PCP


Input: CONCLUSIONS: PCP withdrawal was associated with elevated impulsive choice for SACC, especially in the luteal (vs follicular) phase of the menstrual cycle in female monkeys.

PCP

SACC


Input: A donor-acceptor type organic dye connected with a quinoidal thiophene for dye-sensitized solar cells.

quinoidal thiophene


Input: A donor-acceptor type organic dye connected with a quinoidal thiophene as a pi-conjugated chain, cyano-[5'-(4''-(N, N-dimethylamino) benzylidene)-5H-thiophen-2'-ylidene] acetic acid, was synthesized and applied to dye-sensitized solar cells (DSSCs).

quinoidal thiophene

cyano-[5'-(4''-(N, N-dimethylamino) benzylidene)-5H-thiophen-2'-ylidene] acetic acid


Input: The absorption band of this quinoidal thiophene dye appeared at longer wavelengths than those of dyes with similar pi-conjugation length, indicating the effective pi-conjugation through the quinoidal structure.

quinoidal thiophene


Input: Although the excited state of the quinoidal thiophene dye is deactivated within several picoseconds even in solution, the DSSCs using the quinoidal thiophene dye showed incident photon to current conversion efficiency (IPCE) values of more than 90%, demonstrating the fast and efficient electron injection from the excited dye to TiO (2).

quinoidal thiophene

quinoidal thiophene

TiO (2)


Input: By optimizing the fabrication conditions, the DSSC using this dye afforded a photoelectric conversion efficiency of 5. 2%, without enlarging the molecular size.


Input: Oxidative stress and alteration of biochemical markers in liver and kidney by malathion in rat pups.

malathion


Input: The present study was undertaken to determine the effects of malathion exposure through maternal milk on oxidative stress, functional an metabolic parameters in kidney and liver of rat pups.

malathion


Input: We found that lactational exposure to malation (200 mg/kg, body weight (bw)) induced an oxidative stress status assessed by an increase in malondialdhyde (MDA) content, reflecting lipoperoxidation, a decrease in thiol groups' content as well as depletion of enzyme activities as a superoxide dismutase (SOD) and catalase (CAT) on postnatal days (Pnds) 21 and 51.

malation

malondialdhyde

MDA

thiol

superoxide


Input: Moreover, the current study showed that malathion induced liver and kidney dysfunctions demonstrated by considerable increase in phosphatase alkaline (PAL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as total and direct bilirubin, creatinine urea and acid uric contents.

malathion

aspartate

alanine

bilirubin

creatinine urea

acid uric


Input: We also observed an increase in triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and a decrease in high-density lipoprotein cholesterol (HDL-C) in the plasma of treated rat pups.

triglyceride

cholesterol

cholesterol

cholesterol


Input: These findings evidenced that malathion exposure during lactation through maternal milk of rats pups induced kidney and liver oxidative stress as well as functional and metabolic disorders that play a role in the development of others pathologies as cardiovascular diseases and cancers.

malathion


Input: Interleukin-10 involvement in exposure to low dose of benzene.

benzene


Input: OBJECTIVE: To establish if serum levels of interleukin-10 (IL-10) in subjects exposed to benzene are connected with age, working years, and employment age.

benzene


Input: METHODS: We evaluated serum levels of IL-10 in 51 employees working in oil refinery (group A) and in 16 office workers who resided in the same area (group B).


Input: RESULTS: There was no statistically significant difference between serum concentrations of IL-10 in groups A and B.


Input: There was a statistically significant dependent relationship in group A between age, working years, and serum concentration of IL-10.


Input: There was a statistically significant and positive dependent relationship in group A between serum concentration of IL-10 and employment age.


Input: CONCLUSIONS: The role played by IL-10 in benzene immune suppression may be relevant and attention should be directed toward assessment of age, working years, and employment age in benzene-exposed populations.

benzene

benzene


Input: Regulation of sodium and calcium in Daphnia magna exposed to silver nanoparticles.

sodium

calcium

silver


Input: The toxicity of manufactured silver nanoparticles (AgNPs) has been widely studied, but the influence of AgNPs on the major ions (such as sodium [Na] and calcium [Ca]) regulations are unknown.

silver

sodium

calcium

Ca


Input: In the present study, a freshwater cladoceran Daphnia magna was exposed to commercial AgNPs coated with polyvinylpyrrolidone.

polyvinylpyrrolidone


Input: After 48 h, the Na body content was significantly reduced by AgNO3 exposure, but the Ca body content was significantly increased under AgNO3 and AgNP exposures, respectively.

Ca


Input: No effect was observed on the body concentrations of Na and Ca at 50 to 500 micro g/L AgNPs with 1-micro M cysteine addition.

Ca

cysteine


Input: Exposure of AgNO3 and AgNPs inhibited the Na influx and elevated the Na efflux.


Input: In contrast, their exposure increased the Ca influx, but did not affect the Ca efflux.

Ca

Ca


Input: The results of the present study demonstrated the significant influences of AgNO3 and AgNPs (without cysteine) on Na and Ca regulations.

cysteine

Ca


Input: Such effect of AgNPs on Na and Ca regulation disappeared after cysteine addition, indicating that the soluble Ag released from AgNPs played a major role in the ionoregulatory dysfunction.

Ca

cysteine

Ag


Input: Depletion of molecular chaperones from the endoplasmic reticulum and fragmentation of the Golgi apparatus associated with pathogenesis in Pelizaeus-Merzbacher disease.


Input: Missense mutations in the proteolipid protein 1 (PLP1) gene cause a wide spectrum of hypomyelinating disorders, from mild spastic paraplegia type 2 to severe Pelizaeus-Merzbacher disease (PMD).


Input: Mutant PLP1 accumulates in the endoplasmic reticulum (ER) and induces ER stress.


Input: However, the link between the clinical severity of PMD and the cellular response induced by mutant PLP1 remains largely unknown.


Input: Accumulation of misfolded proteins in the ER generally leads to up-regulation of ER chaperones to alleviate ER stress.


Input: Here, we found that expression of the PLP1-A243V mutant, which causes severe disease, depletes some ER chaperones with a KDEL (Lys-Asp-Glu-Leu) motif, in HeLa cells, MO3. 13 oligodendrocytic cells, and primary oligodendrocytes.

Lys-Asp-Glu-Leu


Input: The same PLP1 mutant also induces fragmentation of the Golgi apparatus (GA).


Input: These organelle changes are less prominent in cells with milder disease-associated PLP1 mutants.


Input: Similar changes are also observed in cells expressing another disease-causing gene that triggers ER stress, as well as in cells treated with brefeldin A, which induces ER stress and GA fragmentation by inhibiting GA to ER trafficking.

brefeldin A


Input: We also found that mutant PLP1 disturbs localization of the KDEL receptor, which transports the chaperones with the KDEL motif from the GA to the ER.


Input: These data show that PLP1 mutants inhibit GA to ER trafficking, which reduces the supply of ER chaperones and induces GA fragmentation.


Input: We propose that depletion of ER chaperones and GA fragmentation induced by mutant misfolded proteins contribute to the pathogenesis of inherited ER stress-related diseases and affect the disease severity.


Input: Topoisomerase II beta deficiency enhances camptothecin-induced apoptosis.

camptothecin


Input: Camptothecin (CPT), a topoisomerase (Top) I-targeting drug that stabilizes Top1-DNA covalent adducts, can induce S-phase-specific cytotoxicity due to the arrest of progressing replication forks.

Camptothecin

CPT


Input: However, CPT-induced non-S-phase cytotoxicity is less well characterized.

CPT


Input: In this study, we have identified topoisomerase II beta (Top2 beta) as a specific determinant for CPT sensitivity, but not for many other cytotoxic agents, in non-S-phase cells.

CPT


Input: First, quiescent mouse embryonic fibroblasts (MEFs) lacking Top2 beta were shown to be hypersensitive to CPT with prominent induction of apoptosis.

CPT


Input: Second, ICRF-187, a Top2 catalytic inhibitor known to deplete Top2 beta, specifically sensitized MEFs to CPT.

CPT


Input: To explore the molecular basis for CPT hypersensitivity in Top2 beta-deficient cells, we found that upon CPT exposure, the RNA polymerase II large subunit (RNAP LS) became progressively depleted, followed by recovery to nearly the original level in wild-type MEFs, whereas RNAP LS remained depleted without recovery in Top2 beta-deficient cells.

CPT

CPT


Input: Concomitant with the reduction of the RNAP LS level, the p53 protein level was greatly induced.


Input: Interestingly, RNAP LS depletion has been well documented to lead to p53-dependent apoptosis.


Input: Altogether, our findings support a model in which Top2 beta deficiency promotes CPT-induced apoptosis in quiescent non-S-phase cells, possibly due to RNAP LS depletion and p53 accumulation.

CPT


Input: Two novel mutations in CYP11B1 and modeling the consequent alterations of the translated protein in classic congenital adrenal hyperplasia patients.


Input: Mutations in the 11 beta-hydroxylase (CYP11B1) gene are the second leading cause of congenital adrenal hyperplasia (CAH), an autosomal recessive disorder characterized by adrenal insufficiency, virilization of female external genitalia, and hypertension with or without hypokalemic alkalosis.


Input: Molecular analysis of CYP11B1 gene in CAH patients with 11 beta-hydroxylase deficiency was performed in this study.


Input: Cycle sequencing of 9 exons in CYP11B1 was performed in 5 unrelated families with 11 beta-hydroxylase deficient children.


Input: Three-dimensional models for the normal and mutant proteins and their affinity to their known substrates were examined.


Input: Analysis of the CYP11B1 gene revealed two novel mutations, a small insertion in exon 7 (InsAG393) and a small deletion in exon 2 (DelG766), and three previously known missense mutations (T318M, Q356X, and R427H).


Input: According to docking results, the affinity of the protein to its substrates is highly reduced by these novel mutations.


Input: DelG766 has more negative impact on the protein in comparison to InsAG393.


Input: The novel mutations, InsAG393 and DelG766, change the folding of the protein and disrupt the enzyme' s active site as it was measured in the protein modeling and substrate binding analysis.


Input: Molecular modeling and sequence conservation were predictive of clinical severity of the disease and correlated with the clinical diagnosis of the patients.


Input: Isolation and synthesis of melodamide A, a new anti-inflammatory phenolic amide from the leaves of Melodorum fruticosum.

melodamide A

phenolic amide


Input: Together with twelve known compounds (2-13), melodamide A (1), a new phenolic amide possessing p-quinol moiety, was purified and characterized from the methanolic extracts of the leaves of Melodorum fruticosum.

melodamide A

phenolic amide

p-quinol


Input: The structure of melodamide A (1) was established with a combination of 2D NMR experiments, HR-ESI-MS and X-ray analyses.

melodamide A


Input: The other known compounds were identified by comparison of their spectroscopic and physical data with those reported in the literature.


Input: Moreover, some isolated compounds were examined for their inhibitory activity towards superoxide anion generation and elastase release in human neutrophils.

superoxide


Input: Among the tested compounds, 1, 3, and 5 exhibited strong inhibition of superoxide anion generation with IC50 values ranging from 5. 25 to 8. 65 micro M.

superoxide


Input: Furthermore, synthesis and biological evaluation of melodamide A (1) and its analogs (14a-p) were described.

melodamide A


Input: Blocking the proliferation of human tumor cell lines by peptidase inhibitors from Bauhinia seeds.


Input: In cancer tumors, growth, invasion, and formation of metastasis at a secondary site play a pivotal role, participating in diverse processes in the development of the pathology, such as degradation of extracellular matrix.


Input: Bauhinia seeds contain relatively large quantities of peptidase inhibitors, and two Bauhinia inhibitors were obtained in a recombinant form from the Bauhinia bauhinioides species, B. bauhinoides cruzipain inhibitor, which is a cysteine and serine peptidase inhibitor, and B. bauhinioides kallikrein inhibitor, which is a serine peptidase inhibitor.

cysteine

serine

serine


Input: While recombinant B. bauhinoides cruzipain inhibitor inhibits human neutrophil elastase cathepsin G and the cysteine proteinase cathepsin L, recombinant B. bauhinioides kallikrein inhibitor inhibits plasma kallikrein and plasmin.

cysteine


Input: The effects of recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor on the viability of tumor cell lines with a distinct potential of growth from the same tissue were compared to those of the clinical cytotoxic drug 5-fluorouracil.


Input: At 12. 5 micro M concentration, recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor were more efficient than 5-fluorouracil in inhibiting MKN-28 and Hs746T (gastric), HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), and THP-1 and K562 (leukemia) cell lines.


Input: Additionally, recombinant B. bauhinoides cruzipain inhibitor inhibited 40% of the migration of Hs746T, the most invasive gastric cell line, while recombinant B. bauhinioides kallikrein inhibitor did not affect cell migration.


Input: Recombinant B. bauhinioides kallikrein inhibitor and recombinant B. bauhinoides cruzipain inhibitor, even at high doses, did not affect hMSC proliferation while 5-fluorouracil greatly reduced the proliferation rates of hMSCs.


Input: Therefore, both recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor might be considered for further studies to block peptidase activities in order to target specific peptidase-mediated growth and invasion characteristics of individual tumors, mainly in patients resistant to 5-fluorouracil chemotherapy.


Input: Mass spectrometry method to identify aging pathways of Sp-and Rp-tabun adducts on human butyrylcholinesterase based on the acid labile P-N bond.

Sp-and Rp-tabun

P-N


Input: The phosphoramidate nerve agent tabun inhibits butyrylcholinesterase (BChE) and acetylcholinesterase by making a covalent bond on the active site serine.

phosphoramidate

tabun

serine


Input: The adduct loses an alkyl group in a process called aging.

alkyl


Input: The mechanism of aging of the tabun adduct is controversial.

tabun


Input: Some studies claim that aging proceeds through deamination, whereas crystal structure studies show aging by O-dealkylation.

O


Input: Our goal was to develop a method that clearly distinguishes between deamination and O-dealkylation.

Our


Input: We began by studying the tetraisopropyl pyrophosphoramide adduct of BChE because this adduct has two P-N bonds.

tetraisopropyl pyrophosphoramide

P-N


Input: Mass spectra showed that the P-N bonds were stable during trypsin digestion at pH 8 but were cleaved during pepsin digestion at pH 2.

P-N


Input: The P-N bond in tabun was also acid labile, whereas the P-O bond was stable.

P-N

tabun

P-O


Input: A scheme to distinguish aging by deamination from aging by O-dealkylation was based on the acid labile P-N bond.

O

P-N


Input: BChE was inhibited with Sp-and Rp-tabun thiocholine nerve agent model compounds to make adducts identical to those of tabun with known stereochemistry.

Sp-and Rp-tabun thiocholine

tabun


Input: After aging and digestion with pepsin at pH 2, peptide FGES198AGAAS from Sp-tabun thiocholine had a mass of 902. 2 m/z in negative mode, indicating that it had aged by deamination, whereas peptide FGES198AGAAS from Rp-tabun thiocholine had a mass of 874. 2 m/z in negative mode, indicating that it had aged by O-dealkylation.

Sp-tabun thiocholine

Rp-tabun thiocholine

O


Input: BChE inhibited by authentic, racemic tabun yielded both 902. 2 and 874. 2 m/z peptides, indicating that both stereoisomers reacted with BChE and aged either by deamination or dealkylation.

racemic tabun


Input: Synthesis of antioxidants for prevention of age-related macular degeneration.


Input: Photooxidation of A2E may be involved in diseases of the macula, and antioxidants could serve as therapeutic agents for these diseases.


Input: Inhibitors of A2E photooxidation were prepared by Mannich reaction of the antioxidant quercetin.

quercetin


Input: These compounds contain water-solubilizing amine groups, and several were more potent inhibitors of A2E photooxidation than quercetin.

amine

quercetin


Input: The mannose 6-phosphate-binding sites of M6P/IGF2R determine its capacity to suppress matrix invasion by squamous cell carcinoma cells.

mannose 6-phosphate


Input: The M6P (mannose 6-phosphate)/IGF2R (insulin-like growth factor II receptor) interacts with a variety of factors that impinge on tumour invasion and metastasis.

mannose 6-phosphate


Input: It has been shown that expression of wild-type M6P/IGF2R reduces the tumorigenic and invasive properties of receptor-deficient SCC-VII squamous cell carcinoma cells.


Input: We have now used mutant forms of M6P/IGF2R to assess the relevance of the different ligand-binding sites of the receptor for its biological activities in this cellular system.


Input: The results of the present study demonstrate that M6P/IGF2R does not require a functional binding site for insulin-like growth factor II for inhibition of anchorage-independent growth and matrix invasion by SCC-VII cells.


Input: In contrast, the simultaneous mutation of both M6P-binding sites is sufficient to impair all cellular functions of the receptor tested.


Input: These findings highlight that the interaction between M6P/IGF2R and M6P-modified ligands is not only important for intracellular accumulation of lysosomal enzymes and formation of dense lysosomes, but is also crucial for the ability of the receptor to suppress SCC-VII growth and invasion.


Input: The present study also shows that some of the biological activities of M6P/IGF2R in SCC-VII cells strongly depend on a functional M6P-binding site within domain 3, thus providing further evidence for the non-redundant cellular functions of the individual carbohydrate-binding domains of the receptor.

carbohydrate


Input: Recombinant Luteinizing Hormone supplementation in poor responders undergoing IVF: a systematic review and meta-analysis.


Input: The results of several studies about the effectiveness of recombinant luteinizing hormone (rLH) supplementation in poor responder in vitro fertilization (IVF) patients were conflicting.


Input: To evaluate the current available data regarding the efficacy of rLH supplementation in poor responders, a meta-analysis was performed.


Input: A systemic search was performed without language limitation but restricted to randomized controlled trial (RCT).


Input: We mainly explored MEDLINE, EMBASE, CNKI and Cochrane Library for the relevant studies.


Input: Three studies were considered eligible for inclusion.


Input: The meta-analysis indicated that rLH supplementation did not increase the ongoing pregnancy rate in poor responders (OR 1. 30, 95% CI: 0. 80, 2. 11).


Input: Furthermore, there was no significant difference in the number of oocytes retrieved, total dose of rFSH used, total duration of stimulation, number of retrieved metaphase II oocytes and cycle cancellation rate between the study and control groups.


Input: In conclusions, the available evidence does not support the addition of rLH in poor responders treated with rFSH and GnRHa for IVF.


Input: It was inconclusive.


Input: Future research should be based on strict criteria to define poor responders, and large, well-designed RCTs are necessary to definitively answer the important question of whether there was need to use rLH in poor responders undergoing IVF.


Input: Catalytic DNAs that harness violet light to repair thymine dimers in a DNA substrate.

thymine


Input: UV1C is an in vitro selected catalytic DNA that shows efficient photolyase activity, using light of < 310 nm wavelength to photo-reactivate CPD thymine dimers within a substrate DNA.

thymine


Input: We show here that a minimal mutational strategy of substituting a guanine analogue, 6MI, for single guanine residues within UV1C extends the DNAzyme' s activity into the violet region of the spectrum.

guanine

guanine


Input: These 6MI point mutant DNAzymes fall into three distinct functional classes, which photo-reactivate the thymine dimer along different pathways.

thymine


Input: Cumulatively, they reveal the modus operandi of the original UV1C DNAzyme to be a surprisingly versatile one.


Input: The interchangeable properties of no less than six of the G --> 6MI point mutants highlight UV1C' s built-in functional flexibility, which may serve as a starting point for the creation of efficient, visible light-harnessing, photolyase DNAzymes for either the prophylaxis or therapy of UV damage to human skin.


Input: Supramolecular hydrogels from in situ host-guest inclusion between chemically modified cellulose nanocrystals and cyclodextrin.


Input: When grafted beta-cyclodextrin is used as targeting sites, Pluronic polymers have been introduced on the surface of cellulose nanocrystals by means of inclusion interaction between beta-cyclodextrin and hydrophobic segment of the polymer.

beta-cyclodextrin

beta-cyclodextrin


Input: Because of the steric stabilization effect, surface poly (ethylene glycol) chains facilitate the dispersion and compatibility of nanocrystals, which also enhance the loading levels of nanocrystals in the hydrogel system.

poly (ethylene glycol)


Input: Meanwhile, uncovered poly (ethylene glycol) segments render the participating inclusion of alpha-cyclodextrin for the architecture of in situ hydrogels.

poly (ethylene glycol)

alpha-cyclodextrin


Input: Surface grafting and inclusion reactions were proved by solid (13) C NMR and FTIR.

(13) C


Input: Grafting efficiency of beta-cyclodextrin and inclusion efficiency of Pluronic on the surface of nanocrystals were confirmed by UV spectroscopy and elemental analysis.

beta-cyclodextrin


Input: A significant enhancement of the structural and thermal stability of in situ hydrogels with high loading levels of modified nanocrystals (> 5. 77 wt%) was observed by rheological analysis.


Input: Further study reveals the performance and behavior of hydrogels under a different pH environment.


Input: Finally, in situ hydrogels were used as drug carrier for in vitro release of doxorubicin and exhibit the behavior of prolonged drug release with special release kinetics.

doxorubicin


Input: Structure of polyelectrolyte brushes subject to normal electric fields.


Input: Molecular dynamic simulations of salt-free polyelectrolyte brushes subject to external fields applied normal to the grafting substrate reveal the three-dimensional monomer and counterion distributions.


Input: It is found that below a critical electric field, local electroneutrality holds for densely grafted brushes and the brush height remains independent of field intensity.


Input: Above this critical field (which scales as 1/3 with grafting density) brush height increases smoothly, and the fraction of condensed counterions decreases.


Input: The brush bifurcates into two subpopulations of stretched and collapsed chains when the grafting density is not low.


Input: At intermediate grafting densities, the majority of chains are stretched and the minority are nonstretched.


Input: At high grafting densities bifurcation and brush height growth occur consecutively.


Input: The majority of the chains are nonstretched at high grafting densities.


Input: Although not observed prior to overstretching of the chain model, it is predicted that the two subpopulations will re-merge to a single highly stretched phase when field intensity reaches a third critical value.


Input: The ability to control subpopulations of chains suggests that utilizing electric fields normal to polyelectrolyte brushes holds potential as controllable gates in microfluidic devices.


Input: Nanocomposites derived from montmorillonite and metallosupramolecular polyelectrolytes: modular compounds for electrorheological fluids.

montmorillonite


Input: Nanocomposites made from Na-montmorillonite and metallo-supramolecular polyelectrolytes (MEPE) based on nickel and ditopic bis-terpyridine ligands are prepared by an aqueous synthesis.

Nanocomposites

montmorillonite

nickel

bis-terpyridine


Input: Intercalation is confirmed by IR-spectroscopy, thermogravimetric analysis, and X-ray powder diffraction.


Input: The rheological response in the presence of an electric field of the dispersed nanocomposites in silicone oil is measured with a rheometer.


Input: The nanocomposites show a distinct electrorheological effect depending on the concentration and the kind of intercalated species.


Input: The effect occurs with a low content of active material while only very small currents are observed.


Input: Adsorption and dilational rheology of mixed beta-casein/DoTAB layers formed by sequential and simultaneous adsorption at the water/hexane interface.

DoTAB

hexane


Input: The interfacial behavior of beta-casein (beta CS) has been investigated in presence of the cationic surfactant dodecyl trimethyl ammonium bromide (DoTAB) at the water/hexane interface and compared to that obtained for the water/air interface.

dodecyl trimethyl ammonium bromide

DoTAB

hexane


Input: The used experimental technique is a drop profile analysis tensiometer specially equipped with a coaxial double capillary, which allows investigation of sequential adsorption of individual components besides the traditional simultaneous adsorption of two species.


Input: This method also provides the dilational rheological measurements based on low frequency harmonic drop oscillations.


Input: The tensiometric results show that the equilibrium states of the mixed beta CS/DoTAB layers built up on the two different routes do not differ significantly, that is, the general compositions of the mixed layers are similar.

DoTAB


Input: However, the results of dilational rheology for the two adsorption strategies are remarkably different indicating different dynamic characteristics of the adsorbed layers.


Input: These findings suggest that the respective mixed layers are more proteinlike if they are formed via sequential adsorption and more surfactant-like after simultaneous adsorption.


Input: In contrast to the W/A interface, at the W/H interface proteins remain at the interface once adsorbed and cannot be displaced just by competitive adsorption of surfactants.


Input: 5-Iodo-2-aminoindan (5-IAI): chemistry, pharmacology, and toxicology of a research chemical producing MDMA-like effects.

MDMA


Input: In 2010, an internet snapshot of EMCDDA anticipated the presence of 5-iodo-2-aminoindan (5-IAI) within the recreational drug market.


Input: In 2011, this compound, a psychoactive derivative of 2-aminoindane, was identified in recreational products sold in the United Kingdom.


Input: 5-IAI is a rigid analogue of p-iodoamphetamine producing MDMA-like effects.

p-iodoamphetamine

MDMA


Input: The aim of this paper is to summarize the clinical, pharmacological, and toxicological information about this new potential drug of abuse.


Input: Morphine withdrawal produces ERK-dependent and ERK-independent epigenetic marks in neurons of the nucleus accumbens and lateral septum.

Morphine


Input: Epigenetic changes such as covalent modifications of histone proteins represent complex molecular signatures that provide a cellular memory of previously experienced stimuli without irreversible changes of the genetic code.


Input: In this study we show that new gene expression induced in vivo by morphine withdrawal occurs with concomitant epigenetic modifications in brain regions critically involved in drug-dependent behaviors.

morphine


Input: We found that naloxone-precipitated withdrawal, but not chronic morphine administration, caused a strong induction of phospho-histone H3 immunoreactivity in the nucleus accumbens (NAc) shell/core and in the lateral septum (LS), a change that was accompanied by augmented H3 acetylation (lys14) in neurons of the NAc shell.

naloxone

morphine

phospho


Input: Morphine withdrawal induced the phosphorylation of the epigenetic factor methyl-CpG-binding protein 2 (MeCP2) in Ser421 both in the LS and the NAc shell.

Morphine

methyl

CpG


Input: These epigenetic changes were accompanied by the activation of members of the ERK pathway as well as increased expression of the immediate early genes (IEG) c-fos and activity-regulated cytoskeleton-associated protein (Arc/Arg3. 1).


Input: Using a pharmacological approach, we found that H3 phosphorylation and IEG expression were partially dependent on ERK activation, while MeCP2 phosphorylation was fully ERK-independent.


Input: These findings provide new important information on the role of the ERK pathway in the regulation of epigenetic marks and gene expression that may concur to regulate in vivo the cellular changes underlying the onset of the opioid withdrawal syndrome.


Input: Motivational properties of D2 and D3 dopamine receptors agonists and cocaine, but not with D1 dopamine receptors agonist and l-dopa, in bilateral 6-OHDA-lesioned rat.

dopamine

cocaine

dopamine

l-dopa


Input: Dopamine dysregulation syndrome in Parkinson' s disease (PD) has been attributed to dopamine replacement therapy (DRT).

Dopamine

dopamine


Input: We hypothesize that DRT can induce a potential rewarding effect in an animal model of PD.


Input: Using the conditioned place preference (CPP) paradigm, we investigated the motivational effects of l-dopa, dopamine receptor agonists (DRAs), and cocaine in rat with a bilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway.

l-dopa

dopamine

cocaine


Input: In 6-OHDA animals, D1 receptors agonist (SKF81297) revealed significantly a conditioned place aversion (CPA) at 3 mg/kg and 9 mg/kg doses.


Input: D2 receptors agonist (bromocriptine) induced both CPP and CPA at 1 mg/kg and 10 mg/kg doses respectively.

bromocriptine


Input: D3 receptors agonist (PD128907) induced a CPP only at 1 mg/kg, comparable to that of cocaine.

cocaine


Input: Sham animals revealed biphasic CPP curves, with significant dose effect, for the intermediate dose of the 3 DRAs.


Input: However, l-dopa induced no significant effect while cocaine induced CPP in both lesioned and sham animals.

l-dopa

cocaine


Input: In conclusion, this study confirms the predominant roles of D2R class, and most specifically D3R subtypes, in rewarding properties of DRT.


Input: New insight into the discharge mechanism of silicon-air batteries using electrochemical impedance spectroscopy.

silicon


Input: The mechanism of discharge termination in silicon-air batteries, employing a silicon wafer anode, a room-temperature fluorohydrogenate ionic liquid electrolyte and an air cathode membrane, is investigated using a wide range of tools.

silicon

silicon


Input: EIS studies indicate that the interfacial impedance between the electrolyte and the silicon wafer increases upon continuous discharge.

silicon


Input: In addition, it is shown that the impedance of the air cathode-electrolyte interface is several orders of magnitude lower than that of the anode.


Input: Equivalent circuit fitting parameters indicate the difference in the anode-electrolyte interface characteristics for different types of silicon wafers.

silicon


Input: Evolution of porous silicon surfaces at the anode and their properties, by means of estimated circuit parameters, is also presented.

silicon


Input: Moreover, it is found that the silicon anode potential has the highest negative impact on the battery discharge voltage, while the air cathode potential is actually stable and invariable along the whole discharge period.

silicon


Input: The discharge capacity of the battery can be increased significantly by mechanically replacing the silicon anode.

silicon


Input: The effect of apricots on the experimental cataract model formed by sodium selenite.

sodium selenite


Input: This study was designed in order to investigate whether sun dried apricots have a preventive effect on the experimental cataract model formed by sodium selenite in rats.

sodium selenite


Input: Fifty-nine Spraque-Dawley rat pups were divided into three groups.


Input: Group 1 (control group) consisted of twenty rat pups, born from the rats nourished ad libitum.


Input: Group 2 consisted of 18 newborn rats, born from the rats nourished ad libitum with 10% sun dried natural apricots.


Input: Group 3 consisted of 21 newborn rats, born from the rats nourished ad libitum.


Input: Subcutaneous (30nmol/gr) sodium selenite injection was applied to all the newborn rats except the control group (Group 1) on postpartum day 10.

sodium selenite


Input: Cataract development was graded by slit-lamp examination and photography.


Input: Encapsulated lenses were analyzed for reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid per oxidation.

glutathione

GSH

malondialdehyde

MDA


Input: Lenses were also analyzed for total nitrite (TN).

nitrite


Input: The presence of oxidative stress in selenite cataract development and its prevention by sun dried apricots.

selenite


Input: Anti-inflammatory activity of patchouli alcohol in RAW264. 7 and HT-29 cells.

patchouli alcohol


Input: Patchouli alcohol (PA) is a chemical compound extracted from patchouli which belongs to the genus Pogostemon, herb of mint family.

Patchouli alcohol


Input: Recently, it has been reported that PA inhibits the production of inflammatory mediators.


Input: However, the biological mechanisms of PA for anti-inflammatory activities have not been studied.


Input: In this study, we investigated whether PA decreases the production of inflammatory mediators through downregulation of the NF-kappa B and ERK pathway.


Input: Our data indicated that PA inhibits the over-expression of iNOS and IL-6 in protein and mRNA levels in LPS-stimulated RAW264. 7 and TNF-alpha stimulated HT-29 cells.


Input: PA inhibited I kappa B-alpha degradation and p65 nuclear translocation, and subsequently suppressed transcriptional activity of NF-kappa B in LPS-stimulated RAW264. 7 and TNF-alpha-stimulated HT-29 cells.


Input: In addition, PA inhibited LPS-or TNF-alpha-stimulated ERK1/2 activation by decreasing phosphorylation of ERK1/2.


Input: These findings suggest that PA shows anti-inflammatory activities through suppressing ERK-mediated NF-kappa B pathway in mouse macrophage and human colorectal cancer cells.


Input: ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein-protein interactions with HPRT1.


Input: Gout, a common form of inflammatory arthritis, is strongly associated with elevated uric acid concentrations in the blood (hyperuricemia).

uric acid


Input: A recent study in Icelanders identified a rare missense single nucleotide polymorphism (SNP) in the ALDH16A1 gene, ALDH16A1 * 2, to be associated with gout and serum uric acid levels.

nucleotide

uric acid


Input: ALDH16A1 is a novel and rather unique member of the ALDH superfamily in relation to its gene and protein structures.


Input: ALDH16 genes are present in fish, amphibians, protista, bacteria but absent from archaea, fungi and plants.


Input: In most mammalian species, two ALDH16A1 spliced variants (ALDH16A1, long form and ALDH16A1 _ v2, short form) have been identified and both are expressed in HepG-2, HK-2 and HK-293 human cell lines.


Input: The ALDH16 proteins contain two ALDH domains (as opposed to one in the other members of the superfamily), four transmembrane and one coiled-coil domains.


Input: The active site of ALDH16 proteins from bacterial, frog and lower animals contain the catalytically important cysteine residue (Cys-302); this residue is absent from the mammalian and fish orthologs.

cysteine

Cys


Input: Molecular modeling predicts that both the short and long forms of human ALDH16A1 protein would lack catalytic activity but may interact with the hypoxanthine-guanine phosphoribosyltransferase (HPRT1) protein, a key enzyme involved in uric acid metabolism and gout.

hypoxanthine

guanine

uric acid


Input: Interestingly, such protein-protein interactions with HPRT1 are predicted to be impaired for the long or short forms of ALDH16A1 * 2.


Input: These results lead to the intriguing possibility that association between ALDH16A1 and HPRT1 may be required for optimal HPRT activity with disruption of this interaction possibly contributing to the hyperuricemia seen in ALDH16A1 * 2 carriers.


Input: Kava for the Treatment of Generalized Anxiety Disorder RCT: Analysis of Adverse Reactions, Liver Function, Addiction, and Sexual Effects.


Input: Presently, little is known about a number issues concerning kava (Piper methysticum), including (i) whether kava has any withdrawal or addictive effects; (ii) if genetic polymorphisms of the cytochrome (CYP) P450 2D6 liver enzyme moderates any potential adverse effects; and (iii) if medicinal application of kava has any negative or beneficial effect on sexual function and experience.


Input: The study design was a 6-week, double-blind, randomized controlled trial (n = 75) involving chronic administration of kava (one tablet of kava twice per day; 120 mg of kavalactones per day, titrated in non-response to two tablets of kava twice per day; 240 mg of kavalactones) or placebo for participants with generalized anxiety disorder.

kavalactones

kavalactones


Input: Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava.


Input: No differences in withdrawal or addiction were found between groups.


Input: Interesting, kava significantly increased female' s sexual drive compared to placebo (p = 0. 040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males.


Input: Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole sample.


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


Input: Evaluation of suppressive and pro-resolving effects of EPA and DHA in human primary monocytes and T-helper cells.

EPA

DHA


Input: Despite their beneficial anti-inflammatory properties, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may increase the infection risk at high doses, likely by generating an immune-depressed state.

eicosapentaenoic acid

EPA

docosahexaenoic acid

DHA


Input: To assess the contribution of different immune cell populations to the immunomodulatory fatty acid effect, we comparatively investigated several aspects of inflammation in human T-helper (Th) cells and monocytes.

fatty acid


Input: Both fatty acids, but DHA to a lesser extent compared with EPA, selectively and dose-dependently reduced the percentage of cytokine-expressing Th cells in a peroxisome proliferator-activated receptor (PPAR) gamma-dependent fashion, whereas the expression of the cell surface marker CD69 was unaltered on activated T cells.

fatty acids

DHA

EPA


Input: In monocytes, both EPA and DHA increased interleukin (IL)-10 without affecting tumor necrosis factor (TNF)-alpha and IL-6.

EPA

DHA


Input: Cellular incorporation of EPA and DHA occurred mainly at the expense of arachidonic acid.

EPA

DHA

arachidonic acid


Input: Concomitantly, thromboxane B (TXB) 2 and leukotriene B (LTB) 4 in supernatants decreased, while levels of TXB3 and LTB5 increased.

thromboxane B (TXB) 2

leukotriene B (LTB) 4


Input: This increase was independent of activation and in accordance with cyclooxygenase expression patterns in monocytes.


Input: Moreover, EPA and DHA gave rise to a variety of mono-and trihydroxy derivatives of highly anti-inflammatory potential, such as resolvins and their precursors.

EPA

DHA

mono-and trihydroxy

resolvins


Input: Our results suggest that EPA and DHA do not generally affect immune cell functions in an inhibitory manner but rather promote pro-resolving responses.

EPA

DHA


Input: Activation of islet autoreactive naive T cells in infants is influenced by homeostatic mechanisms and antigen presenting capacity.


Input: Islet autoimmunity precedes type 1 diabetes onset.


Input: We previously found that islet autoimmunity rarely starts before age six months but reaches its highest incidence already at around 1 year of age.


Input: We now examine whether homeostatic expansion and immune competence changes seen in a maturating immune system may account for this marked variation in islet autoimmunity risk in the first year of life.


Input: We found na i ve proinsulin-and GAD65-responsive T cells in cord blood of healthy newborns, with highest responses observed in children with type 1 diabetes susceptible HLA-DRB1/DQB1 genotypes.


Input: Homeostatic expansion characteristics with increased IL-7 concentrations and enhanced T cell responsiveness to IL-7 were observed throughout the first year of life.


Input: However, the ability of antigen-presenting cells to activate na i ve T cells was compromised at birth, and cord blood monocytes had low surface expression of CD40 and HLA class II.


Input: In contrast, antigen presentation and expression of these molecules had reached competent adult levels by the high incidence age of 8 months.


Input: We propose that temporal changes in islet autoimmunity seroconversion in infants are a consequence of the changing balance between homeostatic drive and antigen presentation competence.


Input: These findings are relevant for early prevention of type 1 diabetes.


Input: Reduction of reactive oxygen species ameliorates metabolism-secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction.

oxygen

lactate


Input: We previously demonstrated that impaired glucose-induced insulin secretion (IS) and ATP elevation in islets of Goto-Kakizaki (GK) rats, a non-obese model of diabetes, were significantly restored by 30 ~ 60 min suppression of endogenous reactive oxygen species (ROS) overproduction.

glucose

ATP

oxygen


Input: In this study, we investigated the effect of longer (12 h) suppression of ROS on metabolism-secretion coupling in beta-cells by exposure to tempol, a superoxide dismutase mimic, plus ebselen, a glutathione peroxidase mimic (TE-treatment).

tempol

superoxide

ebselen

glutathione


Input: In GK islets, both H (2) O (2) and superoxide were sufficiently reduced and glucose-induced IS and ATP elevation were improved by TE-treatment.

H (2) O (2)

superoxide

glucose

ATP


Input: Glucose oxidation, an indicator of Krebs cycle velocity, also was improved by TE-treatment at high glucose, whereas glucokinase activity, which determines glycolytic velocity, was not affected.

Glucose

glucose


Input: Lactate production was markedly increased in GK islets and TE-treatment reduced lactate production and protein expression of lactate dehydrogenase and hypoxia-inducible factor 1 alpha (HIF1 alpha).

Lactate

lactate

lactate


Input: These results indicate that the Warburg-like effect, which is characteristic of aerobic metabolism in cancer cells by which lactate is overproduced with reduced linking to mitochondria metabolism, plays an important role in impaired metabolism-secretion coupling in diabetic beta-cells and suggest that ROS reduction can improve mitochondrial metabolism by suppressinglactate overproduction through inhibition of HIF1 alpha stabilization.

lactate

suppressinglactate


Input: The type 2 diabetes associated gene Ide is required for insulin secretion and suppression of alpha-synuclein levels in beta-cells.


Input: Genome wide association studies have identified several type 2 diabetes (T2D) risk loci linked to impaired beta-cell function.


Input: The identity and function of the causal genes in these susceptibility loci remain, however, elusive.


Input: The HHEX/IDE T2D locus is associated with decreased insulin secretion in response to oral glucose stimulation in humans.

glucose


Input: Here we have assessed beta-cell function in Ide knock-out (KO) mice.


Input: We find that glucose stimulated insulin secretion (GSIS) is decreased in Ide KO mice due to impaired replenishment of the releasable pool of granules and that the Ide gene is haploinsufficient.

glucose


Input: We also show that autophagic flux and microtubule content is reduced in beta-cells of Ide KO mice.


Input: One important cellular role for IDE involves the neutralization of amyloidogenic proteins and we find that alpha-synuclein and IDE levels are inversely correlated in beta-cells of Ide KO mice and T2D patients.


Input: Moreover, we provide evidence that both gain-and loss-of-function of alpha-synuclein in beta-cells in vivo not only impair GSIS but also autophagy.


Input: Together, these data identify the Ide gene as a regulator of GSIS, suggest a molecular mechanism for beta-cell degeneration as a consequence of Ide deficiency, and additionally corroborates and extends a previously established important role for alpha-synuclein in beta-cell function.


Input: Enhanced NF kappa B Activity Impairs Vascular Function through PARP-1, SP-1 and COX2-Dependent Mechanisms in Type 2 Diabetes.


Input: Type 2 diabetes (T2D) is associated with vascular dysfunction.


Input: We hypothesized that increased nuclear factor kappa B (NF kappa B) signaling contributes to vascular dysfunction in T2D.


Input: We have treated type 2 diabetic (db (-)/db (-)) and control (db (-)/db (+)) mice with two NF kappa B inhibitors (DHMEQ, 6mg/kg, twice a week and IKK-NBD peptide, 500 mu g/kg/day) for four weeks.

DHMEQ


Input: Pressure-induced myogenic tone (MT) was significantly potentiated, while endothelium dependent relaxation (EDR) was impaired in small coronary arterioles (CA) and mesenteric resistance artery (MRA) from diabetic mice compared to control.


Input: Interestingly, diabetic mice treated with NF kappa B inhibitors significantly reduced MT potentiation and improved EDR.


Input: Importantly, vascular function was also rescued in db (-)/db (-p50NF kappa B-/-) and db (-)/db (-PARP-1-/-) double knockout mice compared to db (-)/db (-) mice.


Input: Additionally, the acute in vitro down regulation of NF kappa B-p65 using p65NF kappa B shRNA lentivirus in arteries from db (-)/db (-) mice also improved vascular function.


Input: The NF kappa B inhibition did not affect blood glucose level and body weight.

glucose


Input: The RNA levels for Sp-1 and eNOS phosphorylation were decreased, while p65NF kappa B phosphorylation, cleaved PARP-1 and COX-2 expression were increased in arteries from diabetic mice, which were restored after NF kappa B inhibition and in db (-)/db (-p50NF kappa B-/-) and db (-)/db (-PARP-1-/-) mice. In the present study, we provided evidence that enhanced NF kappa B activity impairs vascular function by PARP-1, Sp-1 and COX-2-dependent mechanisms in male type 2 diabetic mice.


Input: Therefore, NF kappa B could be a potential target to overcome diabetes-induced vascular dysfunction.


Input: Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2/M block in breast cancer cells.

curcumin

PLGA


Input: PLGA nanoparticles are among the most studied polymer nanoformulations for several drugs against different kinds of malignant diseases, thanks to their in vivo stability and tumor localization exploiting the well-documented " enhanced permeation and retention " (EPR) effect.

PLGA


Input: In this paper, we have developed uniform curcumin-bearing PLGA nanoparticles by a single-emulsion process, which exhibited a curcumin release following a Fickian-law diffusion over 10 days in vitro.

curcumin

PLGA

curcumin


Input: PLGA nanoparticles were about 120 nm in size, as determined by dynamic light scattering, with a surface negative charge of-30 mV.

PLGA


Input: The loading ratio of encapsulated drug in our PLGA nanoformulation was 8 wt%.

PLGA


Input: PLGA encapsulation provided efficient protection of curcumin from environment, as determined by fluorescence emission experiments.

PLGA

curcumin


Input: Next, we have investigated the possibility to study the intracellular degradation of nanoparticles associated with a specific G2/M blocking effect on MCF7 breast cancer cells caused by curcumin release in the cytoplasm, which provided direct evidence on the mechanism of action of our nanocomplex.

curcumin


Input: This study was carried out using Annexin V-based cell death analysis, MTT assessment of proliferation, flow cytometry, and confocal laser scanning microscopy.

MTT


Input: PLGA nanoparticles proved to be completely safe, suggesting a potential utilization of this nanocomplex to improve the intrinsically poor bioavailability of curcumin for the treatment of severe malignant breast cancer.

PLGA

curcumin


Input: Molecular reorganization in organic field-effect transistors and its effect on two-dimensional charge transport pathways.


Input: Charge transport in organic thin film transistors takes place in the first few molecular layers in contact with the gate dielectric.


Input: Here we demonstrate that the charge transport pathways in these devices are extremely sensitive to the orientational defects of the first monolayers, which arise from specific growth conditions.


Input: Although these defects partially heal during the growth, they cause depletion of charge carriers in the first monolayer, and drive the current to flow in the monolayers above the first one.


Input: Moreover, the residual defects induce lower crystalline order and charge mobility.


Input: These results, which are not intuitively explained by electrostatics arguments, have been obtained by combining in situ real time structural and electrical characterization together with ex situ AFM measurements, on thin films of a relevant n-type organic semiconductor, N, N'-bis (n-octyl)-dicyanoperylene-3, 4: 9, 10-bis dicarboximide grown by sublimation in a quasi-layer-by-layer mode at different substrate temperatures.

N, N'-bis (n-octyl)-dicyanoperylene-3, 4: 9, 10-bis dicarboximide


Input: Sulfated Small Molecules Targeting EBV in Burkitt Lymphoma: From In Silico Screening to the Evidence of In Vitro Effect on Viral Episomal DNA.


Input: Epstein-Barr virus (EBV) infects more than 90% of the world population.


Input: Following primary infection, Epstein-Barr virus persists in an asymptomatic latent state.


Input: Occasionally, it may switch to lytic infection.


Input: Latent EBV infection has been associated with several diseases, such as Burkitt lymphoma (BL).


Input: To date, there are no available drugs to target latent EBV, and the existing broad-spectrum antiviral drugs are mainly active against lytic viral infection.


Input: Thus, using computational molecular docking, a virtual screen of a library of small molecules, including xanthones and flavonoids (described with potential for antiviral activity against EBV), was carried out targeting EBV proteins.

xanthones

flavonoids


Input: The more interesting molecules were selected for further computational analysis, and sub-sequently, the compounds were tested in the Raji (BL) cell line, to evaluate their activity against latent EBV.


Input: This work identified three novel sulfated small molecules capable of decreasing EBV levels in a BL.


Input: Therefore, the in silico screening presents a good approach for the development of new anti-EBV agents.


Input: Genome wide association studies for diabetes: perspective on results and challenges.


Input: Recent results of genome wide association study (GWAS) for diabetes genes, while reaching impressive technical milestones and implicating new findings for research, have been uniformly disappointing in terms of immediate clinical utility.


Input: The relative risk associated with any of the newly reported genetic loci, or even considering all of them together, is far less than simply that which can be obtained by taking a history and a physical exam.


Input: For type 2 diabetes (T2D), GWAS have implicated novel pathways, supported previously known associations, and highlighted the importance of the beta cell and insulin secretion.


Input: Monogenic forms of diabetes, on the other hand, continue to yield interesting insights into genes controlling human beta cell function but most cases of monogenic diabetes are simply not diagnosed.


Input: Here, we briefly review recent results related to type 1, type 2 and maturity onset diabetes of youth (MODY) diabetes and suggest that future studies emphasizing quantitative traits are likely to yield even more insights.


Input: Chiral bicyclic tetramates as non-planar templates for chemical library synthesis.


Input: Chemoselective Dieckmann cyclization reactions may be used on oxazolidine and thiazolidine templates derived from various aldehydes to access bicyclic tetramates, which have potential as templates for chemical library construction.

oxazolidine

thiazolidine

aldehydes


Input: Bioassay against Staphylococcus aureus and Escherichia coli showed that these systems have little or no intrinsic antibacterial bioactivity.


Input: Pyrrolopyrazines as Selective Spleen Tyrosine Kinase Inhibitors.

Pyrrolopyrazines

Tyrosine


Input: We describe the discovery of several pyrrolopyrazines as potent and selective Syk inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies.

pyrrolopyrazines


Input: Ultimately, our mouse model revealed unexpected toxicity that precluded us from further advancing this series.


Input: Termini of bottom-up fabricated graphene nanoribbons.

graphene


Input: Atomically precise graphene nanoribbons (GNRs) can be obtained via thermally induced polymerization of suitable precursor molecules on a metal surface.

graphene


Input: This communication discusses the atomic structure found at the termini of armchair GNRs obtained via this bottom-up approach.


Input: The short zigzag edge at the termini of the GNRs under study gives rise to a localized midgap state with a characteristic signature in scanning tunneling microscopy (STM).


Input: By combining STM experiments with large-scale density functional theory calculations, we demonstrate that the termini are passivated by hydrogen.

hydrogen


Input: Our results suggest that the length of nanoribbons grown by this protocol may be limited by hydrogen passivation during the polymerization step.

hydrogen


Input: Copper (I)-catalyzed borylative exo-cyclization of alkenyl halides containing unactivated double bond.

Copper (I)

alkenyl halides


Input: A borylative exo-cyclization of alkenyl halides has been reported.

alkenyl halides


Input: The reaction includes the regioselective addition of a borylcopper (I) intermediate to unactivated terminal alkenes, followed by the intramolecular substitution of the resulting alkylcopper (I) moiety for the halide leaving groups.

borylcopper (I)

alkenes

alkylcopper (I)

halide


Input: Experimental and theoretical investigations of the reaction mechanism have also been described.


Input: This reaction provides a new method for the synthesis of alkylboronates containing strained cycloalkyl structures from simple starting materials.

alkylboronates


Input: Chemogenomics Approaches to Rationalizing the Mode-of-Action of Traditional Chinese and Ayurvedic Medicines.


Input: Traditional Chinese medicine (TCM) and Ayurveda have been used in humans for thousands of years.


Input: While the link to a particular indication has been established in man, the mode-of-action (MOA) of the formulations often remains unknown.


Input: In this study, we aim to understand the MOA of formulations used in traditional medicine using an in silico target prediction algorithm, which aims to predict protein targets (and hence MOAs), given the chemical structure of a compound.


Input: Following this approach we were able to establish several links between suggested MOAs and experimental evidence.


Input: In particular, compounds from the' tonifying and replenishing medicinal' class from TCM exhibit a hypoglycemic effect which can be related to activity of the ingredients against the Sodium-Glucose Transporters (SGLT) 1 and 2 as well as Protein Tyrosine Phosphatase (PTP).

Sodium

Glucose

Tyrosine


Input: Similar results were obtained for Ayurvedic anticancer drugs.


Input: Here, both primary anticancer targets (those directly involved in cancer pathogenesis) such as steroid-5-alpha-reductase 1 and 2 were predicted as well as targets which act synergistically with the primary target, such as the efflux pump P-glycoprotein (P-gp).

steroid


Input: In addition, we were able to elucidate some targets which may point us to novel MOAs as well as explain side effects.


Input: Most notably, GPBAR1, which was predicted as a target for both' tonifying and replenishing medicinal' and anticancer classes, suggests an influence of the compounds on metabolism.


Input: Understanding the MOA of these compounds is beneficial as it provides a resource for NMEs with possibly higher efficacy in the clinic than those identified by single-target biochemical assays.


Input: Pharmacokinetics, tissue distribution and excretion study of resveratrol and its prodrug 3, 5, 4'-tri-O-acetylresveratrol in rats.

resveratrol

3, 5, 4'-tri-O-acetylresveratrol


Input: 3, 5, 4'-Tri-O-acetylresveratrol (TARES) synthesized by acetylating three hydroxyl groups of resveratrol (RES) is a prodrug of RES.

3, 5, 4'-Tri-O-acetylresveratrol

TARES

hydroxyl

resveratrol

RES

RES


Input: The aim of this study was to investigate and compare the pharmacokinetics, tissue distribution and excretion of TARES and RES in rats following a single intragastric gavage (i. g.) administration.

TARES

RES


Input: After RES is transformed into TARES, its pharmacokinetic properties are improved, such as the t1/2 has been prolonged and the AUC has been enhanced.

RES

TARES


Input: And TARES follows linear plasma pharmacokinetics across the investigated dosage range in rats (77. 5-310mg/kg).

TARES


Input: The major distribution tissues of TARES or RES in rats were liver, spleen, heart and lung.

TARES

RES


Input: TARES can increase the content of RES in lung significantly.

TARES

RES


Input: There was no long-term accumulation of RES in rat tissues.

RES


Input: Whether we administrated to rats of equimolar TARES or RES, total recoveries of RES in urine and feces within 36h were low (0. 99% or 0. 07% in urine and 1. 69% or 0. 15% in feces).

TARES

RES

RES


Input: Biofilm inhibitors that target amyloid proteins.


Input: Bacteria establish stable communities, known as biofilms, that are resistant to antimicrobials.


Input: Biofilm robustness is due to the presence of an extracellular matrix, which for several species-among them Bacillus subtilis-includes amyloid-like protein fibers.


Input: In this work, we show that B. subtilis biofilms can be a simple and reliable tool for screening of molecules with antiamyloid activity.


Input: We identified two molecules, AA-861 and parthenolide, which efficiently inhibited biofilms by preventing the formation of amyloid-like fibers.

parthenolide


Input: Parthenolide also disrupted pre-established biofilms.

Parthenolide


Input: These molecules also impeded the formation of biofilms of other bacterial species that secrete amyloid proteins, such as Bacillus cereus and Escherichia coli.


Input: Furthermore, the identified molecules decreased the conversion of the yeast protein New1 to the prion state in a heterologous host, indicating the broad range of activity of the molecules.


Input: Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): kinase profiling guided optimization of a 1, 2, 3-benzotriazole lead.

amino-pyrimidine

N

1, 2, 3-benzotriazole


Input: A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program.

amino-pyrimidines


Input: Kinase profiling and structure-based drug design guided the optimization from the initial 1, 2, 3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC (50) = 16 and 66 nM, respectively), with bioavailability in rats and suitable for further in vivo pharmacological evaluation.

1, 2, 3-benzotriazole


Input: Comparative properties of A beta 1-42, A beta 11-42, and [Pyr (1) (1)] A beta 11-42 generated from O-acyl isopeptides.

O-acyl


Input: The use of water-soluble O-acyl isopeptides enabled us to investigate the biochemical properties of A beta 11-42 species, by preparing highly concentrated stock solutions after a pretreatment.

O-acyl


Input: A beta 11-42 and [Pyr (11)] A beta 11-42 showed comparable aggregation capability and cytotoxicity, suggesting that the pyroglutamate modification at Glu (11) does not have a crucial role in these events.

Pyr

pyroglutamate

Glu


Input: However, given that A beta 11-42 is converted to [Pyr (11)] A beta 11-42 by a glutamyl cyclase in vivo, the potential aggregative and cytotoxic nature of [Pyr (11)] A beta 11-42 that was observed in the present study provides valuable insights into the pathological functions of pyroglutamate-modified A beta species in Alzheimer' s disease.

Pyr

glutamyl

Pyr

pyroglutamate


Input: Menopause, atherosclerosis, and coronary artery disease.


Input: Women have coronary heart disease (CHD) later than men.


Input: This review describes studies of CHD risk factors or outcomes based on studies of premenopausal women followed through the menopause transition, and prospective cohort studies of younger or older women with CHD risk markers or disease outcomes in the context of their menopause history.


Input: Major early reports from both types of studies are included in order to put more recent work in context.


Input: Most attention has been paid to the Healthy Women Study (HWS), Study of Women' s Health across the Nation (SWAN), the Nurses' Health Study (NHS), and the Rancho Bernardo Study (RBS) because they continue to produce recent publications designed to distinguish the effect of age from the effect of menopause.


Input: Understanding these differences has important implications for women' s cardiovascular health, but remains incomplete.


Input: Transition studies have relatively short (< 10 years) follow-up and exclude women with surgical menopause.


Input: Cohort studies suggest that women with oophorectomy are at greater risk for CHD than intact women, pointing to a greater risk from testosterone deficiency than from estradiol levels.

testosterone

estradiol


Input: Perfluorocarbon-loaded lipid nanocapsules as oxygen sensors for tumor tissue pO (2) assessment.

Perfluorocarbon

oxygen


Input: The assessment of tumor oxygenation is a crucial factor in cancer therapy and may be carried out using fluorine MRI once fluorine probes have been distributed within the tumor.

fluorine

fluorine


Input: However, the deposit of those highly fluorinated compounds often jeopardizes anatomical image quality and requires emulsification of the probes.


Input: Due to the high density and the high lipophilicity of perfluorocarbons, nanoemulsion of these molecules usually requires high-energy processes.

perfluorocarbons


Input: In the present work, we discuss the synthesis and the physico-chemical characterization of perfluorocarbon nanocapsules using a low-energy phase-inversion process.

perfluorocarbon


Input: The nanocapsules were tested on a mouse tumor brain model to assess oxygenation.


Input: Ultrasonic gene and drug delivery using eLiposomes.


Input: eLiposomes are liposomes encapsulating emulsions and therapeutics for targeted delivery.


Input: By applying ultrasound to eLiposomes, emulsion droplets can transform from liquid to gas and rupture the lipid bilayer of the eLiposome to release a drug or plasmid.


Input: In this study, perfluoropentane (PFC5) emulsions were encapsulated inside folated eLiposomes carrying a model drug (calcein) or a model GFP plasmid to examine the effects of a folate ligand, PFC5 emulsion and various ultrasonic acoustic parameters in drug delivery and gene transfection into HeLa cells.

perfluoropentane

calcein

folate


Input: Confocal microscopy was used to quantify drug delivery and the level of plasmid transfection into HeLa cells.


Input: The results showed that drug delivery or transfection was minimal without incorporation of internal PFC5 emulsions and folate ligand on the eLiposome surface.

folate


Input: It was also shown that application of ultrasound greatly enhanced the drug delivery and plasmid transfection.


Input: Delivery of these therapeutics appears to be to the cytosol, indicating that the expansion of the emulsion droplets disrupted both the eLiposomes and the endosomes.


Input: Models of drug-induced liver injury for evaluation of phytotherapeutics and other natural products.


Input: Extracts from medicinal plants, many of which have been used for centuries, are increasingly tested in models of hepatotoxicity.


Input: One of the most popular models to evaluate the hepatoprotective potential of natural products is acetaminophen (APAP)-induced liver injury, although other hepatotoxicity models such as carbon tetrachloride, thioacetamide, ethanol and endotoxin are occasionally used.

acetaminophen

APAP

carbon tetrachloride

thioacetamide

ethanol


Input: APAP overdose is a clinically relevant model of drug-induced liver injury.

APAP


Input: Critical mechanisms and signaling pathways, which trigger necrotic cell death and sterile inflammation, are discussed.


Input: Although there is increasing understanding of the pathophysiology of APAP-induced liver injury, the mechanism is complex and prone to misinterpretation, especially when unknown chemicals such as plant extracts are tested.

APAP


Input: This review discusses the fundamental aspects that need to be considered when using this model, such as selection of the animal species or in vitro system, timing and dose-responses of signaling events, metabolic activation and protein adduct formation, the role of lipid peroxidation and apoptotic versus necrotic cell death, and the impact of the ensuing sterile inflammatory response.


Input: The goal is to enable researchers to select the appropriate model and experimental conditions for testing of natural products that will yield clinically relevant results and allow valid interpretations of the pharmacological mechanisms.


Input: Feasibility of spray drying bacteriophages into respirable powders to combat pulmonary bacterial infections.


Input: The use of bacterial viruses for antibacterial treatment (bacteriophage therapy) is currently being reevaluated.


Input: In this study, we analyze the potential of processing bacteriophages in a dry powder formulation, using a laboratory spray dryer.


Input: The phages were dried in the presence of lactose, trehalose or dextran 35, serving as an excipient to give the resulting powder the necessary bulk mass and offer protection to the delicate phage structure.

lactose

trehalose


Input: Out of the three excipients tested, trehalose was found to be the most efficient in protecting the phages from temperature and shear stress throughout the spray drying process.

trehalose


Input: A low inlet air temperature and atomizing force appeared to be the best parameter conditions for phage survival.


Input: Pseudomonas podovirus LUZ19 was remarkably stable, suffering less than 1 logarithmic unit reduction in phage titer.


Input: The phage titer of Staphyloccus phage Romulus-containing powders, a member of the Myoviridae family, showed more than 2. 5 logarithmic units reduction.


Input: On the other hand, Romulus-containing powders showed more favorable characteristics for pulmonary delivery, with a high percentage of dry powder particles in the pulmonary deposition fraction (1-5 mu m particle diameter).


Input: Even though the parameters for spray drying all phages were not optimized, it was demonstrated that spray drying phages with this industrial relevant and scalable set up was possible.


Input: The resulting powders had desirable size ranges for pulmonary delivery of phages with dry powder inhalers (DPIs).


Input: Sonhafouonic acid, a new cytotoxic and antifungal hopene-triterpenoid from Zehneria scabra camerunensis.

Sonhafouonic acid

hopene

triterpenoid


Input: A new hopene-type triterpenoid, namely sonhafouonic acid 1a was isolated from Zehneria scabra camerunensis, together with eight known compounds.

hopene

triterpenoid

sonhafouonic acid


Input: The structure of 1a was established by extensive NMR and high resolution MS techniques and confirmed by single-crystal X-ray crystallographic analysis.


Input: Compound 1a exhibited inhibitory activity against mycelial growth of two peronosporomycete phytopathogens Pythium ultimum and Aphanomyces cochliodes and cytotoxicity towards brine shrimp larvae (Artemia salina) at 10 mu g/mL.


Input: Pestaloficiols Q-S from the plant endophytic fungus Pestalotiopsis fici.

Pestaloficiols Q-S


Input: Two new isoprenylated chromone derivatives, pestaloficiols Q (1) and R (2), and one new benzofuran derivative, pestaloficiol S (3), along with three known metabolites, anofinic acid (4), siccayne (5), and pyrenophorol (6) were isolated from solid cultures of the plant endophytic fungus Pestalotiopsis fici.

isoprenylated chromone

pestaloficiols Q (1) and R

benzofuran

pestaloficiol S

anofinic acid

siccayne

pyrenophorol


Input: Their structures were elucidated primarily by NMR spectroscopy, and the absolute of the C-6 secondary alcohol in 1 was deduced on the basis of circular dichroism (CD) data.

secondary alcohol


Input: Compound 5 showed cytotoxic activity against the human cancer cell lines, HeLa and HT29, with IC50 values of 48. 2 and 33. 9 mu M, respectively.


Input: Syntheses and anti-allergic activity of 2-((bis (trimethylsilyl) methylthio/methylsulfonyl) methyl)-5-aryl-1, 3, 4-oxadiazoles.

2-((bis (trimethylsilyl) methylthio/methylsulfonyl) methyl)-5-aryl-1, 3, 4-oxadiazoles


Input: A new class of sila-substituted 1, 3, 4-oxadiazoles was synthesized by a convenient synthetic method.

sila-substituted 1, 3, 4-oxadiazoles


Input: Both silathio/silasulfonyl acetic acids were efficiently condensed with benzohydrazides in the presence of phosphorus oxychloride to give sila-substituted 1, 3, 4-oxadiazoles in high yields.

silathio/silasulfonyl acetic acids

benzohydrazides

phosphorus oxychloride

sila-substituted 1, 3, 4-oxadiazoles


Input: The compounds displayed variable extent of anti-allergic activity on IgE/Ag-stimulated RBL-2H3 cells at 50 and 100 mu M concentrations.


Input: Compounds having sulfonyl moiety with bis (trimethylsilyl)-1, 3, 4-oxadiazoles (5a-c), exhibited better anti-allergic activities than those of compounds having sulphur moiety with bis (trimethylsilyl)-1, 3, 4-oxadiazoles (4a-c).

sulfonyl

bis (trimethylsilyl)-1, 3, 4-oxadiazoles

sulphur

bis (trimethylsilyl)-1, 3, 4-oxadiazoles


Input: Anti-hepatitis B virus and anti-cancer activities of novel isoflavone analogs.

isoflavone


Input: We have synthesized a series of novel isoflavone analogs and evaluated their anti-HBV and anti-cancer activities in vitro.

isoflavone


Input: The bioassays showed that the majority of the resultant compounds exerted inhibitory effects on HBsAg and HBeAg levels, HBV DNA replication, as well as the growth of four human cancer cell lines to various extents, which supported the rationale of the design.


Input: In particular, compound 8f showed the highest activity against HBV infection and HBV-related liver cancer.


Input: Compound 7l (IC50 = 0. 47 mu M) also exerted remarkable inhibitory effect on the growth lung cancer cell line A-549.


Input: Design, synthesis and SAR of piperidyl-oxadiazoles as 11 beta-hydroxysteroid dehydrogenase 1 inhibitors.

piperidyl-oxadiazoles

11 beta-hydroxysteroid


Input: The potential roles of 11 beta-HSD1 inhibitors in metabolic syndrome, T2D and obesity were well established and currently several classes of 11 beta-HSD1 inhibitors have been developed as promising agents against metabolic diseases.


Input: To find potent compounds with good pharmacokinetics, we used the bioisosterism approach, and designed the compound 2 and 3 bearing an 1, 2, 4-oxadiazole ring to replace the amide group in compound 1.

1, 2, 4-oxadiazole

amide


Input: Guided by docking study, we then transformed compound 3 into a potent lead compound 4a by changing sulfonamide group to amide.

sulfonamide

amide


Input: To elaborate this series of piperidyl-oxadiazole derivatives as human 11 beta-HSD1 inhibitors, we explored the structure-activity relationship of several parts of the lead compound.

piperidyl-oxadiazole


Input: Based on their potency toward human 11 beta-HSD1 two compounds 4h and 4q were advanced to pharmacokinetic study.


Input: It was found that 4h and 4q are potent and selective human 11 beta-HSD1 inhibitors with better pharmacokinetic properties than those of the original piperidine-3-carboxamide compound 1, and suitable for further in vivo preclinical study in primate model.


Input: (E)-4-Aryl-4-oxo-2-butenoic acid amides, chalcone-aroylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization.

(E)-4-Aryl-4-oxo-2-butenoic acid amides

chalcone-aroylacrylic acid


Input: Antiproliferative activity of twenty-nine (E)-4-aryl-4-oxo-2-butenoic acid amides against three human tumor cell lines (HeLa, FemX, and K562) is reported.

(E)-4-aryl-4-oxo-2-butenoic acid amides


Input: Compounds showed antiproliferative activity in one-digit micromolar to submicromolar concentrations.


Input: The most active derivatives toward all the cell lines tested bear alkyl substituents on the aroyl moiety of the molecules.

alkyl


Input: Fourteen compounds showed tubulin assembly inhibition at concentrations < 20 mu M.


Input: The most potent inhibitor of tubulin assembly was unsubstituted compound 1, with IC50 = 2. 9 mu M.


Input: Compound 23 had an oral LD50in vivo of 45 mg/kg in mice.


Input: Cell cycle analysis on K562 cells showed that compounds 1, 2 and 23 caused accumulation of cells in the G2/M phase, but inhibition of microtubule polymerization is not the principal mode of action of the compounds.


Input: Nevertheless, they may be useful leads for the design of a new class of antitubulin agents.


Input: Design, synthesis and biological evaluation of novel hybrid compounds of imidazole scaffold-based 2-benzylbenzofuran as potent anticancer agents.

imidazole


Input: A series of novel hybrid compounds between 2-benzylbenzofuran and imidazole has been prepared and evaluated in vitro against a panel of human tumor cell lines.

imidazole


Input: The results suggest that the existence of benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl or 4-methoxyphenacyl group were vital for modulating cytotoxic activity.

benzimidazole

imidazolyl

naphthylacyl


Input: In particular, hybrid compounds 46 and 47 were found to be the most potent derivatives against 5 strains human tumor cell lines and more active than cisplatin (DDP), and exhibited cytotoxic activities selectively against breast carcinoma (MCF-7) and myeloid liver carcinoma (SMMC-7721), respectively.

cisplatin

DDP


Input: Inhibition of enterovirus 71 infections and viral IRES activity by Fructus gardeniae and geniposide.

geniposide


Input: Fructus gardeniae has long been used by traditional Chinese medical practitioners for its anti-inflammatory, anti-oxidant, anti-tumor and anti-hyperlipidemic characteristics.


Input: Here we describe our finding that F. gardeniae greatly reduces anti-enterovirus 71 (EV71) activity, resulting in significant decreases in EV71 virus yields, EV71 infections, and internal ribosome entry site activity.


Input: We also found that geniposide, a primary F. gardeniae component, inhibited both EV71 replication and viral IRES activity.

geniposide


Input: Our data suggest the presence of a mechanism that blocks viral protein translation.


Input: According to our findings, F. gardeniae and geniposide deserve a closer look as potential chemopreventive agents against EV71 infections.

geniposide


Input: Multifunctional terpolymeric MRI contrast agent with superior signal enhancement in blood and tumor.


Input: A new multifunctional terpolymeric system for simultaneous imaging and drug delivery has been recently developed in our laboratory.


Input: Herein we report the investigation of terpolymeric contrast agent for magnetic resonance imaging and doxorubicin (Dox) delivery.

doxorubicin

Dox


Input: The polymer was synthesized by graft polymerization of methacrylic acid (MAA) and polysorbate 80 (PS 80) onto starch with multiple, chemically bound diethylenetriaminepenta acetic acid (DTPA) groups for gadolinium chelating.

methacrylic acid

MAA

polysorbate 80

PS 80

diethylenetriaminepenta acetic acid

DTPA

gadolinium


Input: The terpolymer self-assembled to form nanoparticles upon addition of doxorubicin which binds with the PMAA chain.

doxorubicin

PMAA


Input: The physicochemical, biological and pharmacokinetic properties of the polymeric system were characterized and their contrast enhancement capability was evaluated in vitro and in vivo.


Input: The polymer was able to load gadolinium with high thermodynamic stability and exhibited low cytotoxicity.

gadolinium


Input: The Gd-loaded polymer (PolyGd), and Gd-Dox co-loaded nanoparticles (PolyGd-Dox) significantly enhanced MR signals, with ionic T1 relaxivities 3-5 times higher than those from Omniscan (R), a small molecule contrast agent.

Gd

PolyGd

Gd

Dox

PolyGd-Dox

Omniscan


Input: In vivo studies showed superior and prolonged contrast enhancement compared to Omniscan (R) at one fourth the equivalent dose, without adverse effects.

Omniscan


Input: The PolyGd and PolyGd-Dox accumulated in the tumor and painted the tumor boundaries clearly for at least 48h.

Dox


Input: The PolyGd also enhanced angiogram contrast with contrast to noise ratio values of up to 55-fold and a blood half-life time of 200min.


Input: Seven days after intravenous administration, only relatively small amounts of gadolinium could be detected in the major organs of the mice (supplementary materials).

gadolinium


Input: These results suggest that the new terpolymeric system is useful as a theranostic platform for contrast enhanced MR imaging of vasculature and tumor as well as Dox delivery.

Dox


Input: Silica-lipid hybrid (SLH) formulations enhance the oral bioavailability and efficacy of celecoxib: An in vivo evaluation.

Silica

celecoxib


Input: This study is the first to demonstrate in canines the ability of silica-lipid hybrid (SLH) microparticles to enhance the bioavailability and efficacy of a poorly water-soluble drug after oral administration.

silica


Input: Spray-dried SLH microparticles comprising Capmul MCM (mono-diglycerides of C8/C12 fatty acids) and silica nanoparticles (Aerosil (R) 380) were shown to significantly enhance the fasted state oral bioavailability of celecoxib (CEL) (6. 5 fold, relative to an aqueous suspension and more than 2-fold higher relative to the fed state) after oral administration to beagle dogs.

Capmul MCM

mono-diglycerides

fatty acids

silica

Aerosil

celecoxib

CEL


Input: Comparable bioavailability was observed between the SLH microparticle formulation and a conventional Capmul lipid solution, however, plasma concentrations were observed to be higher (Cmax, 1. 1 +/- 0. 06 vs. 0. 8 +/- 0. 03 mu g/mL) (p <= 0. 05) with the SLH microparticle system.

Capmul


Input: The enhanced bioavailability of CEL observed with the SLH microparticles was reflected in a subsequent efficacy study conducted in an adjuvant-induced arthritis model in the rat.

CEL


Input: Reduced clinical and histological severity was observed at a dose of 3mg/kg/day, with the progression of arthritic symptoms and tissue damage reduced to a similar degree to that of a higher dose administered at 5mg/kg/day and prepared in an aqueous suspension., The enhanced bioavailability and improved efficacy observed with the SLH microparticles were attributed to the maintenance of CEL in a solubilised form during digestion of the lipid vehicle.

CEL


Input: We hypothesise that the presence of silica in the formulation may have contributed to the prevention of drug precipitation in the intestinal lumen by providing an alternative binding site for CEL to adsorb to prior to re-solubilisation and absorption.

silica

CEL


Input: The study highlights the potential utility of novel SLH microparticle formulations as stable dry powders that possess the properties of a lipid-based formulation for the enhanced delivery and efficacy of poorly water-soluble drugs.


Input: Gender-specific effects of fluoxetine on hippocampal glucocorticoid receptor phosphorylation and behavior in chronically stressed rats.

fluoxetine


Input: Chronic psychosocial isolation stress (CPSI) modulates glucocorticoid receptor (GR) functioning in Wistar male rat hippocampus (HIPPO) through alteration of nuclear GR phosphorylation and its upstream kinases signaling, which parallels animal depressive-like behavior.


Input: The current study investigated potential gender specificities regarding the effect of chronic therapy by an antidepressant fluoxetine (FLU) on GR signaling in HIPPO and depressive-like behavior in CPSI animals.

fluoxetine

FLU


Input: FLU was administrated to female and male na i ve or CPSI rats for 21 days and GR protein, its phosphorylation status and upstream kinases, as well as GR and BDNF mRNA were followed in HIPPO together with animal serum corticosterone (CORT) and depressive-like behavior.

FLU

corticosterone

CORT


Input: The results showed that CPSI increased immobility in males versus hyperactivity in females and disrupted nuclear pGR232-Cdk5 pathway and JNK signaling in a gender-specific way.


Input: In contrast, in both genders CPSI increased the nuclear levels of GR and pGR246 but decreased CORT and mRNA levels of GR and BDNF.

CORT


Input: Concomitant FLU normalized the depressive-like behavior and altered the nuclear pGR232-Cdk5 signaling in a gender-specific manner.

FLU


Input: In both females and males, FLU reversed the nuclear levels of GR and pGR246 without affecting CORT and GR mRNA levels.

FLU

CORT


Input: In contrast, FLU exhibited gender-specific effect on BDNF mRNA in CPSI animals, by increasing it in females, but not in males.

FLU


Input: In spite of normalization the total nuclear GR level upon FLU treatment in both gender, down-regulation of GR mRNA is possibly maintained through prevalence of pGR232 isoform only in males.

FLU