Input: Bioaccumulation by filter-feeding bivalves and fish and subsequent transfer through the food web results in the potentially fatal human illnesses, paralytic shellfish poisoning and saxitoxin pufferfish poisoning.

saxitoxin


Input: These illnesses are a result of saxitoxin' s ability to bind to the voltage-gated sodium channel, blocking the passage of nerve impulses and leading to death via respiratory paralysis.

saxitoxin

sodium


Input: Recent advances in saxitoxin research are discussed, including the molecular biology of toxin synthesis, new protein targets, association with metal-binding motifs and methods of detection.

saxitoxin


Input: The eco-evolutionary role (s) PSTs may serve for phytoplankton species that produce them are also discussed.


Input: Modulation of the JAK/ERK/STAT signaling in melanocortin-induced inhibition of local and systemic responses to myocardial ischemia/reperfusion.


Input: The janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) pathways have been shown to play a cardioprotective role.


Input: We previously gave evidence that melanocortins afford cardioprotection in conditions of myocardial ischemia/reperfusion.


Input: Here we aimed to investigate the influence of melanocortins on the JAK/ERK/STAT signaling in cardiac and systemic responses to prolonged myocardial ischemia/reperfusion.


Input: Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30min.


Input: At the end of the 2-h reperfusion, western blot analysis of the cardioprotective transcription factors pJAK2, pERK1/2, pTyr-STAT3 and pSer-STAT3, the inflammatory mediator tumor necrosis factor-alpha (TNF-alpha), the pro-apoptotic factors BAX and c-jun N-terminal kinases (pJNK), the anti-apoptotic protein Bcl-XL, as well as of the cardioprotective enzyme heme oxygenase-1 (HO-1), was performed in the left ventricle and spleen.


Input: Intravenous treatment, during coronary artery occlusion, with the melanocortin analogs [Nle (4), D-Phe (7)] alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) and adrenocorticotropic hormone 1-24 [ACTH-(1-24)], induced a left ventricle up-regulation of pJAK2, pERK1/2 and pTyr-STAT3 (JAK-dependent), and a reduction in pJNK and TNF-alpha levels; these effects of NDP-alpha-MSH and ACTH-(1-24) were associated with over-expression of the pro-survival proteins HO-1 and Bcl-XL, and marked decrease of the myocardial infarct size.

Nle

D-Phe


Input: Melanocortin treatment did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and BAX levels.


Input: In the spleen, NDP-alpha-MSH and ACTH-(1-24) induced similar effects on the expression of the above transcription factors/proteins, except for pERK1/2 (down-regulated) and HO-1 (unaffected).


Input: Blockade of JAK and ERK pathways with AG490 and U0126, respectively, abrogated the myocardial infarct size reduction by NDP-alpha-MSH.


Input: These results indicate that melanocortins inhibit local and systemic inflammatory and apoptotic cascades triggered by prolonged myocardial ischemia/reperfusion, with consequent reduction in myocardium infarct size, seemingly via activation of the JAK/STAT signaling and with modulation of an ERK (STAT unrelated) signaling pathway.


Input: Global increases in both common and rare copy number load associated with autism.


Input: Children with autism have an elevated frequency of large, rare copy number variants (CNVs).


Input: However, the global load of deletions or duplications, per se, and their size, location and relationship to clinical manifestations of autism have not been documented.


Input: We examined CNV data from 516 individuals with autism or typical development from the population-based Childhood Autism Risks from Genetics and Environment (CHARGE) study.


Input: We interrogated 120 regions flanked by segmental duplications (genomic hotspots) for events > 50 kbp and the entire genomic backbone for variants > 300 kbp using a custom targeted DNA microarray.


Input: This analysis was complemented by a separate study of five highly dynamic hotspots associated with autism or developmental delay syndromes, using a finely tiled array platform (> 1 kbp) in 142 children matched for gender and ethnicity.


Input: In both studies, a significant increase in the number of base pairs of duplication, but not deletion, was associated with autism.


Input: Significantly elevated levels of CNV load remained after the removal of rare and likely pathogenic events.


Input: Further, the entire CNV load detected with the finely tiled array was contributed by common variants.


Input: The impact of this variation was assessed by examining the correlation of clinical outcomes with CNV load.


Input: The level of personal and social skills, measured by Vineland Adaptive Behavior Scales, negatively correlated (Spearman' s r =-0. 13, P = 0. 034) with the duplication CNV load for the affected children; the strongest association was found for communication (P = 0. 048) and socialization (P = 0. 022) scores.


Input: We propose that CNV load, predominantly increased genomic base pairs of duplication, predisposes to autism.


Input: Controlling potassium selectivity and proton blocking in a hybrid biological/solid-state polymer nanoporous membrane.

potassium


Input: Specific separations of protons and cations are usually performed by electromembrane processes, which require external electric energy.


Input: An easier process would be using a membrane able to separate both entities by passive diffusion.


Input: Presently, such synthetic nanoporous membranes do not exist.


Input: Here, we report the production of a robust hybrid biological/artificial solid-state membrane, which allows selective permeation of alkali metal cations without competing or concurrent permeation of protons.


Input: This membrane is simple to prepare and is based on the hydrophobic nature of the polymeric pore walls, and the confined gramicidin A molecules within.


Input: This work opens a new route for separation in the domain of nanobiofiltration, especially for tunable nanodevices based on differential ion conduction, with a fundamental understanding of the confinement mechanism.


Input: Comparing the sensitivity of geographically distinct Lemna minor populations to atrazine.

atrazine


Input: The objectives of this study were to compare the sensitivities of field populations and a laboratory culture of a duckweed species (Lemna minor) to the herbicide atrazine using three different endpoints and to determine whether sensitivity to atrazine was affected by past exposure to the herbicide.

atrazine

atrazine


Input: L. minor cultures were purchased commercially or collected from field sites within an agricultural watershed and exposed to atrazine for 7 days under greenhouse conditions.

atrazine


Input: Populations differed significantly in their sensitivity to atrazine.

atrazine


Input: Biomass was more sensitive than frond number, while chlorophyll fluorescence was not a sensitive endpoint.


Input: Overall, the sensitivity of the various populations to atrazine was not strongly related to measures of past exposure to agriculture stressors.

atrazine


Input: Positive correlations between biomass twenty-five percent inhibition concentrations (IC25s), biomass estimated marginal means and in-stream atrazine concentrations were observed, providing evidence that atrazine exposure is linked to a decrease in sensitivity to atrazine.

atrazine

atrazine

atrazine


Input: However, IC25s generated for each population were similar, ranging from 19 to 40 and 57 to 92 mu g/L atrazine for biomass and frond data respectively, and likely do not represent biologically significant differences in atrazine sensitivity.

atrazine

atrazine


Input: Given the small range in sensitivity observed between populations, commercial laboratory cultures appear to provide a good estimate of the sensitivity of field populations of L. minor to atrazine and should continue to be used in regulatory phytotoxicity testing.

atrazine


Input: Challenges and approaches for the development of safer immunomodulatory biologics.


Input: Immunomodulatory biologics, which render their therapeutic effects by modulating or harnessing immune responses, have proven their therapeutic utility in several complex conditions including cancer and autoimmune diseases.


Input: However, unwanted adverse reactions--including serious infections, malignancy, cytokine release syndrome, anaphylaxis and hypersensitivity as well as immunogenicity--pose a challenge to the development of new (and safer) immunomodulatory biologics.


Input: In this article, we assess the safety issues associated with immunomodulatory biologics and discuss the current approaches for predicting and mitigating adverse reactions associated with their use.


Input: We also outline how these approaches can inform the development of safer immunomodulatory biologics.


Input: beta-Ionone arrests cell cycle of gastric carcinoma cancer cells by a MAPK pathway.

beta-Ionone


Input: beta-Ionone is an end ring analog of beta-carotenoid which has been shown to possess potent anti-proliferative activity both in vitro and in vivo.

beta-Ionone


Input: To investigate the possible inhibitory effects of beta-ionone, we studied cell growth characteristics, DNA synthesis, cell cycle progression, as well as mitogen-activated protein kinases (MAPKs) pathways in the human gastric adenocarcinoma cancer cell line (SGC-7901).

beta-ionone


Input: Our results show that cell growth and DNA synthesis were inhibited, and the cell cycle was arrested at the G0/G1 phase in a dose-dependent manner in cells treated with beta-ionone (25, 50, 100 and 200 mu mol/L) for 24 h.

beta-ionone


Input: We found that the beta-ionone significantly decreased the extracellular signal-regulated kinase protein expression and significantly increased the levels of p38 and Jun-amino-terminal kinase protein expression (P < 0. 01).

beta-ionone

amino


Input: beta-Ionone also inhibited cell cycle-related proteins of Cdk4, Cyclin B1, D1 and increased p27 protein expression in SGC-7901 cells.

beta-Ionone


Input: These results suggested that the cell cycle arrest observed may be regulated through a MAPK pathway by transcriptional down-regulation of cell cycle proteins.


Input: These results demonstrate potent ability of beta-ionone to arrest cell cycle of SGC-7901 cells and decrease proliferation.

beta-ionone


Input: Regulation of neutrophil extracellular trap formation by anti-inflammatory drugs.


Input: The formation of neutrophil extracellular traps (NETs) is a newly described phenomenon that increases the bacteria killing ability and the inflammatory response of neutrophils.


Input: Because NET generation occurs in an inflammatory microenvironment, we examined its regulation by anti-inflammatory drugs.


Input: Treatment of neutrophils with dexamethasone had no effect while acetylsalicylic acid (ASA) treatment prevented NET formation.

dexamethasone

acetylsalicylic acid

ASA


Input: NETosis was also abrogated by the presence of BAY 11-7082 and Ro 106-9920, two structurally unrelated NF-kappa B inhibitors.

BAY 11-7082

Ro 106-9920


Input: The decrease in NET formation mediated by ASA, BAY-11-7082 and Ro 106-9920 was correlated with a significant reduction in the phosphorylation of NF-kappa B p65 subunit, indicating that the activation of this transcription factor is a relevant signaling pathway involved in the generation of DNA traps.

ASA

Ro 106-9920


Input: The inhibitory effect of these drugs was also observed when NET generation was induced under acidic or hyperthermic conditions, two stress signals of the inflammatory microenvironment.


Input: In a mouse peritonitis model, while pretreatment of animals with ASA or BAY 11-7082 resulted in a marked suppression of NET formation along with increased bacteremia, dexamethasone had no effect.

ASA

BAY 11-7082

dexamethasone


Input: Our results show that NETs have an important role in the local control of infection and that ASA and NF-kappa B blockade could be useful therapies to avoid undesired effect of persistent neutrophil activation.

ASA


Input: Fasting Plasma Glucose at 24-28 Weeks to Screen for Gestational Diabetes Mellitus: New evidence from China.

Glucose


Input: OBJECTIVETo evaluate the usefulness of a fasting plasma glucose (FPG) at 24-28 weeks' gestation to screen for gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODSThe medical records and results of a 75-g 2-h oral glucose tolerance test (OGTT) of 24, 854 pregnant women without known pre-GDM attending prenatal clinics in 15 hospitals in China were examined. RESULTSFPG cutoff value of 5. 1 mmol/L identified 3, 149 (12. 1%) pregnant women with GDM.

glucose

glucose


Input: FPG cutoff value of 4. 4 mmol/L ruled out GDM in 15, 369 (38. 2%) women.


Input: With use of this cutoff point, 12. 2% of patients with mild GDM will be missed.


Input: The positive predictive value is 0. 322, and the negative predictive value is 0. 928. CONCLUSIONSFPG at 24-28 weeks' gestation could be used as a screening test to identify GDM patients in low-resource regions.


Input: Women with an FPG between >= 4. 4 and <= 5. 0 mmol/L would require a 75-g OGTT to diagnose GDM.


Input: This would help to avoid approximately one-half (50. 3%) of the formal 75-g OGTTs in China.


Input: Efficacy and Safety of Lixisenatide Once-Daily Morning or Evening Injections in Type 2 Diabetes Inadequately Controlled on Metformin (GetGoal-M).

Metformin


Input: OBJECTIVEExamine the efficacy and safety of lixisenatide (20 mu g once daily, administered before the morning or evening meal) as add-on therapy in type 2 diabetes patients insufficiently controlled with metformin alone. RESEARCH DESIGN AND METHODSA 24-week, randomized, double-blind, placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes (HbA1c 7-10% [53-86 mmol/mol]).

metformin


Input: Patients were randomized to lixisenatide morning (n = 255), lixisenatide evening (n = 255), placebo morning (n = 85), or placebo evening (n = 85) injections. RESULTSLixisenatide morning injection significantly reduced mean HbA1c versus combined placebo (mean change-0. 9% [9. 8 mmol/mol] vs.-0. 4% [4. 4 mmol/mol]; least squares [LS] mean difference vs. placebo-0. 5% [5. 5 mmol/mol], P < 0. 0001).


Input: HbA1c was significantly reduced by lixisenatide evening injection (mean change-0. 8% [8. 7 mmol/mol] vs.-0. 4% [4. 4 mmol/mol]; LS mean difference-0. 4% [4. 4 mmol/mol], P < 0. 0001).


Input: Lixisenatide morning injection significantly reduced 2-h postprandial glucose versus morning placebo (mean change-5. 9 vs.-1. 4 mmol/L; LS mean difference-4. 5 mmol/L, P < 0. 0001).

glucose


Input: LS mean difference in fasting plasma glucose was significant in both morning (-0. 9 mmol/L, P < 0. 0001) and evening (-0. 6 mmol/L, P = 0. 0046) groups versus placebo.

glucose


Input: Mean body weight decreased to a similar extent in all groups.


Input: Rates of adverse events were 69. 4% in both lixisenatide groups and 60. 0% in the placebo group.


Input: Rates for nausea and vomiting were 22. 7 and 9. 4% for lixisenatide morning and 21. 2 and 13. 3% for lixisenatide evening versus 7. 6 and 2. 9% for placebo, respectively.


Input: Symptomatic hypoglycemia occurred in 6, 13, and 1 patient for lixisenatide morning, evening, and placebo, respectively, with no severe episodes. CONCLUSIONSIn patients with type 2 diabetes inadequately controlled on metformin, lixisenatide 20 mu g once daily administered in the morning or evening significantly improved glycemic control, with a pronounced postprandial effect, and was well tolerated.

metformin


Input: Tumor Suppressor Protein p53 Negatively Regulates Human Pregnane X Receptor Activity.

Pregnane


Input: The human pregnane X receptor (PXR) regulates genes involved in drug metabolism and disposition.


Input: PXR associates with multiple corepressors that attenuate, and coactivators that enhance its activity.


Input: PXR plays a vital role in the drug metabolism pathway, and a comprehensive examination of PXR-associated proteins will provide greater insight into the regulation of the receptor and possible therapeutic implications.


Input: We performed a mass spectrometric screen to identify PXR-associated proteins.


Input: Here we report that the tumor suppressor protein p53 can associate with PXR and downregulate its activity.


Input: A loss-of-function p53 mutant (R175H) interacts with PXR but does not repress its activity.


Input: Mutant p53 can relieve the suppressive effect of wild-type p53 by competing with its interaction with PXR, suggesting that protein-protein interaction is required but not sufficient for p53 to repress PXR activity.


Input: Interestingly, a PXR variant with a naturally occurring deletion of a conserved, unique sequence in the ligand binding domain (PXR174-210) did not interact with p53, indicating that the PXR-p53 interaction is specific.


Input: Using a chromatin immunoprecipitation assay, we showed that p53 inhibits the binding of PXR to the CYP3A4 promoter.


Input: The loss of p53 function in tumor cells leads to aberrant cell proliferation, apoptosis, carcinogenesis, and altered sensitivity to chemotherapeutic drugs, while PXR contributes to chemoresistance in many cancer cells.


Input: Our findings show for the first time that wild-type p53 can negatively regulate PXR by physically associating with it.


Input: Thus, PXR and p53 appear to play important yet opposing roles in the sensitivity of tumor cells to chemotherapy.


Input: Efficient anodic allylation and benzylation of carbons using allyl and benzyl trimethylsilanes.

carbons

allyl

benzyl trimethylsilanes


Input: An easy process for allylation and benzylation of different carbon materials, primarily of glassy carbon, in acetonitrile solutions containing tetraalkyammonium salts is described.

carbon

glassy carbon

acetonitrile

tetraalkyammonium


Input: The method relies on the capability of C (sp (2)) zones of glassy carbon (graphite and fullerene-like inclusions) to be anodically charged at potentials > 1. 5 V versus Ag/AgCl to form electrophilic centers reacting with substituted trimethylsilanes RSiMe3.

C

glassy carbon

graphite

fullerene

Ag

AgCl

trimethylsilanes RSiMe3


Input: Great propensity of the trimethylsilyl group (TMS (+)) to act as a cationic leaving group facilitates electrophilic reactions of the charged anodic surface with R-carrying silylated precursors, permitting efficient grafting of a large variety of R groups.

trimethylsilyl

TMS (+)


Input: The present preliminary work focuses only on the efficient grafting of benzyl and allyl moieties.

benzyl

allyl


Input: Hydrocarbon-soluble nanocatalysts with no bulk phase: coplanar, two-coordinate arrays of the base metals.

Hydrocarbon


Input: A structurally unique class of hydrocarbon-soluble, ancillary-ligand-free, tetrametallic Co (I) and Ni (I) clusters is reported.

hydrocarbon

Co (I)

Ni (I)


Input: The highly unsaturated complexes are supported by simple, sterically bulky phosphoranimide ligands, one per metal.

phosphoranimide


Input: The electron-rich nitrogen centers are strongly bridging but sterically limited to bimetallic interactions.

nitrogen


Input: The hydrocarbon-soluble clusters consist of four coplanar metal centers, mutually bridged by single nitrogen atoms.

hydrocarbon

nitrogen


Input: Each metal center is monovalent, rigorously linear, and two-coordinate.


Input: The clusters are in essence two-dimensional atomic-scale " molecular squares, " a structural motif adapted from supramolecular chemistry.


Input: Both clusters exhibit high solution-phase magnetic susceptibility at room temperature, suggesting the potential for applications in molecular electronics.


Input: Designed to be catalyst precursors, both clusters exhibit high activity for catalytic hydrogenation of unsaturated hydrocarbons at low pressure and temperature.

unsaturated hydrocarbons


Input: Spray drying method for large-scale and high-performance silicon negative electrodes in li-ion batteries.

silicon

li


Input: Nanostructured silicon electrodes have shown great potential as lithium ion battery anodes because they can address capacity fading mechanisms originating from large volume changes of silicon alloys while delivering extraordinarily large gravimetric capacities.

silicon

lithium

silicon


Input: Nonetheless, synthesis of well-defined silicon nanostructures in an industrially adaptable scale still remains as a challenge.

silicon


Input: Herein, we adopt an industrially established spray drying process to enable scalable synthesis of silicon-carbon composite particles in which silicon nanoparticles are embedded in porous carbon particles.

silicon

carbon

silicon

carbon


Input: The void space existing in the porous carbon accommodates the volume expansion of silicon and thus addresses the chronic fading mechanisms of silicon anodes.

carbon

silicon

silicon


Input: The composite electrodes exhibit excellent electrochemical performance, such as 1956 mAh/g at 0. 05C rate and 91% capacity retention after 150 cycles.


Input: Moreover, the spray drying method requires only 2 s for the formation of each particle and allows a production capability of ~ 10 g/h even with an ultrasonic-based lab-scale equipment.


Input: This investigation suggests that established industrial processes could be adaptable to the production of battery active materials that require sophisticated nanostructures as well as large quantity syntheses.


Input: Enantioselective Iron-Catalyzed Azidation of beta-Keto Esters and Oxindoles.

Iron

beta-Keto Esters

Oxindoles


Input: The first example of Fe-catalyzed enantioselective azidations of beta-keto esters and oxindoles using a readily available N3-transfer reagent is reported.

Fe

beta-keto esters

oxindoles


Input: A number of alpha-azido-beta-keto esters were obtained with up to 93% ee, and this methodology also generates 3-substitued 3-azidooxindoles with high enantioselectivities (up to 94%).

alpha-azido-beta-keto esters

3-substitued 3-azidooxindoles


Input: Design of pH responsive clickable prodrugs applied to histone deacetylase inhibitors: A new strategy for anticancer therapy.


Input: The aim of this study was to develop clickable prodrugs bearing a tunable pH responsive linker designed for acidic pH-mediated release of histone deacetylase inhibitors.


Input: HDACi are an important class of molecules belonging to the epigenetic modulators used for innovative cancer strategies.


Input: The behavior of these prodrugs was determined by a bioluminescence resonance energy transfer assay in living tumor cells.


Input: This work demonstrated that this innovative type of clickable prodrugs entered cancer cells and showed restored anti proliferative properties attributed to the effective release of the HDAC inhibitors.


Input: A correlation between kinetic studies, dose responses, and biological activities was obtained, making such clickable prodrugs good candidates for new strategies in epigenetic-oriented anticancer therapies.


Input: Antioxidant and micronutrient-rich milk formula reduces lead poisoning and related oxidative damage in lead-exposed mice.


Input: Lead poisoning is a global environmental disease that induces lifelong adverse health effects.


Input: The effect of a milk formula consisting of antioxidant of bamboo leaves (AOB), vitamin C (Vc), calcium lactate (CaLac), ferrous sulfate (FeSO4) and zinc sulfate (ZnSO4) on the reduction of lead and lead-induced oxidative damage in lead-exposed mice was studied.

vitamin C

calcium lactate

CaLac

ferrous sulfate

zinc sulfate


Input: The lead-reducing effect of milk formula was investigated via a 7-week toxicokinetics study and a tissue distribution level examination.


Input: The ameliorating effect of milk formula on lead-induced oxidative damage was investigated.


Input: Results demonstrated current milk formula could effectively reduce blood lead levels (BLLs) and lead distribution levels of liver, kidneys, thighbones and brain in mice based on metal ion-mediated antagonism and chelation mechanisms.


Input: This milk formula could not only protect lead-susceptible tissues against lead poisoning, but also maintain normal absorption and distribution of essential elements in vivo.


Input: Meanwhile, current milk formula could prevent the reduction of delta-aminolevulinic acid dehydratase (delta-ALAD) activity and enhancement of free erythrocyte protoporphyrins (FEP) levels in blood erythrocytes of mice.

delta-aminolevulinic acid

protoporphyrins


Input: Also, this formula could indirectly protect blood cell membranes against lead-induced lipid peroxidation.


Input: We conclude that current optimized milk formula effectively reduces lead poisoning and lead-induced in vivo oxidative damage in lead-exposed mice.


Input: Oxidative stress and myocardial dysfunction in young rabbits after short term anabolic steroids administration.


Input: The present study focuses on the short term effects of repeated low level administration of turinabol and methanabol on cardiac function in young rabbits (4months-old).

turinabol

methanabol


Input: The experimental scheme consisted of two oral administration periods, lasting 1month each, interrupted by 1-month wash-out period.


Input: Serial echocardiographic evaluation at the end of all three experimental periods was performed in all animals.


Input: Oxidative stress markers have also been monitored at the end of each administration period.


Input: Treated animals originally showed significantly increased myocardial mass and systolic cardiac output, which normalized at the end of the wash out period.


Input: Re-administration led to increased cardiac output, at the cost though of a progressive myocardial mass reduction.


Input: A dose-dependent trend towards impaired longitudinal systolic, diastolic and global myocardial function was also observed.


Input: The adverse effects were more pronounced in the methanabol group.

methanabol


Input: For both anabolic steroids studied, the low dose had no significant effects on oxidative stress markers monitored, while the high dose created a hostile oxidative environment.


Input: In conclusion, anabolic administration has been found to create a possible deleterious long term effect on the growth of the immature heart and should be strongly discouraged especially in young human subjects.


Input: Effects of lactational and/or in utero exposure to environmental contaminants on the glucocorticoid stress-response and DNA methylation of the glucocorticoid receptor promoter in male rats.


Input: Perinatal events can reprogram the hypothalamo-pituitary-adrenal axis for the entire lifespan leading to abnormal glucocorticoid stress-response (GSR) in adulthood: a phenomenon reported to be mediated by changes in DNA methylation of the glucocorticoid receptor (GR) gene promoter.


Input: We examined whether in utero and/or lactational exposure to mixtures of environmental contaminants can also induce abnormal GSR during adulthood.


Input: The experiment included nine treatment groups.


Input: From gestation day (GD) 0 until postnatal day (PND) 20, dams were fed daily with a cookie laced with corn oil (control) or a chemical mixture (M) [polychlorinated biphenyls (PCBs), organochlorine pesticides, and methylmercury] at 0. 5 or 1. 0mg/kg/day (0. 5M, and M).

polychlorinated biphenyls

PCBs

organochlorine

methylmercury


Input: At birth, some control (C) and M litters were cross-fostered to create four groups with the following in utero/postnatal exposure: C/C, M/C, C/M, M/M.


Input: Other dams received 1. 8ng/kg/day of a mixture of aryl hydrocarbon receptor (AhR) agonists (non-ortho PCBs, PC-dibenzodioxins and PC-dibenzofurans) without or with 0. 5M (0. 5MAhR).

hydrocarbon

non-ortho PCBs

PC-dibenzodioxins

PC-dibenzofurans


Input: In adult male offspring the abundance of GR in treated groups was not different from the control, but the AhR and M groups were significantly different from each other with opposite effects in the hippocampus and liver.


Input: There was no change in DNA methylation of the GR promoter (exon-17 and-110).


Input: Abnormal GSRs were detected in the AhR, 0. 5MAhR, CM, and MM groups.


Input: The literature associates abnormal GSR with metabolic and mental health impairments, thus these results support further investigation of the influence of developmental exposure to environmental contaminants and predisposition to stress-induced diseases.


Input: Similar pyruvate kinase modifications in glioblastoma cells by 7 beta-hydroxycholesterol and glutamine withdrawal.

pyruvate

7 beta-hydroxycholesterol

glutamine


Input: Oxysterols possess anti-proliferative properties that may be used with much effect in the treatment of cancer.

Oxysterols


Input: We have demonstrated previously that 7 beta-hydroxycholesterol (7b-HC) provokes both metabolic stress, as witnessed by AMPK activation, and changes in lipid raft composition in C6 glioblastoma cells.

7 beta-hydroxycholesterol


Input: These observations suggested that glycolysis might have been changed.


Input: Here we will show that 7b-HC increases cell cycle time and that it changes the affinity of pyruvate kinase to its substrate, phosphoenol pyruvate.

pyruvate

phosphoenol pyruvate


Input: The latter effect is mimicked by glutamine withdrawal.

glutamine


Input: Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells.

Nobiletin


Input: Hepatocyte growth factor (HGF), and its receptor, c-Met activation has recently been shown to play important roles in cancer invasion and metastasis in a wide variety of tumor cells.


Input: We use HGF as an invasive inducer of human HepG2 cells to investigate the effect of four flavones including apigenin, tricetin, tangeretin, and nobiletin on HGF/c-Met-mediated tumor invasion and metastasis.

apigenin

tricetin

tangeretin

nobiletin


Input: Among them, nobiletin markedly inhibited HGF-induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and transwell-chamber invasion/migration assay under non-cytotoxic concentrations.

nobiletin


Input: Data also showed nobiletin inhibited HGF-induced cell scattering and cytoskeleton changed such as filopodia and lamellipodia.

nobiletin


Input: Furthermore, nobiletin could inhibit HGF-induced the membrane localization of phosphorylated c-Met, ERK2, and Akt, but not phosphorylated JNK1/2 and p38.

nobiletin


Input: Next, nobiletin significantly decreased the levels of phospho-ERK2 and phospho-Akt in ERK2 or Akt siRNA-transfected cells concomitantly with a marked reduction on cell invasion and migration.

nobiletin

phospho

phospho


Input: In conclusion, nobiletin attenuates HGF-induced HepG2 cells metastasis involving both ERK and PI3K/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma.

nobiletin


Input: Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus.

curcumin

methicillin


Input: Methicillin-resistant Staphylococcus aureus (MRSA) are spread among infected patients, with infection rates increasing at an alarming rate.

Methicillin


Input: Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of infectious diseases worldwide.


Input: Under the selection pressure of exposure to antibiotics, microorganisms evolve to survive against the new conditions imposed by therapy.


Input: Therefore, there exists a need to develop alternative natural or combination drug therapies.


Input: Curcumin (CCM), a natural polyphenolic flavonoid isolated from the rhizome of a plant, Curcuma longa Linn e., has been found to possess many beneficial biological activities.

Curcumin

CCM

polyphenolic flavonoid


Input: The aim of this study was to investigate the synergistic effect of curcumin and antibiotics as well as to determine the antibacterial activity of CCM against specific MRSA strains.

curcumin

CCM


Input: The antibacterial activity of CCM was assessed by the broth microdilution method (by calculating the minimal inhibitory concentration [MIC]), checkerboard dilution test, and time-kill assay.

CCM


Input: Antimicrobial activity of CCM was observed against all tested strains.

CCM


Input: The MICs of CCM against 10 strains of S. aureus ranged from 125 to 250 mu g/ml.

CCM


Input: In the checkerboard test, CCM markedly reduced the MICs of the antibiotics oxacillin (OXI), ampicillin (AMP), ciprofloxacin (CIP), and norfloxacin (NOR) used against MRSA.

CCM

oxacillin

OXI

ampicillin

AMP

ciprofloxacin

CIP

norfloxacin

NOR


Input: The time-kill curves showed that a combined CCM and OXI treatment reduced the bacterial counts below the lowest detectable limit after 24h.

CCM

OXI


Input: This study suggested that CCM reduced the MICs of several antibiotics tested, notably of OXI, AMP, CIP, and NOR, and that CCM in combination with antibiotics could lead to the development of new combination of antibiotics against MRSA infection.

CCM

OXI

AMP

CIP

NOR

CCM


Input: The birth and early years of INA, the International Neurotoxicology Association.


Input: The International Neurotoxicology Association (INA) is a scientific society whose members have interest and expertise in the discipline of neurotoxicology.


Input: The idea of forming INA was born in 1984, as a follow-up to a NATO-sponsored meeting on Toxicology of the Nervous System.


Input: INA held its first meeting in the Netherlands in 1987 and has had continuous meetings every other year since then.


Input: INA is registered as a scientific society in the Netherlands, and is an affiliated society of IUTOX.


Input: This paper presents a personal account of the events that led to the birth of INA, and of the first fifteen years of this association.


Input: Anticancer activity of novel hybrid molecules containing 5-benzylidene thiazolidine-2, 4-dione.

5-benzylidene thiazolidine-2, 4-dione


Input: Hybridization of two different bioactive molecules with different mechanism of action is one of the methods that are being adopted to treat cancer.


Input: Molecules bearing a thiazolidine-2, 4-dione scaffold have been recognized as antineoplastic agents with a broad spectrum of activity against many cancer cell lines.

thiazolidine-2, 4-dione


Input: In this manuscript we have described the synthesis and biological evaluation of two series of N-3-substituted-5-arylidene thiazolidine-2, 4-diones, bearing the alpha-bromoacryloylamido moiety at the para-or meta-position on the phenyl of the arylidene portion.

N-3-substituted-5-arylidene thiazolidine-2, 4-diones

alpha-bromoacryloylamido

phenyl

arylidene


Input: We have observed that selected compounds 5a, 5c and 5g suppress proliferation of human myeloid leukaemia HL-60 and U937 cells by triggering morphological changes and internucleosomal DNA fragmentation, which are well-known features of apoptosis.


Input: Finally, our results indicated that the investigated compounds induced apoptotic cell death through a mechanism that involved activation of multiple caspases and was also associated with the release of cytochrome c from the mitochondria.


Input: Genetic diversity revealed by single nucleotide polymorphism markers in a worldwide germplasm collection of durum wheat.


Input: Evaluation of genetic diversity and genetic structure in crops has important implications for plant breeding programs and the conservation of genetic resources.


Input: Newly developed single nucleotide polymorphism (SNP) markers are effective in detecting genetic diversity.


Input: In the present study, a worldwide durum wheat collection consisting of 150 accessions was used.


Input: Genetic diversity and genetic structure were investigated using 946 polymorphic SNP markers covering the whole genome of tetraploid wheat.


Input: Genetic structure was greatly impacted by multiple factors, such as environmental conditions, breeding methods reflected by release periods of varieties, and gene flows via human activities.


Input: A loss of genetic diversity was observed from landraces and old cultivars to the modern cultivars released during periods of the Early Green Revolution, but an increase in cultivars released during the Post Green Revolution.


Input: Furthermore, a comparative analysis of genetic diversity among the 10 mega ecogeographical regions indicated that South America, North America, and Europe possessed the richest genetic variability, while the Middle East showed moderate levels of genetic diversity.


Input: Transcriptional Analysis of Drought-Induced Genes in the Roots of a Tolerant Genotype of the Common Bean (Phaseolus vulgaris L.).


Input: In Brazil, common bean (Phaseolus vulgaris L.) productivity is severely affected by drought stress due to low technology cultivation systems.


Input: Our purpose was to identify differentially expressed genes in roots of a genotype tolerant to water deficit (BAT 477) when submitted to an interruption of irrigation during its development.


Input: A SSH library was constructed taking as " driver " the genotype Carioca 80SH (susceptible to drought).


Input: After clustering and data mining, 1572 valid reads were obtained, resulting in 1120 ESTs (expressed sequence tags).


Input: We found sequences for transcription factors, carbohydrates metabolism, proline-rich proteins, aquaporins, chaperones and ubiquitins, all of them organized according to their biological processes.

carbohydrates

proline


Input: Our suppressive subtractive hybridization (SSH) library was validated through RT-qPCR experiment by assessing the expression patterns of 10 selected genes in both genotypes under stressed and control conditions.


Input: Finally, the expression patterns of 31 ESTs, putatively related to drought responses, were analyzed in a time-course experiment.


Input: Our results confirmed that such genes are more expressed in the tolerant genotype during stress; however, they are not exclusive, since different levels of these transcripts were also detected in the susceptible genotype.


Input: In addition, we observed a fluctuation in gene regulation over time for both the genotypes, which seem to adopt and adapt different strategies in order to develop tolerance against this stress.


Input: Diketopiperazine Derivatives from the Marine-Derived Actinomycete Streptomyces sp.

Diketopiperazine


Input: FXJ7. 328.


Input: Five new diketopiperazine derivatives, (3Z, 6E)-1-N-methyl-3-benzy lidene-6-(2S-methyl-3-hydroxypropylidene) piperazine-2, 5-dione (1), (3Z, 6E)-1-N-methyl-3-benzylidene-6-(2R-methyl-3-hydroxypropylidene) piperazine-2, 5-dione (2), (3Z, 6Z)-3-(4-hydroxybenzylidene)-6-isobutylidenepiperazine-2, 5-dione (3), (3Z, 6Z)-3-((1H-imidazol-5-yl)-methylene)-6-isobutylidenepiperazine-2, 5-dione (4), and (3Z, 6S)-3-benzylidene-6-(2S-but-2-yl) piperazine-2, 5-dione (5), were isolated from the marine-derived actinomycete Streptomyces sp.

diketopiperazine

(3Z, 6E)-1-N-methyl-3-benzy lidene-6-(2S-methyl-3-hydroxypropylidene) piperazine-2, 5-dione

(3Z, 6E)-1-N-methyl-3-benzylidene-6-(2R-methyl-3-hydroxypropylidene) piperazine-2, 5-dione

(3Z, 6Z)-3-(4-hydroxybenzylidene)-6-isobutylidenepiperazine-2, 5-dione

(3Z, 6Z)-3-((1H-imidazol-5-yl)-methylene)-6-isobutylidenepiperazine-2, 5-dione

(3Z, 6S)-3-benzylidene-6-(2S-but-2-yl) piperazine-2, 5-dione


Input: FXJ7. 328.


Input: The structures of 1-5 were determined by spectroscopic analysis, CD exciton chirality, the modified Mosher' s, Marfey' s and the C3 Marfey' s methods.


Input: Compound 3 showed modest antivirus activity against influenza A (H1N1) virus with an IC50 value of 41. 5 +/- 4. 5 mu M.


Input: In addition, compound 6 and 7 displayed potent anti-H1N1 activity with IC50 value of 28. 9 +/- 2. 2 and 6. 8 +/- 1. 5 mu M, respectively.


Input: Due to the lack of corresponding data in the literature, the 13C NMR data of (3Z, 6S)-3-benzylidene-6-isobutylpiperazine-2, 5-dione (6) were also reported here for the first time.

(3Z, 6S)-3-benzylidene-6-isobutylpiperazine-2, 5-dione


Input: Sponge-Derived Kocuria and Micrococcus spp. as Sources of the New Thiazolyl Peptide Antibiotic Kocurin.

Thiazolyl

Kocurin


Input: Forty four marine actinomycetes of the family Microccocaceae isolated from sponges collected primarily in Florida Keys (USA) were selected from our strain collection to be studied as new sources for the production of bioactive natural products.


Input: A 16S rRNA gene based phylogenetic analysis showed that the strains are members of the genera Kocuria and Micrococcus.


Input: To assess their biosynthetic potential, the strains were PCR screened for the presence of secondary metabolite genes encoding nonribosomal synthetase (NRPS) and polyketide synthases (PKS).


Input: A small extract collection of 528 crude extracts generated from nutritional microfermentation arrays was tested for the production of bioactive secondary metabolites against clinically relevant strains (Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii and Candida albicans).

methicillin


Input: Three independent isolates were shown to produce a new anti-MRSA bioactive compound that was identified as kocurin, a new member of the thiazolyl peptide family of antibiotics emphasizing the role of this family as a prolific resource for novel drugs.

kocurin

thiazolyl


Input: A simple and versatile microfluidic cell density gradient generator for quantum dot cytotoxicity assay.


Input: In this work, a simple and versatile microfluidic cell density gradient generator was successfully developed for cytotoxicity of quantum dots (QDs) assay.


Input: The microfluidic cell density gradient generator is composed of eight parallel channels which are respectively surrounded by 1-8 microwells with optimized length and width.


Input: The cells fall into microwells by gravity and the cell densities are obviously dependent of microwell number.


Input: In a case study, HepG2 and MCF-7 cells were successfully utilized for generating cell density gradients on the microfluidic chip.


Input: The microfluidic cell density gradient generator was proved to be easily handled, cell-friendly and could be used to conduct the subsequent cell-based assay.


Input: As a proof-of-concept, QD cytotoxicity was evaluated and the results exhibited obvious cell density-dependence.


Input: For comparison, QD cytotoxicity was also investigated with a series of cell densities infused by pipette tips.


Input: Higher reproducibility was observed on the microfluidic cell density gradient generator and cell density was demonstrated to be a vital factor in cytotoxic study.


Input: With higher efficiency, controllability and reproducibility, the microfluidic cell density gradient generator could be integrated into microfluidic analysis systems to promote chip-based biological assay.


Input: Antidiabetic attributes of desert and steppic plants: a review.


Input: The rapidly increasing incidence of diabetes mellitus is becoming a serious threat to mankind' s health in all parts of the world.


Input: In fact, known cases reflect only part of the problem, as many diabetics, especially with type 2 diabetes, are unaware of their disease, which initially shows no definitive symptoms.


Input: Despite the great efforts invested in diabetes research, its prevalence continues to grow, while current medications do not cover all of the symptoms and complications of the disease.


Input: The present review highlights a plethora of studies focusing on the antidiabetic properties of desert and semidesert (steppic) plants, many of them being used for centuries in traditional medicine by Bedouins living in the arid zones of the Middle East and also by ethnic groups in other arid and semiarid parts of the world.


Input: The review concludes in summarizing the work done on the subject and also in pointing to the yet existing gaps in diabetes research of desert and steppic plants, and suggests directions for future exploration.


Input: Cardiac natriuretic Peptide gene expression and plasma concentrations during the first 72 hours of life in piglets.


Input: Plasma measurement of cardiac natriuretic peptides constitutes promising markers of congenital heart disease.


Input: However, concentrations change rapidly and dramatically during the first days after delivery even in healthy neonates, which complicates clinical interpretation.


Input: It is unknown whether these changes in plasma concentrations are explained by corresponding changes in the cardiac gene expression.


Input: We quantified the chamber-specific mRNA levels of ANP (A-type natriuretic peptide) and BNP (B-type natriuretic peptide) and plasma pro-ANP and BNP-32 concentrations in healthy piglets during the first 72 hours of life (from 2 litters, n = 44).


Input: Chamber-specific ANP and BNP mRNA levels reflected hemodynamic neonate changes at birth but did not correlate with circulating natriuretic peptide concentrations.


Input: However, plasma pro-ANP and creatinine concentrations were closely correlated (P <. 0001; r = 0. 73).

creatinine


Input: Plasma pro-ANP levels were highest on the day of delivery (5580 pmol/L [4320-6786] decreasing to 2484 pmol/L [1602-2898] after 72 hours, P <. 0001).


Input: During the 72 hours, gel chromatography suggested that the translational products in circulation and in atrial tissue were immature, ie, unprocessed pro-ANP.


Input: In contrast to pro-ANP, BNP-32 plasma concentrations were low at delivery and peaked after 48 hours (12 [10. 5-20. 6] vs. 88. 8 [71. 7-101. 4] pmol/L, P <. 0001).


Input: To conclude, ANP and BNP gene expression differs considerably between cardiac chambers in the first 72 hours of life in healthy piglets, resembling the transition from fetal to neonate circulation.


Input: However, the cardiac gene expression does not explain plasma concentrations.


Input: Use of human in vitro skin models for accurate and ethical risk assessment: metabolic considerations.


Input: Several human skin models employing primary cells and immortalised cell lines, used as monocultures or combined to produce reconstituted 3D skin constructs, have been developed.


Input: Furthermore, these models have been included in European genotoxicity and sensitization/irritation assay validation projects.


Input: In order to help interpret data, Cosmetics Europe (formerly COLIPA) facilitated research projects that measured a variety of defined phase 1 and 2 enzyme activities and created a complete proteomic profile of xenobiotic metabolising enzymes (XMEs) in native human skin and compared them with data obtained from a number of in vitro models of human skin.


Input: Here, we have summarised our findings on the current knowledge of the metabolic capacity of native human skin and in vitro models, and make an overall assessment of the metabolic capacity from gene expression, proteomic expression and substrate metabolism data.


Input: The known low expression and function of phase 1 enzymes in native whole skin was reflected in the in vitro models.


Input: Some XMEs in whole skin were not detected in in vitro models and vice versa, and some major hepatic XMEs such as cytochrome P450-monooxygenases were absent or measured only at very low levels in the skin.


Input: Conversely, despite varying mRNA and protein levels of phase 2 enzymes, functional activity of glutathione S-transferases, N-acetyltransferase 1, and UDP-glucuronosyltransferases were all readily measurable in whole skin and in vitro skin models at activity levels similar to those measured in the liver.

glutathione S

N

UDP


Input: These projects have enabled a better understanding of the contribution of XMEs to toxicity endpoints.


Input: Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies.

orvepitant


Input: Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a potential antidepressant mechanism.


Input: The selective NK1 antagonist orvepitant (GW823296) was used to test this hypothesis.

orvepitant


Input: A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies in patients with major depressive disorder (MDD).


Input: Displacement of central [(11) C] GR205171 binding indicated that oral orvepitant doses of 30-60 mg/day provided > 99% receptor occupancy for >= 24 h.

[(11) C] GR205171

orvepitant


Input: Studies 733 and 833 randomized patients with MDD and 17-item Hamilton Depression Rating Scale (HAM-D) >= 22 to double-blind treatment with orvepitant 30 mg/day, orvepitant 60 mg/day or placebo (1: 1: 1).

orvepitant

orvepitant


Input: Primary outcome measure was change from baseline in 17-item HAM-D total score at Week 6 analyzed using mixed models repeated measures.


Input: Study 733 (n = 328) demonstrated efficacy on the primary endpoint (estimated drug-placebo differences of 30 mg:-2. 41, 95% confidence interval (CI) (-4. 50 to-0. 31) p = 0. 0245; 60 mg:-2. 86, 95% CI (-4. 97 to-0. 75) p = 0. 0082).


Input: Study 833 (n = 345) did not show significance (estimated drug-placebo differences of 30 mg:-1. 67, 95% CI (-3. 73 to 0. 39) p = 0. 1122; 60 mg:-0. 76, 95% CI (-2. 85 to 1. 32) p = 0. 4713).


Input: The results support the hypothesis that full, long lasting blockade of central NK1 receptors may be an efficacious mechanism for the treatment of MDD.


Input: Heart failure therapy in patients with coronary artery disease.


Input: Heart failure and coronary artery disease share many risk factors.


Input: Coronary artery disease often pre-dates the development of heart failure with reduced ejection fraction.


Input: A diagnosis of heart failure should be considered in any patient with a history of coronary artery disease who presents with breathlessness, ankle oedema or fatigue.


Input: Several therapies, such as renin-angiotensin antagonists and B blockers, have been proven to improve survival in patients with heart failure with reduced ejection fraction but evidence for effectiveness in heart failure with preserved ejection fraction is lacking.


Input: The management of heart failure and coronary artery disease overlaps considerably but can also be conflicting.


Input: Optimal risk factor management is key to preventing progression to heart failure in patients with coronary artery disease.


Input: Interleukin-23: a promising therapeutic target in seronegative spondyloarthropathy.


Input: Particular therapeutic challenges are raised by the spondyloarthropathies which represent a key area of unmet medical need.


Input: Recent investigations have shown that these conditions are characterised both by altered responsiveness to interleukin (IL)-23 and expansion of IL-23 responsive cells as well as increased production of IL-23.


Input: The gut in particular has emerged as a key site of IL-23 production, and gut inflammation is known to be strongly clinically associated with these conditions.


Input: Moreover, HLA-B27, which is strongly associated with spondyloarthropathy, has also been shown to stimulate IL-23 production.


Input: The view is thus emerging that dysregulation of IL-23 biology is a unifying feature of spondyloarthropathy, suggesting that treatments targeting this cytokine are likely to be highly efficacious.


Input: Molar Mass, Entanglement, and Associations of the Biofilm Polysaccharide of Staphylococcus epidermidis.


Input: Biofilms are microbial communities that are characterized by the presence of a viscoelastic extracellular polymeric substance (EPS).


Input: Studies have shown that polysaccharides, along with proteins and DNA, are a major constituent of the EPS and play a dominant role in mediating its microstructure and rheological properties.


Input: Here, we investigate the possibility of entanglements and associative complexes in solutions of extracellular polysaccharide intercellular adhesin (PIA) extracted from Staphylococcus epidermidis biofilms.


Input: We report that the weight average molar mass and radius of gyration of PIA isolates are 2. 01 x 10 (5) +/- 1200 g/mol and 29. 2 +/- 1. 2 nm, respectively.


Input: The coil overlap concentration, c *, was thus determined to be (32 +/- 4) x 10 (-4) g/mL.


Input: Measurements of the in situ concentration of PIA (cPIA, biofilm) was found to be (10 +/- 2) x 10 (-4) g/mL.


Input: Thus, cPIA, biofilm < c * and the amount of PIA in the biofilm is too low to cause polymer chain entanglements.


Input: In the pH range 3. 0-5. 5, PIA was found to both self-associate and to form complexes with bovine serum albumin (BSA).


Input: By static light scattering, both self-association and complex formation with 0. 5% (w/v) BSA were found to occur at PIA concentrations of 0. 30 x 10 (-4) g/mL and greater, which is about 30 times lower than the measured cPIA, biofilm.


Input: These results suggest that the microscopic origin of EPS viscoelasticity is unlikely to be due to polysaccharide entanglements.


Input: Furthermore, the onset of self-association and protein complexation of PIA occurs at concentrations far lower than the native PIA concentration in biofilms.


Input: This finding therefore suggests a critical role for those two association mechanisms in mediating biofilm viscoelasticity.


Input: The Arabidopsis Nucleosome Remodeler DDM1 Allows DNA Methyltransferases to Access H1-Containing Heterochromatin.


Input: Nucleosome remodelers of the DDM1/Lsh family are required for DNA methylation of transposable elements, but the reason for this is unknown.


Input: How DDM1 interacts with other methylation pathways, such as small-RNA-directed DNA methylation (RdDM), which is thought to mediate plant asymmetric methylation through DRM enzymes, is also unclear.


Input: Here, we show that most asymmetric methylation is facilitated by DDM1 and mediated by the methyltransferase CMT2 separately from RdDM.


Input: We find that heterochromatic sequences preferentially require DDM1 for DNA methylation and that this preference depends on linker histone H1.


Input: RdDM is instead inhibited by heterochromatin and absolutely requires the nucleosome remodeler DRD1.


Input: Together, DDM1 and RdDM mediate nearly all transposon methylation and collaborate to repress transposition and regulate the methylation and expression of genes.


Input: Our results indicate that DDM1 provides DNA methyltransferases access to H1-containing heterochromatin to allow stable silencing of transposable elements in cooperation with the RdDM pathway.


Input: Asymmetric Collapse in Biomimetic Complex Coacervates Revealed by Local Polymer and Water Dynamics.


Input: Complex coacervation is a phenomenon characterized by the association of oppositely charged polyelectrolytes into micrometer-scale liquid condensates.


Input: This process is the purported first step in the formation of underwater adhesives by sessile marine organisms, as well as the process harnessed for the formation of new synthetic and protein-based contemporary materials.


Input: Efforts to understand the physical nature of complex coacervates are important for developing robust adhesives, injectable materials, or novel drug delivery vehicles for biomedical applications; however, their internal fluidity necessitates the use of in situ characterization strategies of their local dynamic properties, capabilities not offered by conventional techniques such as X-ray scattering, microscopy, or bulk rheological measurements.


Input: Herein, we employ the novel magnetic resonance technique Overhauser dynamic nuclear polarization enhanced nuclear magnetic resonance (DNP), together with electron paramagnetic resonance (EPR) line shape analysis, to concurrently quantify local molecular and hydration dynamics, with species-and site-specificity.


Input: We observe striking differences in the structure and dynamics of the protein-based biomimetic complex coacervates from their synthetic analogues, which is an asymmetric collapse of the polyelectrolyte constituents.


Input: From this study we suggest charge heterogeneity within a given polyelectrolyte chain to be an important parameter by which the internal structure of complex coacervates may be tuned.


Input: Acquiring molecular-level insight to the internal structure and dynamics of dynamic polymer complexes in water through the in situ characterization of site-and species-specific local polymer and hydration dynamics should be a promising general approach that has not been widely employed for materials characterization.


Input: Biocompatible Polylactide-block-Polypeptide-block-Polylactide Nanocarrier.

Polylactide

Polylactide


Input: Polypeptides are successfully incorporated into poly (l-lactide) (PLLA) chains in a ring-opening polymerization (ROP) of l-lactide by using them as initiators.

poly (l-lactide)

PLLA

l-lactide


Input: The resulting ABA triblock copolymers possess molecular weights up to 11000 g. mol (-1) and polydispersities as low as 1. 13, indicating the living character of the polymerization process.


Input: In a nonaqueous emulsion, peptide-initiated polymerization of l-lactide leads to well-defined nanoparticles, consisting of PLLA-block-peptide-block-PLLA copolymer.

l-lactide

PLLA

PLLA


Input: These nanoparticles are easily loaded by dye-encapsulation and transferred into aqueous media without aggregation (average diameter of 100 nm) or significant dye leakage.


Input: Finally, internalization of PLLA-block-peptide-block-PLLA nanoparticles by HeLa cells is demonstrated by a combination of coherent anti-Stokes Raman spectroscopy (CARS) and fluorescence microscopy.

PLLA

PLLA


Input: This demonstrates the promise of their utilization as cargo delivery vehicles.


Input: A Coffee Ring Biosensor for Rapid Protein Detection.


Input: We introduce a new biosensing platform for rapid protein detection that combines one of the simplest methods for biomolecular concentration, coffee ring formation, with a sensitive aptamer-based optical detection scheme.


Input: In this approach, aptamer beacons are utilized for signal transduction where a fluorescence signal is emitted in the presence of the target molecule.


Input: Signal amplification is achieved by concentrating aptamer-target complexes within liquid droplets, resulting in the formation of coffee ring " spots ".


Input: Surfaces with various chemical coatings were utilized to investigate the correlation between surface hydrophobicity, concentration efficiency and signal amplification.


Input: Based on our results, we found that the increase in coffee ring diameter with larger droplet volumes is independent of surface hydrophobicity.


Input: Furthermore, we show that highly hydrophobic surfaces produce enhanced particle concentration, via coffee ring formation, resulting in signal intensities 6-fold greater than those on hydrophilic surfaces.


Input: To validate this biosensing platform for the detection of clinical samples, we detected alpha-thrombin in human serum and 4x diluted whole blood.


Input: Based on our results, coffee ring spots produced detection signals 40x larger than samples in liquid droplets.


Input: Additionally, this biosensor exhibits a lower limit of detection of 2 ng/mL (54 pM) in serum, and 4 ng/mL (105 pM) in blood.


Input: Based on its simplicity and high performance, this platform demonstrates immense potential as an inexpensive diagnostic tool for the detection of disease biomarkers, particularly for use in developing countries that lack the resources and facilities required for conventional biodetection practices.


Input: Androgen deprivation from pre-puberty to peripuberty interferes in proteins expression in pubertal and adult rat epididymis.

Androgen


Input: Few studies have focused on experimental testosterone deprivation in immature animals.

testosterone


Input: Therefore, this study used sexually immature rats aiming to evaluate the testes and epididymis histology and proteins expression in these organs on PND50 and 75, after premature antiandrogen exposure, from PND21 to 44.


Input: Although the androgen deprivation from pre-puberty up to peripuberty did not alter the histological organization of the testes and epididymis either at puberty or at adulthood, the treatment impaired the expression of specific proteins in epididymal tissue at puberty and adulthood (androgen receptor, calmodulin, Rab11A).

androgen

androgen


Input: These changes may be related to impaired epididymal function, sperm quality and fertility capacity as observed in a previous study.


Input: Further studies are necessary to better investigate the molecular mechanisms involved in the impairment on reproductive competence of male rats after precocious hormonal injury.


Input: Anti-inflammatory effect of essential oil and its constituents from fingered citron (Citrus medica L. var. sarcodactylis) through blocking JNK, ERK and NF-kappa B signaling pathways in LPS-activated RAW 264. 7 cells.


Input: We investigated the composition of essential oil from fingered citron (Citrus medica L. var. sarcodactylis) (FCEO) peels by GC-MS and its anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW 264. 7) cells.


Input: Fifteen compounds, representing 98. 97% of the essential oil, were tentatively identified; the main constituents were limonene (52. 44%) and gamma-terpinene (28. 41%).

limonene

gamma-terpinene


Input: FCEO significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) by suppressing the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, respectively.

nitric oxide

NO

prostaglandin E2

nitric oxide


Input: Additionally, FCEO suppressed the production of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6.


Input: FCEO attenuated LPS-induced nuclear factor-kappa B (NF-kappa B) activation via inhibition of inhibitor kappa B-alpha phosphorylation.


Input: Furthermore, FCEO blocked activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not that of p38 mitogen-activated protein kinase.


Input: These results indicate that FCEO inhibits LPS-stimulated inflammation by blocking the NF-kappa B, JNK, and ERK pathways in macrophages, and demonstrate that FCEO possesses anti-inflammatory properties.


Input: Aldosterone-induced ENaC and basal Na (+)/K (+)-ATPase trafficking via protein kinase D1-phosphatidylinositol 4-kinaseIII beta trans Golgi signalling in M1 cortical collecting duct cells.

Aldosterone

Na (+)

K (+)

phosphatidylinositol


Input: Aldosterone regulates Na (+) transport in the distal nephron through multiple mechanisms that include the transcriptional control of epithelial sodium channel (ENaC) and Na (+)/K (+)-ATPase subunits.

Aldosterone

Na (+)

Na (+)

K (+)


Input: Aldosterone also induces the rapid phosphorylation of Protein Kinase D1 (PKD1).

Aldosterone


Input: PKD isoforms regulate protein trafficking, by the control of vesicle fission from the trans Golgi network (TGN) through activation of phosphatidylinositol 4-kinaseIII beta (PI4KIII beta).

phosphatidylinositol


Input: We report rapid ENaC gamma translocation to the plasma membrane after 30min aldosterone treatment in polarized M1 cortical collecting duct cells, which was significantly impaired in PKD1 shRNA-mediated knockdown cells.


Input: In PKD1-deficient cells, the ouabain-sensitive current was significantly reduced and Na (+)/K (+)-ATPase alpha and beta subunits showed aberrant localization.

ouabain

Na (+)

K (+)


Input: PKD1 and PI4KIII beta localize to the TGN, and aldosterone induced an interaction between PKD1 and PI4KIII beta following aldosterone treatment.

aldosterone

aldosterone


Input: This study reveals a novel mechanism for rapid regulation of ENaC and the Na (+)/K (+)-ATPase, via directed trafficking through PKD1-PI4KIII beta signalling at the level of the TGN.

Na (+)

K (+)


Input: Glycyrrhetinic acid and its analogs: A new class of antifilarial agents.

Glycyrrhetinic acid


Input: Although a number of chemicals have been isolated from Glycyrrhiza glabra, only a few have been evaluated for their biological significance.


Input: As part of our drug discovery program for antifilarial agents from Indian medicinal plants, the roots of G. glabra were chemically investigated, which resulted in the isolation and characterization of an antifilarial agent, glycyrrhetinic acid (GA, 1a) effective against microfilariae (mf) in vitro (LC100: 12. 5 mu M; IC50: 1. 20 mu M), but was inactive against adult worms.

glycyrrhetinic acid


Input: Further, GA (1a) was converted into six analogs (2a-7a) and their antifilarial potential was evaluated by studying in vitro motility and MTT reduction assays employing mf and adult worms of Brugia malayi.

MTT


Input: The results showed that out of six GA analogs, the benzyl amide analog (6a) killed adults and mf at 25 and 50 mu M concentration, respectively, and inhibited 49% MTT reduction potential of the adult parasites.

benzyl amide

MTT


Input: The IC50 values were found to be 8. 8 and 2. 2 mu M for adults and mf, respectively.


Input: The SI of the compound was > 60.


Input: On the other hand the octylamide analog (7a) required much higher concentration to adversely affect the parasites.

octylamide


Input: Finally, both active amide analogs (6a and 7a) were in vivo evaluated using B. malayi-jird model, which showed that analog 6a possesses promising macrofilaricidal activity at 100mg/kg, s. c.

amide


Input: x 5days and around 40% of the treated animals showed calcified masses of worm fragments in peritoneal cavity of the animals.


Input: To the best of our knowledge this is the first ever report on the antifilarial potential of GA analogs.


Input: Further work on optimization of the antifilarial lead is under progress.


Input: Discovery of a series of novel 5H-pyrrolo [2, 3-b] pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors.

5H-pyrrolo [2, 3-b] pyrazine-2-phenyl ethers


Input: We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo [2, 3-b] pyrazine scaffold.

ATP

5H-pyrrolo [2, 3-b] pyrazine


Input: The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family.


Input: Computational and crystallographic analysis suggested that the phenyl ether moiety possessed a favorable vector to achieve selectivity.


Input: Exploration of this vector resulted in the identification of 12b and 12d, as potent JAK3 inhibitors, demonstrating improved JAK family and kinase selectivity.


Input: The Decapping Scavenger Enzyme DCS-1 Controls MicroRNA Levels in Caenorhabditis elegans.


Input: In metazoans, microRNAs play a critical role in the posttranscriptional regulation of genes required for cell proliferation and differentiation.


Input: MicroRNAs themselves are regulated by a multitude of mechanisms influencing their transcription and posttranscriptional maturation.


Input: However, there is only sparse knowledge on pathways regulating the mature, functional form of microRNA.


Input: Here, we uncover the implication of the decapping scavenger protein DCS-1 in the control of microRNA turnover.


Input: In Caenorhabditis elegans, mutations in dcs-1 increase the levels of functional microRNAs.


Input: We demonstrate that DCS-1 interacts with the exonuclease XRN-1 to promote microRNA degradation in an independent manner from its known decapping scavenger activity, establishing two molecular functions for DCS-1.


Input: Our findings thus indicate that DCS-1 is part of a degradation complex that performs microRNA turnover in animals.


Input: Two antagonistic clock-regulated histidine kinases time the activation of circadian gene expression.

histidine


Input: The cyanobacterial circadian pacemaker consists of a three-protein clock-KaiA, KaiB, and KaiC-that generates oscillations in the phosphorylation state of KaiC.


Input: Here we investigate how temporal information encoded in KaiC phosphorylation is transduced to RpaA, a transcription factor required for circadian gene expression.


Input: We show that phosphorylation of RpaA is regulated by two antagonistic histidine kinases, SasA and CikA, which are sequentially activated at distinct times by the Kai clock complex.


Input: SasA acts as a kinase toward RpaA, whereas CikA, previously implicated in clock input, acts as a phosphatase that dephosphorylates RpaA.


Input: CikA and SasA cooperate to generate an oscillation of RpaA activity that is distinct from that generated by either enzyme alone and offset from the rhythm of KaiC phosphorylation.


Input: Our observations reveal how circadian clocks can precisely control the timing of output pathways via the concerted action of two oppositely acting enzymes.


Input: Signaling pathways mediating the effects of insulin-like growth factor-I in bovine muscle satellite cells.


Input: The objective of this study was to identify the signaling pathways mediating the effects of IGF-I on muscle cell proliferation, protein synthesis, and protein degradation in a physiologically more relevant muscle cell model.


Input: We isolated muscle satellite cells from adult cattle and expanded them as myoblasts or induced them to form myotubes in culture.


Input: We determined the effects of IGF-I on proliferation of myoblasts and protein synthesis and degradation in myotubes in the presence or absence of specific signaling inhibitors.


Input: Our data suggest that both the MEK/ERK and PI3K/AKT pathways mediate the stimulatory effect of IGF-I on myoblast proliferation and that the PI3K/AKT pathway mediates this effect through cyclin D2.


Input: Our data also suggest that both the MEK/ERK and PI3K/AKT pathways mediate the stimulatory effect of IGF-I on protein synthesis through p70S6K and that the PI3K/AKT pathway mediates the inhibitory effect of IGF-I on protein degradation through FoxO3a.


Input: The effects of RFRP-3, the mammalian ortholog of GnIH, on the female pig reproductive axis in vitro.


Input: RFamide-related peptide-3 (RFRP-3) has been proposed as a key inhibitory regulator of mammalian reproduction.

RFamide-related peptide-3


Input: To further determine the potential mechanisms and sites of action of RFRP-3, we systematically investigated the direct effect of RFRP-3 on the female pig reproductive axis in vitro.


Input: Initially, we confirmed that G protein-coupled receptor 147 (GPR147) was distributed in isolated hypothalamic, anterior pituitary and ovarian granulosa cells, suggesting that RFRP-3 could act on these cells in vitro.


Input: Subsequently, the direct effects of RFRP-3 on hormone and steroid secretion, the synthesis of subunit genes and the expression of proteins related to proliferation in the hypothalamus, pituitary and ovary were evaluated.

steroid


Input: Our results demonstrate that different doses of RFRP-3 inhibited the release and synthesis of gonadotrophin releasing hormone, gonadotrophin and steroid hormones and impacted the relative gene expression of KISS1 and GnRHR and the protein expression of cyclin B1, PCNA and ERK 1/2.

steroid


Input: Genome-wide association studies on serum sex steroid levels.

steroid


Input: Even though the levels of circulating sex steroid hormones are to a large extent heritable, their genetic determinants are largely unknown.

steroid


Input: With the advent of genome-wide association studies (GWAS), much progress has been made and several genetic loci have been identified to be associated with serum levels of dehydroepiandrosterone sulfate, testosterone and sex hormone-binding globulin.

dehydroepiandrosterone sulfate

testosterone


Input: The variants identified so far only explain a small amount of the overall heritability, but may help to elucidate the role of sex steroid hormones in common disorders such as hypogonadism, type 2 diabetes and hormone-sensitive cancers.

steroid


Input: This review provides an overview of the current state of knowledge of the genetic determinants of sex steroid hormones, with a focus on recent GWAS and brief directions for elucidating the remaining heritability.

steroid


Input: Steric Complementarity in the Decoding Center Is Important for tRNA Selection by the Ribosome.


Input: Accurate tRNA selection by the ribosome is essential for the synthesis of functional proteins.


Input: Previous structural studies indicated that the ribosome distinguishes between cognate and near-cognate tRNAs by monitoring the geometry of the codon-anticodon helix in the decoding center using the universally conserved 16S ribosomal RNA bases G530, A1492 and A1493.


Input: These bases form hydrogen bonds with the 2'-hydroxyl groups of the codon-anticodon helix, which are expected to be disrupted with a near-cognate codon-anticodon helix.

hydrogen


Input: However, a recent structural study showed that G530, A1492 and A1493 form hydrogen bonds in a manner identical with that of both cognate and near-cognate codon-anticodon helices.

hydrogen


Input: To understand how the ribosome discriminates between cognate and near-cognate tRNAs, we made 2'-deoxynucleotide and 2'-fluoro substituted mRNAs, which disrupt the hydrogen bonds between the A site codon and G530, A1492 and A1493.

hydrogen


Input: Our results show that multiple 2'-deoxynucleotide substitutions in the mRNA substantially inhibit tRNA selection, whereas multiple 2'-fluoro substitutions in the mRNA have only modest effects on tRNA selection.


Input: Furthermore, the miscoding antibiotics paromomycin and streptomycin rescue the defects in tRNA selection with the multiple 2'-deoxynucleotide substituted mRNA.


Input: These results suggest that steric complementarity in the decoding center is more important than the hydrogen bonds between the A site codon and G530, A1492 and A1493 for tRNA selection.

hydrogen


Input: The in vitro cytotoxicity and genotoxicity of cigarette smoke particulate matter with reduced toxicant yields.


Input: Tobacco smoke contains more than 5600 constituents, of which approximately 150 are toxicants.


Input: This paper describes the activities in the Neutral Red uptake (NRU) assay, the Salmonella mutagenicity test (SAL), the mouse lymphoma mammalian cell mutation assay (MLA) and the in vitro micronucleus test (IVMNT) of Particulate Matter (PM) obtained from experimental cigarettes (ECs), designed to produce reduced levels of toxicants.

Neutral Red


Input: The designs included tobacco substitute sheet (TSS) containing glycerol, which dilutes toxicants in smoke, or the incorporation of blend-treated (BT) tobacco to reduce the levels of nitrogenous toxicant precursors and some polyphenols.

glycerol

polyphenols


Input: All samples were cytotoxic in the NRU, however TSS reduced PM cytotoxicity in this assay.


Input: All PMs were mutagenic in the SAL, MLA and IVMNT.


Input: Reductions in bacterial mutagenicity were observed in the SAL, for cigarettes with BT tobacco, compared with their respective controls.


Input: The quantitative changes in bacterial mutagenicity could be explained by analytical chemistry data on smoke generated from the ECs used in the study.


Input: These observations, and the absence of consistent qualitative differences in the activities of the experimental, control and reference cigarettes, suggest that reduced toxicity cigarettes, as measured by the tests described in this paper, may be developed without introducing any additional cytotoxic or genotoxic hazards, but the impact of this on human health risks remains unknown.


Input: In vivo and in vitro anti-inflammatory activity of Lentinus polychrous extract.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Lentinus polychrous is a Thai local edible mushroom, traditionally used for the treatments of fever and inflammation due to snake or scorpion envenomation.


Input: AIM OF STUDY: The present study aimed to investigate an anti-inflammatory effect of Lentinus polychrous mycelial extract (LPME) both in vitro and in vivo.


Input: MATERIALS AND METHODS: The cytotoxicity and suppressive effects of LPME on nitric oxide production, intracellular O2 (-) production, pro-inflammatory mediator expression, TNF-alpha production were determined by using LPS-activated RAW 264. 7 cells.

nitric oxide

O2 (-)


Input: In addition, Anti-inflammatory effect of LPME was evaluated by using carageenan-induced paw edema in rats.


Input: RESULTS: The LPME exhibited cytotoxicity with 50% inhibitory concentration (IC50) of 280. 25 +/- 10. 10 mu g/ml and significantly suppressed the productions of NO and intracellular O2 (-) with dose-dependent manner.

NO

O2 (-)


Input: LPME decreased the expressions of iNOS, IL-1 beta, IL-6, TNF-alpha and COX-2 and significantly decreased the TNF-alpha production in LPS-activated macrophage with dose-dependent manners.


Input: Moreover, LPME showed significant suppressive effect on paw edema in rats.


Input: CONCLUSION: The results clearly revealed that the LPME inhibited NO and pro-inflammatory productions by down-regulating the gene expressions of pro-inflammatory mediators leading to the decrease paw edema in rat which support the traditional use.

NO


Input: Oxidative status in ICU patients with septic shock.


Input: The aim of this pilot study was to investigate variability of oxidative stress during sepsis evolution.


Input: ICU patients with the diagnosis of septic shock were included.


Input: Thiobarbituric-acid reactive substances, total antioxidant capacity, protein carbonyls in plasma, reduced, oxidized glutathione and catalase activity in erythrocyte lysate were assessed in the 1st, 3rd, 5th and 8thday after sepsis appearance.

Thiobarbituric-acid

carbonyls

glutathione


Input: A total of 17 patients were divided in two groups: survivors (n = 7) and non-survivors (n = 10).


Input: APACHE II was 11. 5 +/- 5. 4 and 19. 9 +/- 4. 97 in survivors and non-survivors respectively (p = 0. 005), while mean age and SOFA score at sepsis diagnosis, were similar between the two groups.


Input: GSH levels, catalase activity and protein carbonyls presented significant different course in time between survivors and non-survivors (p < 0. 05).

GSH

carbonyls


Input: Catalase activity was significantly higher in survivors (238. 8 +/- 51. 5) than non-survivors (166. 4 +/- 40. 2; p = 0. 005), while protein carbonyls levels were significantly lower in survivors (0. 32 +/- 0. 09) than non-survivors (0. 48 +/- 0. 16; p = 0. 036) on the 1stday.

carbonyls


Input: Yet, non-survivors exhibited a declining course in GSH levels during time, while GSH levels were maintained in survivors.

GSH

GSH


Input: Conclusively, a longstanding antioxidant deficiency in non-surviving patients was noted.


Input: This phenomenon was clearly prominent in patients' erythrocytes.


Input: SPIO-PICsome: Development of a highly sensitive and stealth-capable MRI nano-agent for tumor detection using SPIO-loaded unilamellar polyion complex vesicles (PICsomes).


Input: Size controllable polyion complex vesicles (PICsomes), composed of biocompatible poly (ethylene glycol) (PEG) and poly (amino acid) s, have an extremely prolonged lifetime in the bloodstream that enables them to accumulate effectively in tumors via the enhanced permeability and retention (EPR) effect.

poly (ethylene glycol)

PEG

poly (amino acid) s


Input: The purpose of this study was to use PICsomes to synthesize a highly sensitive MRI contrast agent for more precise tumor detection.


Input: We synthesized SPIO-Cy5-PICsomes (superparamagnetic iron oxide nanoparticle-loaded Cy5-cross-linked Nano-PICsomes) and characterized them using dynamic light scattering and transmission electron microscopy in vitro and evaluated their ability to detect subcutaneously grafted tumors in vivo with MRI.

iron oxide


Input: The transverse relaxivity (r2) of the SPIO-Cy5-PICsomes (r2 = 663 +/- 28mM (-1) s (-1)) was 2. 54 times higher than that of bare clinically-used SPIO.


Input: In in vivo MRI experiments on mice subcutaneously grafted with colon-26 tumor cells, the tumor signal was significantly altered at 3h after SPIO-Cy5-PICsome administration and persisted for at least 24h.


Input: Small and early-stage in vivo tumors (3days after grafting, approximately 4mm (3)) were also clearly detected with MRI.


Input: SPIO-loaded PICsomes are sensitive MRI contrast agents that can act as a powerful nanocarrier to detect small tumors for early diagnosis.


Input: Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: Involvement of 5-HT7 receptors.

corticosterone


Input: Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress.

Serotonin


Input: We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT7 receptor antagonist); 2) 5-HT7 receptor-like immunoreactivity (5-HT7-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA), and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI) in AG and tryptophan hydroxylase (TPH) protein in PVN and AG.

corticosterone

CORT

5-hydroxyindolacetic acid

tryptophan


Input: On day 15, animals were subdivided into Treatment and No treatment groups.


Input: Treatment animals received an i. p. injection of vehicle or SB-656104; No Treatment animals received no injection.


Input: Sixty min later, Treatment animals were either decapitated with no further stress (0 min) or submitted to acute restraint (10, 30, 60 or 120 min); hormone serum levels were measured.


Input: No Treatment animals were employed for the rest of measurements.


Input: CRS decreased body weight gain and increased adrenal weight.


Input: In CTRL animals, acute restraint increased ACTH and CORT secretion in a time of restraint-dependent manner; both responses were inhibited by SB-656104.

CORT


Input: Exposure to CRS abolished ACTH but magnified CORT responses to restraint as compared to CTRL conditions; SB-656104 had no effect on ACTH levels but significantly inhibited sensitized CORT responses.

CORT

CORT


Input: In CTRL animals, 5-HT7-LI was detected in magnocellular and parvocellular subdivisions of PVN and sparsely in adrenal cortex.


Input: Exposure to CRS decreased 5-HT7-LI and protein in the PVN, but increased 5-HT7-LI in the adrenal cortex and protein in whole AG.


Input: Higher 5-HT and 5-HIAA levels were detected in PVN and AG from CRS animals but 5-HIAA/5-HT ratio increased in AG only.


Input: Finally, whereas 5-HT-LI was sparsely observed in the adrenal cortex of CTRL animals, it strongly increased in the adrenal cortex of CRS animals.


Input: No TPH protein was detected in AG from both animal groups.


Input: Results suggest that CRS promotes endocrine disruption involving decreased ACTH and sensitized CORT responses to acute restraint.

CORT


Input: This phenomenon may be associated with increased function and expression of 5-HT7 receptors as well as 5-HT turnover in AG.


Input: 5-Hydroxy-3, 6, 7, 8, 3' 4'-hexamethoxyflavone inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-kappa B suppression and Nrf-2-dependent heme oxygenase-1 induction.

5-Hydroxy-3, 6, 7, 8, 3' 4'-hexamethoxyflavone

nitric oxide


Input: In this study, we found that 5-hydroxy-3, 6, 7, 8, 3' 4'-hexamethoxyflavone (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase (iNOS) in BV2 microglia.

5-hydroxy-3, 6, 7, 8, 3' 4'-hexamethoxyflavone

NO

NO


Input: In addition, 5HHMF blocked LPS-induced phosphorylation of I kappa B, resulting in suppression of the nuclear translocation of nuclear factor-kappa B (NF-kappa B) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression.


Input: Pyrrolidine dithiocarbamate (PDTC), a specific NF-kappa B inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-kappa B activity.

Pyrrolidine dithiocarbamate

PDTC


Input: Thus, we found that 5HHMF enhances heme oxygenase-1 (HO-1) expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation.


Input: In addition, cobalt protoporphyrin (CoPP), a specific HO-1 inducer, predominantly suppressed LPS-induced NO production.

cobalt protoporphyrin

CoPP

NO


Input: In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, showed a partial suppressive effect of 5HHMF on LPS-induced NO production.

zinc protoporphyrin

ZnPP

NO


Input: Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity.

NO


Input: Taken together, our findings indicate that 5HHMF suppresses NO production through modulation of iNOS, consequently suppressing NF-kappa B activity and induction of Nrf2-dependent HO-1 activity.

NO


Input: Pulmonary DWCNT exposure causes sustained local and low-level systemic inflammatory changes in mice.


Input: Carbon nanotubes (CNTs) represent promising vectors to facilitate cellular drug delivery and to overcome biological barriers, but some types may also elicit persistent pulmonary inflammation based on their fibre characteristics.

Carbon


Input: Here, we show the pulmonary response to aqueous suspensions of block copolymer dispersed, double-walled carbon nanotubes (DWCNT, length 1-10 mu m) in mice by bronchoalveolar lavage (BAL) analysis, and BAL and blood cytokine and lung antioxidant profiling.

carbon


Input: The intratracheally instilled dose of 50 mu g DWCNT caused significant pulmonary inflammation that was not resolved during a 7-day observation period.


Input: Light microscopy investigation of the uptake of DWCNT agglomerates revealed no particle ingestion for granulocytes, but only for macrophages.


Input: Accumulating macrophage, multinucleated macrophage and lymphocyte numbers in the alveolar region further indicated ineffective resolution with chronification of the inflammation.


Input: The local inflammatory impairment of the lung was accompanied by pulmonary antioxidant depletion and haematological signs of systemic inflammation.


Input: While the observed inflammation during its acute phase was dominated by neutrophils and neutrophil recruiting cytokines, the contribution of macrophages and lymphocytes with related cytokines became more significant after day 3 of exposure.


Input: This study confirms that acute pulmonary toxicity can occur on exposure of high doses of DWCNT agglomerates and offers further insight for improved nanotube design parameters to avoid potential long-term toxicity.


Input: The effects of 17-alpha-ethinylestradiol (EE2) on molecular signaling cascades in mummichog (Fundulus heteroclitus).


Input: Exposures to <= 10ng/L of 17-alpha-ethinylestradiol (EE2) will reduce or shut down egg production in freshwater fish models, while mummichog (Fundulus heteroclitus), an estuarine species, are able to produce eggs at EE2 concentrations > 3000ng/L.


Input: The objective of this study was to gain mechanistic insight into how mummichog are able to produce eggs during exposures to high EE2.


Input: Mummichog were exposed to 0, 50 or 250ng/L of EE2 for 14d.


Input: There were no changes in gonadosomatic index, liversomatic index, gonad development, or plasma estradiol levels after exposure to EE2.

estradiol


Input: However, testosterone significantly decreased with EE2 exposures (50, 250ng/L).


Input: Microarray analysis in the liver revealed that cell processes associated with lipids were affected by EE2 at the transcriptome level.


Input: Based on the transcriptomics data, we hypothesize that mummichog are able to maintain lipid transport and uptake into the ovary and this may be associated with apolipoproteins, facilitating normal oocyte development.


Input: Novel gene regulatory networks for protein modification targets were also constructed to learn more about the potential roles of estrogens in the teleost liver.

estrogens


Input: Although post-translational modifications (PTMs) are important regulatory mechanisms, the roles of PTMs in protein regulation in fish and the susceptibility of PTMs to aquatic pollutants are largely unexplored and may offer novel insight into mechanisms of endocrine disruption.


Input: Leptin as regulator of pulmonary immune responses: Involvement in respiratory diseases.


Input: Leptin is an adipocyte-derived hormone, recognized as a critical mediator of the balance between food intake and energy expenditure by signalling through its functional receptor (Ob-Rb) in the hypothalamus.


Input: Structurally, leptin belongs to the long-chain helical cytokine family, and is now known to have pleiotropic functions in both innate and adaptive immunity.


Input: The presence of the functional leptin receptor in the lung together with evidence of increased airspace leptin levels arising during pulmonary inflammation, suggests an important role for leptin in lung development, respiratory immune responses and eventually pathogenesis of inflammatory respiratory diseases.


Input: The purpose of this article is to review our current understanding of leptin and its functional role on the different resident cell types of the lung in health as well as in the context of three major respiratory conditions being chronic obstructive pulmonary disease (COPD), asthma, and pneumonia.


Input: Commentary to Gebel 2012: a quantitative review should apply meta-analytical methods.


Input: Gebel (2012) performed a quantitative review of inhalation rat studies on the association of granular biopersistent dust exposures and lung cancer risk.


Input: The analytical methods applied are unreliable because they do not fulfil the requirements of current meta-analytical methods.


Input: RNAi silencing of three homologues of S-adenosylmethionine decarboxylase gene in tapetal tissue of tomato results in male sterility.

S-adenosylmethionine


Input: Polyamines play very important role in various cellular metabolic functions, including floral induction, floral differentiation and fertility regulation.

Polyamines


Input: In the present study, S-adenosylmethionine decarboxylase (SAMDC), a key gene involved in polyamine biosynthesis, has been targeted in tapetal tissue of tomato using RNAi to examine its effect on tapetum development and pollen viability.

S-adenosylmethionine

polyamine


Input: The target SAMDC gene fragments of three homologues were cloned in a hairpin RNA construct under the control of tapetal-specific A9 promoter, which was used to generate several RNAi tomato plants.


Input: These RNAi lines expressed the intended small interfering RNAs in the anther and showed the aborted and sterile pollen exhibiting shrunken and distorted morphology.


Input: These RNAi tomato plants having sterile pollen, failed to set fruits but female fertility of the plants remained unaffected as cross pollination resulted in fruit setting.


Input: Expression profiling of SAMDC genes showed considerable decrease in transcripts of SAMDC1 (5-8 fold) and SAMDC2 and SAMDC3 (2-3 fold) in the anthers of RNAi plants.


Input: The other polyamine biosynthesis genes, ADC and SPDSYN exhibited ~ 1. 5 fold decrease in their transcript levels.

polyamine


Input: Presence of siRNA molecules specific to SAMDC homologues in anther and tapetal-specific activity of A9 promoter as shown with GUS reporter system of RNAi plants suggested down-regulation of the target genes in tapetum by RNAi.


Input: These observations indicate the importance of SAMDC, in turn polyamines in pollen development, and thus tapetum-specific down-regulation of SAMDC genes using RNAi can be used for developing male sterile plants.

polyamines


Input: A Re-evaluation of the Role of hCTR1, the Human High Affinity Cu Transporter in Pt-Drug Entry into Human Cells.

Cu

Pt


Input: Cisplatin (cDDP) is an anti-cancer drug used in a number of malignancies including testicular, ovarian, cervical, bladder, lung, head, and neck cancers.

Cisplatin

cDDP


Input: Its use is limited by the development of resistance, often rationalized via effects on cellular uptake.


Input: It has been claimed that hCTR1, the human high affinity copper transporter, is the major entry pathway for cDDP and related drugs via a mechanism that mimics copper.

copper

cDDP


Input: This is an unexpected property of hCTR1, a highly selective copper (I) transporter.


Input: We compared the uptake rates of copper with cDDP (and several analogs) into HEK293 cells over-expressing wild-type or mutant hCTR1, mouse embryonic fibroblasts (mefs) that do or do not express CTR1, and human ovarian tumor cells, sensitive or resistant to cDDP.

cDDP


Input: We have also compared the effects of extracellular copper, which causes regulatory endocytosis of hCTR1, to those of cDDP.

copper

cDDP


Input: We confirm the correlation between higher hCTR1 levels and higher Pt-drug uptake in tumor cells sensitive to the drug.

Pt


Input: However, we show that hCTR1 is not the major entry route of platinum-drugs and that the copper transporter is not internalized in response to extracellular drug.

platinum

copper


Input: Our data suggest the major entry pathway for platinum-drugs is not saturable at relevant concentrations and not protein-mediated.

platinum


Input: Clinical trials have been initiated that depend upon regulating membrane levels of hCTR1.


Input: If reduced drug uptake is a major factor in resistance, hCTR1 is unlikely to be a productive target in attempts to enhance efficacy, although the proteins involved in copper homeostasis may play a role.

copper


Input: Radioiodide induces apoptosis in human thyroid tissue in culture.

Radioiodide


Input: Radioiodide ((131) I) is routinely used for the treatment of toxic adenoma, Graves' disease, and for ablation of thyroid remnant after thyroidectomy in patients with thyroid cancer.

Radioiodide

(131) I


Input: The toxic effects of ionizing radiations on living cells can be mediated by a necrotic and/or apoptotic process.


Input: The involvement of apoptosis in radiation-induced cell death in the thyrocytes has been questioned.


Input: The knowledge of the mechanisms that underlie the thyrocyte death in response to radiations can help to achieve a successful treatment with the lowest (131) I dose.

(131) I


Input: We developed a method to study the effects of (131) I in human thyroid tissue in culture, by which we demonstrated that (131) I induces thyroid cell apoptosis.

(131) I

(131) I


Input: Human thyroid tissues of about 1 mm (3) were cultured in vitro and cell viability was determined up to 3 weeks by the MTT assay.

MTT


Input: Radioiodide added to the culture medium was actively taken up by the tissues.

Radioiodide


Input: The occurrence of apoptosis in the thyrocytes was assessed by measuring the production of a caspase-cleavage fragment of cytokeratin 18 (M30) by an enzyme-linked immunoassay.


Input: Neither variation of cell number nor spontaneous apoptosis was revealed after 1 week of culture.


Input: (131) I added to the culture medium induced a dose-dependent and a time-dependent generation of M30 fragment.

(131) I


Input: The apoptotic process was confirmed by the generation of caspase-3 and PARP cleavage products.


Input: These results demonstrate that (131) I induces apoptosis in human thyrocytes.

(131) I


Input: Human thyroid tissue cultures may be useful to investigate the cell death pathways induced by (131) I.

(131) I


Input: Aqua Mediated Synthesis of Bio-active Compounds.


Input: Recently the aqueous medium has attracted the interest of organic chemists, and many.


Input: Moreover, in the past 20 years, the drug-discovery process has undergone extraordinary changes, and high-throughput biological screening of potential drug candidates has led to an ever-increasing demand for novel drug-like compounds.


Input: Noteworthy advantages were observed during the course of study on aqua mediated synthesis of compounds of medicinal importance.


Input: The established advantages of water as a solvent for reactions are, water is the most abundant and available resource on the planet and many biochemical processes occur in aqueous medium.


Input: This review will focus on describing new developments in the application of water in medicinal chemistry for the synthesis of bio-active compounds possessing various biological properties.


Input: Self-Assembling Behavior of Cellulose Nanoparticles during Freeze-Drying: Effect of Suspension Concentration, Particle Size, Crystal Structure, and Surface Charge.


Input: Cellulose nanocrystals and cellulose nanofibers with I and II crystalline allomorphs (designated as CNC I, CNC II, CNF I, and CNF II) were isolated from bleached wood fibers by alkaline pretreatment and acid hydrolysis.


Input: The effects of concentration, particle size, surface charge, and crystal structure on the lyophilization-induced self-assembly of cellulose particles in aqueous suspensions were studied.


Input: Within the concentration range of 0. 5 to 1. 0 wt%, cellulose particles self-organized into lamellar structured foam composed of aligned membrane layers with widths between 0. 5 and 3 mu m.


Input: At 0. 05 wt%, CNC I, CNF I, CNC II, and CNF II self-assembled into oriented ultrafine fibers with mean diameters of 0. 57, 1. 02, 1. 50, and 1. 00 mu m, respectively.


Input: The size of self-assembled fibers became larger when more hydroxyl groups and fewer sulfates (weaker electrostatic repulsion) were on cellulose surfaces.

hydroxyl

sulfates


Input: Possible formation mechanism was inferred from ice growth and interaction between cellulose nanoparticles in liquid-crystalline suspensions.


Input: Theoretical Strategy to Build Structural Models of Microhydrated Inorganic Systems for the Knowledge of Their Vibrational Properties: The Case of the Hydrated Nitrate Aerosols.

Hydrated Nitrate


Input: This study provides theoretical anharmonic calculations for microhydrated NaNO3-labeled (NaNO3, nH2O) x with a water-to-solute ratio (n) ranging from 1 to 3.

(NaNO3, nH2O) x


Input: A representative geometrical model of these forms was first investigated by simulating the molecular clusters as (NaNO3, 1H2O) x with x = 1 to 4.

(NaNO3, 1H2O) x


Input: The comparison between the calculated time independent anharmonic frequencies using the B3LYP-D/6-311 + G (d, p) method and their experimental counterparts led to the choice of a supercluster model.