Input: The finely regulating well-defined functional polymeric nanocarriers for anti-tumor immunotherapy.


Input: Cancer is the second leading cause of death around the world.


Input: Cancer may be induced by viral infection (EBV, HBV and HPV), bacterial infection (Helicobacter pylori), carcinogen, ultraviolet (UV) radiation exposure, and genetic mutation.


Input: Tumor can be suppressed by traditional surgery, radiotherapy, and/or chemotherapy with devastating side effects and very poor quality of postoperative life.


Input: The therapeutic index has been further promoted by the newly developed nanomedicine.


Input: However, the disseminated tumor cells can result in micrometastases.


Input: So the cancer can just be supresssed but not cured by these ways.


Input: Fortunately, the developments of immunology have successfully improved many disciplines with special effort on oncology.


Input: Various immune cells including B cells, T-lymphocytes (TL), natural killer (NK) cells, dendritic cells (DCs), macrophages, and polymorphonuclear leukocytes are recruited to the tumor.


Input: These immune cells can recognize, eliminate, and protect the body from viral, bacterial infections, and the transformed cells (pre-cancer cell) extension.


Input: The modification of host immune system, and/or the utilization of components of the immune system for cancer treatment are called immunotherapy.


Input: The immunotherapy is not only to target and kill tumor cells in aspecific manner, but also to alert the immune system to eradicate the disseminated tumor cells present in the blood circulation and micro-metastases in remote organs.


Input: Herein, the development of immunology, cancer immunotherapy, tumor immuno escape was introduced firstly.


Input: Then the correlations between host, the tumor and the nano particulates were proposed.


Input: And how to improve the cancer immunotherapy by finely nanocarrier' s engineering (nanoimmunotherapy) was systematically illustrated with special focus on the unique pathology of tumor microenviroments and properties of immuno cells.


Input: A new sesquiterpene lactone from Salvia plebeia.

sesquiterpene lactone


Input: A new eudesmanolide, 1 alpha-acetoxy-8 alpha, 9 beta-dihydroxy-2-oxo-eudesman-3, 7 (11)-dien-8, 12-olide (2), together with a known eudesmanolide, 1 alpha-acetoxy-8 alpha-hydroxy-2-oxo-eudesman-3, 7 (11)-dien-8, 12-olide (1), and a known flavone, 4', 5, 7-trihydroxy-6-methoxyflavone (3), was isolated from the plant of Salvia plebeia.

eudesmanolide

1 alpha-acetoxy-8 alpha, 9 beta-dihydroxy-2-oxo-eudesman-3, 7 (11)-dien-8, 12-olide

eudesmanolide

1 alpha-acetoxy-8 alpha-hydroxy-2-oxo-eudesman-3, 7 (11)-dien-8, 12-olide

flavone

4', 5, 7-trihydroxy-6-methoxyflavone


Input: Three compounds were structurally elucidated by spectroscopic and chemical methods.


Input: The role of endothelin system in cardiovascular disease and the potential therapeutic perspectives of its inhibition.


Input: Since its identification in 1988 and the recognition of its primary role as a potent vasoconstrictor, endothelin has been extensively studied and is now considered as a ubiquitous protein, involved in important aspects of human homeostasis as well as in several pathophysiological pathways, mostly associated with cardiovascular disease.


Input: From an evolutionary point of view, endothelin consists a primitive molecule with the rare characteristic of being exactly the same in all mammals, thus permitting scientists to perform experiments in animals and doing predictions for humans.


Input: The understanding of its contribution to the genesis, evolution and maintenance of disease through activation of special receptor subtypes has led to the development of both selective and unselective receptor antagonists.


Input: Despite the disappointing results of these antagonists in the field of heart failure, almost from the initial animal trials of bosentan, a dual endothelin receptor antagonist, in pulmonary arterial hypertension, it has been demonstrated that the drug leads at least to hemodynamic and clinical improvement of the patients, thus receiving official approval for the management of this rare but eventually lethal disease.

bosentan


Input: Resistant hypertension is another area where endothelin receptor blockers might potentially play a role, while the pathophysiological role of endothelin in atherosclerotic coronary artery disease is well-established and the relative research goes on.


Input: The main goal of this review is to describe the endothelin system and mostly to enlighten its role in pathophysiologic pathways, as well to state the relative research in the various fields of cardiovascular disease and also highlight its prognostic significance wherever there exists one.


Input: Asymmetric Dimethylarginine (ADMA): A Promising Biomarker for Cardiovascular Disease?

Asymmetric Dimethylarginine

ADMA


Input: Asymmetric Dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) production.

Asymmetric Dimethylarginine

ADMA

nitric oxide

NO


Input: ADMA is generated from methylation of arginine residues by protein arginine methyltransferases (PRMTs) and subsequent proteolysis, while its elimination is achieved mainly by degradation with dimethylarginine dimethylaminohydrolase (DDAH).

ADMA

arginine

arginine

dimethylarginine


Input: Oxidative stress, endothelial nitric oxide synthase (eNOS) inhibition, eNOS uncoupling, inflammation and shear stress play a pivotal role in ADMA pathophysiology by managing PRMT/DDAH expression and NO synthesis and leading to a common result-endothelial dysfunction.

nitric oxide

ADMA

NO


Input: Endothelial dysfunction seems to be the common finding in studies investigating the role of ADMA in cardiovascular disease (CVD).

ADMA


Input: High-performance liquid chromatography (HPLC), mass spectrometry (MS) and enzyme-linked immunosorbent assay (ELISA) are the existing methods for ADMA quantification.

ADMA


Input: However, none of them fulfils all the criteria to be characterized as " gold standard ".


Input: ADMA is significantly associated with risk factors for CVD and almost with every disease of the cardiovascular system; showing an independent, strong prognostic value for mortality and future cardiovascular events.

ADMA


Input: This article aims to review the current knowledge about ADMA biology and metabolism, pathophysiological mechanisms implicating ADMA in CVD, methods for the determination of ADMA and its association with CVD risk factors and established CVDs.

ADMA

ADMA

ADMA


Input: Chitosan-thioglycolic Acid as a versatile antimicrobial agent.

thioglycolic Acid


Input: As functionalized chitosans hold great potential for the development of effective and broad-spectrum antibiotics, representative chitosan derivatives were tested for antimicrobial activity in neutral media: trimethyl chitosan (TMC), carboxy-methyl chitosan (CMC), and chitosan-thioglycolic acid (TGA; medium molecular weight: MMW-TGA; low molecular weight: LMW-TGA).

trimethyl

carboxy-methyl

thioglycolic acid

TGA

TGA

TGA


Input: Colony forming assays indicated that LMW-TGA displayed superior antimicrobial activity over the other derivatives tested: a 30 min incubation killed 100% Streptococcus sobrinus (Gram-positive bacteria) and reduced colony counts by 99. 99% in Neisseria subflava (Gram-negative bacteria) and 99. 97% in Candida albicans (fungi).

TGA


Input: To elucidate LMW-TGA effects at the cellular level, microscopic studies were performed.

TGA


Input: Use of fluorescein isothiocyanate (FITC)-labeled chitosan derivates in confocal microscopy showed that LMW-TGA attaches to microbial cell walls, while transmission electron microscopy indicated that this derivative severely affects cell wall integrity and intracellular ultrastructure in all species tested.

fluorescein isothiocyanate

FITC

TGA


Input: We therefore propose LMW-TGA as a promising and effective broad-band antimicrobial compound.

TGA


Input: New surface-enhanced Raman scattering platforms: composite calcium carbonate microspheres coated with astralen and silver nanoparticles.

calcium carbonate

silver


Input: Surface-enhanced Raman scattering (SERS) microspectroscopy is a very promising label-free, noncontact, and nondestructive method for real-time monitoring of extracellular matrix (ECM) development and cell integration in scaffolds for tissue engineering.


Input: Here, we prepare a new type of micrometer-sized SERS substrate, core-shell microparticles composed of solid carbonate core coated with silver nanoparticles and polyhedral multishell fullerene-like structure, astralen.

carbonate

silver

fullerene


Input: Astralen has been assembled with polyallylamine hydrochloride (PAH) by the layer-by-layer manner followed by Ag nanoparticle formation by means of a silver mirror reaction, giving the final structure of composite particles CaCO3 (PAH/astralen) x/Ag, where x = 1-3.

polyallylamine hydrochloride

PAH

Ag

silver

PAH

Ag


Input: The components of the microparticle carry multiple functionalities: (i) an easy identification by Raman imaging (photostable astralen) and (ii) SERS due to a rough surface of Ag nanoparticles.

Ag


Input: A combination of Ag and astralen nanoparticles provides an enhancement of astralen Raman signal by more than 1 order of magnitude.

Ag


Input: Raman signals of commonly used scaffold components such as polylactide and polyvinyl alcohol as well as ECM component (hyaluronic acid) are significantly enhanced.

polylactide

polyvinyl alcohol


Input: Thus, we demonstrate that new mechanically robust and easily detectable (by astralen signal or optically) core-shell microspheres based on biocompatible CaCO3 can be used as SERS platform.


Input: Particle design opens many future perspectives for fabrication of SERS platforms with multiple functions for biomedical applications, for example, for theranostic.


Input: Safety assessment of Apoaequorin, a protein preparation: Subchronic toxicity study in rats.


Input: Apoaequorin, a calcium-binding protein originally isolated from jellyfish is available commercially as a dietary supplement.

calcium


Input: The objective of the present study was to investigate potential adverse effects, if any, of Apoaequorin, a recombinant protein preparation, in rats following subchronic administration.


Input: For this study, Sprague-Dawley (Hsd: SD (R)) rats (10/sex/group) were administered via oral gavage 0 (control), 92. 6, 462. 9, and 926. 0mg/kg body weight (bw)/day of Apoaequorin preparation, for 90days.


Input: The corresponding amount of Apoaequorin protein was 0, 66. 7, 333. 3 and 666. 7mg/kg bw/day, respectively.


Input: Administration of the Apoaequorin preparation did not result in any mortality.


Input: There were no clinical or ophthalmological signs, body weight, body weight gain, food consumption, food efficiency, clinical pathology or histopathological changes attributable to administration of Apoaequorin.


Input: Any changes noted were incidental and in agreement with those historically observed in the age and strain of rats used in this study.


Input: Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for Apoaequorin was determined as 666. 7mg/kg bw/day, the highest dose tested.


Input: Environmental stress, oxytocin receptor gene (OXTR) polymorphism, and mental health following collective stress.

oxytocin


Input: We examined whether the oxytocin receptor gene (OXTR) single nucleotide polymorphism (SNP) rs53576 genotype buffers the combined impact of negative social environments (e. g., interpersonal conflict/constraint) and economic stress on post-traumatic stress (PTS) symptoms and impaired daily functioning following collective stress (September 11th terrorist attacks).

oxytocin

nucleotide


Input: Saliva was collected by mail and used to genotype 704 respondents.


Input: Participants completed Web-based assessments of pre-9/11 mental health, acute stress 9-23days after 9/11, the quality of social environments 1year post-9/11, economic stress 18months post-9/11, and PTS symptoms and impaired functioning 2 and 3years post-9/11.


Input: Interactions between negative social environments and economic stress were examined separately based on OXTR rs53576 genotype (GG vs. any A allele).


Input: For individuals with an A allele, a negative social environment significantly increased PTS symptoms without regard to the level of economic stress experienced.


Input: However, for respondents with a GG genotype, negative social environments predicted elevated PTS symptoms only for those also experiencing high economic stress.


Input: Gender moderated associations between negative social environments, economic stress, and impaired functioning.


Input: The functioning of females was most affected by negative social environments regardless of genotype and economic stress, whereas the functioning of males was differentially susceptible to economic stress depending on OXTR genotype and negative social environments.


Input: These findings suggest that it is important to consider the combined impact of gender and ongoing stress in different domains as moderators of genetic vulnerability following collective stress.


Input: Oroxylin A reverses P-glycoprotein-mediated multidrug resistance of MCF7/ADR cells by G2/M arrest.

Oroxylin A


Input: Oroxylin A is a naturally occurring monoflavonoid isolated from the root of Scutellaria baicalensis Georgi, which has been used in traditional Chinese medicine for its anti-tumor, anti-inflammatory and anti-bacterial properties.

Oroxylin A

monoflavonoid


Input: The purpose of this study is to investigate the reversal effect and the fundamental mechanisms of oroxylin A in MCF7/ADR cells.

oroxylin A


Input: Data indicated that oroxylin A showed strong reversal potency in MCF7/ADR cells and the reversal fold (RF) reached 4. 68.

oroxylin A


Input: After treatment with oroxylin A, MCF7/ADR cells displayed reduced functional activity and expression of MDR1 at both the protein and mRNA levels.

oroxylin A


Input: Meanwhile, oroxylin A induced cells G2/M arrest in a concentration-dependent manner by increasing the expression of p-Chk2 (Thr68).

oroxylin A


Input: Moreover, western blot and EMSA assays were used to reveal the inhibition of NF-kappa B in nucleus and the suppression of NF-kappa B binding activity by oroxylin A.

oroxylin A


Input: NSC 109555 ditosylate-Chk2 inhibitor partly dismissed G2/M arrest induced by oroxylin A, reversed the increased trend of p-Chk2 and p-P53 (Ser20), inhibited the decreasing effect of oroxylin A on the expression of P-gp and decreased the reversal fold of 90 mu M oroxylin A from 4. 68 fold to 1. 73 fold.

NSC 109555 ditosylate

oroxylin A

oroxylin A

oroxylin A


Input: In conclusion, we suggested that oroxylin A reversed MDR by G2/M arrest and the underlying mechanism attributed to the suppression of P-gp expression via Chk2/P53/NF-kappa B signaling pathway.

oroxylin A


Input: Neurotrophin 3 genotype and emotional adverse effects of osmotic-release oral system methylphenidate (OROS-MPH) in children with attention-deficit/hyperactivity disorder.

methylphenidate

MPH


Input: Neurotrophin 3 (NTF3) has been studied in relation to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and mood disorders as well as psychostimulant action.


Input: We hypothesized that the risk of an emotional side effect to methylphenidate (MPH) treatment may be associated with NTF3 genotypes.

methylphenidate

MPH


Input: Ninety-six medication-na i ve children with ADHD (mean age 8. 70, standard deviation 1. 41 years, 79 males) were genotyped and treated with MPH.

MPH


Input: At baseline, which was prior to MPH treatment, and after two weeks of medication, investigators asked children and their parents or caregivers about adverse events using a symptom rating scale.

MPH


Input: ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest' Emotionality' and' Over-focus/euphoria' factor scores, followed by those with the G/A genotype and those with the G/G genotype (p = 0. 042 and p = 0. 045, respectively).


Input: ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest' Proneness to crying' and' Nail biting' item scores, followed by those with the G/A genotype and those with the G/G genotype (p = 0. 047 and p = 0. 017, respectively).


Input: These data provide preliminary evidence that genetic variation in the NTF3 gene is related to susceptibility to emotional side effects in response to MPH treatment in Korean children with ADHD.

MPH


Input: Resveratrol protects against arsenic trioxide-induced nephrotoxicity by facilitating arsenic metabolism and decreasing oxidative stress.

Resveratrol

arsenic trioxide

arsenic


Input: Arsenic trioxide (As2O3) is an environmental toxicant and a potent antineoplastic agent.

Arsenic trioxide


Input: Exposure to arsenic causes renal cancer.

arsenic


Input: Resveratrol is a well-known polyphenolic compound that is reported to reduce As2O3-induced cardiotoxicity.

Resveratrol

polyphenolic


Input: The present study aimed to investigate the effect of resveratrol on As2O3-induced nephrotoxicity and arsenic metabolism.

resveratrol

arsenic


Input: Chinese Dragon-Li cats were injected with 1 mg/kg As2O3 on alternate days; resveratrol (3 mg/kg) was administered via the forearm vein 1 h before the As2O3 treatment.

resveratrol


Input: On the sixth day, the cats were killed to determine the histological renal damage, renal function, the accumulation of arsenic, and antioxidant activities in the kidney.

arsenic


Input: Urine samples were taken for arsenic speciation.

arsenic


Input: In the resveratrol + As2O3-treated group, activities of glutathione peroxidase, catalase, and superoxide dismutase, the ratio of reduced glutathione to oxidized glutathione, the total arsenic concentrations, and the percentage of methylated arsenic in urine were significantly increased.

resveratrol

glutathione

superoxide

glutathione

oxidized glutathione

arsenic

methylated arsenic


Input: The concentrations of renal malondialdehyde, reactive oxygen species, 8-hydroxydeoxyguanosine, serum creatinine, blood urea nitrogen, and renal arsenic accumulation were significantly decreased and reduced renal morphologic injury was observed compared with the As2O3-treated group.

malondialdehyde

oxygen

creatinine

urea nitrogen

arsenic


Input: These results demonstrate that resveratrol could significantly scavenge reactive oxygen species, inhibit As2O3-induced oxidative damage, and significantly attenuate the accumulation of arsenic in renal tissues by facilitating As2O3 metabolism.

resveratrol

oxygen

arsenic


Input: These data suggest that use of resveratrol as postremission therapy for acute promyelocytic leukemia as well as adjunctive therapy in patients with exposure to arsenic may decrease arsenic nephrotoxicity.

resveratrol

arsenic

arsenic


Input: Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants.

His2 zinc


Input: Cys2-His2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans.

zinc


Input: A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes.


Input: As a first step in this process, we have characterized the DNA-binding specificities of 129 zinc finger sets from Drosophila using a bacterial one-hybrid system.

zinc


Input: This data set contains the DNA-binding specificities for at least one encoded ZFP from 70 unique genes and 23 alternate splice isoforms representing the largest set of characterized ZFPs from any organism described to date.


Input: These recognition motifs can be used to predict genomic binding sites for these factors within the fruit fly genome.


Input: Subsets of fingers from these ZFPs were characterized to define their orientation and register on their recognition sequences, thereby allowing us to define the recognition diversity within this finger set.


Input: We find that the characterized fingers can specify 47 of the 64 possible DNA triplets.


Input: To confirm the utility of our finger recognition models, we employed subsets of Drosophila fingers in combination with an existing archive of artificial zinc finger modules to create ZFPs with novel DNA-binding specificity.

zinc


Input: These hybrids of natural and artificial fingers can be used to create functional zinc finger nucleases for editing vertebrate genomes.

zinc


Input: Cobicistat: A New Boost for the Treatment of Human Immunodeficiency Virus Infection.

Cobicistat


Input: Ritonavir is commonly used as a pharmacokinetic booster for antiretroviral regimens in the management of human immunodeficiency virus infections.

Ritonavir


Input: Limitations to ritonavir boosting include increased pill burden, adverse effects, and a wide range of clinically significant drug-drug interactions.

ritonavir


Input: Cobicistat is a new pharmacokinetic booster that is a selective inhibitor of cytochrome P450 3A, the main metabolizing pathway of several antiretrovirals.

Cobicistat


Input: Cobicistat has been studied as a booster for elvitegravir, a second-generation integrase inhibitor, and protease inhibitors.

Cobicistat

elvitegravir


Input: Based on successful clinical trials, a new single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir has been approved for the management of treatment-na i ve patients.

elvitegravir

cobicistat

emtricitabine

tenofovir


Input: Additional studies are underway investigating the safety and efficacy of cobicistat-boosted protease inhibitor regimens for both treatment-na i ve and treatment-experienced patients.

cobicistat


Input: Cobicistat is well tolerated and may become a preferred booster for antiretroviral regimens, as it can be coformulated with several agents to create simpler regimens.

Cobicistat


Input: Tumor-suppressive Maspin Functions as a Reactive Oxygen Species Scavenger: IMPORTANCE OF CYSTEINE RESIDUES.

Oxygen

CYSTEINE


Input: Maspin is a member of the serine protease inhibitor (serpin) superfamily and displays tumor-suppressing activity by controlling cell migration, proliferation, apoptosis, and adhesion.


Input: Here, we provide evidence that maspin acts as a reactive oxygen species (ROS) scavenger through oxidation of three structurally exposed cysteine thiols to sulfenic acid.

oxygen

cysteine thiols

sulfenic acid


Input: Ablation of these cysteine residues in maspin resulted in a significant increase in total ROS production in mouse mammary TM40D cells.

cysteine


Input: Also, cells containing a triple-cysteine mutant of maspin showed elevated ERK1/2 activity, a downstream target of ROS, and enhanced proliferation and colony formation.

cysteine


Input: These findings establish a novel mechanism by which maspin utilizes its cysteine thiols to inhibit oxidative stress and cell growth.

cysteine thiols


Input: Biosafety data as confidential business information.


Input: Removal of confidentiality claims on biosafety data is necessary to adhere to standard scientific procedures of quality assurance, to increase transparency, to minimize impacts of conflicts of interests, and ultimately to improve public confidence in GMOs.


Input: Global iodine nutrition: where do we stand in 2013?

iodine


Input: Background: Dietary iodine intake is required for the production of thyroid hormone.

iodine

thyroid hormone


Input: Consequences of iodine deficiency include goiter, intellectual impairments, growth retardation, neonatal hypothyroidism, and increased pregnancy loss and infant mortality.

iodine


Input: Summary: In 1990, the United Nations World Summit for Children established the goal of eliminating iodine deficiency worldwide.

iodine


Input: Considerable progress has since been achieved, largely through programs of universal salt iodization.


Input: Approximately 70% of all households worldwide currently have access to adequately iodized salt.


Input: In 2013, as defined by a national or subnational median urinary iodine concentration of 100-299 mu g/L in school-aged children, 111 countries have sufficient iodine intake.

iodine

iodine


Input: Thirty countries remain iodine-deficient; 9 are moderately deficient, 21 are mildly deficient, and none are currently considered severely iodine-deficient.

iodine

iodine


Input: Ten countries have excessive iodine intake.

iodine


Input: In North America, both the United States and Canada are generally iodine-sufficient, although recent data suggest pregnant U. S. women are mildly iodine-deficient.

iodine

iodine


Input: Emerging issues include discrepancies between urinary iodine status in pregnant women compared to school-aged children in some populations, the problem of re-emerging iodine deficiency in parts of the developed world, the importance of food industry use of iodized salt, regions of iodine excess, and the potential effects of initiatives to lower population sodium consumption on iodine intake.

iodine

iodine

iodine

sodium

iodine


Input: Conclusions: Although substantial progress has been made over the last several decades, iodine deficiency remains a significant health problem worldwide and affects both industrialized and developing nations.

iodine


Input: The ongoing monitoring of population iodine status remains crucially important, and particular attention may need to be paid to monitoring the status of vulnerable populations, such as pregnant women and infants.

iodine


Input: There is also need for ongoing monitoring of iodized salt and other dietary iodine sources in order to prevent excess as well as insufficient iodine nutrition.

iodine

iodine


Input: Finally, it will be essential to coordinate interventions designed to reduce population sodium intake with salt iodization programs in order to maintain adequate levels of iodine nutrition as salt intake declines.

sodium

iodine


Input: In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation.

citrate

glutamine


Input: Hypoxic and VHL-deficient cells use glutamine to generate citrate and lipids through reductive carboxylation (RC) of alpha-ketoglutarate.

glutamine

citrate

alpha-ketoglutarate


Input: To gain insights into the role of HIF and the molecular mechanisms underlying RC, we took advantage of a panel of disease-associated VHL mutants and showed that HIF expression is necessary and sufficient for the induction of RC in human renal cell carcinoma (RCC) cells.


Input: HIF expression drastically reduced intracellular citrate levels.

citrate


Input: Feeding VHL-deficient RCC cells with acetate or citrate or knocking down PDK-1 and ACLY restored citrate levels and suppressed RC.

acetate

citrate

citrate


Input: These data suggest that HIF-induced low intracellular citrate levels promote the reductive flux by mass action to maintain lipogenesis.

citrate


Input: Using [(1-13) C] glutamine, we demonstrated in vivo RC activity in VHL-deficient tumors growing as xenografts in mice.

[(1-13) C] glutamine


Input: Lastly, HIF rendered VHL-deficient cells sensitive to glutamine deprivation in vitro, and systemic administration of glutaminase inhibitors suppressed the growth of RCC cells as mice xenografts.

glutamine


Input: The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression.


Input: RNA-binding proteins are at the heart of posttranscriptional gene regulation, coordinating the processing, storage, and handling of cellular RNAs.


Input: We show here that GRSF1, previously implicated in the binding and selective translation of influenza mRNAs, is targeted to mitochondria where it forms granules that colocalize with foci of newly synthesized mtRNA next to mitochondrial nucleoids.


Input: GRSF1 preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long noncoding RNAs for cytb and ND5, each of which contains multiple consensus binding sequences.


Input: RNAi-mediated knockdown of GRSF1 leads to alterations in mitochondrial RNA stability, abnormal loading of mRNAs and lncRNAs on the mitochondrial ribosome, and impaired ribosome assembly.


Input: This results in a specific protein synthesis defect and a failure to assemble normal amounts of the oxidative phosphorylation complexes.


Input: These data implicate GRSF1 as a key regulator of posttranscriptional mitochondrial gene expression.


Input: Adipose subtype-selective recruitment of TLE3 or Prdm16 by PPAR gamma specifies lipid storage versus thermogenic gene programs.


Input: Transcriptional effectors of white adipocyte-selective gene expression have not been described.


Input: Here we show that TLE3 is a white-selective cofactor that acts reciprocally with the brown-selective cofactor Prdm16 to specify lipid storage and thermogenic gene programs.


Input: Occupancy of TLE3 and Prdm16 on certain promoters is mutually exclusive, due to the ability of TLE3 to disrupt the physical interaction between Prdm16 and PPAR gamma.


Input: When expressed at elevated levels in brown fat, TLE3 counters Prdm16, suppressing brown-selective genes and inducing white-selective genes, resulting in impaired fatty acid oxidation and thermogenesis.

fatty acid


Input: Conversely, mice lacking TLE3 in adipose tissue show enhanced thermogenesis in inguinal white adipose depots and are protected from age-dependent deterioration of brown adipose tissue function.


Input: Our results suggest that the establishment of distinct adipocyte phenotypes with different capacities for thermogenesis and lipid storage is accomplished in part through the cell-type-selective recruitment of TLE3 or Prdm16 to key adipocyte target genes.


Input: Mechanistic investigation of seeded growth in triblock copolymer stabilized gold nanoparticles.


Input: We report the seeded synthesis of gold nanoparticles (GNPs) via the reduction of HAuCl4 by (L31 and F68) triblock copolymer (TBP) mixtures.


Input: In the present study, we focused on [TBP]/[Au (III)] ratios of 1-5 (=~ 1 mM HAuCl4) and seed sizes ~ 20 nm.

Au (III)


Input: Under these conditions, the GNP growth rate is dominated by both the TBP and seed concentrations.


Input: With seeding, the final GNP size distributions are bimodal.


Input: Increasing the seed concentration (up to ~ 0. 1 nM) decreases the mean particle sizes 10-fold, from ~ 1000 to 100 nm.


Input: The particles in the bimodal distribution are formed by the competitive direct growth in solution and the aggregative growth on the seeds.


Input: By monitoring kinetics of GNP growth, we propose that (1) the surface of the GNP seeds embedded in the TBP cavities form catalytic centers for GNP growth and (2) large GNPs are formed by the aggregation of GNP seeds in an autocatalytic growth process.


Input: Systematic study of the basis set superposition error in core-electron correlation effects.


Input: In a recent paper, Xu et al.


Input: [J. Phys. Chem. A2012, 116, 11668] emphasized the importance of core-electron correlation effects to describe the Si2H6BH3 complex and related systems properly.


Input: Unexpected large energy differences between a frozen core and all electron treatment were observed.


Input: In the present study, it will be shown that these energy differences are an artifact of an insufficient choice of basis set and can be attributed to an intramolecular basis set superposition error (BSSE).


Input: Although the general problem is known, systematic studies on the effect are scarce.


Input: Therefore, the BSSE in related systems is investigated.


Input: This study shows that the problem of BSSE for core-electron correlation is quite common if inadequate basis sets are applied and that it amounts to 2 kcal mol (-1) on average in binding energies for the given test set (with a maximum of 5. 8 kcal mol (-1)).


Input: Molecular interactions in 1-butanol + IL solutions by measuring and modeling activity coefficients.


Input: Molecular interactions in 1-butanol + ionic liquid (IL) solutions have been investigated by measuring and modeling activity-coefficient data.


Input: The activity coefficients in binary solutions containing 1-butanol and an IL were determined experimentally: the ILs studied were 1-decyl-3-methyl-imidazolium tetracyanoborate ([Im10. 1] (+) [tcb] (-)), 4-decyl-4-methyl-morpholinium tetracyanoborate ([Mo10. 1] (+) [tcb] (-)), 1-decyl-3-methyl-imidazolium bis (trifluoromethylsulfonyl) imide ([Im10. 1] (+) [ntf2] (-)), and 4-decyl-4-methyl-morpholinium bis (trifluoromethylsulfonyl) imide ([Mo10. 1] (+) [ntf2] (-)).

1-decyl-3-methyl-imidazolium tetracyanoborate

tcb

4-decyl-4-methyl-morpholinium tetracyanoborate

tcb

1-decyl-3-methyl-imidazolium bis (trifluoromethylsulfonyl) imide

4-decyl-4-methyl-morpholinium bis (trifluoromethylsulfonyl) imide


Input: The methods used to determine the activity coefficients included vapor-pressure osmometry, headspace-gas chromatography, and gas-liquid chromatography.


Input: The results from all of these techniques were combined to obtain activity-coefficient data over the entire IL concentration range, and the ion-specific interactions of the ILs investigated were identified with 1-butanol.


Input: The highest (1-butanol)-IL interactions of the ILs considered in this work were found for [Im10. 1] (+) [tcb] (-); thus, [Im10. 1] (+) [tcb] (-) showed the highest affinity for 1-butanol in a binary mixture.


Input: The experimental data were modeled with the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT).


Input: PC-SAFT was able to accurately describe the pure IL and (1-butanol)-IL data.


Input: Moreover, the model was shown to be predictive and extrapolative with respect to concentration and temperature.


Input: Chemical informatics uncovers a new role for moexipril as a novel inhibitor of cAMP phosphodiesterase-4 (PDE4).

moexipril

cAMP


Input: PDE4 is one of eleven known cyclic nucleotide phosphodiesterase families and plays a pivotal role in mediating hydrolytic degradation of the important cyclic nucleotide second messenger, cyclic 3' 5' adenosine monophosphate (cAMP).

cyclic nucleotide

cyclic nucleotide

cyclic 3' 5' adenosine monophosphate

cAMP


Input: PDE4 inhibitors are known to have anti-inflammatory properties, but their use in the clinic has been hampered by mechanism-associated side effects that limit maximally tolerated doses.


Input: In an attempt to initiate the development of better-tolerated PDE4 inhibitors we have surveyed existing approved drugs for PDE4-inhibitory activity.


Input: With this objective, we utilised a high-throughput computational approach that identified moexipril, a well tolerated and safe angiotensin-converting enzyme (ACE) inhibitor, as a PDE4 inhibitor.

moexipril

angiotensin


Input: Experimentally we showed that moexipril and two structurally related analogues acted in the micro molar range to inhibit PDE4 activity.

moexipril


Input: Employing a FRET-based biosensor constructed from the nucleotide binding domain of the type 1 exchange protein activated by cAMP, EPAC1, we demonstrated that moexipril markedly potentiated the ability of forskolin to increase intracellular cAMP levels.

nucleotide

cAMP

moexipril

forskolin

cAMP


Input: Finally, we demonstrated that the PDE4 inhibitory effect of moexipril is functionally able to induce phosphorylation of the small heat shock protein, Hsp20, by cAMP dependent protein kinase A.

moexipril

cAMP


Input: Our data suggest that moexipril is a bona fide PDE4 inhibitor that may provide the starting point for development of novel PDE4 inhibitors with an improved therapeutic window.

moexipril


Input: Lipid raft modulation by Rp1 reverses multidrug resistance via inactivating MDR-1 and Src inhibition.


Input: Multidrug resistance (MDR) is a major obstacle to effective cancer therapy.


Input: The membrane transporter MDR-1 (P-gp, ABCB1), a member of the ATP-binding cassette (ABC) transporter family, effluxes anti-cancer drugs from cancer cells.

ATP


Input: Increased activity of MDR-1 is known to be the main mechanism for multidrug resistance.


Input: MDR-1 is known to be localized in the cholesterol-and sphingolipid-enriched plasma membrane microdomains, known as lipid rafts.

cholesterol

sphingolipid


Input: Disruption of lipid rafts by cholesterol depletion alters lipid raft functions, indicating that cholesterol is critical for raft function.

cholesterol

cholesterol


Input: Because ginsenosides are structurally similar to cholesterol, in this study, we investigated the effect of Rp1, a novel ginsenoside derivative, on drug resistance using drug-sensitive OVCAR-8 and drug-resistant NCI/ADR-RES and DXR cells.

ginsenosides

cholesterol

ginsenoside


Input: Rp1 treatment resulted in an accumulation of doxorubicin or rhodamine 123 by decreasing MDR-1 activity in doxorubicin-resistant cells.

doxorubicin

rhodamine 123

doxorubicin


Input: Rp1 synergistically induced cell death with actinomycin D in DXR cells.

actinomycin D


Input: Rp1 appeared to redistribute lipid rafts and MDR-1 protein.


Input: Moreover, Rp1 reversed resistance to actinomycin D by decreasing MDR-1 protein levels and Src phosphorylation with modulation of lipid rafts.

actinomycin D


Input: Addition of cholesterol attenuated Rp1-induced raft aggregation and MDR-1 redistribution.

cholesterol


Input: Rp1 and actinomycin D reduced Src activity, and overexpression of active Src decreased the synergistic effect of Rp1 with actinomycin D.

actinomycin D

actinomycin D


Input: Rp1-induced drug sensitization was also observed with several anti-cancer drugs, including doxorubicin.

doxorubicin


Input: These data suggest that lipid raft-modulating agents can be used to inhibit MDR-1 activity and thus overcome drug resistance.


Input: Robust PEGylated hyaluronic acid nanoparticles as the carrier of doxorubicin: Mineralization and its effect on tumor targetability in vivo.

doxorubicin


Input: The in vivo stability and tumor targetability of self-assembled polymeric nanoparticles are crucial for effective drug delivery.


Input: In this study, to develop biostable nanoparticles with high tumor targetability, poly (ethylene glycol)-conjugated hyaluronic acid nanoparticles (PEG-HANPs) were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method.

poly (ethylene glycol)

PEG

calcium

phosphate


Input: The resulting nanoparticles (M-PEG-HANPs) had a smaller size (153. 7 +/- 4. 5nm) than bare PEG-HANPs (265. 1 +/- 9. 5nm), implying that mineralization allows the formation of compact nanoparticles.

PEG

PEG


Input: Interestingly, when the mineralized nanoparticles were exposed to acidic buffer conditions (< pH6. 5), their sizes increased rapidly due to dissolution of the inorganic minerals.


Input: Doxorubicin (DOX), chosen as the model anticancer drug, was effectively encapsulated into the bare and mineralized nanoparticles.


Input: For bare PEG-HANPs, DOX was released in a sustained manner and its release rate was not dependent on the pH of the solution.


Input: On the other hand, DOX release from M-PEG-HANPs was pH-dependent: i. e. DOX was slowly released from nanoparticles under physiological condition (pH7. 4), whereas its release rates were much higher at mildly acidic environments (< pH6. 5).


Input: From in vivo biodistribution study, it was found that M-PEG-HANPs could reach the tumor site more effectively than bare PEG-HANPs.


Input: The antitumor efficacy of DOX-loaded nanoparticles was evaluated after systemic administration into the tumor-bearing mice.


Input: Of the samples tested, the most effective antitumor efficacy was observed for DOX-loaded M-PEG-HANPs.


Input: Overall, these results suggest that M-PEG-HANPs could be a promising carrier for an anticancer drug.


Input: The role of DNA methylation and histone acetylation in the regulation of progesterone receptor isoforms expression in human astrocytoma cell lines.

progesterone


Input: Many progesterone (P4) effects are mediated by its intracellular receptor (PR), which has two isoforms, PR-A and PR-B, each of them with different function and regulation.

progesterone


Input: Differential PR expression in cancer cells has been associated to a PR isoform-specific promoter methylation.


Input: In astrocytomas, the most frequent and aggressive brain tumors, PR isoforms expression is directly correlated to the tumor' s evolution grade.


Input: However, there is no evidence of the role of epigenetic regulation of PR expression in astrocytomas.


Input: We evaluated the effect of the demethylating agent 5-aza-2'-deoxycytidine (5AzadC) and the histone deacetylase inhibitor trichostatin A (TSA) on PR expression in human astrocytoma cell lines U373 (grade III) and D54 (grade IV) by RT-PCR and Western blot.

trichostatin A

TSA


Input: Total PR expression increased with 5 mu M 5AzadC treatment, whereas PR-B expression increased with 5 and 10 mu M 5AzadC treatment in U373 cells, but not in D54 cells.


Input: In U373 cells, PR-A protein content augmented with 10 mu M 5AzadC treatment, while PR-B content increased with 5 and 10 mu M 5AzadC.


Input: PR-B expression was not modified by the TSA concentrations that were used, and the combination with 5AzadC did not change the effects of the latter.

TSA


Input: The study of 5AzadC effects on the number of astrocytoma cells showed that P4 treatment increased the number of U373 cells, whereas 5AzadC and the combined treatment with P4 reduced it.


Input: Our results suggest that PR-B expression is regulated by methylation and not by histone acetylation in U373 cells, and that DNA demethylation reduced the number of U373 cells.


Input: Neutralization of Apis mellifera bee venom activities by suramin.

suramin


Input: In this work we evaluated the ability of suramin, a polysulfonated naphthylurea derivative, to antagonize the cytotoxic and enzymatic effects of the crude venom of Apis mellifera.

suramin

polysulfonated naphthylurea


Input: Suramin was efficient to decrease the lethality in a dose-dependent way.

Suramin


Input: The hemoconcentration caused by lethal dose injection of bee venom was abolished by suramin (30 mu g/g).

suramin


Input: The edematogenic activity of the venom (0. 3 mu g/g) was antagonized by suramin (10 mu g/g) in all treatment protocols.

suramin


Input: The changes in the vascular permeability caused by A. mellifera (1 mu g/g) venom were inhibited by suramin (30 mu g/g) in the pre-and posttreatment as well as when the venom was preincubated with suramin.

suramin

suramin


Input: In addition, suramin also inhibited cultured endothelial cell lesion, as well as in vitro myotoxicity, evaluated in mouse extensor digitorumlongus muscle, which was inhibited by suramin (10 and 25 mu M), decreasing the rate of CK release, showing that suramin protected the sarcolemma against damage induced by components of bee venom (2. 5 mu g/mL).

suramin

suramin

suramin


Input: Moreover, suramin inhibited the in vivo myotoxicity induced by i. m. injection of A. mellifera venom in mice (0. 5 mu g/g).

suramin


Input: The analysis of the area under the plasma CK vs. time curve showed that preincubation, pre-and posttreatment with suramin (30 mu g/g) inhibited bee venom myotoxic activity in mice by about 89%, 45% and 40%, respectively.

suramin


Input: Suramin markedly inhibited the PLA2 activity in a concentration-dependent way (1-30 mu M).

Suramin


Input: Being suramin a polyanion molecule, the effects observed may be due to the interaction of its charges with the polycation components present in A. mellifera bee venom.

suramin


Input: Effects of perinatal exposure to waterborne fluoxetine on memory processing in the cuttlefish Sepia officinalis.

fluoxetine


Input: Recent ecotoxicological studies highlight the increasing presence of pharmaceuticals discharged in the aquatic environment.


Input: Amongst them is the antidepressant fluoxetine (FLX), a selective serotonin reuptake inhibitor, primarily indicated for treatment of depression.

fluoxetine

FLX

serotonin


Input: The effect of chronic exposure to FLX on memory processing in 1-month-old cuttlefish Sepia officinalis was evaluated.

FLX


Input: Three groups of new-borns were reared in different conditions: one control group (no FLX) and two groups exposed to environmental concentrations of FLX (1 and 100ng/L) from 15 days pre-hatching to 1 month post-hatching.

FLX

FLX


Input: Acquisition and retention performances were assessed using the' prawn-in-the-tube' procedure.


Input: Perinatal exposure to fluoxetine led to significant changes in memory processing of the animals.

fluoxetine


Input: The lowest observed effect concentration of this antidepressant on learning and retention was 1ng/L which is under the range of environmental contamination.


Input: Cuttlefish exposed at low FLX concentration had impaired acquisition capabilities and animals exposed at high FLX concentration displayed a deficit of memory retention compared to the control group that had nonimpaired initial acquisition and retention performances.

FLX

FLX


Input: The results subsequently suggested that FLX-induced changes in cognitive capacities could potentially lead to inappropriate predatory behaviors in the natural environment.

FLX


Input: The study provides the basis for future studies on how pharmaceutical contaminants disrupt cognition in ecologically and economically relevant marine invertebrates.


Input: Synergistic effects between pesticide stress and predator cues: Conflicting results from life history and physiology in the damselfly Enallagma cyathigerum.


Input: There is increasing awareness that the negative effects of anthropogenic stressors may be magnified in the presence of natural stressors.


Input: Very few of these studies have included physiology, yet including physiological studies may help learning about the mechanistic base of such synergisms at the life history level and identify synergistic interactions not translated in life history traits.


Input: We studied in Enallagma cyathigerum damselfly larvae potential synergistic effects between exposure to the pesticide glyphosate and predator cues on a key life history trait, growth rate, its associated behavioural trait, food intake, and three types of physiological traits known to be affected by both stressors in isolation: the stress protein Hsp70, energy storage and variables related to oxidative stress and damage.

glyphosate


Input: The pesticide and predator cues reduced growth rate in an additive way.


Input: Food intake increased under pesticide exposure and was not affected by the predator cues, indicating physiological mediation of the growth reduction.


Input: One potential physiological mechanism was that both stressors additively increased Hsp70 levels, this may also have contributed to the reduced levels of total carbohydrates when exposed to predator cues.

carbohydrates


Input: Chronic exposure to predator cues reduced oxygen consumption, possibly to avoid too high costs of an increased metabolic rate.

oxygen


Input: This reduction did not occur in the presence of the pesticide, reflecting the need for energetically expensive defence mechanisms (such as Hsp70 upregulation).


Input: When both stressors were combined, there was a reduction of the antioxidant enzyme superoxide dismutase activity (SOD) and an associated increase of oxidative damage in lipids.

superoxide


Input: While synergistic interactions were not present for growth rate and food intake, they were identified for antioxidant defence and oxidative damage.


Input: This novel type of " hidden " synergistic interaction may have profound fitness implications, and when ignored will lead to underestimations of the impact of pollutants in natural populations where predators are omnipresent.


Input: Can acetylcholinesterase activity be considered as a reliable biomarker for the assessment of cadmium-induced neurotoxicity?

cadmium


Input: Gon c alves et al.


Input: (2012) recently reported the findings of a long-awaited study on the effects of long-term dietary-induced exposure to cadmium (Cd) on the acetylcholinesterase (AChE) activity of adult rodents' brain regions.

cadmium

Cd


Input: Their study can be regarded as a significant contribution to the field, as there is paucity of information on the AChE activity in brain regions following exposure to Cd.

Cd


Input: However, the Cd-induced modulation of AChE activity is an issue surrounded by controversy.

Cd


Input: We, herein, discuss and summarize the relative in vivo and in vitro experimental data, and set out to answer the straightforward question: can AChE activity be considered as a reliable biomarker for the assessment of Cd-induced neurotoxicity?

Cd


Input: At this time, we can not answer in the affirmative because of the variation in techniques used and conclusions reached.


Input: We make a plea that authors aiming to explore this potential use of brain AChE activity in the future: (a) are aware of the biases that their experimental approach might exert upon this neurochemical parameter, (b) avoid the use of anaesthesia as a mode of sacrifice and clarify its timing, (c) decide upon the use of previously-studied in vivo experimental schemes (so that they can provide comparable results), and finally, (d) identify pharmacological, biochemical and molecular approaches that are appropriate to clarify the implicated mechanism (s) through which Cd modifies AChE activity.

Cd


Input: Frank A. Beach Award: Programming of neuroendocrine function by early-life experience: A critical role for the immune system.


Input: Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system, and several have a striking etiology in development as well.


Input: Our recent evidence using a rodent model of neonatal Escherichiacoli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood, and suggests that the early-life immune history of an individual may be critical to understanding the relative risk of developing later-life mental health disorders in humans.


Input: A single neonatal infection programs the function of immune cells within the brain, called microglia, for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits.


Input: I describe the important role of the immune system, notably microglia, during brain development, and discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, and cognition.


Input: Changes in Insulin Resistance and HbA1c Are Related to Exercise-Mediated Changes in Body Composition in Older Adults With Type 2 Diabetes: Interim outcomes from the GREAT2DO Trial.


Input: OBJECTIVETo investigate changes in body composition after 12 months of high-intensity progressive resistance training (PRT) in relation to changes in insulin resistance (IR) or glucose homeostasis in older adults with type 2 diabetes. RESEARCH DESIGN AND METHODSOne-hundred three participants were randomized to receive either PRT or sham exercise 3 days per week for 12 months.

glucose


Input: Homeostatic model of assessment 2 (HOMA2-IR) and glycosylated hemoglobin (HbA1c) were used as indices of IR and glucose homeostasis.

glucose


Input: Skeletal muscle mass (SkMM) and total fat mass were assessed using bioelectrical impedance.


Input: Visceral adipose tissue, mid-thigh cross-sectional area, and mid-thigh muscle attenuation were quantified using computed tomography. RESULTSWithin the PRT group, changes in HOMA2-IR were associated with changes in SkMM (r =-0. 38; P = 0. 04) and fat mass (r = 0. 42; P = 0. 02).


Input: Changes in visceral adipose tissue tended to be related to changes in HOMA2-IR (r = 0. 35; P = 0. 07).


Input: Changes in HbA1c were related to changes in mid-thigh muscle attenuation (r = 0. 52; P = 0. 001).


Input: None of these relationships were present in the sham group (P > 0. 05).


Input: Using ANCOVA models, participants in the PRT group who had increased SkMM had decreased HOMA2-IR (P = 0. 05) and HbA1c (P = 0. 09) compared with those in the PRT group who lost SkMM.


Input: Increases in SkMM in the PRT group decreased HOMA2-IR (P = 0. 07) and HbA1c (P < 0. 05) compared with those who had increased SkMM in the sham group. CONCLUSIONSImprovements in metabolic health in older adults with type 2 diabetes were mediated through improvements in body composition only if they were achieved through high-intensity PRT.


Input: Mn @Si14 +: a singlet fullerene-like endohedrally doped silicon cluster.

Mn

Si14 +

fullerene-

silicon


Input: The electronic structure of Mn @Si14 (+) is determined using DFT and CASPT2/CASSCF (14, 15) computations with large basis sets.

Mn

Si14 (+)


Input: The endohedrally Mn-doped Si cationic cluster has a D3h fullerene-like structure featuring a closed-shell singlet ground state with a singlet-triplet gap of ~ 1 eV.

Mn-doped Si

fullerene-


Input: A strong stabilizing interaction occurs between the 3d (Mn) and the 2D-shell (Si14) orbitals, and a large amount of charge is transferred from the Si14 cage to the Mn dopant.

Mn

Mn


Input: The 3d (Mn) orbitals are filled by encapsulation, and the magnetic moment of Mn is completely quenched.

Mn

Mn


Input: Full occupation of [2S, 2P, 2D] shell orbitals by 18 delocalized electrons confers the doped Mn @Si14 (+) cluster a spherically aromatic character.

Mn

Si14 (+)


Input: Influence of the novel histamine H3 receptor antagonist ST1283 on voluntary alcohol consumption and ethanol-induced place preference in mice.

histamine

alcohol

ethanol


Input: RATIONALE: Growing evidence supports a role for the central histaminergic system to have a modulatory influence on drug addiction in general and alcohol-use disorders in particular through histamine H3 receptors (H3R).

alcohol

histamine


Input: OBJECTIVE: In the present study, the effects of systemic injection of the newly synthesized H3R antagonist ST1283 on ethanol (EtOH) voluntary intake and EtOH-conditioned reward in mice have been investigated.

ethanol

EtOH

EtOH


Input: METHODS: Oral EtOH, saccharin, and quinine intake was assessed in a two-bottle choice paradigm using escalating concentrations of alcohol or tastant solutions.

EtOH

saccharin

quinine

alcohol


Input: EtOH-induced place preference (CPP), EtOH-induced locomotor activity, and blood ethanol concentration (BEC) were also measured.

EtOH

EtOH

ethanol


Input: RESULTS: Following administration of the H3R antagonist (2. 5, 5, and 10 mg/kg, i. p.), there was a significant dose-dependent decrease in alcohol consumption and preference.

alcohol


Input: Importantly, vehicle-and ST1283 (5 mg/kg)-treated mice showed similar consumption and preference to increasing concentration of both sweet and bitter tastes.


Input: More interestingly, systemic administration of ST1283 inhibited EtOH-CPP and EtOH-enhanced locomotion.

EtOH

EtOH


Input: This inhibition was blocked when mice were pretreated with the selective H3R agonist R-(alpha)-methyl-histamine (10 mg/kg).

R-(alpha)-methyl-histamine


Input: Finally, vehicle-and ST1283-treated mice had similar BECs.


Input: CONCLUSION: Our results show that ST1283 may decrease voluntary EtOH consumption and EtOH-CPP by altering its reinforcing effects, suggesting a novel role for histamine signaling in regulation of alcoholism.

EtOH

EtOH

histamine


Input: Lastly, the results add to the growing literature on H3R modulation in the pharmacotherapy of EtOH addiction.

EtOH


Input: Delineating multiple functions of VEGF-A in the adult brain.


Input: Vascular endothelial growth factor-A (abbreviated throughout this review as VEGF) is mostly known for its angiogenic activity, for its activity as a vascular permeability factor, and for its vascular survival activity [1].


Input: There is a growing body of evidence, however, that VEGF fulfills additional less' traditional' functions in multiple organs, both during development, as well as homeostatic functions in fully developed organs.


Input: This review focuses on the multiple roles of VEGF in the adult brain and is less concerned with the roles played by VEGF during brain development, functions described elsewhere in this review series.


Input: Most functions of VEGF that are essential for proper brain development are, in fact, dispensable in the adult brain as was clearly demonstrated using a conditional brain-specific VEGF loss-of-function (LOF) approach.


Input: Thus, in contrast to VEGF LOF in the developing brain, a process which is detrimental for the growth and survival of blood vessels and leads to massive neuronal apoptosis [2-4], continued signaling by VEGF in the mature brain is no longer required for maintaining already established cerebral vasculature and its inhibition does not cause appreciable vessel regression, hypoxia or apoptosis [4-7].


Input: Yet, VEGF continues to be expressed in the adult brain in a constitutive manner.


Input: Moreover, VEGF is expressed in the adult brain in a region-specific manner and in distinctive spatial patterns incompatible with an angiogenic role (see below), strongly suggesting angiogenesis-independent and possibly also perfusion-independent functions.


Input: Here we review current knowledge on some of these' non-traditional', often unexpected homeostatic VEGF functions, including those unrelated to its effects on the brain vasculature.


Input: These effects could be mediated directly (on non-vascular cells expressing cognate VEGF receptors) or indirectly (via the endothelium).


Input: Experimental approaches aimed at distinguishing between these possibilities for each particular VEGF function will be described.


Input: This review is only concerned with homeostatic functions of VEGF in the normal, non-injured brain.


Input: The reader is referred elsewhere in this series for a review on VEGF actions in response to various forms of brain injury and/or brain pathology.


Input: Selenium Attenuates Adriamycin-Induced Cardiac Dysfunction via Restoring Expression of ATP-Sensitive Potassium Channels in Rats.

Selenium

Adriamycin

ATP

Potassium


Input: The possible mechanism of adriamycin (ADR) and/or selenium (Se) deficiency-induced cardiac dysfunction, and cardioprotective effects of Se against ADR-induced cardiac toxicity were investigated in this study.

adriamycin

ADR

selenium

Se

Se

ADR


Input: Cardiac function was evaluated by plasma brain natriuretic peptide level and echocardiographic and hemodynamic parameters.


Input: Cardiac glutathione peroxidase (GPx) activity was assessed spectrophotometrically.

glutathione


Input: Expression of ATP-sensitive potassium channels (KATP) subunits-SUR2A and Kir6. 2-were examined by real-time PCR and Western blotting.

ATP

potassium


Input: The results showed that cardiac function and cardiac GPx activity decreased remarkably after administration of ADR or Se deficiency; more dramatic impairment of cardiac function and cardiac GPx activity were observed after co-administration of ADR and Se deficiency.

ADR

Se

ADR

Se


Input: Mechanically, it is novel for us to find down-regulation of KATP subunits gene expression in cardiac tissue after administration of ADR or Se deficiency, and more significant inhibition of cardiac KATP gene expression was identified after co-administration of ADR and Se deficiency.

ADR

Se

ADR

Se


Input: Furthermore, cardiac toxicity of ADR was found alleviated by Se supplementation, accompanied by restoring of cardiac GPx activity and cardiac KATP gene expression.

ADR

Se


Input: These results indicate that decreased expression of cardiac KATP is involved in adriamycin and/or Se deficiency-induced cardiac dysfunction; Se deficiency exacerbates adriamycin-induced cardiac dysfunction by future inhibition of KATP expression; Se supplementation seems to protect against adriamycin-induced cardiac dysfunction via restoring KATP expression, showing potential clinical application in cancer chemotherapy.

adriamycin

Se

Se

adriamycin

Se

adriamycin


Input: Characteristics and determinants of adult patients with acute poisoning attending the accident and emergency department of a teaching hospital in Qatar.


Input: Data about etiologic and demographic characteristics of acute poisoning in adults in Qatar are lacking.


Input: This prospective observational study was undertaken to analyze characteristics and possible determinants of acute poisoning in adults in Qatar.


Input: During 2010, 18, 073 patients attended the emergency department of Hamad General Hospital, a teaching hospital in Qatar.


Input: Out of them, 599 (3. 3%) patients were diagnosed as " poisoning case " with either chemical or pharmaceutical substances.


Input: The prevalence rate of poisoning incidence was 35. 3/100, 000 population.


Input: Seven patients died, corresponding with a case-fatality rate of 0. 39/1000.


Input: The majority were male (65%) and the mean age was 34 years.


Input: The poisons involved were mainly chemicals (61. 6%) and pharmaceuticals (38. 4%).


Input: Female, mainly single, suffered more intentional poisoning compared to male.


Input: Of the patients aged 60 years and above (7. 2%), the majority (95. 3%) suffered unintentional poisoning with pharmaceuticals; 56% with warfarin, 12% with digoxin and 7% with insulin.

warfarin

digoxin


Input: Multivariate analysis shows that female gender, single status, younger than 35 years of age, being poisoned by pharmaceutical products, and the need for hospitalization are significant determinants for acute intentional poisoning after adjusting all other possible covariates.


Input: The findings of this study can be used to establish awareness and prophylactic campaigns in Qatar.


Input: Stacking of Short DNA Induces the Gyroid Cubic-to-Inverted Hexagonal Phase Transition in Lipid-DNA Complexes.


Input: Lyotropic phases of amphiphiles are a prototypical example of self-assemblies.


Input: Their structure is generally determined by amphiphile shape and their phase transitions are primarily governed by composition.


Input: In this paper, we demonstrate a new paradigm for membrane shape control where the electrostatic coupling of charged membranes to short DNA (sDNA), with tunable temperature-dependent end-to-end stacking interactions, enables switching between the inverted gyroid cubic structure (QII (G)) and the inverted hexagonal phase (HII (C)).


Input: We investigated the structural shape transitions induced in the QII (G) phase upon complexation with a series of sDNAs (5, 11, 24, and 48 bp) with three types of end structure (" sticky " adenine (A)-thymine (T) (dAdT) overhangs, no overhang (blunt), and " nonsticky " dTdT overhangs) using synchrotron small-angle X-ray scattering.

adenine

thymine


Input: Very short 5 bp sDNA with dAdT overhangs and blunt ends induce coexistence of the QII (G) and the HII (C) phase, with the fraction of QII (G) increasing with temperature.


Input: Phase coexistence for blunt 5 bp sDNA is observed from 27 degrees C to about 65 degrees C, where the HII (C) phase disappears and the temperature dependence of the lattice spacing of the QII (G) phase indicates that the sDNA duplexes melt into single strands.


Input: The only other sDNA for which melting is observed is 5 bp sDNA with dTdT overhangs, which forms the QII (G) phase throughout the studied range of temperature (27 degrees C to 85. 2 degrees C).


Input: The longer 11 bp sDNA forms coexisting QII (G) and HII (C) phases (with the fraction of QII (G) again increasing with temperature) only for " nonsticky " dTdT overhangs, while dAdT overhangs and blunt ends exclusively template the HII (C) phase.


Input: For 24 and 48 bp sDNAs the HII (C) phase replaces the QII (G) phase at all investigated temperatures, independent of sDNA end structure.


Input: Our work demonstrates how the combined effects of sDNA length and end structure (which determine the temperature-dependent stacking length) tune the phase behavior of the complexes.


Input: These findings are consistent with the hypothesis that sDNAs and sDNA stacks with lengths comparable to or larger than the cubic unit cell length disfavor the highly curved channels present in the QII (G) phase, thus driving the QII (G)-to-HII (C) phase transition.


Input: As the temperature is increased, the breaking of stacks due to thermal fluctuations restores increasing percentages of the QII (G) phase.


Input: Sensing of biologically important cations such as na (+), k (+), ca (2 +), cu (2 +), and fe (3 +) using magnetic nanoemulsions.

na (+)

k (+)

ca (2 +)

cu (2 +)

fe (3 +)


Input: We report a simple approach to the ultrasensitive detection of biologically important metal ions using a magnetic nanoemulsion.


Input: The nanoemulsion used in our study was an oil-in-water emulsion droplet of average size ~ 190 nm containing ferrimagnetic iron oxide nanoparticles of average size ~ 10 nm.

iron oxide


Input: In a static magnetic field, the emulsion droplets self-assemble into a nanoarray with distinct interdroplet spacing.


Input: In the presence of cations in the solution, the nanofluid array shows a large blue shift in the diffracted Bragg peak and a visually perceivable color change due to changes in the electrical double layer upon the diffusion of cations.


Input: The colloidal force-distance measurements in the presence of cations show large variations at the onset of repulsion in the presence of cations.


Input: The sensor shows good selectivity to Na (+), K (+), Ca (2 +), Cu (2 +), and Fe (3 +) ions and offers a rapid response compared to conventional techniques.

Na (+)

K (+)

Ca (2 +)

Cu (2 +)

Fe (3 +)


Input: This approach can be useful for the recognition of biologically important cations.


Input: Steroids Glycosylated with Both d-and l-Arabinoses from the South China Sea Gorgonian Dichotella gemmacea.

Steroids

d-and l-Arabinoses


Input: Three new 19-hydroxy steroidal glycosides, namely, junceellosides E-G (2-4), were isolated together with the known analogue junceelloside C (1) from the South China Sea gorgonian Dichotella gemmacea.

19-hydroxy steroidal glycosides

junceellosides E-G

junceelloside C


Input: The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data.


Input: These glycosides are found to have sugar moieties of both beta-l-and beta-d-arabinopyranoses by HPLC analysis of their thiocarbamoyl-thiazolidine derivatives and those of authentic d-and l-arabinoses, leading to the structure revision of junceelloside C (1).

sugar

beta-l-and beta-d-arabinopyranoses

thiocarbamoyl-thiazolidine

d-and l-arabinoses

junceelloside C


Input: This is the first report of steroidal glycosides from the gorgonian D. gemmacea and the first report of glycosides with beta-l-arabinopyranose from marine sources.

beta-l-arabinopyranose


Input: In situ forming reduction-sensitive degradable nanogels for facile loading and triggered intracellular release of proteins.


Input: In situ forming reduction-sensitive degradable nanogels were designed and developed based on poly (ethylene glycol)-b-poly (2-(hydroxyethyl) methacrylate-co-acryloyl carbonate) (PEG-P (HEMA-co-AC)) block copolymers for efficient loading as well as triggered intracellular release of proteins.

poly (ethylene glycol)-b-poly (2-(hydroxyethyl) methacrylate-co-acryloyl carbonate)

PEG-P (HEMA-co-AC)


Input: PEG-P (HEMA-co-AC) copolymers were prepared with controlled Mn of 9. 1, 9. 5, and 9. 9 kg/mol and varying numbers of AC units per molecule of 7, 9 and 11, respectively (denoted as copolymer 1, 2, and 3) by reversible addition-fragmentation chain transfer copolymerization.

PEG-P (HEMA-co-AC)


Input: These copolymers were freely soluble in phosphate buffer but formed disulfide-cross-linked nanogels with defined sizes ranging from 72. 5 to 124. 1 nm in the presence of cystamine via ring-opening reaction with cyclic carbonate groups.

phosphate

disulfide

cystamine

cyclic carbonate


Input: The sizes of nanogels decreased with increasing AC units as a result of increased cross-linking density.


Input: Dynamic light scattering studies showed that these nanogels though stable at physiological conditions were rapidly dissociated in response to 10 mM dithiothreitol (DTT).

dithiothreitol

DTT


Input: Interestingly, FITC-labeled cytochrome C (FITC-CC) could be readily loaded into nanogels with remarkable loading efficiencies (up to 98. 2%) and loading contents (up to 48. 2 wt.%).

FITC

FITC


Input: The in vitro release studies showed that release of FITC-CC was minimal under physiological conditions but significantly enhanced under reductive conditions in the presence of 10 mM DTT with about 96. 8% of FITC-CC released in 22 h from nanogel 1.

FITC

DTT

FITC


Input: In contrast, protein release from 1, 4-butanediamine cross-linked nanogels (reduction-insensitive control) remained low under otherwise the same conditions.

1, 4-butanediamine


Input: MTT assays showed that these nanogels were nontoxic to HeLa cells up to a tested concentration of 2 mg/mL.

MTT


Input: Confocal microscopy results showed that nanogel 1 delivered and released FITC-CC into the perinuclei region of HeLa cells following 8 h incubation.

FITC


Input: CC-loaded reductively degradable nanogels demonstrated apparently better apoptotic activity than free CC as well as reduction-insensitive controls.


Input: These in situ forming, surfactant and oil-free, and reduction-sensitive degradable nanogels are highly promising for targeted protein therapy.


Input: Age-Related Macular Degeneration-Associated Silent Polymorphisms in HtrA1 Impair Its Ability To Antagonize Insulin-Like Growth Factor 1.


Input: Synonymous single nucleotide polymorphisms (SNPs) within a transcript' s coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function.

amino acid


Input: We report that two common variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular age-related macular degeneration (NvAMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons.


Input: The frequent-to-rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1' s conformation and function.


Input: The protein product generated from the SNP-containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti-HtrA1 antibody.


Input: The NvAMD-associated synonymous polymorphisms lie within HtrA1' s putative insulin-like growth factor 1 (IGF-1) binding domain.


Input: They reduced HtrA1' s abilities to associate with IGF-1 and to ameliorate IGF-1-stimulated signaling events and cellular responses.


Input: These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD.


Input: Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress.


Input: The NAD +-dependent deacetylases Sirt1 and Sirt2 mediate cellular stress responses and are highly expressed in vascular endothelial cells.

NAD +


Input: In contrast to the well-documented protective actions of Sirt1, the role of endothelial Sirt2 remains unknown.


Input: Using cDNA microarray and PCR validation, we examined global gene expression changes in response to Sirt2 knock down in primary human umbilical vein endothelial cells under oxidative stress.


Input: We found that Sirt2 knock down changed expression of 340 genes, which are mainly involved in cellular processes including actin binding, cellular amino acid metabolic process, transmembrane receptor protein serine/threonine kinase signaling, ferrous iron transport, protein transport and localization, cell morphogenesis, and functions associated with endosome membrane and the trans-Golgi network.

amino acid

serine

threonine

ferrous iron


Input: These genes and associated functions were largely non-overlapping with those altered by Sirt1 knock down.


Input: Moreover, we showed that pharmacological inhibition of Sirt2 attenuated oxidant-induced cell toxicity in endothelial cells.


Input: These suggest that Sirt2 is functionally important in endothelial cells under oxidative stress, and may have a primarily distinct role as compared to Sirt1.


Input: Our results may provide a basis for future studies aiming to dissect the specific signaling pathway (s) that mediates specific Sirt2 functions in endothelial cells.


Input: Genotoxic effects of the water-soluble fraction of heavy oil in the brackish/freshwater amphipod Quadrivisio aff. lutzi (Gammaridea) as assessed using the comet assay.


Input: Amphipod crustaceans have been widely used as invertebrate models in ecotoxicology due to their importance in the food chain.


Input: However, few studies have evaluated the genotoxic effects of pollutants in this model using the comet assay.


Input: The main obstacle to using amphipods in the comet assay is the difficulty in obtaining enough blood cells from a single individual.


Input: In this study, we evaluated the genotoxic effects of the water-soluble fraction (WSF) of heavy oil on the brackish/freshwater amphipod Quadrivisio aff. lutzi, which is common in the coastal lagoons of southeastern Brazil, using hemocytes obtained from single amphipods (without pooling) after optimizing hemolymph extraction.


Input: The comet assay revealed significantly higher DNA damage levels (2-to 6-fold higher) in treated amphipods compared to untreated ones with a sublethal concentration of 17. 6% of the WSF within 72 h of treatment.


Input: Two independent experiments confirmed an " up and down " pattern of DNA damage, measured as the% of DNA contained in the tail of the comets.


Input: Elevations in DNA damage levels were observed at the 6 and 48 h time points, while very low levels of DNA damage were observed at the 24 and 72 h time points.


Input: Furthermore, the comet assay revealed gender variability in the levels of DNA damage after short-term exposure.


Input: Selective poisoning of Ctnnb1-mutated hepatoma cells in mouse liver tumors by a single application of acetaminophen.

acetaminophen


Input: Mouse liver tumors that harbor activating mutations in Ctnnb1, encoding beta-catenin, express high levels of various cytochromes P450 (CYP), including CYP2E1 and CYP1A2.


Input: Acetaminophen (AAP) is metabolized in hepatocytes by these CYPs to the reactive intermediate N-acetyl-p-benzoquinone-imine, which is toxic to hepatocytes at high doses where depletion of glutathione occurs.

Acetaminophen

AAP

N-acetyl-p-benzoquinone-imine

glutathione


Input: We have induced liver tumors in mice by treatment with the liver carcinogen N-nitrosodiethylamine followed by chronic treatment with the tumor promoter phenobarbital.

N-nitrosodiethylamine

phenobarbital


Input: Under this protocol, ~ 80% of tumors display Ctnnb1 mutations and express high levels of various CYP isoforms.


Input: Tumor-bearing animals were given a single intraperitoneal injection of 300 mg/kg body weight AAP, which was well tolerated by the animals.

AAP


Input: This dose, however, eradicated essentially all larger Ctnnb1-mutated, CYP-positive liver tumors, killing > 90% of hepatoma cells: at 2 days after AAP, large necrotic areas filled with cell debris were observed in tumors.

AAP


Input: These were infiltrated in the following days by immune cells starting from the outer parts of the damaged areas slowly closing the " wounds " left from the poisoned tumor cells.


Input: During this period, there was increased proliferation of normal hepatocytes, but some residual tumor cells were also proliferating.


Input: Our results show that a selective poisoning of Ctnnb1-mutated liver tumors by administration of AAP is possible in this experimental system.

AAP


Input: Application of an adapted protocol could be envisaged for neo-adjuvant treatment of human hepatoblastoma which are frequently mutated in CTNNB1 and often show high expression of CYP2E1.


Input: Theoretical study of the thermodynamic and burning properties of oxygen-rich hydrazine derivatives-green and powerful oxidants for energetic materials.

oxygen

hydrazine


Input: A series of no-chlorine and oxygen-rich hydrazine derivatives (hydrazine modified with-NO2 and NO3 (-) groups) was designed and optimized to obtain molecular geometries and electronic structures at density functional theory-B3PW91/6-311 + + G (3df, 3pd) level.

chlorine

oxygen

hydrazine

hydrazine

NO3 (-)


Input: Some important properties such as bond dissociation enthalpy, density, natural bond orbitals, thermodynamic parameters, molecular orbital energy and burning rate were then calculated.


Input: The simulation results revealed that these compounds exhibit excellent performance, with significant superiority over traditional oxidants found in propellants.


Input: Flavonoids and 3-Arylcoumarin from Pterocarpus soyauxii.

Flavonoids


Input: Phytochemical study on the constituents of the heartwood of Pterocarpus soyauxii led to the isolation of five new isoflavonoids and one new 3-arylcoumarin, pterosonins A-F (1-6), together with 17 known analogues, among which 8, 9, and 18 were reported as natural products for the first time.

isoflavonoids

pterosonins A-F


Input: Structure elucidation was achieved by way of spectroscopic measurements as well as by comparison with literature data.


Input: Only Compound 6 showed potent cytotoxicity against human non-small cell lung cancer (A549), pancreatic cancer (Panc-28), and colon carcinoma (HCT-116) cells with GI50 values at 7. 39, 25, and 19. 17 micro M, respectively; the other isolates showed no cytotoxicity against the above tested cell lines with GI50 values > 50 micro M.


Input: Dyslipidemia in type 2 diabetes: prevalence, pathophysiology, and management.


Input: Dyslipidemia is one of the key risk factors for cardiovascular disease (CVD) in diabetes mellitus.


Input: Despite the mounting clinical trial data, the management of dyslipidemia other than lowering the low density lipoprotein cholesterol (LDL-c) continues to be controversial.

cholesterol


Input: The characteristic features of diabetic dyslipidemia are high plasma triglyceride concentration, reduced high density lipoprotein cholesterol (HDL-c) concentration, and increased concentration of small dense LDL particles.

triglyceride

cholesterol


Input: These changes are caused by increased free fatty acid flux secondary to insulin resistance and aggravated by increased inflammatory adipokines.

fatty acid


Input: The availability of several lipid-lowering drugs and nutritional supplements offers novel and effective options for achieving target lipid levels in people with diabetes.


Input: While initiation of drug therapy based on differences in the lipid profile is an option, most practice guidelines recommend statins as first-line therapy.


Input: Although the evidence for clinical utility of combination of statins with fibrates or nicotinic acid in reducing cardiovascular events remains inconclusive, the preponderance of evidence suggests that a subgroup who have high triglycerides and low HDL-c levels may benefit from combination therapy of statins and fibrates.

fibrates

nicotinic acid

triglycerides

fibrates


Input: The goal of therapy is to achieve at least 30-40% reduction in LDL-c levels.


Input: Preferably the LDL-c should be less than 100 mg/dL in low-risk people and less than 70 mg/dL in those at high risk, including people with established CVD.


Input: Crystal Structures of a Glycoside Hydrolase Family 20 Lacto-N-biosidase from Bifidobacterium bifidum.

N


Input: Human milk oligosaccharides contain a large variety of oligosaccharides, of which lacto-N-biose I (Gal-beta 1, 3-GlcNAc; LNB) predominates as a major core structure.

lacto-N-biose I

Gal-beta 1, 3-GlcNAc

LNB


Input: A unique metabolic pathway specific for LNB has recently been identified in the human commensal bifidobacteria.

LNB


Input: Several strains of infant gut-associated bifidobacteria possess lacto-N-biosidase, a membrane-anchored extracellular enzyme, that liberates LNB from the nonreducing end of human milk oligosaccharides and plays a key role in the metabolic pathway of these compounds.

N

LNB


Input: Lacto-N-biosidase belongs to the glycoside hydrolase family 20, and its reaction proceeds via a substrate-assisted catalytic mechanism.

N


Input: Several crystal structures of GH20 beta-N-acetylhexosaminidases, which release monosaccharide GlcNAc from its substrate, have been determined, but to date, a structure of lacto-N-biosidase is unknown.

N

monosaccharide GlcNAc

N


Input: Here, we have determined the first three-dimensional structures of lacto-N-biosidase from Bifidobacterium bifidum JCM1254 in complex with LNB and LNB-thiazoline (Gal-beta 1, 3-GlcNAc-thiazoline) at 1. 8-A resolution.

N

LNB

LNB-thiazoline

Gal-beta 1, 3-GlcNAc-thiazoline


Input: Lacto-N-biosidase consists of three domains, and the C-terminal domain has a unique beta-trefoil-like fold.

N

C


Input: Compared with other beta-N-acetylhexosaminidases, lacto-N-biosidase has a wide substrate-binding pocket with a-2 subsite specific for beta-1, 3-linked Gal, and the residues responsible for Gal recognition were identified.

N

N

Gal

Gal


Input: The bound ligands are recognized by extensive hydrogen bonds at all of their hydroxyls consistent with the enzyme' s strict substrate specificity for the LNB moiety.

hydrogen

hydroxyls

LNB


Input: The GlcNAc sugar ring of LNB is in a distorted conformation near (4) E, whereas that of LNB-thiazoline is in a (4) C1 conformation.

GlcNAc sugar

LNB

LNB

thiazoline


Input: A possible conformational pathway for the lacto-N-biosidase reaction is discussed.

N


Input: Degradation and Rearrangement of a Lung Surfactant Lipid at the Air-Water Interface during Exposure to the Pollutant Gas Ozone.

Ozone


Input: The presence of unsaturated lipids in lung surfactant is important for proper respiratory function.


Input: In this work, we have used neutron reflection and surface pressure measurements to study the reaction of the ubiquitous pollutant gas-phase ozone, O3, with pure and mixed phospholipid monolayers at the air-water interface.

ozone


Input: The results reveal that the reaction of the unsaturated lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC, with ozone leads to the rapid loss of the terminal C9 portion of the oleoyl strand of POPC from the air-water interface.

1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine

POPC

ozone

oleoyl

POPC


Input: The loss of the C9 portion from the interface is accompanied by an increase in the surface pressure (decrease in surface tension) of the film at the air-water interface.


Input: The results suggest that the portion of the oxidized oleoyl strand that is still attached to the lipid headgroup rapidly reverses its orientation and penetrates the air-water interface alongside the original headgroup, thus increasing the surface pressure.

oleoyl


Input: The reaction of POPC with ozone also leads to a loss of material from the palmitoyl strand, but the loss of palmitoyl material occurs after the loss of the terminal C9 portion from the oleoyl strand of the molecule, suggesting that the palmitoyl material is lost in a secondary reaction step.

POPC

ozone

palmitoyl

palmitoyl

oleoyl

palmitoyl


Input: Further experiments studying the reaction of mixed monolayers composed of unsaturated lipid POPC and saturated lipid dipalmitoyl-sn-glycero-3-phosphocholine, DPPC, revealed that no loss of DPPC from the air-water interface occurs, eliminating the possibility that a reactive species such as an OH radical is formed and is able to attack nearby lipid chains.

POPC

DPPC

DPPC

OH


Input: The reaction of ozone with the mixed films does cause a significant change in the surface pressure of the air-water interface.

ozone


Input: Thus, the reaction of unsaturated lipids in lung surfactant changes and impairs the physical properties of the film at the air-water interface.


Input: MD simulations of the formation of stable clusters in mixtures of alkaline salts and imidazolium-based ionic liquids.

alkaline salts

imidazolium


Input: Structural and dynamical properties of room-temperature ionic liquids containing the cation 1-butyl-3-methylimidazolium ([BMIM] (+)) and three different anions (hexafluorophosphate, [PF6] (-), tetrafluoroborate, [BF4] (-), and bis (trifluoromethylsulfonyl) imide, [NTf2] (-)) doped with several molar fractions of lithium salts with a common anion at 298. 15 K and 1 atm were investigated by means of molecular dynamics simulations.

[BMIM] (+)

hexafluorophosphate

[PF6] (-)

tetrafluoroborate

[BF4] (-)

bis (trifluoromethylsulfonyl) imide

[NTf2] (-)

lithium


Input: The effect of the size of the salt cation was also analyzed by comparing these results with those for mixtures of [BMIM] [PF6] with NaPF6.

[BMIM] [PF6]


Input: Lithium/sodium solvation and ionic mobilities were analyzed via the study of radial distribution functions, coordination numbers, cage autocorrelation functions, mean-square displacements (including the analysis of both ballistic and diffusive regimes), self-diffusion coefficients of all the ionic species, velocity and current autocorrelation functions, and ionic conductivity in all the ionic liquid/salt systems.

Lithium

sodium


Input: We found that lithium and sodium cations are strongly coordinated in two different positions with the anion present in the mixture.

lithium

sodium


Input: Moreover, [Li] (+) and [Na] (+) cations were found to form bonded-like, long-lived aggregates with the anions in their first solvation shell, which act as very stable kinetic entities within which a marked rattling motion of salt ions takes place.

[Li] (+)

[Na] (+)


Input: With very long MD simulation runs, this phenomenon is proved to be on the basis of the decrease of self-diffusion coefficients and ionic conductivities previously reported in experimental and computational results.


Input: The Emerging Use of Ketamine for Anesthesia and Sedation in Traumatic Brain Injuries.

Ketamine


Input: BACKGROUND: Traditionally, the use of ketamine for patients with traumatic brain injuries is contraindicated due to the concern of increasing intracranial pressure (ICP).

ketamine


Input: These concerns, however, originated from early studies and case reports that were inadequately controlled and designed.


Input: Recently, the concern of using ketamine in these patients has been challenged by a number of published studies demonstrating that the use of ketamine was safe in these patients.

ketamine

ketamine


Input: AIMS: The purpose of this article was to review the current literature in regards to using ketamine in patients with traumatic brain injuries in different clinical settings associated with anesthesia, as well as review the potential mechanisms underlying the neuroprotective effects of ketamine.

ketamine

ketamine


Input: RESULTS: Studies examining the use of ketamine for induction, maintenance, and sedation in patients with TBI have had promising results.

ketamine


Input: The use of ketamine in a controlled ventilation setting and in combination with other sedative agents has demonstrated no increase in ICP.

ketamine


Input: CONCLUSIONS: The role of ketamine as a neuroprotective agent in humans remains inconclusive and adequately powered; randomized controlled trials performed in patients undergoing surgery for traumatic brain injury are necessary.

ketamine


Input: Killed Bacillus subtilis spores expressing streptavidin: a novel carrier of drugs to target cancer cells.


Input: Abstract Carriers of drugs in cancer therapy are required to reduce side-effects of the drugs to normal cells.


Input: Here we constructed killed recombinant Bacillus subtilis spores (SA1) that expressed streptavidin as a chimeric fusion to the spore coat protein CotB and used the spores as bioparticle carrier.


Input: When bound with biotinylated cetuximab these spores could specifically target to the epidermal growth factor receptor on HT 29 colon cancer cells, thereby delivered paclitaxel to the cells with 4-fold higher efficiency, as indicated by fluorescent intensity of paclitaxel Oregon Green 488 bound to HT29 cells.

paclitaxel

paclitaxel Oregon Green 488


Input: Based on real-time monitoring of cell index, the IC50 of growth of HT29 cells by paclitaxel-SA1-cetuximab was estimated to be 2. 9 nM approximately 5-fold lower than water-soluble paclitaxel (14. 5 nM).

paclitaxel

paclitaxel


Input: Instability of DNA content was observed when cells were treated with 16 nM paclitaxel-SA1-cetuximab, resulting in a 2-fold enhancement in polyploidy cells.

paclitaxel


Input: Thus, by targeting the release of paclitaxel to HT29 cells, spore-associated cetuximab augmented the inhibitory effect of paclitaxel on cell division and proliferation.

paclitaxel

paclitaxel


Input: The SA1 could be used as a " universal " drug carrier to target specific biomarkers on cancer cells by conjugating with suitable biotinylated antibodies.


Input: 9G DNAChip Technology: Self-Assembled Monolayer (SAM) of ssDNA for Ultra-Sensitive Detection of Biomarkers.


Input: A 9G DNAChip obtained by allowing the formation of a self-assembled monolayer (SAM) of oligonucleotides appended with nine consecutive guanines on the chip surface has been applied in the detection of biomarkers.

guanines


Input: Using a 9G DNAChip, biomarker in the concentration range of 4 pg/mL to 40 fg/mL can be easily differentiated in the buffer matrix.


Input: Moreover, it is the first time that a biomarker with a concentration of 40 fg/mL has been detected in a mixture of proteins without use of any signal amplification technique.


Input: Preclinical Activity of Simvastatin Induces Cell Cycle Arrest in G1 via Blockade of Cyclin D-Cdk4 Expression in Non-Small Cell Lung Cancer (NSCLC).

Simvastatin


Input: Lung cancer is the most common cause of cancer-related death.


Input: Nonetheless, a decrease in overall incidence and mortality has been observed in the last 30 years due to prevention strategies and improvements in the use of chemotherapeutic agents.


Input: In recent studies, Simvastatin (SIM) has demonstrated anti-tumor activity, as well as potent chemopreventive action.

Simvastatin

SIM


Input: As an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), SIM has been shown to stimulate apoptotic cell death.

3-hydroxy-3-methylglutaryl-coenzyme A

HMG

CoA

SIM


Input: In this study, an MTT assay revealed the cytotoxic activity of SIM against human large cell lung cancer (Non-small cell lung cancer; NSCLC) cells (NCI-H460); however, induced apoptosis was not observed in NCI-H460 cells.

MTT

SIM


Input: Protein expression levels of cell cycle regulating proteins Cdk4, Cyclin D1, p16 and p27 were markedly altered by SIM.

SIM


Input: Collectively, our results indicate that SIM inhibits cell proliferation and arrests NCI-H460 cell cycle progression via inhibition of cyclin-dependent kinases and cyclins and the enhancement of CDK inhibitors p16 and p27.

SIM


Input: Our findings suggest that, in addition to the known effects on hypercholesterolemia therapy, SIM may also provide antitumor activity in established NSCLC.

SIM


Input: Substituted 1, 6-diphenylnaphthalenes as FtsZ-targeting antibacterial agents.

1, 6-diphenylnaphthalenes


Input: Bacterial cell division occurs in conjunction with the formation of a cytokinetic Z-ring structure comprised of FtsZ subunits.


Input: Agents that disrupt Z-ring formation have the potential, through this unique mechanism, to be effective against several of the newly emerging multidrug-resistant strains of infectious bacteria.


Input: Several 1-phenylbenzo [c] phenanthridines exhibit notable antibacterial activity.

1-phenylbenzo [c] phenanthridines


Input: Based upon their structural similarity to these compounds, a distinct series of substituted 1, 6-diphenylnaphthalenes were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and Enterococcus faecalis.

1, 6-diphenylnaphthalenes


Input: In addition, the effect of select 1, 6-diphenylnaphthalenes on the polymerization dynamics of S. aureus FtsZ and mammalian beta-tubulin was also assessed.

1, 6-diphenylnaphthalenes


Input: The presence of a basic functional group or a quaternary ammonium substituent on the 6-phenylnaphthalene was required for significant antibacterial activity.

quaternary ammonium


Input: Diphenylnaphthalene derivatives that were active as antibiotics, did exert a pronounced effect on bacterial FtsZ polymerization and do not appear to cross-react with mammalian tubulin to any significant degree.

Diphenylnaphthalene


Input: Characterization of the 5-hydroxymethylcytosine-specific DNA restriction endonucleases.


Input: In T4 bacteriophage, 5-hydroxymethylcytosine (5hmC) is incorporated into DNA during replication.


Input: In response, bacteria may have developed modification-dependent type IV restriction enzymes to defend the cell from T4-like infection.


Input: PvuRts1I was the first identified restriction enzyme to exhibit specificity toward hmC over 5-methylcytosine (5mC) and cytosine.

hmC

cytosine


Input: By using PvuRts1I as the original member, we identified and characterized a number of homologous proteins.


Input: Most enzymes exhibited similar cutting properties to PvuRts1I, creating a double-stranded cleavage on the 3' side of the modified cytosine.

cytosine


Input: In addition, for efficient cutting, the enzymes require two cytosines 21-22-nt apart and on opposite strands where one cytosine must be modified.

cytosines

cytosine


Input: Interestingly, the specificity determination unveiled a new layer of complexity where the enzymes not only have specificity for 5-beta-glucosylated hmC (5 beta ghmC) but also 5-alpha-glucosylated hmC (5 alpha ghmC).

5-beta-glucosylated hmC

5 beta ghmC

5-alpha-glucosylated hmC

5 alpha ghmC


Input: In some cases, the enzymes are inhibited by 5 beta ghmC, whereas in others they are inhibited by 5 alpha ghmC.

5 beta ghmC

5 alpha ghmC


Input: These observations indicate that the position of the sugar ring relative to the base is a determining factor in the substrate specificity of the PvuRts1I homologues.

sugar


Input: Lastly, we envision that the unique properties of select PvuRts1I homologues will permit their use as an additive or alternative tool to map the hydroxymethylome.


Input: Chirality sensing using stereodynamic probes with distinct electronic circular dichroism output.


Input: Circular dichroism (CD) spectroscopy is one of the most useful techniques for the stereochemical analysis of chiral biopolymers and fine chemicals.


Input: It has become invaluable for the assignment of the absolute configuration, the study of conformational isomers, and the determination of racemization kinetics of CD active chiral compounds.


Input: Molecular interactions between a nonracemic chiral substrate and a chromophoric, CD-silent probe that is achiral or exists as a racemic mixture of rapidly interconverting enantiomeric conformations or configurations can induce a strong, characteristic chiroptical readout.


Input: A covalent or noncovalent binding event that coincides with a well-defined asymmetric induction process can effectively imprint the chiral information of the substrate on the stereodynamic sensor and thus generate intense Cotton effects in the UV region of the latter.


Input: The probe can thus function as a stereochemical reporter unit and analysis of the CD spectrum often provides accurate information about the absolute configuration and enantiomeric composition of the substrate used.


Input: In this review, recent developments in circular dichroism analysis of chiral compounds with stereodynamic probes are described and particular emphasis is given to sensor design, chiral induction processes and applications scope.


Input: The induction of mitochondria-mediated apoptosis in cancer cells by ruthenium (ii) asymmetric complexes.

ruthenium (ii)


Input: Four ruthenium (ii) asymmetric complexes, [Ru (bpy) 2 (PAIDH)] (2 +) (bpy = 2, 2'-bipyridine, PAIDH = 2-pyridyl-1H-anthra [1, 2-d] imidazole-6, 11-dione,), [Ru (phen) 2 (PAIDH)] (2 +) (phen = 1, 10-phenanthroline,), [Ru (dmp) 2 (PAIDH)] (2 +) (dmp = 4, 7-dimethyl-1, 10-phenanthroline,) and [Ru (dip) 2 (PAIDH)] (2 +) (dip = 4, 7-diphenyl-1, 10-phenanthroline,), have been synthesized and characterized.

ruthenium (ii)

[Ru (bpy) 2 (PAIDH)] (2 +)

bpy

2, 2'-bipyridine

PAIDH

2-pyridyl-1H-anthra [1, 2-d] imidazole-6, 11-dione

[Ru (phen) 2 (PAIDH)] (2 +)

phen

1, 10-phenanthroline

[Ru (dmp) 2 (PAIDH)] (2 +)

dmp

4, 7-dimethyl-1, 10-phenanthroline

[Ru (dip) 2 (PAIDH)] (2 +)

dip

4, 7-diphenyl-1, 10-phenanthroline


Input: These complexes displayed potent anti-proliferation activity against various cancer cell lines and had high selectivity between tumor cells and normal cells.


Input: HeLa cells exhibited the highest sensitivity to complex, accounting for the greatest cellular uptake.


Input: Complex was shown to accumulate preferentially in the mitochondria of HeLa cells and induced apoptosis via the mitochondrial pathway, which involved ROS generation, mitochondrial membrane potential depolarisation, and Bcl-2 and caspase family members activation.


Input: These results demonstrated that complex induced cancer cell apoptosis by acting on mitochondrial pathways.


Input: Mechanisms of RAS/beta-catenin interactions.


Input: Signaling through the WNT/beta-catenin and the RAS (rat sarcoma)/MAPK (mitogen-activated protein kinase) pathways plays a key role in the regulation of various physiological cellular processes including proliferation, differentiation, and cell death.


Input: Aberrant mutational activation of these signaling pathways is closely linked to the development of cancer in many organs, in humans as well as in laboratory animals.


Input: Over the past years, more and more evidence for a close linkage of the two oncogenic signaling cascades has accumulated.


Input: Using different experimental approaches, model systems, and experimental conditions, a variety of molecular mechanisms have been identified by which signal transduction through WNT/beta-catenin and RAS interact, either in a synergistic or an antagonistic manner.