Input: Catalysis of Cope-type rearrangements of bis-homoallylic hydroxylamines is demonstrated using chiral thiourea derivatives.

bis-homoallylic hydroxylamines


Input: This formal intramolecular hydroamination reaction provides access to highly enantioenriched alpha-substituted pyrrolidine products and represents a complementary approach to metal-catalyzed methods.

pyrrolidine


Input: Comparative study on effects of two different types of titanium dioxide nanoparticles on human neuronal cells.

titanium dioxide


Input: Titanium dioxide (TiO2) are among most frequently used nanoparticles (NPs).

Titanium dioxide


Input: They are present in a variety of consumer products, including food industry in which they are employed as an additive.


Input: The potential toxic effects of these NPs on mammal cells have been extensively studied.


Input: However, studies regarding neurotoxicity and specific effects on neuronal systems are very scarce and, to our knowledge, no studies on human neuronal cells have been reported so far.


Input: Therefore, the main objective of this work was to investigate the effects of two types of TiO2 NPs, with different crystalline structure, on human SHSY5Y neuronal cells.


Input: After NPs characterization, a battery of assays was performed to evaluate the viability, cytotoxicity, genotoxicity and oxidative damage in TiO2 NP-exposed SHSY5Y cells.


Input: Results obtained showed that the behaviour of both types of NPs resulted quite comparable.


Input: They did not reduce the viability of neuronal cells but were effectively internalized by the cells and induced dose-dependent cell cycle alterations, apoptosis by intrinsic pathway, and genotoxicity not related with double strand break production.


Input: Furthermore, all these effects were not associated with oxidative damage production and, consequently, further investigations on the specific mechanisms underlying the effects observed in this study are required.


Input: Complex mixtures: Relevance of combined exposure to substances at low dose levels.


Input: Upon analysis of chemically complex food matrices a forest of peaks is likely to be found.


Input: Identification of these peaks and concurrent determination of the toxicological relevance upon exposure is very time consuming, expensive and often requires animal studies.


Input: Recently, a safety assessment framework based on the Threshold of Toxicological Concern (TTC) was published to assess the safety of chemically complex matrices more efficiently.


Input: In this safety assessment framework, the toxicological relevance of exposure to unidentified substances in chemically complex food matrices can be related to the Cramer class III TTC threshold, currently set at 90 mu g/day.


Input: However, possible additive or synergistic effects of combined exposure is not covered.


Input: The current evaluation describes the relevance of combined low dose exposure to unidentified substances in chemically complex food matrices.


Input: It is concluded that to some extent cumulative effects at exposure levels for each substance at or below the Cramer class III TTC threshold, being present in a complex mixture including food, might occur.


Input: However the health relevance of possible cumulative effects at this dose level is considered to be that low that a need for a correction factor to cover possible cumulative effects is very low to absent.


Input: Anandamide deficiency and heightened neuropathic pain in aged mice.

Anandamide


Input: Damaging of peripheral nerves may result in chronic neuropathic pain for which the likelihood is increased in the elderly.


Input: We assessed in mice if age-dependent alterations of endocannabinoids contributed to the heightened vulnerability to neuropathic pain at old age.


Input: We assessed nociception, endocannabinoids and the therapeutic efficacy of R-flurbiprofen in young and aged mice in the spared nerve injury model of neuropathic pain.

R-flurbiprofen


Input: R-flurbiprofen was used because it is able to reduce neuropathic pain in young mice in part by increasing anandamide.

R-flurbiprofen

anandamide


Input: Aged mice developed stronger nociceptive hypersensitivity after sciatic nerve injury than young mice.


Input: This was associated with low anandamide levels in the dorsal root ganglia, spinal cord, thalamus and cortex, which further decreased after nerve injury.

anandamide


Input: In aged mice, R-flurbiprofen had only weak antinociceptive efficacy and it failed to restore normal anandamide levels after nerve injury.

R-flurbiprofen

anandamide


Input: In terms of the mechanisms, we found that fatty acid amide hydrolase (FAAH) which degrades anandamide, was upregulated after nerve injury at both ages, so that this upregulation likely did not account for the age-dependent differences.

fatty acid amide

anandamide


Input: However, enzymes contributing to oxidative metabolism of anandamide, namely cyclooxygenase-1 and Cyp2D6, were increased in the brain of aged mice, possibly enhancing the oxidative breakdown of anandamide.

anandamide

anandamide


Input: This may overwhelm the capacity of R-flurbiprofen to restore anandamide homeostasis and may contribute to the heightened risk for neuropathic pain at old age.

R-flurbiprofen

anandamide


Input: The novel recreational drug 3, 4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: Self-administration and locomotor activity in rats.

3, 4-methylenedioxypyrovalerone

MDPV


Input: Recreational use of the cathinone derivative 3, 4-methylenedioxypyrovalerone (MDPV; " bath salts ") has increased worldwide in past years, accompanied by accounts of health and legal problems in the popular media and efforts to criminalize possession in numerous jurisdictions.

3, 4-methylenedioxypyrovalerone

MDPV


Input: Minimal information exists on the effects of MDPV in laboratory models.

MDPV


Input: This study determined the effects of MDPV, alongside those of the better studied stimulant d-methamphetamine (METH), using rodent models of intravenous self-administration (IVSA), thermoregulation and locomotor activity.

MDPV

d-methamphetamine

METH


Input: Male Wistar rats were trained to self-administer MDPV or METH (0. 05 mg/kg/infusion, i. v.) or were prepared with radiotelemetry implants for the assessment of body temperature and activity responses to MDPV or METH (0-5. 6 mg/kg s. c.).

MDPV

METH

MDPV

METH


Input: METH and MDPV were consistently self-administered within 10 training sessions (mg/kg/h; METH Mean = 0. 4 and Max = 1. 15; MDPV Mean = 0. 9 and Max = 5. 8).

METH

MDPV

METH

MDPV


Input: Dose-substitution studies demonstrated that behavior was sensitive to dose for both drugs, but MDPV (0. 01-0. 50 mg/kg/inf) showed greater potency and efficacy than METH (0. 1-0. 25 mg/kg/inf).

MDPV

METH


Input: In addition, both MDPV and METH increased locomotor activity at lower doses (0. 5-1. 0 mg/kg, s. c.) and transiently decreased activity at the highest dose (5. 6 mg/kg, s. c.).

MDPV

METH


Input: Body temperature increased monotonically with increasing doses of METH but MDPV had a negligible effect on temperature.

METH

MDPV


Input: Stereotypy was associated with relatively high self-administered cumulative doses of MDPV (~ 1. 5 mg/kg/h) as well as with non-contingent MDPV administration wherein the intensity and duration of stereotypy increased as MDPV dose increased.

MDPV

MDPV

MDPV


Input: Thus, MDPV poses a substantial threat for compulsive use that is potentially greater than that for METH.

MDPV

METH


Input: Discovery of potent selective bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model.


Input: Part II: Optimization studies and demonstration of in vivo efficacy.


Input: Selective phosphodiesterase 2 (PDE2) inhibitors are shown to have efficacy in a rat model of osteoarthritis (OA) pain.


Input: We identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of phosphodiesterase 4 (PDE4) inhibitors, while minimizing PDE4 inhibitory activity.


Input: These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like binding mode orthogonal to the cAMP-like binding mode found in PDE4.

cGMP

cAMP


Input: Extensive structure activity relationship studies ultimately led to identification of pyrazolodiazepinone, 22, which was > 1000-fold selective for PDE2 over recombinant, full length PDEs 1B, 3A, 3B, 4A, 4B, 4C, 7A, 7B, 8A, 8B, 9, 10 and 11.

pyrazolodiazepinone


Input: Compound 22 also retained excellent PDE2 selectivity (241-fold to 419-fold) over the remaining recombinant, full length PDEs, 1A, 4D, 5, and 6.


Input: Compound 22 exhibited good pharmacokinetic properties and excellent oral bioavailability (F = 78%, rat).


Input: In an in vivo rat model of OA pain, compound 22 had significant analgesic activity 1 and 3h after a single, 10mg/kg, subcutaneous dose.


Input: Microglial disruption in young mice with early chronic lead exposure.


Input: The mechanisms by which early chronic lead (Pb) exposure alter brain development have not been identified.

Pb


Input: We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments.

Pb


Input: Pups were exposed via dams' drinking water from birth to post-natal day 28 to low, high or no Pb conditions.

Pb


Input: We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2).


Input: Blood Pb levels in exposed animals at sacrifice (post-natal day 28) ranged from 2. 66 to 20. 31 mu g/dL.

Pb


Input: Only interleukin-6 (IL6) differed between groups and reductions were dose-dependent.


Input: Microglia cell body number also differed between groups and reductions were dose-dependent.


Input: As compared with controls, microglia cell body volume was greater but highly variable in only low-dose animals; dentate gyri volumes in low-and high-dose animals were reduced.


Input: The results did not support a model of increased neuroinflammation.


Input: Instead, early chronic exposure to Pb disrupted microglia via damage to, loss of, or lack of proliferation of microglia in the developing brains of Pb-exposed animals.

Pb

Pb


Input: Nrp2 deficiency leads to trabecular bone loss and is accompanied by enhanced osteoclast and reduced osteoblast numbers.


Input: Neuropilin 1 (Nrp1) and Nrp2 are transmembrane receptors that can bind class 3 semaphorins (Sema3A-G) in addition to VEGF family members to play important roles in axonal guidance, vascularization and angiogenesis, as well as immune responses.


Input: Moreover, recent evidence implicates Sema3A/Nrp-mediated signaling in bone regulation.


Input: However, to date the expression of Nrp2 in bone has not been investigated and a possible role for Nrp2 in the maintenance of bone homeostasis in vivo remains unexplored.


Input: Here we show that Nrp2, together with its possible coreceptors (Plexin A family members and Plexin D1) and class 3 semaphorin ligands, were expressed during in vitro osteogenic differentiation of bone marrow stromal cells.


Input: Moreover, Nrp2 transcript and protein levels were highly induced in hematopoietic bone marrow cell-derived osteoclast cultures.


Input: Osteoblastic as well as osteoclastic Nrp2 expression was confirmed by immunohistochemistry of the long bones of mice.


Input: Interestingly, Nrp2 knockout mice were characterized by a low bone mass phenotype which was accompanied by an increased number of osteoclasts and a decreased osteoblast count.


Input: Collectively, these data point to a physiological role for Nrp2 in bone homeostasis.


Input: Rescue of platinum-damaged oocytes from programmed cell death through inactivation of the p53 family signaling network.

platinum


Input: Non-proliferating oocytes within avascular regions of the ovary are exquisitely susceptible to chemotherapy.


Input: Early menopause and sterility are unintended consequences of chemotherapy, and efforts to understand the oocyte apoptotic pathway may provide new targets for mitigating this outcome.


Input: Recently, the c-Abl kinase inhibitor imatinib mesylate (imatinib) has become the focus of research as a fertoprotective drug against cisplatin.

imatinib mesylate

imatinib

cisplatin


Input: However, the mechanism by which imatinib protects oocytes is not fully understood, and reports of the drug' s efficacy have been contradictory.

imatinib


Input: Using in vitro culture and subrenal grafting of mouse ovaries, we demonstrated that imatinib inhibits the cisplatin-induced apoptosis of oocytes within primordial follicles.

imatinib

cisplatin


Input: We found that, before apoptosis, cisplatin induces c-Abl and TAp73 expression in the oocyte.

cisplatin


Input: Oocytes undergoing apoptosis showed downregulation of TAp63 and upregulation of Bax.


Input: While imatinib was unable to block cisplatin-induced DNA damage and damage response, such as the upregulation of p53, imatinib inhibited the cisplatin-induced nuclear accumulation of c-Abl/TAp73 and the subsequent downregulation of TAp63 and upregulation of Bax, thereby abrogating oocyte cell death.

imatinib

cisplatin

imatinib

cisplatin


Input: Surprisingly, the conditional deletion of Trp63, but not Delta Np63, in oocytes inhibited apoptosis, as well as the accumulation of c-Abl and TAp73 caused by cisplatin.

cisplatin


Input: These data suggest that TAp63 is the master regulator of cisplatin-induced oocyte death.

cisplatin


Input: The expression kinetics of TAp63, c-Abl and TAp73 suggest that cisplatin activates TAp63-dependent expression of c-Abl and TAp73 and, in turn, the activation of TAp73 by c-Abl-induced BAX expression.

cisplatin


Input: Our findings indicate that imatinib protects oocytes from cisplatin-induced cell death by inhibiting c-Abl kinase, which would otherwise activate TAp73-BAX-mediated apoptosis.

imatinib

cisplatin


Input: Thus, imatinib and other c-Abl kinase inhibitors provide an intriguing new way to halt cisplatin-induced oocyte death in early follicles and perhaps conserve the endocrine function of the ovary against chemotherapy. Cell Death and Differentiation advance online publication, 19 April 2013; doi: 10. 1038/cdd. 2013. 31.

imatinib

cisplatin


Input: Use of' split waves' for the measurement of electrocatalytic kinetics: methyl viologen mediated oxygen reduction on a boron-doped diamond electrode.

methyl viologen

oxygen

boron

diamond


Input: The mediated reduction of oxygen via the reduced form of methyl viologen is studied voltammetrically.

oxygen

methyl viologen


Input: The investigation is facilitated through the use of a boron-doped diamond electrode, allowing the catalytic response to be clearly delineated from that of the direct oxygen reduction process at the electrode surface.

boron

diamond

oxygen


Input: From simulation a high homogeneous electron transfer rate (6 x 10 (9) M (-1) s (-1)) is found for the one-electron reduction of oxygen to superoxide.

oxygen

superoxide


Input: This value is in close agreement with that found using non-electrochemical methods and is significantly higher than the values previously reported in electrochemical studies.


Input: In the latter case it is demonstrated that the underestimation of the electron transfer rate arises due to oversimplification of the reaction mechanism.


Input: Reaction kinetics of CO2 absorption in to phosphonium based anion-functionalized ionic liquids.

phosphonium


Input: The reaction kinetics between CO2 and trihexyl (tetradecyl) phosphonium ([P66614])-based ionic liquids (ILs) with prolinate ([Pro]), 2-cyanopyrrolide ([2-CNpyr]), and 3-(trifluoromethyl) pyrazolide ([3-CF3pyra]) anions are studied at temperatures from 22-60 degrees C.

trihexyl (tetradecyl) phosphonium

prolinate

[Pro]

3-(trifluoromethyl) pyrazolide


Input: The absorption of CO2 is carried out in a stirred reactor under pseudo first order conditions.


Input: ILs are diluted to concentrations of 0. 05, 0. 1 and 0. 15 M with tetraglyme-a nonreactive, low volatility solvent with much lower viscosity than the ILs.

tetraglyme


Input: Physical solubility of CO2 in the mixtures is calculated using correlations developed from CO2 solubility measurements in tetraglyme and the N2O-analogy for ILs and dilute IL solutions.

tetraglyme


Input: The diffusivity of CO2 is estimated from viscosity-dependent correlations chosen after a thorough literature review.


Input: The results indicate partial first order reaction kinetics with respect to IL with values ranging from 19 500 L mol (-1) s (-1) ([P66614] [Pro]) to 3200 L mol (-1) s (-1) ([P66614] [3-CF3pyra]) at 22 degrees C.

[P66614] [Pro]

[P66614] [3-CF3pyra]


Input: The second order reaction rate constants follow Arrhenius behavior with the highest activation energy of 43 kJ mol (-1) measured for [P66614] [Pro].

[P66614] [Pro]


Input: ILs with aprotic heterocylic anions (AHA), on the other hand, show small activation energies of 18 and 11 kJ mol (-1) for [P66614] [3-CF3pyra] and [P66614] [2-CNpyr], respectively.

[P66614] [3-CF3pyra]

[P66614] [2-CNpyr]


Input: The ILs studied in this work exhibit reactivity comparable to or higher than common aqueous amines.


Input: High reaction rates and tunable capacity make ILs, and AHA ILs in particular, attractive solvents for CO2 separations.


Input: P300 during response inhibition is associated with ad-lib alcohol consumption in social drinkers.

alcohol


Input: Reduced amplitude of the cortical P300 event-related potential (ERP) component during response inhibition is associated with vulnerability to alcohol use disorders.

alcohol


Input: In the current study, we investigated the effect of an experimental manipulation of response conflict on the amplitude of the P300 component during response inhibition, and examined whether individual differences in the amplitude of this P300 component would predict voluntary ad-lib alcohol consumption, in social drinkers.

alcohol


Input: Using a repeated measures design, 16 participants performed a stop-signal task after receiving instructions that either emphasised or de-emphasised response conflict while their electroencephalogram (EEG) was concurrently recorded, before their ad-lib drinking was assessed.


Input: Results revealed that task instructions had the predicted effects on behavioural indices of response inhibition and the associated P300 components.


Input: Most importantly, individual differences in the amplitude of P300 subcomponents during response inhibition were negatively correlated with ad-lib alcohol consumption.

alcohol


Input: Results provide the first experimental support for theoretical models that posit that reduced amplitude of the P300 during response inhibition is associated with alcohol-seeking behaviour in humans.

alcohol


Input: Npas4 is activated by melatonin, and drives the clock gene Cry1 in the ovine pars tuberalis.

melatonin


Input: Seasonal mammals integrate changes in the duration of nocturnal melatonin secretion to drive annual physiological cycles.

melatonin


Input: Melatonin receptors within the proximal pituitary region, the pars tuberalis (PT), are essential in regulating seasonal neuroendocrine responses.

Melatonin


Input: In the ovine PT, melatonin is known to influence acute changes in transcriptional dynamics coupled to the onset (dusk) and offset (dawn) of melatonin secretion, leading to a potential interval-timing mechanism capable of decoding changes in day-length (photoperiod).

melatonin

melatonin


Input: Melatonin offset at dawn is linked to cAMP accumulation, which directly induces transcription of the clock gene Per1.

Melatonin

cAMP


Input: The rise of melatonin at dusk induces a separate and distinct cohort, including the clock-regulated genes Cry1 and Nampt, but little is known of the up-stream mechanisms involved.

melatonin


Input: Here, we used next generation sequencing of the ovine PT transcriptome at melatonin onset, and identified Npas4 as a rapidly induced bHLH-PAS domain transcription factor.

melatonin


Input: In vivo we show nuclear localisation of NPAS4 protein in presumptive melatonin target cells of the PT (alpha GSU-expressing cells), while in situ hybridisation studies identified acute and transient expression in the PT of Npas4 in response to melatonin.

melatonin

melatonin


Input: In vitro, NPAS4 forms functional dimers with bHLH-PAS domain co-factors ARNT, ARNT2 and ARNTL, transactivating both Cry1 and Nampt ovine promoter reporters.


Input: Using a combination of 5 `deletions and site-directed mutagenesis we show NPAS4: ARNT transactivation to be co-dependent upon two conserved central midline elements (CMEs) within the Cry1 promoter.


Input: Our data thus reveal NPAS4 as a candidate immediate early-response gene in the ovine PT, driving molecular responses to melatonin.

melatonin


Input: Clinical implementation of pharmacogenetics: more than one gene at a time.


Input: Tricyclic antidepressant (TCA) clinical pharmacogenetic implementation guidelines for CYP2D6 and CYP2C19 genotypes highlight the importance of both genes.


Input: However, studies of the combined impact of the two genes are sparse, limiting the ability to make strong recommendations based on both genes.


Input: The warfarin pharmacogenetics literature highlights the strength of a multigenic approach for discovery and clinical implementation.


Input: For optimal impact and interpretation, investigators are encouraged to conduct studies in the context of previously well-defined pharmacogenetics markers.


Input: Flavone C-glycosides from the flowers of Trollius chinensis and their anti-complementary activity.

Flavone C-glycosides


Input: Phytochemical investigation of ethanol extract from the flowers of Trollius chinensis Bunge resulted in the isolation of two new flavone C-glycosides (1-2), along with 10 known compounds (3-12).

ethanol

flavone C-glycosides


Input: The structures of the new compounds were established as 6'''-(3-hydroxy-3-methylglutaroyl)-2''-O-beta-d-galactopyranosyl orientin (1) and 6'''-(3-hydroxy-3-methylglutaroyl)-2''-O-beta-d-galactopyranosyl vitexin (2) on the basis of various spectroscopic analysis (including different 1D and 2D NMR spectroscopies, high-resolution electrospray ionization mass spectrometry) and chemical evidences.

6'''-(3-hydroxy-3-methylglutaroyl)-2''-O-beta-d-galactopyranosyl orientin

6'''-(3-hydroxy-3-methylglutaroyl)-2''-O-beta-d-galactopyranosyl vitexin


Input: Bioassay showed that eight flavonoids inhibited complement activation on the classic pathway in vitro, with their IC50 values ranging from 0. 88 to 4. 02 mM, which may contribute to the applications of the herb in treatment of acute respiratory distress syndrome, etc.

flavonoids


Input: Spatially-Resolved EELS Analysis of Antibody Distribution on Biofunctionalized Magnetic Nanoparticles.


Input: Spatially resolved electron energy loss spectroscopy (SR-EELS) using scanning transmission electron microscope (STEM) allows the identification and determination of the spatial distribution of the components/elements of immuno-functionalized core-shell superparamagnetic magnetite nanoparticles.


Input: Here, we report that SR-EELS measurements allow the direct identification and study of the biological moieties (protein G and anti-HRP antibody) in complex bionanocarriers of relevance for biomedical applications.


Input: Our findings show that the biomacromolecules are located on specific areas on the nanoparticles' surface.


Input: In addition, efficiency of this functionalization was evaluated by means of biochemical techniques.


Input: The receptor binding fragment of alpha-fetoprotein is a promising new vector for the selective delivery of antineoplastic agents.


Input: Abstract The alpha-fetoprotein (AFP) binding protein, a putative AFP receptor, is a tumour marker that is present on the surfaces of malignant cells.


Input: AFP enters cells through receptor-mediated endocytosis.


Input: The recombinant C-terminal fragment of AFP (AFP-3BC, which consists of amino acid residues 473-596) was obtained by the expression in Escherichia coli.

C

amino acid


Input: AFP-3BC was shown to be bound specifically to the AFP putative receptor on tumour cells and accumulated by endocytosis in these cells in a similar manner to that of full-length human AFP.


Input: In lymphocytes, the binding and endocytosis of AFP-3BC were absent.


Input: Thus, the AFP receptor binding site was shown experimentally to be located within the AFP-3BC sequence.


Input: A conjugate of synthesised AFP-3BC with the antitumour antibiotic doxorubicin (DOX-AFP-3BC) demonstrated high antitumour activity in vitro.

doxorubicin

DOX


Input: Thus, AFP-3BC can be used successfully as a vector for the targeted selective delivery of drugs into tumour cells.


Input: Pyranoflavones: A Group of Small-Molecule Probes for Exploring the Active Site Cavities of Cytochrome P450 Enzymes 1A1, 1A2, and 1B1.

Pyranoflavones


Input: Selective inhibition of P450 enzymes is the key to block the conversion of environmental procarcinogens to their carcinogenic metabolites in both animals and humans.


Input: To discover highly potent and selective inhibitors of P450s 1A1, 1A2, and 1B1, as well as to investigate active site cavities of these enzymes, 14 novel flavone derivatives were prepared as chemical probes.

flavone


Input: Fluorimetric enzyme inhibition assays were used to determine the inhibitory activities of these probes toward P450s 1A1, 1A2, 1B1, 2A6, and 2B1.


Input: A highly selective P450 1B1 inhibitor 5-hydroxy-4'-propargyloxyflavone (5H4' FPE) was discovered.

5H4' FPE


Input: Some tested compounds also showed selectivity between P450s 1A1 and 1A2.


Input: alpha-Naphthoflavone-like and 5-hydroxyflavone derivatives preferentially inhibited P450 1A2, while beta-naphthoflavone-like flavone derivatives showed selective inhibition of P450 1A1.

alpha-Naphthoflavone

beta-naphthoflavone

flavone


Input: On the basis of structural analysis, the active site cavity models of P450 enzymes 1A1 and 1A2 were generated, demonstrating a planar long strip cavity and a planar triangular cavity, respectively.


Input: Sustainable diets: Harnessing the nutrition agenda.


Input: There has been rapid growth in the global population over the last century and estimates for 2050 are a global population of over 9billion.


Input: These mouths need to be fed and the nutritional quality of the food received will be a key determinant of future health.


Input: Alongside this expansion in the world' s population, rapid economic growth in China, India and South America is increasing demand for protein-rich foods, especially meat and dairy products, causing concern about the impact this may have on green house gas emissions.


Input: As economies strengthen and dietary and lifestyle patterns become more westernised, the so-called diseases of affluence are becoming ever more evident, often alongside malnutrition.


Input: This paper considers these challenges and the need to embed thinking about nutrition into discussions about sustainability of the food supply.


Input: FAO/INFOODS food composition database for biodiversity.


Input: Nutrient content can vary as much between different varieties of the same foods, as they do among different foods.


Input: Knowledge of varietal differences can therefore mean the difference between nutrient adequacy and inadequacy.


Input: The FAO/INFOODS food composition database for biodiversity has been developed with analytical data for foods described at the level of variety, cultivar and breed, and for underutilized and wild foods.


Input: It contains 6411 food entries and values for 451 components together with the bibliographic references and other information.


Input: The database is in MS Excel format and can be downloaded free-of-charge from the INFOODS website http://www. fao. org/infoods/biodiversity/index _ en. stm.


Input: It is intended to annually publish new editions, making these data available for national and regional food composition databases.


Input: This database could be used to raise the awareness, promote and investigate food biodiversity and help to better estimate nutrient intakes.


Input: Trans fatty acids in a range of UK processed foods.

Trans fatty acids


Input: A survey to determine the trans fatty acid content of a range of processed foods was carried out in response to recent reformulation work by the food industry to lower the artificial trans fatty acid content of processed products.

trans fatty acid

trans fatty acid


Input: Sixty two composite samples, made up of between 5 and 12 sub-samples, were collected in 2010 and were analysed for fatty acids, and a range of nutrients.

fatty acids


Input: The foods analysed included pizza, garlic bread, breakfast cereals, quiche, fat spreads, a range of fish and meat products, chips, savoury snacks, confectionery and ice cream.


Input: Levels of trans fatty acids were reduced considerably compared with previous UK analyses of similar foods where comparisons are possible.

trans fatty acids


Input: Concentrations of trans elaidic acid (t9-C18: 1) from hydrogenated oils in all samples were < 0. 2g/100g food.

trans elaidic acid

t9-C18: 1


Input: These results confirm information provided by the food industry in 2007 on the levels of trans fats in key processed food sectors.


Input: Application of ethnic food composition data for understanding the diet and nutrition of South Asians in the UK.


Input: Lack of food composition data, recipe information and portion sizes for ethnic foods are commonly reported problems for dietary assessment of ethnic minority groups.


Input: One of the main aims of this study was to use food composition data to validate portion sizes, identify important sources of nutrients and describe the characteristics of the South Asian diet.


Input: The top five ethnic foods containing highest levels of selected nutrients were lamb balti (3mg/100g iron), lamb kebab (3. 2mg/100g zinc), mixed dhal (62 mu g/100g folate), fish curry (1. 4 mu g/100g vitamin D), ghee (968 mu g/100g retinol) and toor dhal (9. 1g/100g dietary fibre).

iron

zinc

folate

vitamin D

retinol


Input: Typical adult South Asian diets included traditional cereals (chapatti, rice and paratha) and low consumption of meat dishes; with vegetable curries contributing most towards energy intake.


Input: A higher consumption of full fat milk and fruit juices by toddlers and school children were observed when compared with the National Diet and Nutrition Survey of the UK.


Input: Food composition activities in South Africa.


Input: Researchers at the South African Medical Research Council used the Bangkok Declaration, Thailand, 2009, as a guideline for their food composition activities.


Input: The vision is to build a comprehensive food composition database for the country.


Input: Activities are directed at increasing the number of food items with country-specific nutrient information; encouraging research organisations, universities and the food industry to become involved in nutrient data generation and the generation of yield factors for South African dishes.


Input: The introduction of the South African Food Data System (SAFOODS) website and a symposium were major food composition activities.


Input: Educating users on the correct application of food composition data is an important endeavour.


Input: The national South African Food Data Advisory Group (SAFDAG) formed in 2008, advises and supports food composition activities at SAFOODS.


Input: In conclusion, with the support of SAFDAG, SAFOODS activities are aimed at compiling a country-specific food composition database and promoting its scientific use.


Input: The nutrient composition of three cuts obtained from P-class South African pork carcasses.


Input: The shoulder, loin and leg from P-class pork carcasses were used to determine the nutrient composition of both raw and cooked cuts.


Input: Significantly lower fat content were observed in the current study for the leg (5. 21g/100g) and loin (6. 99g/100g) compared to the shoulder cut (10. 32g/100g).


Input: The overall percentage fat for all three cuts was less than 10% which is recommended by the South African Heart Mark.


Input: The cooked loin cut contained the most protein (27. 50g/100g) of the three cooked cuts.


Input: When compared to other meat products (beef, mutton and chicken) it is clear that pork is a good source of B vitamins, especially vitamin B3.

B vitamins

vitamin B3


Input: The cooked loin cut contained the least vitamin B1 (0. 22mg/100g), B2 (0. 02mg/100g) but the most vitamin B3 (7. 09mg/100g), of the three cooked cuts.

vitamin B1

vitamin B3


Input: The 100g cooked shoulder, loin and leg cuts provide on average 40. 11% protein, 5. 19% magnesium, 3. 37% calcium, 24. 29% phosphorus, 18. 22% zinc, 22. 33% iron and 22. 50% vitamin B1, 2. 57% vitamin B2 and 42. 6% vitamin B3 of Recommended Daily Allowances for males, age 25-50.

magnesium

calcium

phosphorus

zinc

iron

vitamin B1

vitamin B2

vitamin B3


Input: Energy from a 100g portion provides 5. 81% of the Recommended Daily Allowances.


Input: To conclude, the pork cuts are undoubtedly a good source of nutrients that is required for good health because it is high in protein, have a low fat content and are a nutrient-packed choice for the family and compares favourably with the fat, energy, and cholesterol content of many other meats and poultry.

cholesterol


Input: Variability in the contents of pork meat nutrients and how it may affect food composition databases.


Input: Pork meat is generally recognised as a food with relevant nutritional properties because of its content in high biological value proteins, group B vitamins, minerals especially heme iron, trace elements and other bioactive compounds.

heme iron


Input: But pork meat also contributes to the intake of fat, saturated fatty acids, cholesterol, and other substances that, in inappropriate amounts, may result in negative physiologically effects.

saturated fatty acids

cholesterol


Input: However, there are relevant factors affecting the content of many of these substances and somehow such variability should be taken into consideration.


Input: So, genetics, age and even type of muscle have a relevant influence on the amount of fat and the contents in heme iron.

heme iron


Input: Also the composition in fatty acids of triacylglycerols is very sensitive to the contents of cereals in the feed; for instance, polyunsaturated fatty acids may range from 10% to 22% in pork meat.

fatty acids

triacylglycerols

polyunsaturated fatty acids


Input: The content of other nutrients, like vitamins E and A, are also depending on the type of feed.

vitamins E and A


Input: Some bioactive substances like coenzyme Q10, taurine, glutamine, creatine, creatinine, carnosine and anserine show a large dependence on the type of muscle.

coenzyme Q10

taurine

glutamine

creatine

creatinine

carnosine

anserine


Input: This manuscript describes the main factors affecting the composition of pork meat nutrients and how these changes may affect the general food composition databases.


Input: The new on-line Czech Food Composition Database.


Input: The new on-line Czech Food Composition Database (FCDB) was launched on http://www. czfcdb. cz in December 2010 as a main freely available channel for dissemination of Czech food composition data.


Input: The application is based on a complied FCDB documented according to the EuroFIR standardised procedure for full value documentation and indexing of foods by the LanguaL (TM) Thesaurus.


Input: A content management system was implemented for administration of the website and performing data export (comma-separated values or EuroFIR XML transport package formats) by a compiler.


Input: Reference/s are provided for each published value with linking to available freely accessible on-line sources of data (e. g. full texts, EuroFIR Document Repository, on-line national FCDBs).


Input: LanguaL (TM) codes are displayed within each food record as searchable keywords of the database.


Input: A photo (or a photo gallery) is used as a visual descriptor of a food item.


Input: The application is searchable on foods, components, food groups, alphabet and a multi-field advanced search.


Input: Dietary fibre: Challenges in production and use of food composition data.


Input: Dietary fibre is a heterogeneous group of components for which several definitions and analytical methods were developed over the past decades, causing confusion among users and producers of dietary fibre data in food composition databases.


Input: An overview is given of current definitions and analytical methods.


Input: Some of the issues related to maintaining dietary fibre values in food composition databases are discussed.


Input: Newly developed AOAC methods (2009. 01 or modifications) yield higher dietary fibre values, due to the inclusion of low molecular weight dietary fibre and resistant starch.


Input: For food composition databases procedures need to be developed to combine' classic' and' new' dietary fibre values since re-analysing all foods on short notice is impossible due to financial restrictions.


Input: Standardised value documentation procedures are important to evaluate dietary fibre values from several sources before exchanging and using the data, e. g. for dietary intake research.


Input: Codex dietary fibre definition-Justification for inclusion of carbohydrates from 3 to 9 degrees of polymerisation.

carbohydrates


Input: The main controversy about the DF definition, adopted by the commission of Codex Alimentarius, refers to the inclusion of carbohydrates of 3-9 degrees of polymerisation (DP), decision which may be made individually by the authorities of each country.

carbohydrates


Input: Due to the possibility of having two definitions and the negative impact it would cause over the harmonisation of nutritional information, a bibliographic review was carried, from 2009 to 2011, aiming to gather justifications for the inclusion of carbohydrates of 3-9 DP in the definition.

carbohydrates


Input: The current review presents scientific bases that are directed to three topics: physiological aspects; repercussion over the analytical method; and impact on consumers and other users.


Input: The decision of including unavailable carbohydrates of 3-9 DP in the definition of DF may cause effective global harmonisation in the nutritional labelling, considering that the main goal is to help consumers choose healthy foods.

carbohydrates


Input: Biogenic amines content as a measure of the quality of wines of Abruzzo (Italy).

amines


Input: Aim of this research was to study the effect of some agronomic and oenological factors on the content of biogenic amines as quality index of sixty-five Abruzzo wines.

amines


Input: Sum of amines was found to be decreasing in the order: red (19. 3 +/- 12. 8mgL (-1)), ros e (9. 20 +/- 6. 34mgL (-1)), white (7. 67 +/- 3. 84mgL (-1)) wine.

amines


Input: Significant differences in relationship among amines levels and chemical and chemico-physical characteristics of red, white and ros e wine are due to their different biotechnological process and winemaking.

amines


Input: Besides the aging treatment, influential seems to be the effect of the winery, regardless of the area in which it is situated.


Input: The single amines significantly correlated with their sum were putrescine, histamine and tyramine, even if reached levels were below toxicity threshold, demonstrating a good quality of the wines of Abruzzo whose consumption is no risk to the health of the consumer following the rules of proper nutrition.

amines

putrescine

histamine

tyramine


Input: Laboratory performance on analysis of mandatory nutrients and preparation of nutrition labelling.


Input: This study assessed the performance of 17 laboratories in Thailand in analysing mandatory nutrients in salted, fried broad bean and in using data to prepare nutrition labels.


Input: Nutrient levels in the test material, as robust mean (x (*)) and robust standard deviation (s (*)), were assigned in line with ISO 13528.


Input: Data obtained from the laboratories were statistically evaluated against these values.


Input: Laboratories with satisfactory, questionable and unsatisfactory results for each nutrient were identified based on robust z-score.


Input: Laboratories achieving satisfactory analytical results (z-score >= 2) were for lipid, 82%; protein, 85%; Na, 82%; Ca, 62%; Fe, 81%; ash, 70%; and moisture, 62%.

Ca

Fe


Input: Reference values for some nutrients in broad bean powder were developed using data from satisfactorily performing laboratories.


Input: Less than 20% of the laboratories demonstrated good performance in preparing nutrition labels.


Input: Common mistakes were the nutrition information format, estimation of serving size and serving (s) per package.


Input: An electrophoretic mobility shift assay identifies a mechanistically unique inhibitor of protein sumoylation.


Input: The dynamic, posttranslational modification of proteins with a small ubiquitin-like modifier (SUMO) tag has been recognized as an important cellular regulatory mechanism relevant to a number of cancers as well as normal embryonic development.


Input: As part of a program aimed toward the identification of inhibitors of SUMO-conjugating enzymes, we developed a microfluidic electrophoretic mobility shift assay to monitor sumoylation events in real time.


Input: We disclose herein the use of this assay to identify a cell-permeable compound capable of blocking the transfer of SUMO-1 from the E2 enzyme Ubc9 to the substrate.


Input: We screened a small collection of compounds and identified an oxygenated flavonoid derivative that inhibits sumoylation in vitro.

oxygenated flavonoid


Input: Next, we carried out an in-depth mechanistic analysis that ruled out many common false-positive mechanisms such as aggregation or alkylation.


Input: Furthermore, we report that this flavonoid inhibits a single step in the sumoylation cascade: the transfer of SUMO from the E2 enzyme (Ubc9) thioester conjugate to the substrate.

flavonoid


Input: In addition to having a unique mechanism of action, this inhibitor has a discrete structure-activity relationship uncharacteristic of a promiscuous inhibitor.


Input: Cell-based studies showed that the flavonoid inhibits the sumoylation of topoisomerase-I in response to camptothecin treatment in two different breast cancer cell lines, while isomeric analogs are inactive.

camptothecin


Input: Importantly, this compound blocks sumoylation while not affecting ubiquitylation in cells.


Input: This work identifies a point of entry for pharmacologic inhibition of the sumoylation cascade and may serve as the basis for continued study of additional pharmacophores that modulate SUMO-conjugating enzymes such as Ubc9.


Input: In Vitro Reconstitution of Complexes between proMatrix Metalloproteinase-9 and the Proteoglycans Serglycin and Versican.


Input: Previously we have shown that a fraction of the matrix metalloproteinase-9 (MMP-9) synthesized by the macrophage cell line THP-1 was bound to a chondroitin sulphate proteoglycan (CSPG) core protein as a reduction sensitive heteromer.


Input: It was also shown that the hemopexin-like (PEX) domain and the fibronectin-like (FnII) module in the enzyme are involved in the heteromer formation.


Input: In the present work we show that reduction sensitive and SDS-stable heteromers can be reconstituted in vitro by mixing proMMP-9 with either serglycin, versican or CSPGs isolated from various monocytic cell lines.

SDS


Input: In addition, a strong but SDS-soluble proMMP-9. CSPG heteromer was formed.

SDS


Input: The two macromolecules in the SDS-stable reduction sensitive heteromers were not linked together by disulphide bonds.

SDS

disulphide


Input: As for the heteromer isolated from THP-1 cells, the in vitro reconstituted SDS-stable and SDS-soluble heteromers had a weaker binding to gelatin than the proMMP-9 monomer.

SDS

SDS


Input: Furthermore, gelatin inhibited the in vitro reconstitution of the heteromers, showing that the FnII module is involved in the complex formation.


Input: TIMP-1 could not be detected in the formed proMMP-9. CSPG complexes.


Input: However, the presence of TIMP-1 inhibited the formation of the SDS-soluble heteromer, but not the SDS-stable reduction sensitive heteromer.

SDS

SDS


Input: This indicates that different regions in the PEX domain are involved the formation of these heteromers.


Input: This article is protected by copyright.


Input: All rights reserved.


Input: Robust autoactivation, chymotrypsin C independence and diminished secretion define a subset of hereditary pancreatitis associated cationic trypsinogen mutants.


Input: Mutations in human cationic trypsinogen cause hereditary pancreatitis by altering its proteolytic regulation of activation and degradation by chymotrypsin C (CTRC).


Input: CTRC stimulates trypsinogen autoactivation by processing the activation peptide to a shorter form but also promotes degradation by cleaving the calcium binding loop in trypsinogen.

calcium


Input: Mutations render trypsinogen resistant to CTRC-mediated degradation and/or increase processing of the activation peptide by CTRC.


Input: Here we demonstrate that activation peptide mutations D19A, D22G, K23R and K23 _ I24insIDK robustly increased the rate of trypsinogen autoactivation, both in the presence and absence of CTRC.


Input: Degradation of the mutants by CTRC was unchanged and processing of the activation peptide was increased only in the D19A mutant by 4-fold.


Input: Surprisingly, however, this increased processing had only a minimal effect on autoactivation.


Input: The tetra-aspartate motif in the trypsinogen activation peptide binds calcium (KD ~ 1. 6 mM), which stimulates autoactivation.

aspartate

calcium


Input: Unexpectedly, calcium binding was not compromised by any of the activation peptide mutations.

calcium


Input: Despite normal binding, autoactivation of mutants D22G and K23 _ I24insIDK was not stimulated by calcium.

calcium


Input: Finally, the activation peptide mutants exhibited reduced secretion from transfected cells, and secreted trypsinogen levels were inversely proportional with autoactivation rates.


Input: We conclude that D19A, D22G, K23R and K23 _ I24insIDK form a mechanistically distinct subset of hereditary pancreatitis associated mutations, which exert their effect primarily through direct stimulation of autoactivation, independently of CTRC.


Input: The potentially severe clinical impact of the markedly increased autoactivation is offset by diminished secretion, resulting in a clinical phenotype indistinguishable from typical hereditary pancreatitis.


Input: This article is protected by copyright.


Input: All rights reserved.


Input: Synthesis and biological evaluation of phosphorylated flavonoids as potent and selective inhibitors of cholesterol esterase.

phosphorylated flavonoids

cholesterol


Input: A series of phosphorylated flavonoids were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase (CEase) and acetylcholinesterase (AChE).

phosphorylated flavonoids

cholesterol


Input: The results showed that most of the synthesized compounds exhibited nanomolar potency against CEase, much better than the parent flavonoids.

flavonoids


Input: Furthermore, these phosphorylated flavonoids demonstrated good to high selectivity for CEase over AChE, which only showed micromolar potency inhibition of AChE.

phosphorylated flavonoids


Input: The most selective and potent inhibitor of CEase (3e) had IC50 value of 0. 72 nM and 11800-fold selectivity for CEase over AChE.


Input: The structure-activity relationships revealed that the free hydroxyl group at position 5 and phosphate group at position 7 of the phosphorylated flavonoids are favorable to the inhibition of CEase.

hydroxyl

phosphate

phosphorylated flavonoids


Input: The inhibition mechanism and kinetic characterization studies indicated that they are irreversible competitive inhibitors of CEase.


Input: Flies Cope with Uncontrollable Stress by Learned Helplessness.


Input: In a wide range of animals, uncontrollable stressful events can induce a condition called " learned helplessness. " In mammals it is associated with low general activity, poor learning, disorders of sleep and feeding, ulcers, and reduced immune status, as well as with increased serotonin in parts of the brain.

serotonin


Input: It is considered an animal model of depression in humans [1-4].


Input: Here we investigate learned helplessness in Drosophila, showing that this behavioral state consists of a cognitive and a modulatory, possibly mood-like, component.


Input: A fly, getting heated as soon as it stops walking, reliably resumes walking to escape the heat.


Input: If, in contrast, the fly is not in control of the heat, it learns that its behavior has no effect and quits responding.


Input: In this state, the fly walks slowly and takes longer and more frequent rests, as if it were " depressed. " This downregulation of walking behavior is more pronounced in females than in males.


Input: Learned helplessness in Drosophila is an example of how, in a certain situation, behavior is organized according to its expected consequences.


Input: Trimming of damaged 3' overhangs of DNA double-strand breaks by the Metnase and Artemis endonucleases.


Input: Both Metnase and Artemis possess endonuclease activities that trim 3' overhangs of duplex DNA.


Input: To assess the potential of these enzymes for facilitating resolution of damaged ends during double-strand break rejoining, substrates bearing a variety of normal and structurally modified 3' overhangs were constructed, and treated either with Metnase or with Artemis plus DNA-dependent protein kinase (DNA-PK).


Input: Unlike Artemis, which trims long overhangs to 4-5 bases, cleavage by Metnase was more evenly distributed over the length of the overhang, but with significant sequence dependence.


Input: In many substrates, Metnase also induced marked cleavage in the double-stranded region within a few bases of the overhang.


Input: Like Artemis, Metnase efficiently trimmed overhangs terminated in 3'-phosphoglycolates (PGs), and in some cases the presence of 3'-PG stimulated cleavage and altered its specificity.

PGs


Input: The nonplanar base thymine glycol in a 3' overhang severely inhibited cleavage by Metnase in the vicinity of the modified base, while Artemis was less affected.

thymine glycol


Input: Nevertheless, thymine glycol moieties could be removed by Metnase-or Artemis-mediated cleavage at sites farther from the terminus than the lesion itself.

thymine glycol


Input: In in vitro end-joining systems based on human cell extracts, addition of Artemis, but not Metnase, effected robust trimming of an unligatable 3'-PG overhang, resulting in a dramatic stimulation of ligase IV-and XLF-dependent end joining.


Input: Thus, while both Metnase and Artemis are biochemically capable of resolving a variety of damaged DNA ends for the repair of complex double-strand breaks, Artemis appears to act more efficiently in the context of other nonhomologous end joining proteins.


Input: Pathogenesis, current treatments and future directions for idiopathic pulmonary fibrosis.


Input: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) of unknown origin characterized by epithelial cell dysfunctions, accumulation of fibroblasts and myofibroblasts and relentless deposition of extracellular matrix (ECM).


Input: Improved diagnostic accuracy and better trial design have provided important insights from recent clinical trials.


Input: Perhaps the most important insight was the realization that' standard therapy' was actually harmful!


Input: This review summarizes the current understanding of the cell types that are altered in IPF and the pathogenic mechanisms that have been identified.


Input: It also reviews recent clinical trial results and interpretations.


Input: Finally, we highlight attractive biologic targets and therapies in development with recommendations for future therapeutic avenues.


Input: Synergistic enhancement of cancer therapy using a combination of heat shock protein targeted HPMA copolymer-drug conjugates and gold nanorod induced hyperthermia.

HPMA


Input: In the field of nanomedicine, selective delivery to cancer cells is a common goal, where active targeting strategies are often employed to increase tumor accumulation.


Input: In this study, tumor hyperthermia was utilized as a means to increase the active delivery of heat shock protein (HSP) targeted N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-drug conjugates.

N-(2-hydroxypropyl) methacrylamide

HPMA


Input: Following hyperthermia, induced expression of cell surface heat shock protein (HSP) glucose regulated protein 78kDa (GRP78) was utilized for targeted drug therapy.

glucose


Input: Conjugates bearing the anticancer agents aminohexylgeldanamycin (AHGDM), docetaxel (DOC), or cisplatin and the GRP78 targeting peptide WDLAWMFRLPVG were synthesized and characterized.

aminohexylgeldanamycin

AHGDM

docetaxel

DOC

cisplatin


Input: Binding to cell surface expressed heat shock protein GRP78 on the surface of human prostate cancer DU145 cells was evaluated.


Input: HSP targeted AHGDM and DOC conjugates demonstrated active binding comparable to native targeting peptide.

AHGDM

DOC


Input: They were then assessed in vitro for the ability to synergistically induce cytotoxicity in combination with moderate hyperthermia (43 degrees C, 30min).


Input: HSP targeted DOC conjugates exhibited high potency against DU145 cells with an IC50 of 2. 4nM.

DOC


Input: HSP targeted AHGDM and DOC conjugates demonstrated synergistic effects in combination with hyperthermia with combination index values of 0. 65 and 0. 45 respectively.

AHGDM

DOC


Input: Based on these results, HSP targeted DOC conjugates were selected for in vivo evaluation.

DOC


Input: In DU145 tumor bearing mice, a single treatment of tumor hyperthermia, induced via gold nanorod mediated plasmonic photothermal therapy, and intravenous administration of HSP targeted HPMA copolymer-docetaxel at 10mg/kg resulted in maintained tumor regression for a period of 30days.

HPMA

docetaxel


Input: These results demonstrate the potential for tumor hyperthermia to increase the delivery of HSP targeted macromolecular chemotherapeutics.


Input: Cannabinoids increase type 1 cannabinoid receptor expression in a cell culture model of striatal neurons: Implications for Huntington' s disease.


Input: The type 1 cannabinoid receptor (CB1) is a G protein-coupled receptor that is expressed at high levels in the striatum.


Input: Activation of CB1 increases expression of neuronal trophic factors and inhibits neurotransmitter release from GABA-ergic striatal neurons.

GABA


Input: CB1 mRNA levels can be elevated by treatment with cannabinoids in non-neuronal cells.


Input: We wanted to determine whether cannabinoid treatment could induce CB1 expression in a cell culture model of striatal neurons and, if possible, determine the molecular mechanism by which this occurred.


Input: We found that treatment of STHdh (7/7) cells with the cannabinoids ACEA, mAEA, and AEA produced a CB1 receptor-dependent increase in CB1 promoter activity, mRNA, and protein expression.


Input: This response was Akt-and NF-kappa B-dependent.


Input: Because decreased CB1 expression is thought to contribute to the pathogenesis of Huntington' s disease (HD), we wanted to determine whether cannabinoids could increase CB1 expression in STHdh (7/111) and (111/111) cells expressing the mutant huntingtin protein.


Input: We observed that cannabinoid treatment increased CB1 mRNA levels approximately 10-fold in STHdh (7/111) and (111/111) cells, compared to vehicle treatment.


Input: Importantly, cannabinoid treatment improved ATP production, increased the expression of the trophic factor BDNF-2, and the mitochondrial regulator PGC1 alpha, and reduced spontaneous GABA release, in HD cells.

ATP

GABA


Input: Therefore, cannabinoid-mediated increases in CB1 levels could reduce the severity of some molecular pathologies observed in HD.


Input: Chronic social stress during adolescence: Interplay of paroxetine treatment and ageing.

paroxetine


Input: Exposure to chronic stress during developmental periods is a risk factor for a number of psychiatric disorders.


Input: While the direct effects of stress exposure have been studied extensively, little is known about the long-lasting effects and the interaction with ageing.


Input: The same holds true for the treatment with selective serotonin reuptake inhibitors (SSRIs), which have been shown to prevent or reverse some stress-induced effects.

serotonin


Input: Here, we studied the direct and long-lasting impact of chronic social stress during adolescence and the impact of chronic treatment with the SSRI paroxetine in adulthood and aged animals.

paroxetine


Input: Therefore, male CD1 mice at the age of 28 days were subjected to 7 weeks of chronic social stress.


Input: Treatment with paroxetine was performed per os with a dosage of 20 mg/g BW.

paroxetine


Input: We were able to reverse most of the effects of chronic social stress in adult mice (4 months old) and to some extend in aged animals (15 months old) with the SSRI treatment.


Input: Especially the regulation of the HPA axis seems to be affected in aged mice with a shift to the use of vasopressin.

vasopressin


Input: Our results demonstrate that chronic stress exposure and antidepressant treatment at the end of the developmental period can have a significant and long-lasting impact, highly relevant for healthy ageing.


Input: Evaluation of the suitability of chromatographic systems to predict human skin permeation of neutral compounds.


Input: Several chromatographic systems (three systems of high-performance liquid chromatography and two micellar electrokinetic chromatography systems) besides the reference octanol-water partition system are evaluated by a systematic procedure previously proposed in order to know their ability to model human skin permeation.

octanol


Input: The precision achieved when skin-water permeability coefficients are correlated against chromatographic retention factors is predicted within the framework of the solvation parameter model.


Input: It consists in estimating the contribution of error due to the biological and chromatographic data, as well as the error coming from the dissimilarity between the human skin permeation and the chromatographic systems.


Input: Both predictions and experimental tests show that all correlations are greatly affected by the considerable uncertainty of the skin permeability data and the error associated to the dissimilarity between the systems.


Input: Correlations with much better predictive abilities are achieved when the volume of the solute is used as additional variable, which illustrates the main roles of both lipophilicity and size of the solute to penetrate through the skin.


Input: In this way, the considered systems are able to give precise estimations of human skin permeability coefficients.


Input: In particular, the HPLC systems with common C18 columns provide the best performances in emulating the permeation of neutral compounds from aqueous solution through the human skin.


Input: As a result, a methodology based on easy, fast, and economical HPLC measurements in a common C18 column has been developed.


Input: After a validation based on training and test sets, the method has been applied with good results to the estimation of skin permeation of several hormones and pesticides.


Input: Targeting intracellular compartments by magnetic polymeric nanoparticles.


Input: Superparamagnetic iron oxide nanoparticles (SPIONs) show a great promise for a wide specter of bioapplications, due to their characteristic magnetic properties exhibited only in the presence of magnetic field.

iron oxide


Input: Their advantages in the fields of magnetic drug targeting and imaging are well established and their safety is assumed, since iron oxide nanoparticles have already been approved for in vivo application, however, according to many literature reports the bare metal oxide nanoparticles may cause toxic effects on treated cells.

iron oxide


Input: Therefore, it is reasonable to prevent the direct interactions between metal oxide core and surrounding environment.


Input: In the current research ricinoleic acid coated maghemite nanoparticles were successfully synthesized, characterized and incorporated in the polymeric matrix, resulting in nanosized magnetic polymeric particles.

ricinoleic acid

maghemite


Input: The carrier system was shown to exhibit superparamagnetic properties and was therefore responsive towards external magnetic field.


Input: Bioevaluation using T47-D breast cancer cells confirmed internalization of magnetic polymeric nanoparticles (MNPs) and their intracellular localization in various subcellular compartments, depending on presence/absence of external magnetic field.


Input: However, the number of internalized MNPs observed by fluorescent and transmission electron microscopy was relatively low, making such way of targeting effective only for delivery of highly potent drugs.


Input: The scanning electron microscopy of treated cells revealed that MNPs influenced the cell adhesion, when external magnetic field was applied, and that treatment resulted in damaged apical plasma membrane right after exposure to the magnetic carrier.


Input: On the other hand, MNPs showed only reversibly reduced cellular metabolic activity in concentrations up to 200 mu g/ml and, in the tested concentration the cell cycle distribution was within the normal range, indicating safety of the established magnetic carrier system for the treated cells.


Input: Synthesis, radioiodination and in vivo screening of novel potent iodinated and fluorinated radiotracers as melanoma imaging and therapeutic probes.


Input: In order to develop new iodinated and fluorinated matched-pair radiotracers for Single-Photon Emission Computed Tomography (SPECT)/Positron Emission Tomography (PET) imaging and targeted radionuclide therapy of melanoma, we successfully synthesized and radiolabelled with iodine-125 seven new derivatives, starting from our previously described lead structure 3.


Input: The relevance of these radiotracers for gamma scintigraphic imaging of melanoma in rodent was assessed.


Input: The tumoural radioactivity uptake was most often high and specific even at early time points (12. 1-18. 3% ID/g at 3 h p. i. for [(125) I] 39-42) and a fast clearance from the non-target organs was observed.

(125) I


Input: Also, calculated effective doses that could be delivered to tumours when using corresponding [(131) I]-labelled analogues were generally higher than 100 cGy/MBq injected (98. 9-150. 5 cGy/MBq for [(131) I] 39-42).

(131) I

(131) I


Input: These results make compounds 39-42 suitable candidates for (i) PET imaging of melanoma after labelling with fluorine-18 and (ii) targeted radionuclide therapy of disseminated melanoma after labelling with iodine-131.


Input: Triazolothiadiazoles and triazolothiadiazines-Biologically attractive scaffolds.

Triazolothiadiazoles

triazolothiadiazines


Input: Contemporary medicinal chemistry faces diverse challenges from several directions, including the need for both potency and specificity of any therapeutic agent.


Input: Therefore, in the present perspective, the triazolothiadiazoles and triazolothiadiazines with broad spectrum biological profile have matured into indispensable heterocyclic scaffolds.

triazolothiadiazoles

triazolothiadiazines


Input: This review article is an effort to summarize medicinal chemistry investigations over the last decade, in search for new N-bridged heterocycles which can be a rich source of promising biological activities.

N


Input: The Fusarium toxin deoxynivalenol (DON) modulates the LPS induced acute phase reaction in pigs.

deoxynivalenol

DON


Input: The systemic effects of the Fusarium toxin deoxynivalenol (DON) and of bacterial lipopolysaccharides (LPS) were studied in male castrated pigs (40. 4 +/- 3. 7kg) infused intravenously with either DON or LPS alone (100 mu gDON/kg/h, 7. 5 mu g/LPS/kg/h), or together (100 mu gDON plus 7. 5 mu g/LPS/kg/h).

deoxynivalenol

DON

DON

gDON

gDON


Input: The Control group received a saline infusion (n = 6/treatment, 24h observation period).


Input: An additional DON infusion did not exacerbate the clinical signs observed in LPS-infused pigs.

DON


Input: For example, rectal temperature climaxed after 4h (40. 4 +/- 0. 2 degrees C) and 5h (40. 1 +/- 0. 3 degrees C), in the LPS and LPS + DON groups, respectively.

DON


Input: Saline and DON alone did not induce an acute phase reaction as indicated by unaltered plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) while LPS caused a significant rise of both cytokines.

DON


Input: TNF-alpha plasma peak concentrations were significantly higher in the LPS compared to the DON + LPS group (94. 3 +/- 17. 2ng/mL vs. 79. 2 +/- 15. 7ng/mL) while IL-6 climaxed earlier in the latter group (3h p. i. vs. 2h p. i.).

DON


Input: From the tested clinical-chemical plasma characteristics the total bilirubin concentration and the ASAT activity were strongly elevated by the LPS infusion and additionally increased and decreased by DON, respectively.

bilirubin

DON


Input: In conclusion, the LPS-induced effects were only marginally modified by DON.

DON


Input: Thermal inactivation reaction rates for ricin are influenced by pH and carbohydrates.

carbohydrates


Input: Ricin is a lethal protein toxin produced by the castor bean plant.


Input: Ricin is known to possess significant heat resistance.


Input: Therefore, we placed it in a variety of foods to study the influence of the food matrix on behavior of a thermally stable protein toxin.


Input: First order rate constants for the thermal inactivation of ricin in foods and simple buffers were measured using cytotoxicity assays.


Input: We observed greater thermal stability at 75 degrees C for the cytotoxic activity of ricin when it was placed in a yogurt-containing fruit drink compared to its stability when placed in the other foods tested.


Input: We found that galactose and high molecular weight exopolysaccharides present in various dairy products contributed to the thermal stability of ricin.

galactose


Input: Differential scanning calorimetry also showed enhanced thermal stability for ricin at pH 4. 5.


Input: Our results demonstrate the importance of considering pH and the presence of stabilizing ligands in the thermal inactivation of protein toxins in foods.


Input: Short-term toxicity of hexavalent-chromium to epipsammic diatoms of a microtidal estuary (R i o de la Plata): Responses from the individual cell to the community structure.

hexavalent-chromium


Input: Diatoms are an integral and often dominant component of the benthic microalgal assemblage in estuarine and shallow coastal environments.


Input: Different toxic substances discharged into these ecosystems persist in the water, sediments, and biota for long periods.


Input: Among these pernicious agents, the toxicity in diatoms by metal is linked to different steps in the transmembrane and internal movements of the toxicant, causing perturbations in the normal structural and functional cellular components.


Input: These changes constitute an early, nontaxonomic warning signal that could potentially serve as an indicator of this type of pollution.


Input: The aim of this work was to study the environment-reflecting short-term responses at different levels of organization of epipsammic diatoms from the R i o de la Plata estuary, Argentina that had been exposed to hexavalent chromium within experimental microcosms.

hexavalent chromium


Input: To this end we monitored: (i) changes in the proportion of the diatoms in relation to other algal groups at the biofilm community level; (ii) shifts in species composition at the diatom-assemblage level; (iii) projected changes in the densities of the most representative species at the population level through comparison of relative growth rates and generation times; and (iv) the cytological changes at the cellular and subcellular levels as indicated by the appearance of teratological effects on individuals and nuclear alterations.


Input: The epipsammic biofilms were exposed for 96h to chromium at a concentration similar to that measured in highly impacted sites along the coast (80 mu gL (-1)).

chromium


Input: Chromium pollution, at this concentration and short exposure time did not affect the algal biomass and density of these mature biofilms.

Chromium


Input: The biofilm composition, however, did change, as reflected in a decline in cyanophytes and an increment in the proportions of diatoms and chlorophytes; with Hippodonta hungarica, Navicula novaesiberica, Nitzschia palea, and Sellaphora pupula being the most frequent and abundant species.


Input: The most notable shifts related to chromium exposure were a decrease in the relative abundance of H. hungarica and a significant increase in the proportion of N. palea.

chromium


Input: Moreover, the species analyzed in the treatment microcosms showed higher growth rates than in the controls-N. palea grew faster, while H. hungarica replicated more slowly.


Input: The total nuclear abnormalities-as recorded in Fallacia pygmaea and N. novaesiberica-were significantly higher in the treatment microcosms; whereas in N. palea, the dominant species in treatment microcosms, neither nuclear alterations nor abnormal frustules were observed.


Input: MicroRNAs as pharmacological targets in endothelial cell function and dysfunction.


Input: Endothelial cell dysfunction is a term which implies the dysregulation of normal endothelial cell functions, including impairment of the barrier functions, control of vascular tone, disturbance of proliferative, migratory and morphogenic capacities of endothelial cells, as well as control of leukocyte trafficking.


Input: MicroRNAs (miRNAs) are short non-coding RNAs that have emerged as critical regulators of gene expression acting predominantly at the post-transcriptional level.


Input: This review summarizes the latest insights in the identification of endothelial-specific miRNAs and their targets, as well as their roles in controlling endothelial cell functions in both autocrine and paracrine manner.


Input: In addition, we discuss the therapeutic potential for the treatment of endothelial cell dysfunction and associated vascular pathophysiological conditions.


Input: Effect of a Garcinia garderiana (Planchon and Triana) Zappi hydroalcoholic extract on melanogenesis in B16F10 melanoma cells.


Input: ETHNOPHARMACOLOGY RELEVANCE: Garcinia gardneriana (Planchon and Triana) Zappi (Clusiaceae) is popularly called " bacopari " in southern Brazil.


Input: The leaves of this plant are traditionally used to treat skin disorders.


Input: AIM OF STUDY: This study evaluated the effects of a hydroalcoholic extract of Garcinia gardneriana leaves (HEGG) on B16F10 murine melanoma cells in order to search for new depigmenting agents.


Input: MATERIALS AND METHODS: The effects of HEGG were assessed in melanin content assays in B16F10 melanoma cells compared with the reference drug kojic acid (500mM).

kojic acid


Input: Melanin content was measured after spontaneous melanogenesis, UVB-induced melanogenesis and melanogenesis induced by alpha-MSH.


Input: At the same time, cell viability assays were conducted.


Input: Intracellular and mushroom tyrosinase activity assays were employed to evaluate the effect of HEGG on tyrosinase activity.


Input: RESULTS: HEGG decreased the level of melanin under all three experimental conditions of melanin content evaluation without reducing cell viability.


Input: In intracellular tyrosinase assays, the enzyme' s activity was reduced about 19% with extract concentrations ranging 0. 1-10 micro g/mL.


Input: In the mushroom tyrosinase activity assay a maximal inhibition of 35% (1000 micro g/mL) was observed.


Input: CONCLUSION: These results suggest that HEGG inhibition relates to its tyrosinase activity.


Input: Therefore, the hydroalcoholic extract of Garcinia gardneriana shows great potential for use as a depigmenting agent in hyperpigmentation disorders.


Input: Anti-diarrhoeal activity of aqueous extract of Ocimum kilimandscharicum.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Ocimum kilimandscharicum Baker ex G u erke, commonly referred to as Kapur Tulsi, is a medicinal herb that belongs to the family of Lamiaceae.


Input: It is traditionally popular for its gastroprotective effects, including its use as a digestive and anti-diarrhoeal.


Input: AIM OF THE STUDY: The present study aims to prove the anti-diarrhoeal activity of aqueous extract of leaves of Ocimum kilimandscharicum in animal models.


Input: MATERIALS AND METHODS: The aqueous extract was tested at three different dose levels (100, 200 and 400mg/kg, p. o. in rats and the corresponding doses in mice) against castor-oil induced diarrhoea model and castor oil induced enteropooling assay in rats; and charcoal meal test/intestinal motility test in mice.


Input: The parameters observed were the onset of defecation, cumulative faecal weight and consistency of faeces in the castor oil induced diarrhoea model; the weight of intestinal content in castor oil induced enteropooling assay; and the distance travelled by charcoal in the intestinal motility test.


Input: RESULTS: A significant delay in the onset of defecation (p < 0. 05), reduction in the cumulative faecal weight (p < 0. 001), along with a change in the faecal consistency from watery to solid form was observed at the dose of 200mg/kg in the castor oil-induced diarrhoea model.


Input: Similarly, the extract at the doses of 100mg/kg (p < 0. 01) and 200mg/kg (p < 0. 001) significantly decreased the weight of intestinal content in castor oil induced enteropooling assay.


Input: In the charcoal meal test the extract at the dose of 280mg/kg (corresponding to 200mg/kg in rats) significantly (p < 0. 01) reduced the distance travelled by charcoal.


Input: CONCLUSION: The aqueous extract of leaves of Ocimum kilimandscharicum showed anti-diarrhoeal activity, which may be due to its anti-motility and anti-secretory effects, which thus proved the traditional claims.


Input: Electroconvulsive seizures activate anorexigenic signals in the ventromedial nuclei of the hypothalamus.


Input: The ventromedial nucleus of the hypothalamus (VMH) plays an important role in feeding and energy homeostasis.


Input: Electroconvulsive seizure (ECS) therapy is highly effective in the treatment of several psychiatric diseases, including depression, but may also have beneficial effects in other neurological diseases.


Input: Although it has been reported that the neurons of the VMH are strongly activated by ECS stimulation, the specific effects of ECS in this hypothalamic subnucleus remain unknown.


Input: To address this issue, we investigated the changes in gene expression in microdissected-VMH samples in response to ECS in mice, and examined the behavioral effects of ECS on feeding behavior.


Input: ECS significantly induced the expression of immediate-early genes such as Fos, Fosb, and Jun, as well as Bdnf, Adcyap1, Hrh1, and Crhr2 in the VMH.


Input: Given that signals of these gene products are suggested to have anorexigenic roles in the VMH, we also examined the effect of ECS on food intake and body weight.


Input: Repeated ECS had a suppressive effect on food intake and body weight gain under both regular and high-fat diet conditions.


Input: Furthermore, gold-thioglucose-induced hypothalamic lesions, including the VMH and the arcuate nucleus, abolished the anorexigenic effects of ECS, indicating the requirement for the activation of the hypothalamus.

gold-thioglucose


Input: Our data show an effect of ECS on increased expression of anorexigenic factors in the VMH, and suggest a role in the regulation of energy homeostasis by ECS.


Input: Isolation and in vitro partial characterization of hemolytic proteins from the nematocyst venom of the jellyfish Stomolophus meleagris.


Input: Jellyfish venom contains various toxins and can cause itching, edema, muscle aches, shortness of breath, blood pressure depression, shock or even death after being stung.


Input: Hemolytic protein is one of the most hazardous components in the venom.


Input: The present study investigated the hemolytic activity of the nematocyst venom from jellyfish Stomolophus meleagris.


Input: Anion exchange chromatography, DEAE Sepharose Fast Flow, and gel filtration chromatography, Superdex200 had been employed to isolate hemolytic proteins from the nematocyst venom of jellyfish S. meleagris.

DEAE


Input: Hemolysis of chicken red blood cells was used to quantify hemolytic potency of crude nematocyst venom and chromatography fractions during the purification process.


Input: Native-PAGE profile displayed one protein band in the purified hemolytic protein (SmTX); however, two protein bands with apparent molecular weights of ~ 45kDa and 52kDa were observed in the reducing SDS-PAGE analysis.

SDS


Input: Approximately 70 mu g/mL of SmTX caused 50% hemolysis (HU50) of the erythrocyte suspension.


Input: The hemolytic activity of SmTX was shown to be temperature and pH dependent, with the optimum temperature and pH being 37 degrees C and pH 5. 0.


Input: The present study is the first report of isolation and partial characterization of hemolytic proteins from the nematocyst venom of the jellyfish S. meleagris.


Input: The mechanism of the hemolytic activity of SmTX is not clear and deserves further investigation.


Input: Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation.


Input: Recent studies suggest that endocrine disrupting chemicals (EDCs) may form a risk factor for obesity by altering energy metabolism through epigenetic gene regulation.


Input: The goal of this study is to investigate the effects of a range of EDCs with putative obesogenic properties on global DNA methylation and adipocyte differentiation in vitro.


Input: Murine N2A and human SK-N-AS neuroblastoma cells and murine preadipocyte fibroblasts (3T3-L1) were exposed to tributyltin (TBT), diethylstilbestrol (DES), bisphenol A (BPA), 2, 3, 7, 8-tetrachlorodibenzo-[p]-dioxin (TCDD), 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (PCB-153), hexachlorobenzene (HCB), hexabromocyclododecane (HBCD), 2, 2', 4, 4'-tetrabrominated diphenyl ether (BDE-47), perfluorinated octyl acid (PFOA) and perfluorinated octyl sulfonate (PFOS).

tributyltin

TBT

diethylstilbestrol

DES

bisphenol A

BPA

2, 3, 7, 8-tetrachlorodibenzo-[p]-dioxin

TCDD

2, 2', 4, 4', 5, 5'-hexachlorobiphenyl

hexachlorobenzene

HCB

hexabromocyclododecane

HBCD

2, 2', 4, 4'-tetrabrominated diphenyl ether

perfluorinated octyl acid

PFOA

perfluorinated octyl sulfonate

PFOS


Input: A modest decrease in global DNA methylation was observed in N2A cells exposed to 10 mu M DES, BPA, TCDD, BDE-47, PCB-153 and 1 mu M HCB, but no changes were found in the human SK-N-AS cells.

DES

BPA

TCDD

HCB


Input: We reveal for the first time that BDE-47 increases adipocyte differentiation in a dose-dependent manner (2. 5-25 mu M).


Input: Adipocyte differentiation was also enhanced by TBT (<= 10nM) and BPA (> 10 mu M) and inhibited by TCDD (<= 0. 1nM).

TBT

BPA

TCDD


Input: The other chemicals showed either modest or no effects on adipocyte differentiation at the concentrations tested (PFOA, PFOS and HBCD at 10 mu M; PCB-153, 3. 4 mu M and HCB, 1 mu M).

PFOA

PFOS

HBCD

HCB


Input: This study demonstrates that, selected EDCs can induce functional changes in murine adipocyte differentiation in vitro which are accompanied by decreased global DNA methylation.


Input: Cardiovascular effects of Boophone disticha aqueous ethanolic extract on early maternally separated BALB/C mice.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: There are a number of reports from traditional medical practice in Zimbabwe and neighboring countries and few in vitro studies suggesting an effect with extracts of Boophone disticha in some forms of anxiety disorders.


Input: AIM OF THE STUDY: In order to validate the use of Boophone disticha in treatment of anxiety, this study was set to determine the effects of the plant extracts on blood pressure (BP) and heart rate (HR) in adult BALB/c mice subjected to repeated early maternal separation (MS) stress.


Input: MATERIALS AND METHODS: To test whether early life stress increases anxiety in mice, non-invasive tail cuff method was used to examine the autonomic nervous system activity by assessing cardiovascular reactivity and response to acute mixing stress (AMS) and restraint stress (RS) in adult mice subjected to early postnatal stress as compared to control.


Input: AMS-induced cardiovascular response was then evaluated in adult MS mice treated with Boophone disticha as compared to vehicle and diazepam.

diazepam


Input: RESULTS: Comparisons of the BP and HR measurements indicated that MS significantly reduced AMS-induced HR responses in BALB/c mice when compared with control.


Input: Boophone disticha treatment significantly reduced AMS-induced BP response in BALB/c MS as compared to vehicle and diazepam treatments.

diazepam


Input: CONCLUSIONS: Our findings demonstrate for the first time that postnatal stress can induce short-term changes in the sensitivity of the cardiovascular system to subsequent stress which can be reduced by treatment with a freeze dried aqueous ethanolic extract of Boophone disticha.


Input: Multiple treatments with liposomal doxorubicin and ultrasound-induced disruption of blood-tumor and blood-brain barriers improve outcomes in a rat glioma model.

doxorubicin


Input: The blood-brain-barrier (BBB) prevents the transport of most anticancer agents to the central nervous system and restricts delivery to infiltrating brain tumors.


Input: The heterogeneous vascular permeability in tumor vessels, along with several other factors, creates additional barriers for drug treatment of brain tumors.


Input: Focused ultrasound (FUS), when combined with circulating microbubbles, is an emerging noninvasive method to temporarily permeabilize the BBB and the " blood-tumor barrier ".


Input: Here, we tested the impact of three weekly sessions of FUS and liposomal doxorubicin (DOX) in 9L rat glioma tumors.

doxorubicin

DOX


Input: Animals that received FUS + DOX (N = 8) had a median survival time that was increased significantly (P < 0. 001) compared to animals who received DOX only (N = 6), FUS only (N = 8), or no treatment (N = 7).

DOX

DOX


Input: Median survival for animals that received FUS + DOX was increased by 100% relative to untreated controls, whereas animals who received DOX alone had only a 16% improvement.

DOX

DOX


Input: Animals who received only FUS showed no improvement.


Input: No tumor cells were found in histology in 4/8 animals in the FUS + DOX group, and in two animals, only a few tumor cells were detected.

DOX


Input: Adverse events in the treatment group included skin toxicity, impaired activity, damage to surrounding brain tissue, and tissue loss at the tumor site.


Input: In one animal, intratumoral hemorrhage was observed.


Input: These events are largely consistent with known side effects of doxorubicin and with an extensive tumor burden.

doxorubicin


Input: Overall this work demonstrates that multiple sessions using this FUS technique to enhance the delivery of liposomal doxorubicin have a pronounced therapeutic effect in this rat glioma model.

doxorubicin


Input: Global analytical strategy to measure drug-plasma protein interactions: from high-throughput to in-depth analysis.


Input: The selection of drug candidates with improved pharmacokinetics is essential to reduce the attrition rates during drug development and represents one of the big challenges faced by the pharmaceutical industry.


Input: Plasma protein binding (PPB) is an important parameter with significant implications for in vivo drug performance.


Input: Today, the most widely used techniques for PPB measurement in the pharmaceutical community are equilibrium dialysis (ED) and ultrafiltration (UF).


Input: However, these techniques have some limitations.


Input: Thus, we emphasize an alternative strategy, based on a global, new and easy-to-follow methodology, to screen and perform determination of PPB, using orthogonal techniques (i. e. liquid chromatography, capillary electrophoresis (CE), surface plasmon resonance (SPR) based biosensor).


Input: We anticipate that the increased knowledge gained through this strategy will lead to improved drug candidates.


Input: Secular Changes in U. S.


Input: Prediabetes Prevalence Defined by Hemoglobin A1c and Fasting Plasma Glucose: National Health and Nutrition Examination Surveys, 1999-2010.

Glucose


Input: OBJECTIVEUsing a nationally representative sample of the civilian noninstitutionalized U. S. population, we estimated prediabetes prevalence and its changes during 1999-2010. RESEARCH DESIGN AND METHODSData were from 19, 182 nonpregnant individuals aged >= 12 years who participated in the 1999-2010 National Health and Nutrition Examination Surveys.


Input: We defined prediabetes as hemoglobin A1c 5. 7 to < 6. 5% (39 to < 48 mmol/mol, A1C5. 7) or fasting plasma glucose (FPG) 100 to < 126 mg/dL (impaired fasting glucose [IFG]).

glucose

glucose


Input: We estimated the prevalence of prediabetes, A1C5. 7, and IFG for 1999-2002, 2003-2006, and 2007-2010.


Input: We calculated estimates age-standardized to the 2000 U. S. census population and used logistic regression to compute estimates adjusted for age, sex, race/ethnicity, poverty-to-income ratio, and BMI.


Input: Participants with self-reported diabetes, A1C >= 6. 5% (>= 48 mmol/mol), or FPG >= 126 mg/dL were included. RESULTSAmong those aged >= 12 years, age-adjusted prediabetes prevalence increased from 27. 4% (95% CI 25. 1-29. 7) in 1999-2002 to 34. 1% (32. 5-35. 8) in 2007-2010.


Input: Among adults aged >= 18 years, the prevalence increased from 29. 2% (26. 8-31. 8) to 36. 2% (34. 5-38. 0).


Input: As single measures among individuals aged >= 12 years, A1C5. 7 prevalence increased from 9. 5% (8. 4-10. 8) to 17. 8% (16. 6-19. 0), a relative increase of 87%, whereas IFG remained stable.


Input: These prevalence changes were similar among the total population, across subgroups, and after controlling for covariates. CONCLUSIONSDuring 1999-2010, U. S. prediabetes prevalence increased because of increases in A1C5. 7.


Input: Continuous monitoring of prediabetes is needed to identify, quantify, and characterize the population of high-risk individuals targeted for ongoing diabetes primary prevention efforts.


Input: BID-induced structural changes in BAK promote apoptosis.


Input: The BCL-2-family protein BAK is responsible for mitochondrial outer-membrane permeabilization (MOMP), which leads to apoptosis.


Input: The BCL-2 homology 3 (BH3)-only protein BID activates BAK to perform this function.


Input: We report the NMR solution structure of the human BID BH3-BAK complex, which identified the activation site at the canonical BH3-binding groove of BAK.


Input: Mutating the BAK BH1 in the groove prevented activation and MOMP but not the binding of BID.


Input: BAK BH3 mutations allowed BID binding and activation but blunted function by blocking BAK oligomerization.


Input: BAK activation follows a' hit-and-run' mechanism whereby BID dissociates from the trigger site, which allows BAK oligomerization at an overlapping interface.


Input: In contrast, the BH3-only proteins NOXA and BAD are predicted to clash with the trigger site and are not activators of BAK.


Input: These findings provide insights into the early stages of BAK activation.


Input: Thermal and electrical conduction in 6. 4 nm thin gold films.


Input: For sub-10 nm thin metallic films, very little knowledge is available so far on how electron scattering at surface and grain boundaries reduces the thermal transport.


Input: This work reports on the first time characterization of the thermal and electrical conductivities of gold films of 6. 4 nm average thickness.


Input: The electrical (sigma) and thermal (k) conductivities of the Au film are found to be reduced dramatically from their bulk counterparts by 93. 7% (sigma) and 80. 5% (k).

Au


Input: Its Lorenz number is measured as 7. 44 x 10 (-8) W Omega K (-2), almost a twofold increase from the bulk value.


Input: The Mayadas-Shatzkes model is used to interpret the experimental results and reveals very strong electron reflection (77%) at grain boundaries.


Input: The relationship between cocaine self-administration and actigraphy-based measures of sleep in adult rhesus monkeys.

cocaine


Input: RATIONALE: Clinical trials show that chronic cocaine users suffer from sleep disturbances and preclinical research has shown that acute sleep deprivation increases the rate of cocaine self-administration in rats.

cocaine

cocaine


Input: OBJECTIVE: This study examined the effect of cocaine self-administration on behavioral indices of sleep and alternatively the effect of sleep disruption on cocaine-maintained responding by rhesus monkeys.

cocaine

cocaine


Input: METHODS: Seven adult rhesus monkeys, fitted with Actical (R) activity monitors, were trained to respond under a concurrent choice paradigm with food (three 1. 0-g pellets) and cocaine (0. 003-0. 3 mg/kg) or saline presentation.

cocaine


Input: For each monkey, the lowest preferred dose of cocaine (> 80% cocaine choice) was determined.

cocaine

cocaine


Input: Activity data were analyzed during lights out (2000-0600) to determine sleep efficiency, sleep latency, and total activity counts.


Input: Subsequently, the monkeys' sleep was disrupted (every hour during lights-out period) the night prior to food-cocaine choice sessions.

cocaine


Input: RESULTS: Self-administration of the preferred dose of cocaine resulted in a significant decrease in sleep efficiency, with a significant increase in total lights-out activity.

cocaine


Input: Sleep disruption significantly altered behavioral indices of sleep, similar to those seen following cocaine self-administration.

cocaine


Input: However, sleep disruption did not affect cocaine self-administration under concurrent choice conditions.

cocaine


Input: CONCLUSIONS: Based on these findings, cocaine self-administration does appear to disrupt behavioral indices of sleep, although it remains to be determined if treatments that improve sleep measures can affect future cocaine taking.

cocaine

cocaine


Input: Contaminant driven genetic erosion and associated hypotheses on alleles loss, reduced population growth rate and increased susceptibility to future stressors: an essay.


Input: Microevolution due to pollution can occur mainly through genetic drift bottlenecks, especially of small sized populations facing intense lethal pulses of contaminants, through mutations, increasing allelic diversity, and through natural selection, with the disappearance of the most sensitive genotypes.


Input: This loss of genotypes can lead to serious effects if coupled to specific hypothetical scenarios.


Input: These may be categorized as leading, first, to the loss of alleles-the recessive tolerance inheritance hypothesis.


Input: Second, leading to a reduction of the population growth rate-the mutational load and fitness costs hypotheses.


Input: Third, leading to an increased susceptibility of further genetic erosion both at future inputs of the same contaminant-differential physiological recovery, endpoints (dis) association, and differential phenotypic plasticity hypotheses-and at sequential or simultaneous inputs of other contaminants-the multiple stressors differential tolerance hypothesis.


Input: Species in narrowly fluctuating environments (tropics and deep sea) may have a particularly high susceptibility to genetic erosion-the Plus c a change (plus c' est la meme chose) hypothesis.


Input: A discussion on the consequences of these hypotheses is what this essay aimed at.


Input: Inhibitory action of salicylideneamino-2-thiophenol on NF-kappa B signaling cascade and cyclooxygenase-2 in HNE-treated endothelial cells.

HNE


Input: In the present study, the anti-inflammatory effect of salicylideneamino-2-thiophenol (SAL-2), a derivative of salicylate, on a potent oxidant 4-hydroxynonenal (HNE)-induced oxidative stress was investigated using rat prostate endothelial (YPEN-1) cells.

salicylate

HNE


Input: We focused on anti-inflammatory activity of SAL-2 which was determined by its ability to suppress COX-2 and iNOS gene expression through suppression of NF-kappa B and redox regulation.


Input: We found that SAL-2 effectively inhibited HNE-induced reactive species generation, while upregulated GSH/GSSG ratio.

HNE

GSH

GSSG


Input: Prostagrandin (PG) E2 production stimulated by arachidonic acid was suppressed by SAL-2.

(PG) E2

arachidonic acid


Input: SAL-2 also downregulated COX-2 and iNOS expression induced by HNE, but salicylate did not.

HNE

salicylate


Input: We found that SAL-2 inhibited HNE-mediated IKK phosphorylation, I kappa B alpha degradation and nuclear translocation of p65 which are linked to NF-kappa B activation.

HNE


Input: Furthermore, SAL-2 inhibited HNE-induced activation of mitogen-activated protein kinases.

HNE


Input: Collectively, SAL-2 inhibited COX-2 and iNOS gene expression through suppression of NF-kappa B leading to the inhibition of PGE2 synthesis.


Input: Based on these data, we propose that with its combined effect on strong anti-oxidant and anti-inflammatory action, SAL-2 can be a potent anti-inflammatory agent for treatment of inflammatory-related diseases.


Input: Aldose Reductase Inhibitory Compounds from Xanthium strumarium.


Input: As part of our ongoing search for natural sources of therapeutic and preventive agents for diabetic complications, we evaluated the inhibitory effects of components of the fruit of Xanthium strumarium (X. strumarium) on aldose reductase (AR) and galactitol formation in rat lenses with high levels of glucose.

aldose

galactitol

glucose


Input: To identify the bioactive components of X. strumarium, 7 caffeoylquinic acids and 3 phenolic compounds were isolated and their chemical structures were elucidated on the basis of spectroscopic evidence and comparison with published data.

caffeoylquinic acids

phenolic


Input: The abilities of 10 X. strumarium-derived components to counteract diabetic complications were investigated by means of inhibitory assays with rat lens AR (rAR) and recombinant human AR (rhAR).


Input: From the 10 isolated compounds, methyl-3, 5-di-O-caffeoylquinate showed the most potent inhibition, with IC50 values of 0. 30 and 0. 67 mu M for rAR and rhAR, respectively.

methyl-3, 5-di-O-caffeoylquinate


Input: In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate, methyl-3, 5-di-O-caffeoylquinate showed competitive inhibition of rhAR.

methyl-3, 5-di-O-caffeoylquinate


Input: Furthermore, methyl-3, 5-di-O-caffeoylquinate inhibited galactitol formation in the rat lens and in erythrocytes incubated with a high concentration of glucose, indicating that this compound may be effective in preventing diabetic complications.

methyl-3, 5-di-O-caffeoylquinate

galactitol

glucose


Input: Fructose-1, 6-bisphosphate ameliorates lipopolysaccharide-induced dysfunction of blood-brain barrier.

Fructose-1, 6-bisphosphate


Input: Fructose-1, 6-bisphosphate (FBP), a glycolytic intermediate, has neuroprotective effects in various brain injury models.

Fructose-1, 6-bisphosphate

FBP


Input: However, its effects on blood-brain barrier (BBB) are largely unknown.


Input: In this study, we investigated the effects of FBP on lipopolysaccharide (LPS)-induced BBB dysfunction in in vitro BBB model comprising co-culture of mouse brain endothelial cell line, bEnd. 3 and mouse primary astrocyte and explored its action mechanism therein involved.

FBP


Input: LPS induced the impairment of endothelial permeability and transendothelial electrical resistance (TEER).


Input: The functional changes were confirmed by alterations in immunostaining for junctional proteins occludin, ZO-1 and VE-cadherin, such as the loss of cortical staining pattern and appearance of intercellular gaps in endothelial cells.


Input: Co-administration of FBP alleviated the deleterious effects of LPS on BBB permeability and TEER in a dose dependent manner.

FBP


Input: And also FBP inhibited the LPS-induced changes in the distribution of endothelial junctional proteins, resulting in the better preservation of monolayer integrity.

FBP


Input: FBP suppressed the production of reactive oxygen species (ROS) but did not affect cyclooxygenase-2 expression and prostaglandin E2 production in endothelial cells stimulated with LPS.

FBP

oxygen

prostaglandin E2


Input: Taken together, these data suggest that FBP could ameliorate LPS-induced BBB dysfunction through the maintenance of junctional integrity, which might be mediated by downregulation of ROS production.

FBP


Input: The regulation of epidermal melanogenesis via cAMP and/or PKC signaling pathways: insights for the development of hypopigmenting agents.

cAMP


Input: Abnormal pigmentation, particularly hyperpigmentation, is major issue of concern for people with colored skin.


Input: Several hypopigmenting agents, which exert their action by inhibiting tyrosinase activity and/or transcription, have been used for treatment.


Input: However, results have been discouraging.


Input: To manage abnormal pigmentation properly, the mechanisms of melanogenesis should be understood.


Input: Endogenous and exogenous factors affect melanogenesis via intracellular machineries.


Input: cAMP and PKC are critical factors of important transduction pathways and cross-talk between them could amplify the melanogenic effect.

cAMP


Input: Here, factors involved in melanogenesis regulation via cAMP and/or PKC pathways are reviewed with their action mechanisms.

cAMP


Input: The Analog of Ginkgo biloba Extract 761 is a Protective Factor of Cognitive Impairment Induced by Chronic Fluorosis.


Input: Ginkgo biloba extract EGb761 is widely used to treat patients with learning and memory impairment in Alzheimer' s disease and Parkinson' s disease in China.


Input: However, it is not yet clear whether the analog of EGb761 (EGb) has a protective effect on the learning and memory damage induced by chronic fluorosis.