Input: The thymine analog 5-chlorouridine, first reported in the 1950s as anti-tumor agent, is known as an effective mutagen, clastogen and toxicant as well as an effective inducer of sister-chromatid exchange.

thymine


Input: Recently, the first microorganism with a chemically different genome was reported; the selected Escherichia coli strain relies on the four building blocks 5-chloro-2'-deoxyuridine (ClU), A, C and G instead of the standard T, A, C, G alphabet [Marli e re, P., Patrouix, J., D o ring, V., Herdewijn, P., Tricot, S., Cruveiller, S., Bouzon, M. and Mutzel, R. (2011) Chemical evolution of a bacterium' s genome. Angew. Chem. Int. Ed., 50, 7109-7114].

ClU


Input: The residual fraction of T in the DNA of adapted bacteria was < 2% and the switch from T to ClU was accompanied by a massive number of mutations, including > 1500 A to G or G to A transitions in a culture.

ClU


Input: The former is most likely due to wobble base pairing between ClU and G, which may be more common for ClU than T.

ClU

ClU


Input: To identify potential changes in the geometries of base pairs and duplexes as a result of replacement of T by ClU, we determined four crystal structures of a B-form DNA dodecamer duplex containing ClU: A or ClU: G base pairs.

ClU

ClU

ClU


Input: The structures reveal nearly identical geometries of these pairs compared with T: A or T: G, respectively, and no consequences for stability and cleavage by an endonuclease (EcoRI).


Input: The lack of significant changes in the geometry of ClU: A and ClU: G base pairs relative to the corresponding native pairs is consistent with the sustained unlimited self-reproduction of E. coli strains with virtually complete T --> ClU genome substitution.

ClU

ClU

ClU


Input: Circularized synthetic oligodeoxynucleotides serve as promoterless RNA polymerase III templates for small RNA generation in human cells.


Input: Synthetic RNA formulations and viral vectors are the two main approaches for delivering small therapeutic RNA to human cells.


Input: Here we report findings supporting an alternative strategy in which an endogenous human RNA polymerase (RNAP) is harnessed to make RNA hairpin-containing small RNA from synthetic single-stranded DNA oligonucleotides.


Input: We report that circularizing a DNA template strand encoding a pre-microRNA hairpin mimic can trigger its circumtranscription by human RNAP III in vitro and in human cells.


Input: Sequence and secondary structure preferences that appear to promote productive transcription are described.


Input: The circular topology of the template is required for productive transcription, at least in part, to stabilize the template against exonucleases.


Input: In contrast to bacteriophage and Escherichia coli RNAPs, human RNAPs do not carry out rolling circle transcription on circularized templates.


Input: While transfected DNA circles distribute between the nucleus and cytosol, their transcripts are found mainly in the cytosol.


Input: Circularized oligonucleotides are synthetic, free of the hazards of viral vectors and maintain small RNA information in a stable form that RNAP III can access in a cellular context with, in some cases, near promoter-like precision and biologically relevant efficiency.


Input: Melanocortins as innovative drugs for ischemic diseases and neurodegenerative disorders: established data and perspectives.


Input: Ischemic insults and neurodegenerative diseases are by far the leading cause of mortality and disability.


Input: Whole-body hypoperfusion, as it occurs in polytraumatic and hemorrhagic shock, is alike an increasingly frequent condition, especially due to traffic accidents, wars and acts of terrorism.


Input: It is now clearly established that inflammatory processes play a fundamental role in the pathophysiology of both hypoperfusion/ischemia damage (be it generalized to the whole body, as in the case of shock, or limited to individual organs) and neurodegenerative diseases (Alzheimer' s disease, Parkinson' s disease, multiple sclerosis, amyotrophic lateral sclerosis).


Input: On the other hand, concurrent animal and human data show that melanocortin peptides with agonist activity at melanocortin MC3/MC4 receptors are highly effective in different shock conditions as well as in conditions of ischemia/ischemia-reperfusion of individual organs (heart, brain, intestine, kidney, etc.), and accumulating evidence indicates that such effects of melanocortins are mostly due to quite peculiar antiinflammatory mechanisms.


Input: Melanocortins have also long been known (i) to exert important neurotrophic effects, not only during fetal development but also in adulthood, in different animal models of brain lesions; (ii) to reduce the morphological correlates of brain aging; (iii) to retard the behavioral deficits that develop during the aging process.


Input: Moreover, recent data from different laboratories show that after brain ischemic episodes melanocortins activate the transcription of neurotrophins and their receptors in the cerebral cortex and in the hippocampus, and increase the proliferation of progenitor neuron cells.


Input: The above arguments support the view that pharmacokinetically suitable agonists at MC3/MC4 melanocortin receptors may represent a completely innovative class of drugs for an effective treatment of both ischemic and neurodegenerative diseases.


Input: Histone deacetylase inhibitors: an attractive strategy for cancer therapy.


Input: Histone deacetylases are able to catalyze the hydrolysis of N-acetyl lysine residues of histones which package chromosomal DNA.

N-acetyl lysine


Input: Therefore they play an important role in mediating gene expression and cell proliferation.


Input: HDAC inhibitors have not only shown promise as antiparasitic, antineurodegenerative, antirheumatologic agents and immunosuppressant, but as potent anticancer agents by inducing cell cycle arrest, differentiation and apoptosis.


Input: This review highlights recent development in design, synthesis and biological evaluation of HDAC inhibitors for cancer therapy.


Input: Alkyl substituted 2'-benzoylpyridine thiosemicarbazone chelators with potent and selective anti-neoplastic activity: novel ligands that limit methemoglobin formation.

Alkyl substituted 2'-benzoylpyridine thiosemicarbazone


Input: Thiosemicarbazone chelators, including the 2'-benzoylpyridine thiosemicarbazones (BpT) class, show marked potential as anticancer agents.

Thiosemicarbazone

2'-benzoylpyridine thiosemicarbazones

BpT


Input: Importantly, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) has been investigated in > 20 phase I and II clinical trials.

3-aminopyridine-2-carboxaldehyde thiosemicarbazone


Input: However, side effects associated with 3-AP administration include methemoglobinemia.


Input: Considering this problem, novel BpT analogues were designed bearing hydrophobic, electron-donating substituents at the para position of the phenyl group (RBpT).

BpT

phenyl

RBpT


Input: Their Fe (III/II) redox potentials were all within the range accessible to cellular oxidants and reductants, suggesting they can redox cycle.

Fe (III/II)


Input: These RBpT ligands exhibited potent and selective antiproliferative activity, which was comparable or exceeded their BpT counterparts.

RBpT

BpT


Input: Major findings include that methemoglobin formation mediated by the lipophilic t-BuBpT series was significantly (p < 0. 05-0. 001) decreased in comparison to 3-AP in intact red blood cells and were generally comparable to the control.

t-BuBpT


Input: These data indicate the t-BuBpT ligands may minimize methemoglobinemia, which is a marked advantage over 3-AP and other potent thiosemicarbazones.

t-BuBpT

thiosemicarbazones


Input: Besting vitamin E: sidechain substitution is key to the reactivity of naphthyridinol antioxidants in lipid bilayers.

vitamin E

naphthyridinol


Input: A series of naphthyridinol analogs of alpha-tocopherol (alpha-TOH, right) with varying sidechain substitution was synthesized to determine how systematic changes in the lipophilicity of these potent antioxidants impact their radical-trapping activities in lipid bilayers, regenerability by water-soluble reductants, and binding to human tocopherol transport protein (TTP).

naphthyridinol

alpha-tocopherol

alpha-TOH

tocopherol


Input: The activities of the naphthyridinols were assayed in phosphatidylcholine unilamellar liposomes using a recently developed high-throughput assay that employs a boron dipyrromethene conjugate of alpha-TOH (H (2) B-PMHC) that undergoes fluorescence enhancement upon oxidation.

naphthyridinols

phosphatidylcholine

boron dipyrromethene

alpha-TOH


Input: The naphthyridinols afforded a dose-dependent protection of H (2) B-PMHC consistent with unprecedented peroxyl radical-trapping activity in lipid bilayers.

naphthyridinols

peroxyl


Input: While sidechain length and/or branching had no effect on their apparent reactivity, it dramatically impacted reaction stoichiometry, with more lipophilic compounds trapping two peroxyl radicals and more hydrophilic compounds trapping significantly less than one.

peroxyl


Input: It is suggested that the less lipophilic compounds autoxidize rapidly in the aqueous phase and that preferential partitioning of the more lipophilic compounds to the bilayer protects them from autoxidation.


Input: The cooperativity of a lipophilic naphthyridinol with water-soluble reducing agents was also studied in liposomes using H (2) B-PMHC and revealed superior regenerability by each of ascorbate, N-acetylcysteine, and urate when compared to alpha-TOH.

naphthyridinol

ascorbate

N-acetylcysteine

urate

alpha-TOH


Input: Binding assays with human TTP, a key determinant of the bioavailability of the tocopherols, reveal that the naphthyiridinols can be very good ligands for the protein.

tocopherols

naphthyiridinols


Input: In fact, naphthyridinols with sidechains of eight or more carbons had affinities for TTP which were similar to, and in one case 10-fold better than, alpha-TOH.

naphthyridinols

carbons

alpha-TOH


Input: Potential antipsoriatic effect of chondroitin sulfate through inhibition of NF-kappa B and STAT3 in human keratinocytes.

sulfate


Input: Chondroitin sulfate (CS) is a natural glycosaminoglycan, formed by the 1-3 linkage of d-glucuronic acid to N-acetylgalactosamine, present in the extracellular matrix.

sulfate

d-glucuronic acid

N-acetylgalactosamine


Input: It is used as a slow acting disease modifying agent in the treatment of osteoarthritis, and part of its beneficial effects are due to its antiinflammatory properties that result from an inhibitory effect on NF-kappa B signaling pathway.


Input: This ability raises the hypothesis that CS might be effective in other chronic inflammatory processes such as psoriasis, in which a deregulation of NF-kappa B is a key feature.


Input: In addition, psoriasis is characterized by an upregulation of STAT3 signaling pathway that is related to the epidermal hyperplasia.


Input: In the present study we report the pharmacological modulation of the NF-kappa B and STAT3 signaling pathways by CS in normal human keratinocytes.


Input: CS inhibited NF-kappa B activation and the release of some of the key psoriatic cytokines such as TNF alpha, IL-8, IL-6 and CCL27.


Input: Moreover, it impaired STAT3 translocation to the nucleus and significantly reduced STAT3 transcriptional activity by a mechanism that was independent from STAT3 phosphorylation.


Input: Our results confirm the interest of CS as a candidate for future drug research in the therapeutics of psoriasis given the need of more effective and safer oral medications for these patients.


Input: Generating thermal stable variants of protein domains through phage display.


Input: Often in protein design research, one desires to generate thermally stable variants of a protein or domain.


Input: One route to identifying mutations that yield domains that remain folded and active at a higher temperature is through the use of directed evolution.


Input: A library of protein domain variants can be generated by mutagenic PCR, expressed on the surface of bacteriophage M13, and subjected to heat, such that the unfolded forms of the domain, showing reduced or no binding activity, are lost during subsequent affinity selection, whereas variants that still retain binding to their target are selected and enriched with each subsequent round of affinity selection.


Input: This approach takes advantage of the fact that bacteriophage M13 particles are heat stable and resistant to many proteases and protein denaturants.


Input: We present the application of this general approach to generating thermally stable variants of a eukaryotic peptide-binding domain.


Input: The benefits of producing such variants are that they typically express at high levels in Escherichia coli (30-60mg/L shake flask) and remain soluble in solution at higher concentrations for longer periods of time than the wild-type form of the domain.


Input: The process of library generation and screening generally requires about one month of effort, and yields variants with > 10 degrees C increase in thermal stability, as measured in a simple fluorescence-based thermal shift assay.


Input: It is anticipated that thermally stable variants will serve as excellent scaffolds for generating affinity reagents to a variety of targets of interest.


Input: Effects of glyphosate-based herbicides on embryo-larval development and metamorphosis in the Pacific oyster, Crassostrea gigas.

glyphosate


Input: Pesticides may be involved in oyster summer mortality events, not necessarily as a single causative agent but as an additional stressor.


Input: In this context, the present study aimed to assess the toxicity of glyphosate, its by-product, aminomethylphosphonic acid (AMPA) and two commercial formulations, Roundup Express ((R)) (R (EX)) and Roundup All e es et Terrasses ((R)) (R (AT)), containing glyphosate as the active ingredient, on the early life stages of the Pacific oyster, Crassostrea gigas.

glyphosate

aminomethylphosphonic acid

AMPA

glyphosate


Input: The embryotoxicity of these chemicals were quantified by considering both the rates of abnormalities and the arrested development or types of abnormalities in D-shaped larvae after 48 h exposure.


Input: The success of metamorphosis was examined in pediveliger larvae exposed for 24 h.


Input: Experiments involving both endpoints included range finding experiments for herbicide concentrations ranging from 0. 1 to 100, 000 mu g L (-1).


Input: This range was then narrowed down in order to determine precise EC (50) values.


Input: Actual concentrations of the herbicide were determined at the beginning and after 48 h (embryotoxicity) and 24 h (metamorphosis) to evaluate the potential temporal variation in the concentrations.


Input: During embryo-larval development, no mortalities were recorded at any of the concentrations of glyphosate and AMPA, whereas no embryos or D-shaped larvae could be observed after exposure to 10, 000 mu g L (-1) of R (EX) or R (AT).

glyphosate

AMPA


Input: Compared with the controls, no effects on embryo-larval development were recorded between 0. 1 and 1000 mu g L (-1), regardless of the chemical tested.


Input: Above a threshold, which varied according to the chemical used, the gradient of herbicide concentrations correlated with a gradient of severity of abnormality ranging from normal larvae to arrested development (an " old embryo " stage).


Input: The EC (50) values were 28, 315 and 40, 617 mu g L (-1) for glyphosate and its metabolite, respectively, but much lowered values of 1133 and 1675 mu g L (-1) for R (EX) and R (AT), respectively.

glyphosate


Input: Metamorphosis tests also revealed a significant difference between molecules, as the EC (50) values exceeded 100, 000 mu g L (-1) for glyphosate and AMPA but were as low as 6366 and 6060 mu g L (-1) for the commercial formulations, which appeared relatively more toxic.

glyphosate

AMPA


Input: Overall, the embryo-larval development of C. gigas was more sensitive to glyphosate-based herbicides compared to various endpoints studied in regulatory model organisms, and embryos and D-shaped larvae were more sensitive compared to pediveliger larvae.

glyphosate


Input: Ly6C + Ly6G-Myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury.


Input: Acute inflammation is a prominent feature of central nervous system (CNS) insult and is detrimental to the CNS tissue.


Input: Although this reaction spontaneously diminishes within a short period of time, the mechanism underlying this inflammatory resolution remains largely unknown.


Input: In this study, we demonstrated that an initial infiltration of Ly6C (+) Ly6G (-) immature monocyte fraction exhibited the same characteristics as myeloid-derived suppressor cells (MDSCs), and played a critical role in the resolution of acute inflammation and in the subsequent tissue repair by using mice spinal cord injury (SCI) model.


Input: Complete depletion of Ly6C (+) Ly6G (-) fraction prior to injury by anti-Gr-1 antibody (clone: RB6-8C5) treatment significantly exacerbated tissue edema, vessel permeability, and hemorrhage, causing impaired neurological outcomes.


Input: Functional recovery was barely impaired when infiltration was allowed for the initial 24 h after injury, suggesting that MDSC infiltration at an early phase is critical to improve the neurological outcome.


Input: Moreover, intraspinal transplantation of ex vivo-generated MDSCs at sites of SCI significantly reduced inflammation and promoted tissue regeneration, resulting in better functional recovery.


Input: Our findings reveal the crucial role of an Ly6C (+) Ly6G (-) fraction as MDSCs in regulating inflammation and tissue repair after SCI, and also suggests an MDSC-based strategy that can be applied to acute inflammatory diseases.


Input: Concentration of tacrolimus and major metabolites in kidney transplant recipients as a function of diabetes mellitus and cytochrome P450 3A gene polymorphism.

tacrolimus


Input: Abstract 1.


Input: Disposition of tacrolimus and its major metabolites, 13-O-desmethyl tacrolimus and 15-O-desmethyl tacrolimus, was evaluated in stable kidney transplant recipients in relation to diabetes mellitus and genetic polymorphism of cytochrome P450 (CYP) 3A.

tacrolimus

13-O-desmethyl tacrolimus

15-O-desmethyl tacrolimus


Input: Steady-state concentration-time profiles were obtained for 12-hour or 2-hour post-dose, in 20 (11 with diabetes) and 32 (24 with diabetes) patients, respectively.


Input: In addition, single nucleotide polymorphisms of the following genes: CYP3A4 (CYP3A4: CYP3A4 * 1B,-392A > G), 3A5 (CYP3A5: CYP3A5 * 3, 6986A > G) and P-glycoprotein (ABCB1: 3435C > T) were characterized.

nucleotide


Input: Dose-normalized concentrations of tacrolimus or metabolites were higher in diabetic patients.

tacrolimus


Input: CYP3A4 * 1B carriers and CYP3A5 expressers, independently or when assessed as a combined CYP3A4-3A5 genotype, had significantly lower dose-normalized pre-dose (C (0)/dose) and 2-hour post-dose (C (2)/dose) concentrations of tacrolimus and metabolites.

tacrolimus


Input: Non-diabetic patients with at least one CYP3A4 * 1B and CYP3A5 * 1 allele had lower C (0)/dose as compared to the rest of the population.


Input: Genetic polymorphism of CYP3A5 or CYP3A4 influence tacrolimus or metabolites dose-normalized concentrations but not metabolite to parent concentration ratios.

tacrolimus


Input: The effect of diabetes on tacrolimus metabolism is subject to debate and requires a larger sample size of genetically stratified subjects.

tacrolimus


Input: Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas.


Input: Sarcomas of the soft tissue are a heterogeneous, rare and complex group of mesenchymal malignant tumors, accounting for less than 1% of all adult malignancies and about 10-15% of childhood cancer.


Input: Despite local disease control obtained with surgery and pre-or postoperative radiotherapy, roughly one half of patients with high-grade tumors experience metastatic disease.


Input: The adjunction of chemotherapy, either before or after resection, is not currently viewed as standard practice due to the lack of reproducible impact on survival.


Input: The 1997 SMAC meta-analysis based on individual data from randomized studies confirmed a significant impact of adjuvant chemotherapy on both local and metastatic relapse, without any significant benefit on survival.


Input: Further meta-analyses demonstrated a significant benefit also in overall survival.


Input: Yet, the latest adjuvant EORTC trial was disappointedly negative.


Input: To date, adjuvant chemotherapy may be recommended as a reasonable option for the high-risk individual patient who should be well informed on the possible risks and benefits of treatment.


Input: Also the indications for neoadjuvant chemotherapy remain controversial.


Input: A local benefit may be gained, facilitating surgery, but data on survival are limited and affected by a strong patient selection bias.


Input: In order to improve our knowledge on sarcomas and to offer patients the best of current standards, we strongly recommend that all patients be referred to a sarcoma multidisciplinary group, under whose supervision they could receive the correct combined-modality management as well as have access to new clinical trials appropriately stratified for risk and histological and/or molecular subtypes.


Input: Statistical analyses of protein sequence alignments identify structures and mechanisms in signal activation of sensor histidine kinases.

histidine


Input: Statistical analyses of genome sequence-derived protein sequence data can identify amino acid residues that interact between proteins or between domains of a protein.

amino acid


Input: These statistical methods are based on evolution-directed amino acid variation responding to structural and functional constraints in proteins.

amino acid


Input: The identified residues form a basis for determining structure and folding of proteins as well as inferring mechanisms of protein function.


Input: When applied to two-component systems, several research groups have shown they can be used to identify the amino acid interactions between response regulators and histidine kinases and the specificity therein.

amino acid

histidine


Input: Recently, statistical studies between the HisKA and HATPase-ATP-binding domains of histidine kinases identified amino acid interactions for both the inactive and the active catalytic states of such kinases.

histidine

amino acid


Input: The identified interactions generated a model structure for the domain conformation of the active state.


Input: This conformation requires an unwinding of a portion of the C-terminal helix of the HisKA domain that destroys the inactive state residue contacts and suggests how signal-binding determines the equilibrium between the inactive and active states of histidine kinases.

C

histidine


Input: The rapidly accumulating protein sequence databases from genome, metagenome and microbiome studies are an important resource for functional and structural understanding of proteins and protein complexes in microbes.


Input: Self-trimerization of ExsD limits inhibition of the Pseudomonas aeruginosa transcriptional activator ExsA in vitro.


Input: The opportunistic pathogen Pseudomonas aeruginosa ranks among the leading causes of nosocomial infection.


Input: The type III secretion system (T3SS) aids acute Pseudomonas aeruginosa infection by injecting potent cytotoxins into host cells to suppress the host' s innate immune response.


Input: Expression of all T3SS-related genes is strictly dependent on the transcription factor ExsA.


Input: Consequently, ExsA and the biological processes that regulate ExsA function are of great biomedical interest.


Input: The present study focused on the ExsA-ExsC-ExsD-ExsE signaling cascade, which ties host cell contact to the upregulation of T3SS gene expression.


Input: Prior to T3SS induction, the antiactivator protein ExsD binds to ExsA and blocks ExsA-dependent transcription by interfering with ExsA dimerization and promoter interactions.


Input: Upon host cell contact, ExsD is sequestered by the T3SS chaperone ExsC, resulting in the release of ExsA and upregulation of the T3SS.


Input: Previous studies have shown that the ExsD-ExsA interactions are not freely reversible.


Input: Because independently folded ExsD and ExsA were not found to interact, it has been hypothesized that folding intermediates of the two proteins form the complex.


Input: Here, we demonstrate, for the first time, that ExsD alone is sufficient to inhibit ExsA-dependent transcription in vitro and that no other cellular factors are required.


Input: More significantly, we show that independently folded ExsD and ExsA are capable of interacting, but only at 37 degrees C and not at 30 degrees C.


Input: Guided by the crystal structure of ExsD, we designed a monomeric variant of the protein, and demonstrated that ExsD trimerization prevents ExsD from inhibiting ExsA-dependent transcription at 30 degrees C.


Input: We propose that this unique mechanism plays an important role in T3SS regulation.


Input: Morin inhibits STAT3 tyrosine 705 phosphorylation in tumor cells through activation of protein tyrosine phosphatase SHP1.

Morin

tyrosine

tyrosine


Input: The major goal of cancer drug discovery is to find an agent that is safe and affordable, yet effective against cancer.


Input: Here we show that morin (3, 5, 7, 2', 4'-pentahydroxyflavone) has potential against cancer cells through suppression of the signal transducer and activator of transcription 3 (STAT3) pathway, which is closely linked to the transformation, survival, proliferation, and metastasis of cancer.

morin

3, 5, 7, 2', 4'-pentahydroxyflavone


Input: We found that morin completely suppressed inducible and constitutively activated STAT3 and blocked the nuclear translocation of STAT3 and its DNA binding in multiple myeloma and head and neck squamous carcinoma cells.

morin


Input: Morin inhibited activated Src, JAK-1, and JAK-2, all of which are linked to STAT3 activation, while up-regulating a protein inhibitor of activated STAT3, PIAS3.

Morin


Input: Pervanadate reversed the effects of morin on STAT3 phosphorylation, indicating the role of a protein tyrosine phosphatase.

morin

tyrosine


Input: Furthermore, morin induced SHP1 expression at both the mRNA and protein levels, and silencing of SHP1 abrogated the effect of morin on STAT3 phosphorylation, indicating that morin mediates its effects on STAT3 through SHP1.

morin

morin

morin


Input: Suppression of STAT3 correlated with the down-regulation of various gene products linked to tumor survival, proliferation, and angiogenesis and led to sensitization of tumor cells to thalidomide and bortezomib.

thalidomide

bortezomib


Input: Comparing the activities of morin with those of four structurally related flavonols demonstrated the importance of hydroxyl groups in the B ring in inhibiting STAT3 activation.

morin

flavonols

hydroxyl


Input: These findings suggest that morin suppresses the STAT3 pathway, leading to the down-regulation of STAT3-dependent gene expression and chemosensitization of tumor cells.

morin


Input: Blood pressure and levels of Fe, Ca, Mg, Zn, Cu, Na and K in the hair of young Bantu men from Tanzania.

Fe

Ca

Mg

Zn

Cu

K


Input: Mineral imbalance in the body may significantly contribute to the development and course of hypertension.


Input: In this paper, blood pressure figures have been linked to the levels of Fe, Ca, Mg, Zn, Cu, Na and K in hair.

Fe

Ca

Mg

Zn

Cu

K


Input: The research sample was composed of young men (n = 91) aged 13-21, from the town of Mafinga, Iringa District, Tanzania.


Input: The data collected included their age, tribal background and weekly diet.


Input: Based on body mass index, the participants were categorised into pre-defined subgroups.


Input: To examine how the minerals in question affect blood pressure, correlation analysis and multiple ridge regression analysis were performed.


Input: Analysis of ridge regression findings for the researched group (n = 91) shows that the minerals under scrutiny account for systolic blood pressure variation in 13% and in 15% for diastolic blood pressure variation.


Input: After including two additional variables-calendar age and body mass index-in regression analysis, the ultimate coefficient of determination (R (2)) changes for systolic blood pressure and remains the same for diastolic blood pressure (R (2) = 0. 194 and R (2) = 0. 156, respectively).


Input: Nutritional analysis shows that the students included in the study received insufficient calories per day (1, 500-2, 200 kcal).


Input: The group of students with abnormal blood pressure were not aware of their poor health.


Input: Research findings may result from progressive environmental changes and poor nutrition in terms of food quantity and quality, which had an impact on the subjects' blood pressure.


Input: Hair analysis used to determine mineral content in the body may be an auxiliary tool in identifying the links between factors leading to the development of hypertension.


Input: Mussel-inspired adhesive binders for high-performance silicon nanoparticle anodes in lithium-ion batteries.

silicon

lithium


Input: Conjugation of mussel-inspired catechol groups to various polymer backbones results in materials suitable as silicon anode binders.

catechol

silicon


Input: The unique wetness-resistant adhesion provided by the catechol groups allows the silicon nanoparticle electrodes to maintain their structure throughout the repeated volume expansion and shrinkage during lithiation cycling, thus facilitating substantially improved specific capacities and cycle lives of lithium-ion batteries.

catechol

silicon

lithium


Input: Revising the absolute configurations of coatlines via density functional theory calculations of electronic circular dichroism spectra.

coatlines


Input: Coatline A (1) and alpha-epi-coatline A (4) co-occur in the trunk extract of Andira coriacea.

Coatline A

alpha-epi-coatline A


Input: Inspection of their chiroptical properties led to intriguing results.


Input: After a careful examination of the experimental data used for the previously reported absolute configuration of these compounds, some uncertainties were identified.


Input: A combined theoretical approach including conformational analyses and calculation of electronic circular dichroism (ECD) spectra, in addition with experimental data obtained for schoepfin A (5) and the new schoepfin D (6) isolated from Senna quinquangulata, allowed the revision of the absolute configuration of coatlines A (1) and B (2).

schoepfin A

schoepfin D

coatlines


Input: Relative importance of direct and trophic uranium exposures in the crayfish Orconectes limosus: Implication for predicting uranium bioaccumulation and its associated toxicity.

uranium

uranium


Input: Pollutants that occur at sublethal concentrations in the environment may lead to chronic exposure in aquatic organisms.


Input: If these pollutants bioaccumulate, then organisms higher in the food chain may also be at risk.


Input: Increased attention has thus been focused on the relative importance of dietary uptake, but additional knowledge of the cellular distribution of metals after dietary exposure is required to assess the potential toxicity.


Input: The authors address concerns relating to increasing uranium (U) concentrations (from 12 micro g/L to 2 mg/L) in the freshwater ecosystem caused by anthropogenic activities.

uranium

U


Input: The objective of the present study is to compare uranium bioaccumulation levels in tissues and in the subcellular environment.

uranium


Input: The authors focused on the cytosol fraction and its microlocalization (TEM-EDX) in the gills and the hepatopancreas (HP) of the crayfish Orconectes limosus after 10 d of direct exposure (at concentrations of 20, 100, and 500 micro g/L) and five trophic exposure treatments (at concentrations from 1 to 20 micro g/g).


Input: Results indicated that adsorption of uranium on the cuticle represents the main contribution of total uranium accumulation to the animal.

uranium

uranium


Input: Accumulation in the gills should be considered only as a marker of waterborne uranium exposure.

uranium


Input: Accumulation in the HP after trophic environmental exposure conditions was higher (18. 9 +/- 3. 8 micro g/g) than after direct exposure.


Input: Moreover, no significant difference in the subcellular distribution of uranium (50%) in HP was observed between animals that had been exposed to both types of treatment.

uranium


Input: A potential toxic effect after uranium accumulation could therefore exist after trophic exposure.

uranium


Input: This confirms the need to focus further studies on the metal (uranium) risk assessment.

uranium


Input: Photoactivable amino acid bioisosteres and mass spectrometry: snapshots of in vivo 3D protein structures.

amino acid


Input: From folded to crosslinked proteins.


Input: A new promising photo-crosslinking/mass spectrometry method for the structural characterisation of folded proteins is highlighted.


Input: A reactive photo-leucine can clamp the front residues in beta-turn and beta-hairpin domains, thus allowing us to look into the specific native 3D structure of proteins.

leucine


Input: Assessment of density functional methods for reaction energetics: iridium-catalyzed water oxidation as case study.

iridium


Input: We investigate basis set convergence for a series of density functional theory (DFT) functionals (both hybrid and nonhybrid) and compare to coupled-cluster with single and double excitations and perturbative triples [CCSD (T)] benchmark calculations.


Input: The case studied is the energetics of the water oxidation reaction by an iridium-oxo complex.

iridium-oxo


Input: Complexation energies for the reactants and products complexes as well as the transition state (TS) energy are considered.


Input: Contrary to the expectation of relatively weak basis set dependence for DFT, the basis set effects are large, for example, more than 10 kcal mol (-1) difference from converged basis for the activation energy with " small " basis sets (DZ/6-31G * * for Ir/other atoms, or SVP) and still more than 6 kcal mol (-1) for def2-TZVPP/6-31G * *.

Ir


Input: Inclusion of the dispersion correction in DFT-D3 schemes affects the energies of reactant complex (RC), TS, and product complex (PC) by almost the same amount; it significantly improves the complexation energy (the formation of RC), but has little effect on the activation energy with respect to RC.


Input: With converged basis, some pure GGAs (PBE-D3, BP86-D3) as well as the hybrid functional B3LYP-D3 are very accurate compared to benchmark CCSD (T) calculations.


Input: Effect of molecular crowding on the temperature-pressure stability diagram of ribonuclease A.


Input: FT-IR spectroscopic and thermodynamic measurements were designed to explore the effect of a macromolecular crowder, dextran, on the temperature and pressure-dependent phase diagram of the protein Ribonuclease A (RNase A), and we compare the experimental data with approximate theoretical predictions based on configuration entropy.


Input: Exploring the crowding effect on the pressure-induced unfolding of proteins provides insight in protein stability and folding under cell-like dense conditions, since pressure is a fundamental thermodynamic variable linked to molecular volume.


Input: Moreover, these studies are of relevance for understanding protein stability in deep-sea organisms, which have to cope with pressures in the kbar range.


Input: We found that not only temperature-induced equilibrium unfolding of RNase A, but also unfolding induced by pressure is markedly prohibited in the crowded dextran solutions, suggesting that crowded environments such as those found intracellularly, will also oppress high-pressure protein unfolding.


Input: The FT-IR spectroscopic measurements revealed a marked increase in unfolding pressure of 2 kbar in the presence of 30 wt% dextran.


Input: Whereas the structural changes upon thermal unfolding of the protein are not significantly influenced in the presence of the crowding agent, through stabilization by dextran the pressure-unfolded state of the protein retains more ordered secondary structure elements, which seems to be a manifestation of the entropic destabilization of the unfolded state by crowding.


Input: Proteome profiling of peripheral mononuclear cells from human blood.


Input: Peripheral blood mononuclear cells (MNCs) are accessible through blood collection and represent a useful source for investigations on disease mechanisms and treatment response.


Input: Aiming to build a reference proteome database, we generated three proteome data sets from MNCs using a combination of SDS-PAGE and nanoflow LC-MS.

SDS


Input: Experiments were performed in triplicates and 514 unique proteins were identified by at least two non-redundant peptides with 95% confidence for all replicates.


Input: Identified proteins are associated with a range of dermatologic, inflammatory and neurological conditions as well as molecular processes, such as free radical scavenging and cellular growth and proliferation.


Input: Mapping the MNC proteome provides a valuable resource for studies on disease pathogenesis and the identification of therapeutic targets.


Input: Bifunctional nanoparticles constructed using one-pot encapsulation of a fluorescent polymer and magnetic (Fe3O4) nanoparticles in a silica shell.

silica


Input: Integration of biocompatible silica with a fluorescent polymer (PDDF) and superparamagnetic iron oxide nanoparticles (Fe3 O4) to form uniform core-shell nanostructures has the great potential to form particles for use in multimodal bioimaging applications.

silica

iron oxide

Fe3 O4


Input: Core-shell nanoparticles (PDDF/Fe3 O4 @SiO2) exhibit fluorescent and magnetic properties that are favorable for their use in magnetic separation and guiding applications, as well as optical and magnetic resonance (MR) imaging capabilities.

Fe3 O4


Input: With the biological analysis in an in vitro intracellular permeation and cytotoxicity test, chemical conjugation of the surface using folic acid (FA) molecules can provide the nanoparticles with cell-targeting properties, localizing the nanoparticles to folate receptors (FRs) on target KB cells that over-express the FRs.

folic acid

folate


Input: Inclusion of pediatric samples in an opt-out biorepository linking DNA to de-identified medical records: pediatric BioVU.


Input: The Vanderbilt DNA repository, BioVU, links DNA from leftover clinical blood samples to de-identified electronic medical records (EMRs).


Input: After initiating adult sample collection, pediatric extension required consideration of ethical concerns specific to pediatrics and implementation of specialized DNA extraction methods.


Input: In the first year of pediatric sample collection, more than 11, 000 samples from individuals younger than 18 years were included.


Input: We compared data from the pediatric BioVU cohort with those from the overall Vanderbilt University Medical Center pediatric population and found similar demographic characteristics; however, the BioVU cohort had higher rates of select diseases, medication exposures, and laboratory testing, demonstrating enriched representation of severe or chronic disease.


Input: The fact that the sample accumulation is not balanced may accelerate research in some cohorts while limiting the study of relatively benign conditions and the accrual of unaffected and unbiased control samples.


Input: BioVU represents a feasible model for pediatric DNA biobanking but involves both ethical and practical considerations specific to the pediatric population.


Input: Is this the dose for you?: the role of modeling.


Input: To make an informed benefit-risk evaluation of a drug, a range of doses needs to be evaluated and its dose-response and exposure-response relationships for safety and effectiveness assessed during drug development (International Conference on Harmonisation E4).


Input: Once a safe and effective population dose (or doses) has been determined for indicated use (s), the individual patient dose can then be adjusted based on patient-specific factors (e. g., age, race, genetics, organ functions, concomitant medications).


Input: One-pot assembly of a hetero-dimeric DNA origami from chip-derived staples and double-stranded scaffold.


Input: Although structural DNA nanotechnology, and especially scaffolded DNA origami, hold great promise for bottom-up fabrication of novel nanoscale materials and devices, concerns about scalability have tempered widespread enthusiasm.


Input: Here we report a single-pot reaction where both strands of double-stranded M13-bacteriophage DNA are simultaneously folded into two distinct shapes that then heterodimerize with high yield.


Input: The fully addressable, two-dimensional heterodimer DNA origami, with twice the surface area of standard M13 origami, formed in high yield (81% of the well-formed monomers undergo dimerization).


Input: We also report the concurrent production of entire sets of staple strands by a unique, nicking strand-displacement amplification (nSDA) involving reusable surface-bound template strands that were synthesized in situ using a custom piezoelectric inkjet system.


Input: The combination of chip-based staple strand production, double-sized origami, and high-yield one-pot assembly markedly increases the useful scale of DNA origami.


Input: In vivo biodistribution of mixed shell micelles with tunable hydrophilic/hydrophobic surface.


Input: The miserable targeting performance of nanocarriers for cancer therapy arises largely from the rapid clearance from blood circulation and the major accumulation in the organs of the reticuloendothelial system (RES), leading to inefficient enhanced permeability and retention (EPR) effect after intravenous injection (i. v.).


Input: Herein, we reported an efficient method to prolong the blood circulation of nanoparticles and decrease their deposition in liver and spleen.


Input: In this work, we fabricated a series of mixed shell micelles (MSMs) with approximately the same size, charge and core composition but with varied hydrophilic/hydrophobic ratios in the shell through spontaneously self-assembly of block copolymers poly (ethylene glycol)-block-poly (l-lysine) (PEG-b-PLys) and poly (N-isopropylacrylamide)-block-poly (aspartic acid) (PNIPAM-b-PAsp) in aqueous medium.

poly (ethylene glycol)-block-poly (l-lysine)

PEG-b-PLys

poly (N-isopropylacrylamide)-block-poly (aspartic acid)

PNIPAM-b-PAsp


Input: The effect of the surface heterogeneity on the in vivo biodistribution was systematically investigated through in vivo tracking of the (125) I-labeled MSMs determined by Gamma counter.

(125) I


Input: Compared with single PEGylated micelles, some MSMs were proved to be significantly efficient with more than 3 times lower accumulation in liver and spleen and about 6 times higher concentration in blood at 1 h after i. v..


Input: The results provide us a novel strategy for future development of long-circulating nanocarriers for efficient cancer therapy.


Input: Tetrahydropyrroloquinolinone type dual inhibitors of aromatase/aldosterone synthase as a novel strategy for breast cancer patients with elevated cardiovascular risks.

Tetrahydropyrroloquinolinone

aldosterone


Input: The application of aromatase inhibitors to postmenopausal breast cancer patients increases the risk of cardiovascular diseases (CVD), which is believed to be caused by the abnormally high concentrations of aldosterone as a consequence of the estrogen deficiency.

aldosterone

estrogen


Input: Dual inhibitors of aromatase (CYP19) and aldosterone synthase (CYP11B2) are therefore proposed as a novel strategy for the adjuvant therapy to reduce the CVD risk for these patients.

aldosterone


Input: By combining decisive structural features of CYP11B2 and CYP19 inhibitors into a common template, a series of pyridinylmethyl substituted 1, 2, 5, 6-tetrahydro-pyrrolo [3, 2, 1-ij] quinolin-4-ones were designed and synthesized.

pyridinylmethyl substituted 1, 2, 5, 6-tetrahydro-pyrrolo [3, 2, 1-ij] quinolin-4-ones


Input: Interestingly, the substituents on the methylene bridge showed strong influences on the inhibitory activities leading to opposite effects, that is, a given substituent showed an increase in inhibition of one enzyme, while it led to a decrease for the other enzyme.

methylene


Input: The compromise of this conflict led to compounds 3j, 3k, 3n, and 3p as potent and selective dual inhibitors of CYP19 and CYP11B2, especially compound 3p, which exhibited IC (50) values of 32 and 41 nM for CYP19 and CYP11B2, respectively, and a high selectivity toward CYP17 and CYP11B1.


Input: This compound is considered as a candidate for further evaluation in vivo.


Input: Absolute configuration and conformational analysis of brevipolides, bioactive 5, 6-dihydro-alpha-pyrones from Hyptis brevipes.

brevipolides

5, 6-dihydro-alpha-pyrones


Input: The (6' S)-configuration of brevipolides A-J (1-10), isolated from Hyptis brevipes, was established by X-ray diffraction analysis of 9 in conjunction with Mosher' s ester analysis of the tetrahydro derivative 11 obtained from both geometric isomers 8 and 9 as well as by chemical correlations.

brevipolides A-J

Mosher' s ester


Input: The structure of the new brevipolide J (10) was characterized through NMR and MS data as having the same 6-heptyl-5, 6-dihydro-2H-pyran-2-one framework possessing the cyclopropane moiety of all brevipolides but substituted by an isoferuloyl group instead of the p-methoxycinnamoyl moiety found in 8 and 9.

brevipolide J

6-heptyl-5, 6-dihydro-2H-pyran-2-one

cyclopropane

brevipolides

isoferuloyl

p-methoxycinnamoyl


Input: Conformational analysis of these cytotoxic 6-heptyl-5, 6-dihydro-alpha-pyrones was carried out on compound 9 by application of a protocol based on comparison between experimental and DFT-calculated vicinal (1) H-(1) H NMR coupling constants.

6-heptyl-5, 6-dihydro-alpha-pyrones

(1) H-(1) H


Input: Molecular modeling was used to correlate minimum energy conformers and observed electronic circular dichroism transitions for the isomeric series of brevipolides.

brevipolides


Input: Compounds 7-10 exhibited moderate activity (ED (50) 0. 3-8. 0 mu g/mL) against a variety of tumor cell lines.


Input: Treatment and prevention of various therapeutic conditions using OX receptor antagonistic activity (WO2012081692).


Input: Application WO2012081692 from Taisho Pharmaceutical Co.


Input: Ltd. claims pyrazole-based antagonists of the orexin-1 and orexin-2 receptors.

pyrazole


Input: Utility in a number of therapeutic areas is claimed, including the treatment of sleep disorders; the most likely use of the claimed compounds.


Input: Data from in vitro functional assays are presented, with the claimed compounds typically being dual orexin receptor antagonists (DORAs) or having moderate selectivity for orexin-1.


Input: Structurally, the claimed compounds represent a variation on established DORA SAR themes and translate features of clinical compounds into a pyrazole-based scaffold.

pyrazole


Input: Example 52, the most potent molecule in the application, has similar molecular weight and lipophilicity to suvorexant, the most advanced DORA, with broadly comparable potency in functional assays.

suvorexant


Input: Highly sensitive fluorescent and colorimetric pH sensor based on polyethylenimine-capped silver nanoclusters.

polyethylenimine

silver


Input: Silver nanoclusters capped by hyperbranched polyethylenimine (PEI) have been developed as a highly sensitive fluorescent and colorimetric pH sensor.

Silver

polyethylenimine

PEI


Input: The probe responds rapidly to pH fluctuations and has such absorption characteristics that the color changes from the colorless or a nearly colorless state to a colored state with increasing acidity, so PEI-capped Ag nanoclusters could be used as a color indicator for colorimetric pH detection.

PEI

Ag


Input: Quantitatively, the fluorescence intensity of PEI-capped Ag nanoclusters exhibits a linear fashion over the pH range of 5. 02-7. 96 and increases by around 10-fold approximately with greater fluorescence at higher pH values.

PEI

Ag


Input: The repulsion development and conformational change of PEI with decreasing pH induce the aggregation of Ag nanoclusters, leading to an obvious color change and fluorescence quenching of Ag nanoclusters at low pH values.

PEI

Ag

Ag


Input: As expected, the pH probe is also sensitive to the different buffer solutions, except for those containing some anions that could react with Ag nanoclusters.

Ag


Input: Besides, the ionic strength of the buffers has a little influence on the pH-responsive behavior.


Input: Our pH sensor with nanoscaled physical dimensions would be a promising candidate in the applications in biological, medical, and pharmaceutical fields.


Input: Multicolor fluorescent semiconducting polymer dots with narrow emissions and high brightness.


Input: Fluorescent semiconducting polymer dots (Pdots) have attracted great interest because of their superior characteristics as fluorescent probes, such as high fluorescence brightness, fast radiative rates, and excellent photostability.


Input: However, currently available Pdots generally exhibit broad emission spectra, which significantly limit their usefulness in many biological applications involving multiplex detections.


Input: Here, we describe the design and development of multicolor narrow emissive Pdots based on different boron dipyrromethene (BODIPY) units.

boron dipyrromethene

BODIPY


Input: BODIPY-containing semiconducting polymers emitting at multiple wavelengths were synthesized and used as precursors for preparing the Pdots, where intraparticle energy transfer led to highly bright, narrow emissions.

BODIPY


Input: The emission full width at half-maximum of the resulting Pdots varies from 40 to 55 nm, which is 1. 5-2 times narrower than those of conventional semiconducting polymer dots.


Input: BODIPY 520 Pdots were about an order of magnitude brighter than commercial Qdot 525 under identical laser excitation conditions.

BODIPY


Input: Fluorescence imaging and flow cytometry experiments indicate that the narrow emissions from these bright Pdots are promising for multiplexed biological detections.


Input: Characterization of arsenic induced cytotoxicity in liver with stress in erythrocytes and its reversibility with Pleurotus florida lectin.

arsenic


Input: Arsenic is one of the most hazardous substances in the environment known to cause toxicity in multiple organs.

Arsenic


Input: Cell adhesion, morphological alterations, cell proliferation, terminal deoxyuridine triphosphate nick-end labeling (TUNEL) and caspase-3/CPP32 fluorometric protease assay were important biomarkers to assess apoptosis in cells.

deoxyuridine triphosphate


Input: This study aimed to evaluate arsenic-induced apoptosis in the hepatocytes of rat and its protective efficacy with coadministration of ascorbic acid (AA) and Pleurotus florida lectin (PFL) individually.

arsenic

ascorbic acid


Input: Results of the present study also showed that arsenic caused cytotoxicity by elevating morphological alterations, TUNEL-positive nuclei, caspase-3 activity and DNA damage and reducing cell adhesion and cell proliferation in a time-dependent manner.

arsenic


Input: The apoptosis in hepatocytes was reverted to normal value after coadministration of mushroom lectin in arsenic-exposed rat.

arsenic


Input: The study provided significant evidence that PFL has antiapoptotic property against arsenic-induced toxicity.

arsenic


Input: The beneficial effect of PFL was proportional to its duration of exposure.


Input: Retard activities of superoxide dismutase and catalase, enhanced lipid peroxidation as well as protein carbonyl in erythrocytes caused by arsenic could also be maintained toward normalcy by supplementation of AA and PFL.

superoxide

carbonyl

arsenic


Input: These antioxidative effects were exhibited in a time-dependant manner.


Input: In rat, treatment with AA and PFL prevented alteration of plasma enzyme activities caused by arsenic.

arsenic


Input: The results concluded that treatment with PFL has significant role in protecting animals from arsenic-induced erythrocytic damage.

arsenic


Input: This finding might be of therapeutic benefit in people suffering from chronic exposure to arsenic from natural sources, a global problem especially relevant to millions of people on the Indian subcontinent.

arsenic


Input: Control of transcriptional fidelity by active center tuning as derived from RNA polymerase endonuclease reaction.


Input: Precise transcription by cellular RNA polymerase requires the efficient removal of noncognate nucleotide residues that are occasionally incorporated.

nucleotide


Input: Mis-incorporation causes the transcription elongation complex to backtrack, releasing a single strand 3'-RNA segment bearing a noncognate residue, which is hydrolyzed by the active center that carries two Mg (2 +) ions.

Mg (2 +)


Input: However, in most x-ray structures only one Mg (2 +) is present.

Mg (2 +)


Input: This Mg (2 +) is tightly bound to the active center aspartates, creating an inactive stable state.

Mg (2 +)

aspartates


Input: The first residue of the single strand RNA segment in the backtracked transcription elongation complex strongly promotes transcript hydrolytic cleavage by establishing a network of interactions that force a shift of stably bound Mg (2 +) to release some of its aspartate coordination valences for binding to the second Mg (2 +) thus enabling catalysis.

Mg (2 +)

aspartate

Mg (2 +)


Input: Such a rearrangement that we call active center tuning (ACT) occurs when all recognition contacts of the active center-bound RNA segment are established and verified by tolerance to stress.


Input: Transcription factor Gre builds on the ACT mechanism in the same reaction by increasing the retention of the second Mg (2 +) and by activating the attacking water, causing 3000-4000-fold reaction acceleration and strongly reinforcing proofreading.

Mg (2 +)


Input: The unified mechanism for RNA synthesis and degradation by RNA polymerase predicts that ACT also executes NTP selection thereby contributing to high transcription fidelity.


Input: Discovery of 5-benzyl-3-phenyl-4, 5-dihydroisoxazoles and 5-benzyl-3-phenyl-1, 4, 2-dioxazoles as potent firefly luciferase inhibitors.

5-benzyl-3-phenyl-4, 5-dihydroisoxazoles

5-benzyl-3-phenyl-1, 4, 2-dioxazoles


Input: Luciferase reporter assays are commonly used in high-throughput screening methods.


Input: Here, we report new firefly luciferase (FLuc) inhibitors based on 5-benzyl-3-phenyl-4, 5-dihydroisoxazoles and 5-benzyl-3-phenyl-1, 4, 2-dioxazoles, which showed up as " false positives " in a luciferase reporter gene-based assay for nuclear receptor antagonists.

5-benzyl-3-phenyl-4, 5-dihydroisoxazoles

5-benzyl-3-phenyl-1, 4, 2-dioxazoles


Input: The inhibition was shown to be noncompetitive for both natural enzyme substrates (d-luciferin and ATP) and selective to FLuc and proven to arise from a direct interaction between the enzyme and the inhibitor.

d-luciferin

ATP


Input: Of the 63 evaluated compounds, 28 showed significantly better inhibition potency than the well-known inhibitor resveratrol (IC (50) = 59 nM), with five compounds having distinctly subnanomolar IC (50) values.

resveratrol


Input: The most efficient compounds inhibited the luminescence at concentrations lower than (1)/(100) in comparison to resveratrol (lowest IC (50) = 0. 26 nM) and can thus be considered to belong to the most potent FLuc inhibitors reported thus far.

resveratrol


Input: Overall, the novel inhibitors form a unique molecular library for structure-activity relationship (SAR) analyses.


Input: Design and implementation of two-dimensional polymer adsorption models: evaluating the stability of Candida antarctica lipase B/solid-support interfaces by QCM-D.


Input: A two-dimensional model of a solid-supported enzyme catalyst bead is fabricated on a quartz crystal microbalance with dissipation monitoring (QCM-D) sensor to measure in situ interfacial stability and mechanical properties of Candida antarctica Lipase B (CAL B) under varied conditions relating to ring-opening polymerization.

quartz


Input: The model was fabricated using a dual photochemical approach, where poly (methyl methacrylate) (PMMA) thin films were cross-linked by a photoactive benzophenone monolayer and blended cross-linking agent.

poly (methyl methacrylate)

PMMA

benzophenone


Input: This process produces two-dimensional, homogeneous, rigid PMMA layers, which mimic commercial acrylic resins in a QCM-D experiment.

PMMA

acrylic


Input: Adsorption of CAL B to PMMA in QCM-D under varied buffer ionic strengths produces a viscoelastic enzyme surface that becomes more rigid as ionic strength increases.

PMMA


Input: The rigid CAL B/PMMA interface demonstrates up to 20% desorption of enzyme with increasing trace water content.

PMMA


Input: Increased polycaprolactone (PCL) binding at the enzyme surface was also observed, indicating greater PCL affinity for a more hydrated enzyme surface.

polycaprolactone

PCL

PCL


Input: The enzyme layer destabilized with increasing temperature, yielding near complete reversible catalyst desorption in the model.


Input: Effects of the benzimidazole anthelmintic drug flubendazole on rat embryos in vitro.

benzimidazole

flubendazole


Input: Filarial diseases affect millions of people in poverty-stricken areas.


Input: In 2011, an investigation of the potential of flubendazole as a safe, highly efficacious, and field-usable macrofilaricidal drug was begun by Drug for Neglected Diseases initiative.

flubendazole


Input: As part of the preclinical development program, whole embryo culture was used to investigate the potential embryotoxicity of flubendazole and its metabolites, reduced and hydrolyzed flubendazole.

flubendazole

flubendazole


Input: Albendazole was included as a comparator.

Albendazole


Input: Flubendazole and albendazole showed similar potency in affecting rat embryonic development in vitro, inducing retardation of growth and dysmorphogenic effects at concentrations >= 0. 5 mu g/mL.

Flubendazole

albendazole


Input: The head, optic and otic systems, branchial arches and posterior body portion were affected.


Input: Diffuse areas of cell death were seen in various embryonic districts.


Input: The No Observed Effect Level (NOEL) was 0. 25 mu g/mL for both drugs.


Input: Reduced and hydrolyzed flubendazole were less embryotoxic than the parent compound, with NOELs 4-fold and > 40-fold higher than that of flubendazole, respectively.

flubendazole

flubendazole


Input: Effect of pigeon pea (Cajanus cajan L.) on high-fat diet-induced hypercholesterolemia in hamsters.


Input: Obesity is associated with increased systemic and airway oxidative stress, which may result from a combination of adipokine imbalance and antioxidant defenses reduction.


Input: Obesity-mediated oxidative stress plays an important role in the pathogenesis of dyslipidemia, vascular disease, and nonalcoholic hepatic steatosis.


Input: The antidyslipidemic activity of pigeon pea were evaluated by high-fat diet (HFD) hamsters model, in which the level of high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and total triglyceride (TG) were examined.

cholesterol

cholesterol

cholesterol

triglyceride


Input: We found that pigeon pea administration promoted cholesterol converting to bile acid in HFD-induced hamsters, thereby exerting hypolipidemic activity.

cholesterol

bile acid


Input: In the statistical results, pigeon pea significantly increased hepatic carnitine palmitoyltransferase-1 (CPT-1), LDL receptor, and cholesterol 7 alpha-hydroxylase (also known as cytochrome P450 7A1, CYP7A1) expression to attenuate dyslipidemia in HFD-fed hamsters; and markedly elevated antioxidant enzymes in the liver of HFD-induced hamsters, further alleviating lipid peroxidation.

carnitine

cholesterol


Input: These effects may attribute to pigeon pea contained large of unsaturated fatty acids (UFA; C18: 2) and phytosterol (beta-sitosterol, campesterol, and stigmasterol).

unsaturated fatty acids

UFA

phytosterol

beta-sitosterol

campesterol

stigmasterol


Input: Moreover, the effects of pigeon pea on dyslipidemia were greater than beta-sitosterol administration (4%), suggesting that phytosterone in pigeon pea could prevent metabolic syndrome.

beta-sitosterol

phytosterone


Input: Novel treatment options for epilepsy: focus on perampanel.

perampanel


Input: Perampanel is a new chemical entity recently approved in the United States (US) and European Union (EU) as adjunctive treatment of partial-onset seizures with and without secondary generalization in patients with epilepsy aged 12 years and older.

Perampanel


Input: Pharmacological studies suggest that perampanel acts with a new mechanism of action via non-competitive antagonism of the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor of glutamate, the main mediator of excitatory neurotransmission in the central nervous system.

perampanel

alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid

AMPA

glutamate


Input: Perampanel is completely absorbed after oral administration.

Perampanel


Input: The drug is 95% bound to plasma proteins and is extensively metabolized by oxidation followed by glucuronidation.


Input: Perampanel has an elimination half-life of approximately 52-129h, allowing once daily dosing, with peak plasma levels observed 0. 25-2h post-dose.

Perampanel


Input: Randomized placebo-controlled trials of adjunctive treatment have demonstrated that once-daily perampanel doses of 4-12mg/day significantly reduced partial-onset seizure frequency in patients with pharmacoresistant epilepsy along with a favorable tolerability profile.

perampanel


Input: In perampanel pivotal trials, the most frequently reported treatment emergent adverse events (> 10%) included dizziness, somnolence, fatigue and headache.

perampanel


Input: Perampanel therapeutic response was maintained in patients included in the long term open-label extension studies for up to 4 years.

Perampanel


Input: Based on these data, perampanel offers a valuable option in the add-on treatment of partial-onset and secondarily generalized seizures.

perampanel


Input: SAR analysis of novel non-peptidic NPBWR1 (GPR7) antagonists.


Input: In this Letter we report on the advances in our NPBWR1 antagonist program aimed at optimizing the 5-chloro-2-(3, 5-dimethylphenyl)-4-(4-methoxyphenoxy) pyridazin-3 (2H)-one lead molecule previously obtained from a high-throughput screening (HTS)-derived hit.

5-chloro-2-(3, 5-dimethylphenyl)-4-(4-methoxyphenoxy) pyridazin-3 (2H)-one


Input: Synthesis and structure-activity relationships (SAR) studies around the 3, 5-dimethylphenyl and 4-methoxyphenyl regions resulted in the identification of a novel series of non-peptidic submicromolar NPBWR1 antagonists based on a 5-chloro-4-(4-alkoxyphenoxy)-2-(benzyl) pyridazin-3 (2H)-one chemotype.

3, 5-dimethylphenyl

5-chloro-4-(4-alkoxyphenoxy)-2-(benzyl) pyridazin-3 (2H)-one


Input: Amongst them, 5-chloro-2-(9H-fluoren-9-yl)-4-(4-methoxyphenoxy) pyridazin-3 (2H)-one 9h (CYM50769) inhibited NPW activation of NPBWR1 with a submicromolar IC (50), and displayed high selectivity against a broad array of off-targets with pharmaceutical relevance.

5-chloro-2-(9H-fluoren-9-yl)-4-(4-methoxyphenoxy) pyridazin-3 (2H)-one


Input: Our medicinal chemistry study provides innovative non-peptidic selective NPBWR1 antagonists that may enable to clarify the biological role and therapeutic utility of the target receptor in the regulation of feeding behavior, pain, stress, and neuroendocrine function.


Input: Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model.

iodide


Input: A biologically based dose-response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis.

iodide


Input: Model calibrations, carried out by adjusting key model parameters, were used as a technique to evaluate HPT axis adaptations to dietary iodide intake in euthyroid (4. 1-39 micro g iodide/day) and iodide-deficient (0. 31 and 1. 2 micro g iodide/day) conditions.

iodide

iodide

iodide

iodide


Input: Iodide-deficient conditions in both the dam and the pup were described with increased blood flow to the thyroid gland, TSH-mediated increase in thyroidal uptake of iodide and binding of iodide in the thyroid gland (organification), and, in general, reduced thyroid hormone production and metabolism.

Iodide

iodide

iodide

thyroid hormone


Input: Alterations in thyroxine (T4) homeostasis were more apparent than for triiodothyronine (T3).

thyroxine

triiodothyronine


Input: Model-predicted average daily area-under-the-serum-concentration-curve (nM-day) values for T4 at steady state in the dam and pup decreased by 14-15% for the 1. 2 micro g iodide/day iodide-deficient diet and 42-52% for the 0. 31 micro g iodide/day iodide-deficient diet.

iodide

iodide

iodide

iodide


Input: In rat pups that were iodide deficient during gestation and lactation, these decreases in serum T4 levels were associated with declines in thyroid hormone in the fetal brain and a suppression of synaptic responses in the hippocampal region of the brain of the adult offspring (Gilbert et al., 2013).

iodide

thyroid hormone


Input: Perspectives on the reaction force constant.


Input: A synchronous, concerted chemical process is rigorously divided by the reaction force F (R), the negative gradient of V (R), into " reactant " and " product " regions which are dominated by structural changes and an intervening " transition " region which is electronically intensive.


Input: The reaction force constant kappa (R), the second derivative of V (R), is negative throughout the transition region, not just at the nominal transition state, at which kappa (R) has a minimum.


Input: This is consistent with experimental evidence that there is a transition region, not simply a specific point.


Input: We show graphically that significant nonsynchronicity in the process is associated with the development of a maximum of kappa (R) in the transition region, which increases as the process becomes more nonsynchronous.


Input: (We speculate that for a nonconcerted process this maximum is actually positive.) Thus, kappa (R) can serve as an indicator of the level of nonsynchronicity.


Input: Inhibition of matrix metalloproteinase-9 expression by docosahexaenoic acid mediated by heme oxygenase 1 in 12-O-tetradecanoylphorbol-13-acetate-induced MCF-7 human breast cancer cells.

docosahexaenoic acid

heme


Input: Matrix metalloproteinase-9 (MMP-9) plays a crucial role in tumor metastasis.


Input: Previous studies showed that polyunsaturated fatty acids exhibit an anti-cancer effect in various human carcinoma cells, but the effect of docosahexaenoic acid (DHA) and linoleic acid (LA) on metastasis of breast cancer cells is not fully clarified.

polyunsaturated fatty acids

docosahexaenoic acid

DHA

linoleic acid


Input: We studied the anti-metastasis potential of DHA and LA in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells.

DHA

TPA


Input: We found that TPA (100 ng/ml) induced MMP-9 enzyme activity both dose-and time-dependently, and 200 mu M DHA and LA significantly inhibited MMP-9 mRNA and protein expression, enzyme activity, cell migration, and invasion.

TPA

DHA


Input: Treatment with PD98059 (10 mu M), wortmannin (10 mu M), and GF109203X (0. 5 mu M) decreased TPA-induced MMP-9 protein expression and enzyme activity.

wortmannin

TPA


Input: TPA-induced activation of ERK1, Akt, and PKC delta was attenuated by DHA, whereas LA attenuated only ERK1 activation.

TPA

DHA


Input: GF109203X also suppressed ERK1 activation.


Input: EMSA showed that DHA, LA, PD98059, and wortmannin decreased TPA-induced NF-kappa B and AP-1 DNA-binding activity.

DHA

wortmannin

TPA


Input: Furthermore, DHA rather than LA dose-dependently increased HO-1 expression.

DHA


Input: HO-1 siRNA alleviated the inhibition by DHA of TPA-induced MMP-9 protein expression and enzyme activity in MCF-7 cells, and HO-1 knockdown reversed the DHA inhibition of cell migration.

DHA

TPA

DHA


Input: These results suggest that DHA and LA have both similar and divergent signaling pathways in the suppression of TPA-induced MCF-7 metastasis.

DHA

TPA


Input: Calculation of wave-functions with frozen orbitals in mixed quantum mechanics/molecular mechanics methods.


Input: II.


Input: Application of the local basis equation.


Input: The application of the local basis equation (Ferenczy and Adams, J. Chem. Phys. 2009, 130, 134108) in mixed quantum mechanics/molecular mechanics (QM/MM) and quantum mechanics/quantum mechanics (QM/QM) methods is investigated.


Input: This equation is suitable to derive local basis nonorthogonal orbitals that minimize the energy of the system and it exhibits good convergence properties in a self-consistent field solution.


Input: These features make the equation appropriate to be used in mixed QM/MM and QM/QM methods to optimize orbitals in the field of frozen localized orbitals connecting the subsystems.


Input: Calculations performed for several properties in divers systems show that the method is robust with various choices of the frozen orbitals and frontier atom properties.


Input: With appropriate basis set assignment, it gives results equivalent with those of a related approach [G. G. Ferenczy previous paper in this issue] using the Huzinaga equation.


Input: Thus, the local basis equation can be used in mixed QM/MM methods with small size quantum subsystems to calculate properties in good agreement with reference Hartree-Fock-Roothaan results.


Input: It is shown that bond charges are not necessary when the local basis equation is applied, although they are required for the self-consistent field solution of the Huzinaga equation based method.


Input: Conversely, the deformation of the wave-function near to the boundary is observed without bond charges and this has a significant effect on deprotonation energies but a less pronounced effect when the total charge of the system is conserved.


Input: The local basis equation can also be used to define a two layer quantum system with nonorthogonal localized orbitals surrounding the central delocalized quantum subsystem.


Input: Materials for the active layer of organic photovoltaics: ternary solar cell approach.


Input: Power conversion efficiencies in excess of 7% have been achieved with bulk heterojunction (BHJ)-type organic solar cells using two components: p-and n-doped materials.


Input: The energy level and absorption profile of the active layer can be tuned by introduction of an additional component.


Input: Careful design of the additional component is required to achieve optimal panchromatic absorption, suitable energy-level offset, balanced electron and hole mobility, and good light-harvesting efficiency.


Input: This article reviews the recent progress on ternary organic photovoltaic systems, including polymer/small molecule/functional fullerene, polymer/polymer/functional fullerene, small molecule/small molecule/functional fullerene, polymer/functional fullerene I/functional fullerene II, and polymer/quantum dot or metal/functional fullerene systems.

fullerene

fullerene

fullerene

fullerene

fullerene

fullerene


Input: Cell wounding activates phospholipase D in primary mouse keratinocytes.


Input: Plasma membrane disruptions occur in mechanically active tissues such as the epidermis and can lead to cell death if the damage remains unrepaired.


Input: Repair occurs through fusion of vesicle patches to the damaged membrane region.


Input: The enzyme phospholipase D (PLD) is involved in membrane traffickiing; therefore, the role of PLD in membrane repair was investigated.


Input: Generation of membrane disruptions by lifting epidermal keratinocytes from the substratum induced PLD activation, whereas removal of cells from the substratum via trypsinization had no effect.


Input: Pretreatment with 1, 25-dihydroxyvitamin D 3, previously shown to increase PLD1 expression and activity, had no effect on, and a PLD2-selective (but not a PLD1-selective) inhibitor decreased, cell lifting-induced PLD activation, suggesting PLD2 as the isoform activated.

1, 25-dihydroxyvitamin D 3


Input: PLD2 interacts functionally with the glycerol channel aquaporin-3 (AQP3) to produce phosphatidylglycerol (PG); however, wounding resulted in decreased PG production, suggesting a potential PG deficiency in wounded cells.

glycerol

phosphatidylglycerol


Input: Cell lifting-induced PLD activation was transient, consistent with a possible role in membrane repair, and PLD inhibitors inhibited membrane resealing upon laser injury.


Input: In an in vivo full-thickness mouse skin wound model, PG accelerated wound healing.


Input: These results suggest that PLD and the PLD2/AQP3 signaling module may be involved in membrane repair and wound healing.


Input: Bone marrow NR4A expression is not a dominant factor in the development of atherosclerosis or macrophage polarization in mice.


Input: The formation of the atherosclerotic lesion is a complex process influenced by an array of inflammatory and lipid metabolism pathways.


Input: We previously demonstrated that NR4A nuclear receptors are highly induced in macrophages in response to inflammatory stimuli and modulate the expression of genes linked to inflammation in vitro.


Input: Here we used mouse genetic models to assess the impact of NR4A expression on atherosclerosis development and macrophage polarization.


Input: Transplantation of wild-type, Nur77-/-, or Nor1-/-null hematopoetic precursors into LDL receptor (LDLR)-/-recipient mice led to comparable development of atherosclerotic lesions after high-cholesterol diet.

cholesterol


Input: We also observed comparable induction of genes linked to M1 and M2 responses in wild-type and Nur77-null macrophages in response to lipopolysaccharides and interleukin (IL)-4, respectively.


Input: In contrast, activation of the nuclear receptor liver X receptor (LXR) strongly suppressed M1 responses, and ablation of signal transductor and activator of transcription 6 (STAT6) strongly suppressed M2 responses.


Input: Recent studies have suggested that alterations in levels of Ly6C (lo) monocytes may be a contributor to inflammation and atherosclerosis.


Input: In our study, loss of Nur77, but not Nor1, was associated with decreased abundance of Ly6C (lo) monocytes, but this change was not correlated with atherosclerotic lesion development.


Input: Collectively, our results suggest that alterations in the Ly6C (lo) monocyte population and bone marrow NR4A expression do not play dominant roles in macrophage polarization or the development of atherosclerosis in mice.


Input: Visualizing the perturbation of cellular cyclic di-GMP levels in bacterial cells.

cyclic di-GMP


Input: Cyclic di-GMP (c-di-GMP) has emerged as a prominent intracellular messenger that coordinates biofilm formation and pathogenicity in many bacterial species.

Cyclic di-GMP

c-di-GMP


Input: Developing genetically encoded biosensors for c-di-GMP will help us understand how bacterial cells respond to environmental changes via the modulation of cellular c-di-GMP levels.

c-di-GMP

c-di-GMP


Input: Here we report the design of two genetically encoded c-di-GMP fluorescent biosensors with complementary dynamic ranges.

c-di-GMP


Input: By using the biosensors, we found that several compounds known to promote biofilm dispersal trigger a decline in c-di-GMP levels in Escherichia coli cells.

c-di-GMP


Input: In contrast, cellular c-di-GMP levels were elevated when the bacterial cells were treated with subinhibitory concentrations of biofilm-promoting antibiotics.

c-di-GMP


Input: The biosensors also revealed that E. coli cells engulfed by macrophages exhibit lower c-di-GMP levels, most likely as a response to the enormous pressures of survival during phagocytosis.

c-di-GMP


Input: On the azo/hydrazo equilibrium in Sudan I azo dye derivatives.

azo

hydrazo

Sudan I azo


Input: In this study, Raman, infrared, UV/vis, NMR, and single crystal X-ray diffraction spectroscopies are used to elucidate the tautomeric equilibrium of azo dyes derived from 1-phenyl-azo-2-naphthol (Sudan I).

azo

Sudan I


Input: A new crystallographic structure is described for Sudan I, revealing the presence of intramolecular hydrogen bonds and supramolecular interactions, such as the unconventional C-H... O hydrogen bond type, pi-stacking, and charge-dipole interactions.

Sudan I

hydrogen

C-H

O hydrogen


Input: All of these weak intermolecular interactions play a role in the stability of the crystalline structure.


Input: Theoretical calculations are also reported for geometries, energy, and spectroscopic properties.


Input: The predicted spectra are in accordance with the experiments carried out in the solid state and in solution of dichloromethane, carbon tetrachloride, and chloroform, suggesting the hydrazo form as the preferable tautomer in gas and condensate phases for Sudan I and its derivatives.

dichloromethane

carbon tetrachloride

chloroform

hydrazo

Sudan I


Input: Stereoselective Rh2 (S-IBAZ) 4-catalyzed cyclopropanation of alkenes, alkynes, and allenes: asymmetric synthesis of diacceptor cyclopropylphosphonates and alkylidenecyclopropanes.

Rh2 (S-IBAZ) 4

alkenes

alkynes

allenes

cyclopropylphosphonates

alkylidenecyclopropanes


Input: A mild and highly stereoselective rhodium (II)-catalyzed cyclopropanation of alkenes, alkynes, and allenes with diacceptor diazo compounds is reported.

rhodium (II)

alkenes

alkynes

allenes

diazo


Input: Using the phosphonate moiety as an efficient trans-directing group, the first catalytic asymmetric route to diacceptor cycloprop (en) ylphosphonates was developed by employing an alpha-cyano diazophosphonate and Rh (2) (S-IBAZ) (4) as chiral catalyst.

phosphonate

cycloprop (en) ylphosphonates

alpha-cyano diazophosphonate

Rh (2) (S-IBAZ) (4)


Input: The isosteric character of phosphonic and carboxylic acid derivatives allowed the alternative use of an alpha-cyano diazo ester in the process, leading to alpha-cyano cycloprop (en) ylcarboxylates in high yields and stereoselectivities.

phosphonic and carboxylic acid

alpha-cyano diazo ester

alpha-cyano cycloprop (en) ylcarboxylates


Input: Taking advantage of the particular reactivity of the cyanocarbene intermediates involved in this system, the scope of compatible substrates could be extended to substituted allenes, leading to the development of the first catalytic enantioselective method for the synthesis of diacceptor alkylidenecyclopropanes.

cyanocarbene

allenes

alkylidenecyclopropanes


Input: Discovery of thiazolidine-2, 4-dione/biphenylcarbonitrile hybrid as dual PPAR alpha/gamma modulator with antidiabetic effect: in vitro, in silico and in vivo approaches.

thiazolidine-2, 4-dione

biphenylcarbonitrile


Input: A small series of thiazolidine-2, 4-dione and barbituric acid derivatives 1-4 was prepared using a short synthetic route, and all compounds were characterized by elemental analysis, mass spectrometry, and NMR ((1) H, (13) C) spectroscopy.

thiazolidine-2, 4-dione

barbituric acid

(1) H

(13) C


Input: Their in vitro relative expression of peroxisome proliferator-activated receptor alpha and peroxisome proliferator-activated receptor gamma was evaluated.


Input: Compound 1 showed an increase in the mRNA expression of both peroxisome proliferator-activated receptor isoforms, as well as the GLUT-4 levels.


Input: The antidiabetic activity of compound 1 was determined at 50 mg/kg single dose using a non-insulin-dependent diabetes mellitus rat model.


Input: The results indicated a significant decrease in plasma glucose levels.

glucose


Input: Additionally, we performed a molecular docking of compound 1 into the ligand binding pocket of peroxisome proliferator-activated receptor alpha and peroxisome proliferator-activated receptor gamma.


Input: In these binding models, compound 1 may bind into the active site of both isoforms showing important short contacts with the peroxisome proliferator-activated receptor gamma residues: Tyr 473, His 449, Ser 289, His 323; and peroxisome proliferator-activated receptor alpha residues: Tyr 464, His 440, Ser 280 and Tyr 314.

Tyr

His

Ser

His

Tyr

His

Ser

Tyr


Input: Anti-diabetic property of Tinospora cordifolia and its active compound is mediated through the expression of Glut-4 in L6 myotubes.


Input: Tinospora cordifolia is a well reported plant possessing numerous medicinal values including anti-diabetic property.


Input: Aim of the present study is to study the mechanism of action of Tinospora cordifolia and its active compound in differentiated myocytes, L6 cells.


Input: Key marker of diabetes in cells is the insulin dependent glucose transporter-4 (Glut-4) which also responds to exogenous chemicals, and is over expressed up to 5-and 4-fold, by Tinospora cordifolia and palmatine, respectively.

glucose

palmatine


Input: Next to Glut-4, the predominant protein influencing glucose metabolism is PPAR alpha and gamma whose expressions were also positively modulated.

glucose


Input: Further, the inhibitors of insulin pathway prevented glucose uptake mediated by Tinospora cordifolia and palmatine which shows that the activity is majorly mediated through insulin pathway.

glucose

palmatine


Input: Dissolution of tablet-in-tablet formulations studied with ATR-FTIR spectroscopic imaging.


Input: This work uses ATR-FTIR spectroscopic imaging to study the dissolution of delayed release and pH resistant compressed coating pharmaceutical tablets.


Input: Tablets with an inner core and outer shell were constructed using a custom designed compaction cell.


Input: The core of the delayed release tablets consisted of hydroxypropyl methylcellulose (HPMC) and caffeine.

hydroxypropyl

caffeine


Input: The shell consisted of microcrystalline cellulose (MCC) and glucose.

glucose


Input: The core of the pH resistant formulations was an ibuprofen and PEG melt and the shell was constructed from HPMC and a basic buffer.

ibuprofen

PEG


Input: UV/vis spectroscopy was used to monitor the lag-time of drug release and visible optical video imaging was used as a complementary imaging technique with a larger field of view.


Input: Two delayed release mechanisms were established.


Input: For tablets with soluble shell sections, lag-time was dependent upon rapid shell dissolution.


Input: For tablets with less soluble shells, the lag-time was controlled by the rate of dissolution medium ingress through the shell and the subsequent expansion of the wet HPMC core.


Input: The pH resistant formulations prevented crystallization of the ibuprofen in the core during dissolution despite an acidic dissolution medium.

ibuprofen


Input: FTIR imaging produced important information about the physical and chemical processes occurring at the interface between tablet sections during dissolution.


Input: Study of the recrystallization in coated pellets-Effect of coating on API crystallinity.


Input: Coated diltiazem hydrochloride-containing pellets were prepared using the solution layering technique.

diltiazem hydrochloride


Input: Unusual thermal behavior was detected with differential scanning calorimetry (DSC) and its source was determined using thermogravimetry (TG), X-ray powder diffraction (XRPD) and hot-stage microscopy.


Input: The coated pellets contained diltiazem hydrochloride both in crystalline and amorphous form.

diltiazem hydrochloride


Input: Crystallization occurs on heat treatment causing an exothermic peak on the DSC curves that only appears in pellets containing both diltiazem hydrochloride and the coating.

diltiazem hydrochloride


Input: Results indicate that the amorphous fraction is situated in the coating layer.


Input: The migration of drugs into the coating layer can cause changes in its degree of crystallinity.


Input: Polymeric coating materials should therefore be investigated as possible crystallization inhibitors.


Input: Substituted phenyl groups improve the pharmacokinetic profile and anti-inflammatory effect of urea-based soluble epoxide hydrolase inhibitors in murine models.

phenyl

urea

epoxide


Input: Soluble epoxide hydrolase inhibitors (sEHIs) are anti-inflammatory, analgesic, anti-hypertensive, cardio-and renal-protective in multiple animal models.

epoxide


Input: However, the earlier adamantyl-containing urea-based inhibitors are rapidly metabolized.

adamantyl

urea


Input: Therefore, new potent inhibitors with the adamantyl group replaced by a substituted phenyl group were synthesized to presumptively offer better pharmacokinetic (PK) properties.

adamantyl

phenyl


Input: Here we describe the improved PK profile of these inhibitors and the anti-inflammatory effect of the most promising one in a murine model.


Input: The PK profiles of inhibitors were determined following p. o. administration and serial bleeding in mice.


Input: The anti-inflammatory effect of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), the most promising inhibitor among the five sEHIs tested, was investigated in a lipopolysaccharide (LPS)-challenged murine model.

1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea

TPPU


Input: The earlier broadly-used adamantyl-containing sEHI, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), was used for comparison.

adamantyl

trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid

t-AUCB


Input: Compared with the earlier adamantyl-containing urea-based inhibitors, substituted phenyl-containing urea-based inhibitors afford more favorable PK properties, such as higher Cmaxs, larger AUCs and longer t1/2s, which, as expected, show more stable metabolic stability.

adamantyl

urea

phenyl

urea


Input: Moreover, oral administration of TPPU dramatically reversed the shifts caused by LPS-challenge in plasma levels of inflammatory cytokines, epoxides and corresponding diols, which is more potent than t-AUCB.

TPPU

epoxides

t-AUCB


Input: The substituted phenyl-containing sEHIs are more metabolically stable than those with adamantyl group, resulting in more potent efficacy in vivo.

phenyl

adamantyl


Input: This indicates a new strategy for development of sEHIs for further study toward clinical trials.


Input: The oral cavity as a biological barrier system: Design of an advanced buccal in vitro permeability model.


Input: An important area for future research lies in finding a drug delivery system across or into the oral mucosa.


Input: However, to design such systems, simplified biological models are necessary so that the mechanisms and/or interactions of interest can readily be studied.


Input: The oral epithelium is covered by a complex mucus layer, which enables exchange of nutrients and provides lubrication.


Input: However, it has been demonstrated that mucus has an impact on the mobility of nanoparticles and drug molecules.


Input: Thus, we aimed to develop an advanced buccal in vitro model for studying transport of nanoparticles, taking the mucus layer into account.


Input: First, animal mucins (porcine gastric, bovine submaxillary) were compared with natural human mucin regarding chemical and morphological structure.


Input: Second, an " external " mucus layer was prepared by a film method and deposited onto an oral cell line (TR 146), cultured on transwells (R).


Input: Adherence of the mucin fibers was evaluated and the viability of the model was assessed.


Input: Nanoparticle transport studies were performed with this advanced in vitro model and an ex vivo diffusion system.


Input: The results revealed that porcine mucin is most similar to human natural mucin in chemical structure and morphology.


Input: Both the bovine and porcine mucin fibers adhered onto the oral cells: Due to the different morphology of bovine mucin, the viability of the oral cells decreased, whereas porcine mucin maintained the viability of the model for more than 48h.


Input: Comparison of in vitro data with ex vivo data suggested reliability of the advanced buccal in vitro model.


Input: Additionally, it was demonstrated that the mucus layer in the oral cavity also acts as a strong barrier for the mobility of nanoparticles.


Input: Antioxidant activities of thiosemicarbazones from substituted benzaldehydes and N-(tetra-O-acetyl-beta-D-galactopyranosyl) thiosemicarbazide.

thiosemicarbazones

benzaldehydes

N-(tetra-O-acetyl-beta-D-galactopyranosyl) thiosemicarbazide


Input: Reaction of N-(2, 3, 4, 6-tetra-O-acetyl-beta-d-galactopyranosyl) thiosemicarbazide and different substituted benzaldehydes gave some new substituted benzaldehyde N-(2, 3, 4, 6-tetra-O-acetyl-beta-d-galactopyranosyl) thiosemicarbazones.

N-(2, 3, 4, 6-tetra-O-acetyl-beta-d-galactopyranosyl) thiosemicarbazide

benzaldehydes

benzaldehyde N-(2, 3, 4, 6-tetra-O-acetyl-beta-d-galactopyranosyl) thiosemicarbazones


Input: The reaction was performed using conventional and microwave-assisted heating methods.


Input: The structures of thiosemicarbazones were confirmed by spectroscopic (IR, (1) H NMR, (13) C NMR and ESI-MS) method.

thiosemicarbazones

(1) H

(13) C


Input: The antioxidant activity of these thiosemicarbazones was evaluated in vitro and in vivo, and it' s shown that some of these compounds had significant antioxidant activity.

thiosemicarbazones


Input: Amongst the compounds screened for antioxidant activity, thiosemicarbazones 4a, 4b and 4c showed good antioxidant activity on DPPH.

thiosemicarbazones

DPPH


Input: The compounds 4g, 4i, 4l caused significant elevation of SOD activity and 4e, 4g, 4i, 4l had higher catalase activity, and only compounds 4c and 4f expressed the GSH-Px activity.

GSH


Input: Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer' s disease.

cholesterol


Input: The disturbances of the cholesterol synthesis and metabolism described in Alzheimer' s disease (AD) may be both a consequence of the neurodegenerative process and a contributor to the pathogenesis.

cholesterol


Input: These putative relationships and their underlying mechanisms are not well understood.


Input: The aim of this study was to evaluate the relationship between the cerebral and extracerebral cholesterol synthesis and metabolism, and the AD pathology as reflected by CSF markers in humans.

cholesterol


Input: We evaluated the relationships between the plasma and the cerebrospinal fluid (CSF) concentrations of cholesterol, the cholesterol precursors lanosterol, lathosterol and desmosterol, and the cholesterol elimination products 24S-hydroxycholesterol and 27-hydroxycholesterol, and the CSF markers for AD pathology A beta 1-42 and p-tau181 in 86 subjects with normal cognition and in 107 AD patients.

cholesterol

cholesterol

lanosterol

lathosterol

desmosterol

cholesterol


Input: CSF desmosterol, cholesterol and 24S-hydroxycholesterol in the AD group, and CSF 24S-hydroxycholesterol in the control group correlated with the p-tau181 levels.

desmosterol

cholesterol


Input: Neither CSF nor plasma concentrations of the included compounds correlated with the CSF A beta 1-42 levels.


Input: In multivariate regression tests including age, gender, albumin ratio, number of the APOE epsilon 4 alleles, and diagnosis, p-tau181 levels independently predicted the CSF desmosterol, cholesterol and 24S-hydroxycholesterol concentrations.

desmosterol

cholesterol


Input: The associations remained significant for CSF cholesterol and 24S-hydroxycholesterol when analyses were separately performed in the AD group.

cholesterol


Input: The results suggest that alterations of CNS cholesterol de novo genesis and metabolism are related to neurodegeneration and in particular to the cerebral accumulation of phosphorylated tau.

cholesterol


Input: Toxic effects of lead exposure in Wistar rats: involvement of oxidative stress and the beneficial role of edible jute (Corchorus olitorius) leaves.


Input: Lead (Pb) is considered to be a multi-target toxicant.

Pb


Input: The present study was undertaken to evaluate the protective effect of aqueous extract of Corchorus olitorius leaves against Pb-acetate induced toxic manifestation in blood, liver, kidney, brain and heart of Wistar rats.

Pb-acetate


Input: The Pb-acetate (5mg/kg body weight) treated rats exhibited a significant inhibition of co-enzymes Q, antioxidant enzymes and reduced glutathione levels in the tissues.

Pb-acetate

co-enzymes Q

glutathione


Input: In addition, the extent of lipid peroxidation, DNA fragmentation and haematological parameters were significantly altered in the Pb-acetate treated rats as compared to control.

Pb-acetate


Input: Simultaneous administration of test extract (25, 50 and 100mg/kg body weight), could significantly restore the biochemical and haematological parameters near to the normal status through antioxidant activity and/or by preventing bioaccumulation of Pb within the tissues of experimental rats.

Pb


Input: Presence of substantial quantity of phenolics and flavonoids in the extract may be responsible for the observed protective role against Pb-intoxication.

phenolics

flavonoids

Pb


Input: Chemical composition and anticancer activity of essential oils of Mediterranean sage (Salvia officinalis L.) grown in different environmental conditions.


Input: Salvia officinalis L. can be found worldwide and its leaves are commonly used as ingredient in food industry.


Input: Sage essential oil is applied in the treatment of a range of diseases and has been shown to possess different biological activities.


Input: The objectives of our research were to study the effects of environment on crop, chemical composition and anticancer activity on S. officinalis essential oil.


Input: Sage was cultivated at eighteen experimental sites in south-central Italy (Molise) in different growing environments.


Input: The essential oils (S1-S18), extracted by hydrodistillation, were analyzed by GC and CG/MS.


Input: Results show that the main components were alpha-thujone, camphor, borneol, gamma-muurolene and sclareol for all the samples, but the percentages of these compounds varied depending on environmental factors such as altitude, water availability and pedo-climatic conditions.

alpha-thujone

camphor

borneol

gamma-muurolene

sclareol


Input: The growth-inhibitory and proapoptotic effects of the eighteen sage essential oils were evaluated in three human melanoma cell lines, A375, M14, and A2058.


Input: Alkyl esters of gallic acid as anticancer agents: a review.

Alkyl esters

gallic acid


Input: The current review presents the antitumoral properties of gallic acid and its ester derivatives.

gallic acid

ester


Input: Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid, and that this activity is related to their hydrophobic moiety.

alkyl esters

gallic acid


Input: All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type.


Input: The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer, either alone or in combination with other antitumor drugs to potentiate their effects.


Input: Chlamydophila pneumoniae endonuclease IV prefers to remove mismatched 3' ribonucleotides: implication in proofreading mismatched 3'-terminal nucleotides in short-patch repair synthesis.

3' ribonucleotides

nucleotides


Input: DNA polymerase I (DNApolI) catalyzes DNA synthesis during Okazaki fragment maturation, base excision repair, and nucleotide excision repair.

nucleotide


Input: Some bacterial DNApolIs are deficient in 3'-5' exonuclease, which is required for removing an incorrectly incorporated 3'-terminal nucleotide during DNA elongation by DNA polymerase activity.

nucleotide


Input: The key amino acid residues in the exonuclease center of Chlamydophila pneumoniae DNApolI (CpDNApolI) are naturally mutated, resulting in the loss of 3'-5' exonuclease.

amino acid


Input: Hence, the manner by which CpDNApolI proofreads the incorrectly incorporated nucleotide during DNA synthesis warrants clarification.

nucleotide


Input: C. pneumoniae encodes three 3'-5' exonuclease activities: one endonuclease IV and two homologs of the epsilon subunit of replicative DNA polymerase III.


Input: The three proteins were biochemically characterized using single-and double-stranded DNA substrate.


Input: Among them, C. pneumoniae endonuclease IV (CpendoIV) possesses 3'-5' exonuclease activity that prefers to remove mismatched 3'-terminal nucleotides in the nick, gap, and 3' recess of a double-stranded DNA (dsDNA).

nucleotides


Input: Finally, we reconstituted the proofreading reaction of the mismatched 3'-terminal nucleotide using the dsDNA with a nick or 3' recess as substrate.

nucleotide


Input: Upon proofreading of the mismatched 3'-terminal nucleotide by CpendoIV, CpDNApolI can correctly reincorporate the matched nucleotide and the nick is further sealed by DNA ligase.

nucleotide

nucleotide


Input: Based on our biochemical results, we proposed that CpendoIV was responsible for proofreading the replication errors of CpDNApolI.


Input: Nuclear receptor CAR specifically activates the two-pore K + channel Kcnk1 gene in male mouse livers, which attenuates phenobarbital-induced hepatic hyperplasia.

K +

phenobarbital


Input: KCNK1, a member of the family of two-pore K (+) ion channels, is specifically induced in the livers of male mice after phenobarbital treatment.

K (+)

phenobarbital


Input: Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized KCNK1 as a phenobarbital-inducible antihyperplasia factor.

phenobarbital


Input: Upon activation by phenobarbital, nuclear receptor CAR binds the 97-bp response element (-2441/-2345) within the Kcnk1 promoter.

phenobarbital