Input: This review describes: 1-some muscle and non-muscle factors that are altered in asthma that may lead to airway narrowing and asthma symptoms; 2-some technologies such as the forced oscillation technique that have the potential to unveil the role of ASM in airway narrowing in vivo; and 3-some data from ex vivo and in vitro methods that probe the possibility that airway hyperresponsiveness is due to the altered environment surrounding the ASM or, alternatively, to a hypercontractile ASM phenotype that can be either innate or acquired.


Input: Cost-effectiveness of alendronate for the treatment of osteopenic postmenopausal women in Japan.

alendronate


Input: Many postmenopausal women have osteopenia, a condition characterized by loss of bone mineral density (BMD) that is not as severe as in osteoporosis.


Input: The objective of this study was to estimate the cost-effectiveness of alendronate to prevent fractures in osteopenic postmenopausal women without a history of fracture in Japan.

alendronate


Input: An individual simulation model was developed to predict lifetime costs and quality-adjusted life years (QALYs) of 5 years of preventive alendronate therapy versus no preventive therapy.

alendronate


Input: The risk of hip and vertebral fracture associated with age and BMD was derived from epidemiologic studies in Japan.


Input: We ran the model with different combinations of age (65, 70, and 75 years), BMD (70%, 75%, and 80% of young adult mean [YAM]), and additional clinical risk factors.


Input: For 70-year-old women with a BMD of 70% of the YAM having one of the following risk factors: a family history of hip fracture, high alcohol intake, or current smoking, the incremental cost-effectiveness ratio (ICER) of alendronate was $92, 937, $126, 251, and $129, 067 per QALY, respectively.

alcohol

alendronate


Input: These results were sensitive to age, BMD, and number of clinical risk factors.


Input: Probabilistic sensitivity analysis for the base case showed that in the presence of one, two, and three risk factors, alendronate was cost-effective in 0. 2% to 2. 6%, 13. 1% to 56. 1%, and 99. 1% of the simulations, respectively, if society is willing to pay $50, 000 per QALY.

alendronate


Input: Additional analysis indicated that alendronate can be a good value in osteopenic women if the 10-year probability for a osteoporotic hip or vertebral fracture is more than 26. 2%.

alendronate


Input: Our results indicate that whether to treat osteopenia with alendronate should be determined on the basis of age, BMD, and number of clinical risk factors in terms of cost-effectiveness.

alendronate


Input: Targeted disruption of inducible nitric oxide synthase protects against aging, S-nitrosation, and insulin resistance in muscle of male mice.

nitric oxide

S


Input: Accumulating evidence has demonstrated that S-nitrosation of proteins plays a critical role in several human diseases.

S


Input: Here, we explored the role of inducible nitric oxide synthase (iNOS) in the S-nitrosation of proteins involved in the early steps of the insulin-signaling pathway and insulin resistance in the skeletal muscle of aged mice.

nitric oxide


Input: Aging increased iNOS expression and S-nitrosation of major proteins involved in insulin signaling, thereby reducing insulin sensitivity in skeletal muscle.


Input: Conversely, aged iNOS-null mice were protected from S-nitrosation-induced insulin resistance.


Input: Moreover, pharmacological treatment with an iNOS inhibitor and acute exercise reduced iNOS-induced S-nitrosation and increased insulin sensitivity in the muscle of aged animals.


Input: These findings indicate that the insulin resistance observed in aged mice is mainly mediated through the S-nitrosation of the insulin-signaling pathway.

S


Input: Variation in osteocyte lacunar morphology and density in the human femur--a synchrotron radiation micro-CT study.


Input: In recent years there has been growing interest in the spatial properties of osteocytes (including density and morphology) and how these potentially relate to adaptation, disease and aging.


Input: This interest has, in part, arisen from the availability of increasingly high-resolution 3D imaging modalities such as synchrotron radiation (SR) micro-CT.


Input: As resolution increases, field of view generally decreases.


Input: Thus, while increasingly detailed spatial information is obtained, it is unclear how representative this information is of the skeleton or even the isolated bone.


Input: The purpose of this research was to describe the variation in osteocyte lacunar density, morphology and orientation within the femur from a healthy young male human.


Input: Multiple anterior, posterior, medial and lateral blocks (2 mm x 2 mm) were prepared from the proximal femoral shaft and SR micro-CT imaged at the Advanced Photon Source.


Input: Average lacunar densities (+/- standard deviation) from the anterior, posterior, medial and lateral regions were 27, 169 +/- 1935, 26, 3643 +/- 1262, 37, 521 +/- 6416 and 33, 972 +/- 2513 lacunae per mm (3) of bone tissue, respectively.


Input: These values were significantly different between the medial and both the anterior and posterior regions (p < 0. 05).


Input: The density of the combined anterior and posterior regions was also significantly lower (p = 0. 001) than the density of the combined medial and lateral regions.


Input: Although no difference was found in predominant orientation, shape differences were found; with the combined anterior and posterior regions having more elongated (p = 0. 004) and flattened (p = 0. 045) lacunae, than those of the medial and lateral regions.


Input: This study reveals variation in osteocyte lacunar density and morphology within the cross-section of a single bone and that this variation can be considerable (up to 30% difference in density between regions).


Input: The underlying functional significance of the observed variation in lacunar density likely relates to localized variations in loading conditions as the pattern corresponds well with mechanical axes.


Input: Lower density and more elongate shapes being associated with the antero-posterior oriented neutral axis.


Input: Our findings demonstrate that the functional and pathological interpretations that are increasingly being drawn from high resolution imaging of osteocyte lacunae need to be better situated within the broader context of normal variation, including that which occurs even within a single skeletal element.


Input: In vivo imaging of retinal ganglion cell apoptosis.


Input: Apoptosis, or programmed cell death, plays a vital role in normal development and ageing.


Input: However, dysregulation of this process is responsible for many disease states including; cancer, autoimmune and neurodegeneration.


Input: For this reason, in vivo visualisation of apoptosis may prove a useful tool for both laboratory research and clinical diagnostics.


Input: Glaucoma comprises a distinctive group of chronic optic neuropathies, characterised by the progressive loss of retinal ganglion cells (RGCs).


Input: Early diagnosis of glaucoma remains a clear and unmet need.


Input: Recently, there have been significant advances in the detection of apoptosis in vivo using fluorescent probes to visualise single RGCs undergoing apoptosis, specifically DARC (Detection of Apoptotic Retinal Cells) [1] and capQ technology [2 (* *)].


Input: Microtubule network is required for insulin-induced signal transduction and actin remodeling.


Input: Both microtubule and actin are required for insulin-induced glucose uptake.

glucose


Input: However, the roles of these two cytoskeletons and their relationship in insulin action still remain unclear.


Input: In this work, we examined the morphological change of microtubule/actin and their involvement in insulin signal transduction using rat skeletal muscle cells.


Input: Insulin rapidly led to microtubule clustering from ventral to dorsal surface of the cell.


Input: Microtubule filaments were rearranged to create space where new actin structures formed.


Input: Disruption of microtubule prevented insulin-induced actin remodeling and distal insulin signal transduction, with reduction in surface glucose transporter isoform 4 (GLUT4) and glucose uptake.

glucose

glucose


Input: Though microtubule mediated actin remodeling through PKC zeta, reorganization of microtubule depended on tyrosine phosphorylation of insulin receptor, the mechanism is different from insulin-induced actin remodeling, which relied on the activity of PI3-kinase and PKC zeta.

tyrosine


Input: We propose that microtubule network is required for insulin-induced signal transduction and actin remodeling in skeletal muscle cells.


Input: Selective regulation of nicotine and polyamines biosynthesis in tobacco cells by enantiomers of ornithine.

nicotine

polyamines

ornithine


Input: L-and D-amino acids have diverse functions and effects on the metabolism, growth, and development of plants.

L-and D-amino acids


Input: Ornithine (Orn) plays a main role in the biosynthesis of many amino acids, nicotinic alkaloids, and polyamines in tobacco.

Ornithine

Orn

amino acids

nicotinic alkaloids

polyamines


Input: This investigation describes the impact of Orn enantiomers on the production and distribution of free, conjugated, and bound polyamines, as well as nicotine in tobacco cells.

Orn

polyamines

nicotine


Input: It was recognized that the biosynthesis of metabolites was differently upregulated by each enantiomer.


Input: Putrescine was abundantly produced by exogenous L-ornithine (L-Orn), and both spermidine and spermine were significantly accumulated in D-ornithine (D-Orn)-supplied tobacco cells.

Putrescine

L-ornithine

L-Orn

spermidine

spermine

D-ornithine

D-Orn


Input: Furthermore, nicotine production was highly upregulated by L-Orn, while the addition of D-Orn had no effect on the nicotine content of tobacco cells.

nicotine

L-Orn

D-Orn

nicotine


Input: It was observed that transcript expression of S-adenosylmethionine decarboxylase, as the key enzyme of spermidine/spermine biosynthesis, is coincident with their metabolic levels and is highly upregulated by D-Orn, as opposed to L-Orn.

S-adenosylmethionine

spermidine

spermine

D-Orn

L-Orn


Input: These results indicate that both enantiomers of Orn can trigger selected biosynthetic pathways in the cells, at the transcript level.

Orn


Input: Regarding these observations, it is proposed that L-and D-Orn function differently in the same biological pathways in which the latter, D-Orn specifically regulates important polyamines in the plant cells.

L-and D-Orn

D-Orn

polyamines


Input: Human gastric TFF2 peptide contains an N-linked fucosylated N, N'-diacetyllactosediamine (LacdiNAc) oligosaccharide.

N-linked fucosylated N, N'-diacetyllactosediamine

LacdiNAc


Input: In the human stomach, the peptide trefoil factor family 2 (TFF2) is secreted together with the mucin MUC6 by mucous neck cells (MNCs) and antral gland cells.


Input: TFF2 is strongly associated with the gastric mucus and promotes gastric restitution.


Input: Here, TFF2 was purified from the human corpus and antrum, respectively, by size-exclusion chromatography, and the N-linked glycan structure at N-15 of the mature peptide was determined.

N


Input: As a hallmark, the unusual monofucosylated N, N'-diacetylhexosediamine (tentatively assigned as GalNAc beta 1 --> 4GlcNAc, LacdiNAc) modification was detected as the terminal structure of a bi-antennary complex type N-glycan exhibiting also core fucosylation.

monofucosylated N, N'-diacetylhexosediamine

GalNAc beta 1 --> 4GlcNAc

LacdiNAc

N


Input: Replicate analyses did not show microheterogeneities in the fraction of peptide-N-glycosidase F cleaved and permethylated N-glycans when analyzed by matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS).

N

N


Input: On the glycopeptide level, a minor glycan microheterogeneity was evident in liquid chromatography-electrospray ionization (ESI)-MS, demonstrating the presence of underfucosylated species.


Input: The tryptic TFF2 N-glycopeptide p34-39 (LSPHNR N-glycosylated with Fuc3Hex3HexNAc6) was identified by both ESI-tandem mass spectrometry and MALDI-post-source decay analysis.

N


Input: Lectin analyses with the Wisteria floribunda agglutinin indicated the potential presence of LacdiNAc terminating glycans and revealed minor differences between TFF2 from fundic units, i. e. MNCs, and antral units, i. e. antral gland cells.

LacdiNAc


Input: Strikingly, on the level of the primary structure, there was no indication that the formation of the proposed LacdiNAc structure is cis-controlled by a peptidic determinant related to the published sequences.

LacdiNAc


Input: Altering the way the optic nerve head responds to intraocular pressure-a potential approach to glaucoma therapy.


Input: Over the past decade, engineering principles have been used to explain why a mechanical load, intraocular pressure, can lead to the development of glaucomatous optic neuropathy.


Input: This has led to the' biomechanical theory' of glaucoma, which posits that the behavior of optic nerve head connective tissues (specifically within the peripapillary sclera and lamina cribrosa) in response to intraocular pressure (regardless of its magnitude) can directly and indirectly influence the physiology and pathophysiology of the optic nerve head.


Input: Given that the biomechanics of the sclera and lamina cribrosa probably influence retinal ganglion cell loss in glaucoma, the idea that altering biomechanical behavior might be protective against glaucoma is an appealing notion.


Input: There is some evidence to suggest that stiffening the peripapillary sclera may be protective against the development of glaucoma in an animal model.


Input: It is technically possible to stiffen the sclera in vivo using collagen cross-linking techniques already applied in vivo to the cornea in the treatment of keratoconus.


Input: It has yet to be established whether scleral cross-linking is safe in humans and that it confers anything more than a theoretical advantage in terms of reducing the risk of glaucomatous damage.


Input: Maintenance of retinal ganglion cell mitochondrial functions as a neuroprotective strategy in glaucoma.


Input: Loss of vision in glaucoma occurs because retinal ganglion cells (RGCs) die.


Input: RGCs have probably more mitochondria than any other neurone in the CNS.


Input: It is proposed that stress to mitochondria of individual RGCs is a major trigger of the disease and also provides an explanation why different RGCs die at different times.


Input: Pharmacological agents that can maintain mitochondrial functions, in particular to attenuate oxidative stress and to sustain energy production, might therefore provide a novel way of slowing down RGC death and help in the treatment of glaucoma.


Input: Cannabinoid CB 1 receptor in the modulation of stress coping behavior in mice: the role of serotonin and different forebrain neuronal subpopulations.

serotonin


Input: The endocannabinoid system (ECS) may either enhance or inhibit responses to aversive stimuli, possibly caused by its modulatory activity on diverse neurotransmitters.


Input: The aim of this work was to investigate the involvement of serotonin (5-HT) and catecholamines, as well as the role of glutamatergic and GABAergic cannabinoid type 1 (CB (1)) receptor, in responses to the antidepressant-like doses of the CB (1) receptor agonist Delta (9)-tetrahydrocannabinol (THC) and the antagonist rimonabant in the forced swim test (FST).

serotonin

catecholamines

Delta (9)-tetrahydrocannabinol

THC

rimonabant


Input: Mice received acute injections of low doses of THC (0. 1 or 0. 5 mg/kg) or high dose of rimonabant (3 or 10 mg/kg) after treatment with the 5-HT synthesis inhibitor pCPA (100 mg/kg, 4 days), the 5-HT (1A) receptor antagonist WAY100635 (1 mg/kg, acute) or the non-selective blocker of catecholamine synthesis, AMPT (20 mg/kg, acute).

THC

rimonabant

pCPA

catecholamine

AMPT


Input: THC and rimonabant were also tested in mutant mice lacking CB (1) receptor in specific forebrain neuronal subpopulations.

THC

rimonabant


Input: Both THC and rimonabant induced antidepressant-like effects, quantified as immobility in the FST.

THC

rimonabant


Input: However, only THC effects were reversed by pCPA or WAY100635.

THC

pCPA


Input: In contrast, only AMPT could attenuate the rimonabant effect.

AMPT

rimonabant


Input: We also found decreased immobility in mice lacking the CB (1) receptor in glutamatergic cortical neurons, but not in forebrain GABAergic neurons, as compared with wild-type controls.


Input: The effect of THC persisted in mutant mice with CB (1) receptor inactivation in GABAergic neurons, whereas rimonabant effects were alleviated in these mutants.

THC

rimonabant


Input: Thus, employing both pharmacological and genetic tools, we could show that the ECS regulates stress responses by influencing GABAergic, glutamatergic and monoaminergic transmission.


Input: The antidepressant-like action of THC depends on serotonergic neurotransmission, whereas rimonabant effects are mediated by CB (1) receptor on GABAergic neurons and by catecholamine signaling.

THC

rimonabant

catecholamine


Input: Pharmacological targeting of endoplasmic reticulum stress signaling in cancer.


Input: The endoplasmic reticulum (ER) stress response constitutes a cellular process that can be triggered by a great variety of conditions that cause imbalances in intracellular homeostasis and threaten proper cell functioning.


Input: In response, the ER stress response activates an adaptive effort aimed at neutralizing these threats and reestablishing homeostasis.


Input: However, if these countermeasures are unsuccessful and severe imbalances persist, the ER stress response may abandon its pro-survival efforts and instead may initiate a pro-apoptotic program to eliminate the faulty cell for the benefit of the organism as a whole.


Input: Because vigorous growth of malignant tumors may create stressful conditions, such as hypoglycemia, hypoxia, or accumulation of misfolded proteins during revved up protein synthesis, the adaptive, pro-survival components of the ER stress response system (e. g., GRP78/BiP) are frequently found chronically activated in tumor cells.


Input: This differential to non-stressed normal cells has been proposed to represent an Achilles' heel of tumor cells that may be exploitable by therapeutic intervention.


Input: In this model, the goal would be to further aggravate the pre-existing stress conditions in tumor cells with appropriate pharmacological agents, so that the already engaged pro-survival mechanism would be overwhelmed and the ER stress response forced to switch to its pro-apoptotic mode (e. g., CHOP/GADD153).


Input: This review will discuss the principle of pharmacological ER stress aggravation, and will present preclinical models with promise for cancer therapeutic applications.


Input: The risky cocktail: what combination effects can we expect between ecstasy and other amphetamines?

ecstasy

amphetamines


Input: The recreational and illicit use of amphetaminic designer compounds, specially 3, 4-methylenedioxymethamphetamine (MDMA; Ecstasy), is of concern worldwide.

3, 4-methylenedioxymethamphetamine

MDMA

Ecstasy


Input: Such psychostimulating drugs are frequently present as complex mixtures in' rave' pills, making concomitant polysubstance use a common trend.


Input: However, the understanding of possible combination effects with these substances is still scarce.


Input: The present study was aimed at predicting the cytotoxic effects of mixtures of four amphetaminic derivatives: MDMA, methamphetamine, 4-methylthioamphetamine and d-amphetamine in a human hepatoma cell line.

MDMA

methamphetamine

d-amphetamine


Input: Concentration-response curves for all single-mixture components were recorded by the MTT assay.

MTT


Input: Data obtained for individual agents were then used to compute the additivity expectations for mixtures of definite composition, using the pharmacological models of concentration addition (CA) and independent action.


Input: By comparing the predicted calculations with the experimentally observed effects, we concluded that CA accurately predicts the combination of amphetamines, which act together to generate additive effects over a large range of concentrations.

amphetamines


Input: Notably, we observed substantial mixture effects even when each drug was present at low concentrations, which individually produced unnoticeable effects.


Input: Nonetheless, for all tested mixtures, a small deviation from additivity was observed towards higher concentrations, particularly at high effect levels.


Input: A possible metabolic interaction, which could explain such deviation, was investigated, and it was observed that at higher mixture concentrations increased MDMA metabolism could be contributing to divergences from additivity.

MDMA


Input: In conclusion, the present work clearly demonstrates that potentially harmful interactions among amphetaminic drugs are expected when these drugs are taken concomitantly.


Input: Resistin knockout mice exhibit impaired adipocyte glucose-dependent insulinotropic polypeptide receptor (GIPR) expression.

glucose


Input: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that also plays a regulatory role in fat metabolism.

Glucose


Input: In 3T3-L1 cells, resistin was demonstrated to be a key mediator of GIP stimulation of lipoprotein lipase (LPL) activity, involving activation of protein kinase B (PKB) and reduced phosphorylation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK).

AMP


Input: The current study was initiated to determine whether resistin has additional roles in GIP-regulated adipocyte functions.


Input: Analysis of primary adipocytes isolated from Retn (-/-), Retn (+/-), and Retn (+/+) mice found that GIP stimulated the PKB/LKB1/AMPK/LPL pathway and fatty acid uptake only in Retn (+/+) adipocytes, suggesting that GIP signaling and/or GIP responsiveness were compromised in Retn (+/-) and Retn (-/-) adipocytes.

fatty acid


Input: GIP receptor (GIPR) protein and mRNA were decreased in Retn (+/-) and Retn (-/-) adipocytes, but resistin treatment rescued LPL responsiveness to GIP.


Input: In addition, genes encoding tumor necrosis factor (TNF), TNF receptor 2 (TNFR2), and the signaling proteins stress-activated protein kinase (SAPK)/Jun NH (2)-terminal kinase (JNK), were downregulated, and phosphorylated levels of SAPK/JNK/c-Jun were decreased in Retn (-/-) mice.

NH (2)


Input: Chromatin immunoprecipitation assays were used to identify a 12-O-tetradecanoylphorbol-13-acetate (TPA)-response element (TRE-III) responsible for c-Jun-mediated transcriptional activation of Gipr.

TPA


Input: Blunted GIP responsiveness in Retn (+/-) and Retn (-/-) adipocytes was therefore largely due to the greatly reduced GIPR expression associated with decreased c-Jun-mediated transcriptional activation of Gipr.


Input: When did decapods invade hydrothermal vents?


Input: Clues from the Western Pacific and Indian Oceans.


Input: Hydrothermal vents are typically located in midocean ridges and back-arc basins and are usually generated by the movement of tectonic plates.


Input: Life thrives in these environments despite the extreme conditions.


Input: In addition to chemoautotrophic bacteria, decapod crustaceans are dominant in many of the hydrothermal vents discovered to date.


Input: Contrary to the hypothesis that these species are remnants of relic fauna, increasing evidence supports the notion that hydrothermal vent decapods have diversified in more recent times with previous research attributing the origin of alvinocarid shrimps to the Miocene.


Input: This study investigated seven representative decapod species from four hydrothermal vents throughout the Western Pacific and Indian Oceans.


Input: A partitioned mix-model phylogenomic analysis of mitochondrial DNA produced a consistent phylogenetic topology of these vent-endemic species.


Input: Additionally, molecular dating analysis calibrated using multiple fossils suggested that both bythograeid crabs and alvinocarid shrimps originated in the late Mesozoic and early Cenozoic.


Input: Although of limited sampling, our estimates support the extinction/repopulation hypothesis, which postulates recent diversification times for most hydrothermal vent species due to their mass extinction by global deep-water anoxic/dysoxic events during the Late Cretaceous and Early Tertiary.


Input: The continental-derived property of the West Pacific province is compatible with the possibility that vent decapods diversified from ancestors from shallow-water regions such as cold seeps.


Input: Our results move us a step closer toward understanding the evolutionary origin of hydrothermal vent species and their distribution in the Western Pacific-Indian Ocean Region.


Input: Cellular and molecular mechanisms of hepatocellular carcinoma: an update.


Input: Hepatocellular carcinoma (HCC) is the most common primary malignant tumor that accounts for ~ 80% of all liver cancer cases worldwide.


Input: It is a multifactorial disease caused by a variety of risk factors and often develops in the background of underlying cirrhosis.


Input: A number of cellular phenomena, such as tumor microenvironment, inflammation, oxidative stress, and hypoxia act in concert with various molecular events to facilitate tumor initiation, progression, and metastasis.


Input: The emergence of microRNAs and molecular-targeted therapies adds a new dimension in our efforts to combat this deadly disease.


Input: Intense research in this multitude of areas has led to significant progress in our understanding of cellular processes and molecular mechanisms that occur during multistage events that lead to hepatocarcinogenesis.


Input: In this review, we discuss the current knowledge of HCC, focusing mainly on advances that have occurred during the past 5 years and on the development of novel therapeutics for liver cancer.


Input: The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain.


Input: The present study was designed to evaluate the effects of chronic fluorosis on the dynamics (including fusion and fission proteins), fragmentation, and distribution of mitochondria in the cortical neurons of the rat brain in an attempt to elucidate molecular mechanisms underlying the brain damage associated with excess accumulation of fluoride.

fluoride


Input: Sixty Sprague-Dawley rats were divided randomly into three groups of 20 each, that is, the untreated control group (drinking water naturally containing < 0. 5 mg fluoride/l, NaF), the low-fluoride group (whose drinking water was supplemented with 10 mg fluoride/l) and the high-fluoride group (50 mg fluoride/l).

fluoride

NaF

fluoride

fluoride

fluoride

fluoride


Input: After 6 months of exposure, the expression of mitofusin-1 (Mfn1), fission-1 (Fis1), and dynamin-related protein-1 (Drp1) at both the protein and mRNA levels were detected by Western blotting, immunohistochemistry, and real-time PCR, respectively.


Input: Moreover, mitochondrial morphology and distribution in neurons were observed by transmission electron or fluorescence microscopy.


Input: In the cortices of the brains of rats with chronic fluorosis, the level of Mfn1 protein was clearly reduced, whereas the levels of Fis1 and Drp1 were elevated.


Input: The alternations of expression of the mRNAs encoding all three of these proteins were almost the same as the corresponding changes at the protein levels.


Input: The mitochondria were fragmented and the redistributed away from the axons of the cortical neurons.


Input: These findings indicate that chronic fluorosis induces abnormal mitochondrial dynamics, which might in turn result in a high level of oxidative stress.


Input: Cyclooxygenase (COX)-1 and COX-2 both play an important role in the protection of the duodenal mucosa in cats.


Input: Although nonsteroidal anti-inflammatory drugs often cause ulcers in the duodenum in humans, the role of cyclooxygenase (COX) isoforms in the pathogenesis of duodenal ulcers has not been fully elucidated.


Input: We examined in cats the 1) ulcerogenic effects of selective COX-1 (SC-560, ketorolac) and COX-2 (celecoxib, meloxicam) inhibitors on the gastrointestinal mucosa, 2) effect of feeding and cimetidine on the expression of COX isoforms and prostaglandin E (2) (PGE (2)) level in the duodenum, and 3) localization of COX isoforms in the duodenum.

ketorolac

celecoxib

meloxicam

cimetidine

prostaglandin E (2)

PGE (2)


Input: COX inhibitors were administered after the morning meal in cats once daily for 3 days.


Input: Gastrointestinal lesions were examined on day 4.


Input: Localization and expression of COX isoforms (by immunohistochemistry, Western blot) and PGE (2) level (by enzyme immunoassay) were examined.

PGE (2)


Input: Results were as follows.


Input: First, selective COX-1 or COX-2 inhibitors alone produced marked ulcers in the duodenum but did not cause obvious lesions in the small intestine.


Input: Coadministration of SC-560 and celecoxib produced marked lesions in the small intestine.

celecoxib


Input: Second, feeding increased both the expression of COX isoforms and PGE (2) level in the duodenum, and the effects were markedly inhibited by pretreatment with cimetidine.

PGE (2)

cimetidine


Input: Third, COX-1 was localized in goblet and Brunner' s gland cells, Meissner' s and Auerbach' s plexus, smooth muscle cells, and arterioles; and COX-2 was observed in capillaries, venules, and basal granulated cells.


Input: The expression of COX isoforms in the duodenum is up-regulated by feeding, and inhibition of either COX-1 or COX-2 causes ulcers in the duodenum, suggesting that both isoforms play an important role in the protection of the duodenal mucosa.


Input: Development of a live tissue microtome: reflections of an amateur machinist.


Input: Live circular tissue slices of nearly identical diameter and thickness can be generated from most tissues by the use of two instruments; a coring tool to cut cylindrical tissue cores which are subsequently sliced by a microtome into thin circular sections 5-8 mm in diameter and 50-300 microns thick.


Input: The sections are of very similar geometry permitting direct comparisons without normalization.


Input: Both instruments operate submerged in a cold isotonic medium that caries the cut slices outside the microtome.


Input: The slices are cut by a rapidly oscillating disposable Gillette blade mounted at an angle of 20 degrees to the vertical main axis of the tissue core.


Input: The latter is advanced against the oscillating blade by a weighted plunger pushing it against a screw adjustable limit plate that defines the desired slice thickness.


Input: Both instruments can be sterilized and slices can be obtained at a rate of approximately one every ten seconds.


Input: pH-and thermo-sensitive pluronic/poly (acrylic acid) in situ hydrogels for sustained release of an anticancer drug.

pluronic

poly (acrylic acid)


Input: In this study, we developed oral in situ gelling formulations composed of pluronic (Plu) and polyacrylic acid (PAA) for the delivery of an anticancer drug, epirubicin (Epi).

pluronic

Plu

polyacrylic acid

PAA

epirubicin

Epi


Input: We investigated various Plu/PAA/Epi formulations for their physicochemical properties and in vitro permeation and accumulation, as well as for in vivo pharmacokinetic and antitumor efficacy.

Plu

PAA

Epi


Input: A scanning electron microscopic (SEM) image of Plu 14%/PAA 0. 75%/Epi hydrogel showed a sponge-like structure.

Plu

PAA

Epi


Input: This formulation has suitable gelation time, water content, bioadhesive force, structural stability, and a high permeation percentage of Epi, with sustained drug release characteristics for 96 h.

Epi


Input: This hydrogel was retained at the end of the ileum near the colon of Sprague-Dawley (SD) rats for at least 12 h.


Input: An in vivo pharmacokinetic study using SD rats showed that after oral administration in this formulation, Epi had prolonged half-life, greater area under the curve, and higher relative bioavailability than in an oral Epi solution.

Epi

Epi


Input: In vivo tumor growth inhibition of Epi in this formulation was more pronounced compared with oral Epi and intravenous Epi solutions in CT-26 mouse colon adenocarcinoma bearing Balb/c mice.

Epi

Epi

Epi


Input: This study highlights the advantages of using oral in situ temperature-and pH-sensitive hydrogels for future cancer therapy.


Input: For whom the bell tolls: Distress signals from long-lived osteocytes and the pathogenesis of metabolic bone diseases.


Input: Osteocytes are long-lived and far more numerous than the short-lived osteoblasts and osteoclasts.


Input: Immured within the lacunar-canalicular system and mineralized matrix, osteocytes are ideally located throughout the bone to detect the need for, and accordingly choreograph, the bone regeneration process by independently controlling rate limiting steps of bone resorption and formation.


Input: Consistent with this role, emerging evidence indicates that signals arising from apoptotic and old/or dysfunctional osteocytes are seminal culprits in the pathogenesis of involutional, post-menopausal, steroid-, and immobilization-induced osteoporosis.

steroid


Input: Osteocyte-originated signals may also contribute to the increased bone fragility associated with bone matrix disorders like osteogenesis imperfecta, and perhaps the rapid reversal of bone turnover above baseline following discontinuation of anti-resorptive treatments, like denosumab.


Input: This article is part of a Special Issue entitled " The Osteocyte ".


Input: The continuing saga of snake venom disintegrins.


Input: Disintegrins, a family of polypeptides released in the venoms of viperid snakes (vipers and rattlesnakes) by the proteolytic processing of multidomain metalloproteinases, selectively block the function of beta (1) and beta (3) integrin receptors.


Input: Few of the proteins isolated and characterized from snake venoms have proven to be more structural and functional versatile than the disintegrins.


Input: Not surprisingly, 25 years after their discovery, our knowledge on the evolutionary history and the molecular determinants modulating the integrin inhibitory activity of disintegrins still remain fragmentary.


Input: This paper highlights some seminal contributions, including personal accounts of pioneer authors, related to basic and applied research on disintegrins.


Input: Investigators have evaluated disintegrin applications in therapies for a number of pathologies in which integrin receptors play relevant roles, particularly myocardial infarction and inappropriate tumor angiogenesis.


Input: Completing the continuing story of the disintegrin family by applying novel research approaches may hold the key to learn how to use deadly toxins as therapeutic agents.


Input: Development of histopathological indices in a commercial marine bivalve (Ruditapes decussatus) to determine environmental quality.


Input: Bivalve histopathology is an acknowledged tool in environmental toxicology studies, however geographically restricted, limited to a few species and still lacking the degree of detail needed to develop effective (semi) quantitative approaches.


Input: A first-time detailed histopathological screening was performed on grooved carpet shell clams collected from commercial shellfish beds in distinct coastal ecosystems of the Southern Portuguese coast: two parted sites within an impacted estuary (S (1) and S (2)), an inlet channel of a fish farm at a considered pristine estuary (site M) and a site allocated in a clean coastal lagoon (A).


Input: A total of thirty histopathological lesions and alterations were analysed in the gills and digestive glands following a weighted condition indices approach, including inflammation-related responses, necrosis, neoplastic diseases and parasites.


Input: Digestive glands were consistently more damaged than gills, except for animals collected from site M, where the most severe lesions were found in both organs, immediately followed by S (2).


Input: Clams from sites S (1) and A were overall the least damaged.


Input: Neoplastic diseases were infrequent in all cases.


Input: Inflammation-related traits were some of the most common alterations progressing in animals enduring severe lesions such as digestive tubule (diverticula) and intertubular tissue necrosis.


Input: Some alterations, such as lipofuscin aggregates within digestive tubule cells, did not relate to histological lesions.


Input: Granulocytomas only occurred in heavily infected tissues.


Input: Animals from M and A presented the highest infections in the digestive gland, especially by protozoa.


Input: Gill infections were more similar between sites.


Input: Still, the level of infection does not account for all histopathological lesions in either organ.


Input: Overall, the results are in accordance with environmental parameters, such as distance to pollution sources, sediment type and hydrodynamics, and show that the combination of multiple histopathological features in these clams provides good sensitivity for inter-site distinction even when low or moderate anthropogenic impacts are at stake.


Input: Changes in trace elements during lactation in a marine top predator, the grey seal.


Input: Lactation in pinnipeds represents the most significant cost to mothers during the reproductive cycle.


Input: Dynamics of trace elements and their mobilization associated with energy reserves during such an intense physiological process remains poorly understood in marine mammals.


Input: The changes in tissue concentrations of 11 elements (Ca, Cd, Cr, Cu, Fe, Hg, Ni, Pb, Se, V, and Zn) were investigated in a longitudinal study during the lactation period and during the post-weaning fast period.

Ca

Cd

Cr

Cu

Fe

Hg

Ni

Pb

Se

V

Zn


Input: Blood, milk, blubber, and hair samples were collected sequentially from 21 mother-pup pairs of grey seals (Halichoerus grypus) from the Isle of May in Scotland.


Input: Maternal transfer through the milk was observed for all trace elements, except for Cd.

Cd


Input: As an indicator of the placental transfer, levels in pup lanugo (natal coat) revealed also the existence of maternal transfer and accumulation of all assayed trace elements during the foetal development.


Input: The placental and mammary barriers against non-essential metal transfer to offspring appear to be absent or weak in grey seals.


Input: Examining the contamination levels showed that this grey seal population seems more highly exposed to Pb than other phocid populations (2. 2 mg/kg dw of grey seal hair).

Pb


Input: In contrast, blood and hair levels reflected a lower Hg exposure in grey seals from the Isle of May than in harbour seals from the southeastern North Sea.

Hg


Input: This study also showed that trace element concentrations in blood and blubber could change rapidly over the lactation period.


Input: Such physiological processes must be considered carefully during biomonitoring of trace elements, and potential impacts that rapid fluctuations in concentrations can exert on seal health should be further investigated.


Input: Iodinated nano-emulsions as contrast agents for preclinical X-ray imaging: Impact of the free surfactants on the pharmacokinetics.


Input: This study presents new important aspects in the design of contrast agents for X-ray preclinical imaging.


Input: The first one is a new simple formulation of long circulating contrast agents, formulated from a commercial iodinated oil, and resulting in CT contrast agents containing more than twice the iodine concentration commercial contrast agents.

iodine


Input: The second point is a methodological aspect, utilizing tangential filtration for reducing the residual surfactants in the bulk phase and serving as well for concentrating droplets (and iodine) in the suspension.

iodine


Input: The last point is a more general aspect regarding the influence of the free surfactant on the pharmacokinetics and biodistribution of the nano-emulsion droplets on mice.


Input: We showed that cross-flow filtration is efficient for concentrating the droplets and reducing the concentration of free surfactant from 10wt.% to 1wt.%, without any changes in the nano-emulsion droplet morphologies or surface properties.


Input: We also showed that the presence of free surfactant has a significant impact on the elimination way of the nano-emulsion droplets, shared between liver and kidneys.


Input: The purified nano-emulsions are preferentially eliminated by the kidneys in contrast to raw nano-emulsions, predominantly eliminated by the liver.


Input: In practice, for two similar suspensions, half-life decreases from 4. 1 +/- 1. 10h to 2. 5 +/- 0. 77h before and after purification.


Input: Since the design and development of long circulating systems are critical in numerous domains, and not for preclinical CT imaging, this study presents important results in that field, taken under a formulation and technical point of view.


Input: Medium and high oxidation state metal/non-metal fluoride and oxide-fluoride complexes with neutral donor ligands.

metal/non-metal fluoride

oxide

fluoride


Input: While most high and medium oxidation state (O. S. >= 3) metal and non-metal fluorides and oxide fluorides are strong Lewis acids, exploration of their coordination chemistry with neutral ligands has been limited and mostly non-systematic.

metal and non-metal fluorides

oxide fluorides

Lewis acids


Input: This is despite the very different properties conferred on the acceptor centre by the small electronegative fluoride ligands compared to the heavier halides.

fluoride

halides


Input: This article sets out these key differences, discusses possible synthetic routes, the key characterisation techniques, and appropriate bonding models.


Input: Current knowledge of the coordination chemistry of d, f and p-block fluorides and oxide fluorides with neutral ligands (with donor atoms drawn from Groups 15 and 16 and including N-heterocyclic carbenes) is then presented and discussed, and the differences in properties compared to complexes containing the heavier halides are illustrated.

fluorides

oxide fluorides

N-heterocyclic carbenes

halides


Input: The emphasis is on work published post 1990, but earlier work is also included as essential background and where no more recent information exists.


Input: Attention is drawn to unexplored areas meriting investigation and to possible applications of these complexes.


Input: Caffeine, extraversion and working memory.

Caffeine


Input: Research has shown that extraverts performing a working memory task benefit more from caffeine than do introverts.

caffeine


Input: The present study aimed to replicate this and extend our knowledge by using a lower dose of caffeine (65 mg) and a range of tasks related to different components of working memory.

caffeine


Input: In addition, tasks assessing psychomotor speed and the encoding of new information were included to determine whether caffeine-extraversion interactions were restricted to working memory tasks.

caffeine


Input: A double-blind design was used, with 128 participants being randomly assigned to caffeinated or de-caffeinated coffee conditions.


Input: The results showed that caffeine interacted with extraversion in the predicted direction for serial recall and running memory tasks.

caffeine


Input: Caffeine improved simple reaction time and the speed of encoding of new information, effects which were not modified by extraversion.

Caffeine


Input: These results suggest possible biological mechanisms underlying effects of caffeine on cognitive performance.

caffeine


Input: Quantitative analysis of the interaction of constitutive androstane receptor with chemicals and steroid receptor coactivator 1 using surface plasmon resonance biosensor systems: a case study of the Baikal seal (Pusa sibirica) and the mouse.

androstane

steroid


Input: The constitutive androstane receptor (CAR) not only displays a high basal transcriptional activity but also acts as a ligand-dependent transcriptional factor.

androstane


Input: It is known that CAR exhibits different ligand profiles across species.


Input: However, the mechanisms underlying CAR activation by chemicals and the species-specific responses are not fully understood.


Input: The objectives of this study are to establish a high-throughput tool to screen CAR ligands and to clarify how CAR proteins from the Baikal seal (bsCAR) and the mouse (mCAR) interact with chemicals and steroid receptor coactivator 1 (SRC1).

steroid


Input: We developed the surface plasmon resonance (SPR) system to assess quantitatively the interaction of CAR with potential ligands and SRC1.


Input: The ligand-binding domain (LBD) of bsCAR and mCAR was synthesized in a wheat germ cell-free system.


Input: The purified CAR LBD was then immobilized on the sensor chip for the SPR assay, and the kinetics of direct interaction of CARs with ligand candidates was measured.


Input: Androstanol and androstenol, estrone, 17 beta-estradiol, TCPOBOP, and CITCO showed compound-specific but similar affinities for both CARs.

Androstanol

androstenol

estrone

17 beta-estradiol

TCPOBOP

CITCO


Input: The CAR-SRC1 interaction was ligand dependent but exhibited a different ligand profile between the seal and the mouse.


Input: The results of SRC1 interaction assay accounted for those of our previous in vitro CAR-mediated transactivation assay.


Input: In silico analyses also supported the results of CAR-SRC1 interaction; there is little structural difference in the ligand-binding pocket of bsCAR and mCAR, but there is a distinct discrimination in the helix 11 and 12 of these receptors, suggesting that the interaction of ligand-bound CAR and SRC1 is critical for determining species-specific and ligand-dependent transactivation over the basal activity.


Input: The SPR assays demonstrated a potential as a high-throughput screening tool of CAR ligands.


Input: Obesity and addiction: neurobiological overlaps.


Input: Drug addiction and obesity appear to share several properties.


Input: Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards.


Input: Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres.

dopamine


Input: The abrupt dopamine increases, in vulnerable individuals, can override the brain' s homeostatic control mechanisms.

dopamine


Input: These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity.


Input: Predictably, they also engendered a heated debate.


Input: Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits.


Input: The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness.


Input: In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake.


Input: Here, we focus on the shared neurobiological substrates of obesity and addiction.


Input: Cellular assessment of the extract of bambangan (Mangifera pajang) as a potential cytoprotective agent for the human hepatocellular HepG2 cell line.


Input: This study was conducted to investigate the potential of bambangan (Mangifera pajang) fruit extracts in the protection against oxidative damage caused by tert-butyl hydroperoxide in the human hepatocellular HepG2 cell line.

tert-butyl hydroperoxide


Input: Proteins which might be involved in the cytoprotective mechanism were investigated using western blotting technique.


Input: Quercetin was used as a positive control.

Quercetin


Input: The results showed that only the kernel extract of M. pajang and quercetin displayed cytoprotective activity in HepG2 cells, with EC (50) values of 1. 2 and 5. 3 mu g/ml, respectively.

quercetin


Input: Expression of quinone reductase, glutathione reductase and methionine sulfoxide reductase A proteins were significantly up-regulated by quercetin, suggesting their involvement in the cytoprotective activity of quercetin.

quinone

glutathione

methionine sulfoxide

quercetin

quercetin


Input: However, expressions of only glutathione reductase and methionine sulfoxide reductase A proteins were significantly up-regulated by the kernel extract, again suggesting their involvement in the cytoprotective activity of bambangan kernel extract.

glutathione

methionine sulfoxide


Input: Future study is needed to investigate the involvement of other cytoprotective proteins in the cytoprotection mechanism.


Input: Stability of bioactive polyphenols from honey during different extraction methods.

polyphenols


Input: The LC-MS/MS technique was applied to the stability study of several flavonoids and phenolic acids in honey samples during the ultrasonic extraction (USE) and microwave-assisted extraction (MAE).

flavonoids

phenolic acids


Input: Phenolic compounds from the standard mixture were stable under ultrasounds action with the mean recovery of (90. 4% +/- 7. 1%), but during microwave-assisted extraction the benzoic acid derivatives and aglycones of flavonoids showed lower recovery (70-80%).

Phenolic

benzoic acid

flavonoids


Input: In honey matrix, the phenolic acids and the glycosides exhibited the high stability for MAE and USE treatments.

phenolic acids


Input: However, the recoveries of tested aglycones were below 10%.


Input: In the presence of an artificial sugar matrix, flavonols were almost completely degraded after successive treatment under MAE and USE conditions.

sugar

flavonols


Input: The obtained results indicated that standard addition method for flavonoids quantification in honey samples should not be recommended.

flavonoids


Input: Application of the USE conditions provided higher and/or similar extraction yields for phenolic acids than usually applied shaking with solvent.

phenolic acids


Input: It also allowed shortening the time required for the whole sample preparation procedure.


Input: Phenolic acids and glycosides such as quercetrin, rutin and hesperidin appeared to be stable under such conditions.

Phenolic acids

quercetrin

rutin

hesperidin


Input: A novel one-step microbial transformation of betulin to betulinic acid catalysed by Cunninghamella blakesleeana.

betulin

betulinic acid


Input: Betulinic acid and its derivatives are potential bioactive compounds present in nature.

Betulinic acid


Input: This study investigated the biotransformation of betulin to betulinic acid by Cunninghamella blakesleeana cells.

betulin

betulinic acid


Input: LC-MS analysis demonstrated that betulin could be transformed into at least five products from cultured C. blakesleeana cells, among which betulinic acid was the most important.

betulin

betulinic acid


Input: The presented method provides an attractive alternative approach to chemical synthesis, because is less time-consuming and more environmentally friendly.


Input: C. blakesleeana can transform betulin into potent derivatives with high pharmacological activities.

betulin


Input: Bioefficacy of EPA-DHA from lipids recovered from fish processing wastes through biotechnological approaches.

EPA

DHA


Input: The effect of fish oil recovered from fish visceral waste (FVW-FO) on serum and liver lipids, activity of HMG-CoA reductase in liver microsomes and EPA + DHA incorporation in liver, heart and brain were evaluated.

HMG-CoA

EPA

DHA


Input: Rats were fed different concentrations of FVW-FO providing 1. 25%, 2. 50%, 5. 0% EPA + DHA recovered by either fermentation or enzymatic hydrolysis for 8weeks.

EPA

DHA


Input: Feeding FVW-FO reduce triacylglycerols (5. 96-20. 3%), total cholesterol (7. 9-21. 5%) and LDL (7. 39-21. 7%) cholesterol levels in serum compared to group fed on a control diet (groundnut oil).

triacylglycerols

cholesterol

cholesterol


Input: The activity of HMG-CoA reductase was reduced (p < 0. 05) in the FVW-FO fed groups compared to the control.

HMG-CoA


Input: EPA + DHA level in serum, liver, brain and heart increased with increments in dietary EPA + DHA.

EPA

DHA

EPA

DHA


Input: Results show the hypolipidemic property of FVW-FO and reduced HMG-CoA reductase activity which is proportional to the incorporation of EPA + DHA.

HMG-CoA

EPA

DHA


Input: Recovery of FVW-FO will address the increasing demand for fish oil and reduce pollution problems.


Input: C-dideoxyhexosyl flavones from the stems and leaves of Passiflora edulis Sims.

C-dideoxyhexosyl flavones


Input: The stems and leaves of Passiflora edulis Sims, are used as a folk medicine for treating both anxiety and nervousness in American countries.


Input: Phytochemical investigation of the n-butanol (n-BuOH) fraction of this plant led to the isolation of four new 2, 6-dideoxyhexose-C-glycosyl flavones, including luteolin-8-C-beta-digitoxopyranosyl-4'-O-beta-d-glucopyranoside (1), apigenin-8-C-beta-digitoxopyranoside (2), apigenin-8-C-beta-boivinopyranoside (3) and luteolin-8-C-beta-boivinopyranoside (4), together with five known compounds (5-9).

n-butanol

n-BuOH

2, 6-dideoxyhexose-C-glycosyl flavones

luteolin-8-C-beta-digitoxopyranosyl-4'-O-beta-d-glucopyranoside


Input: The structures of these compounds were elucidated by extensive spectroscopic methods.


Input: All compounds were evaluated for their neurite outgrowth enhancing activities and the results indicated that luteolin (7) enhanced NGF-induced neurite outgrowth in PC12 cells at 50. 0 mu M.

luteolin


Input: Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity.


Input: The goal of this study was to monitor the anti-proliferative activity of Rosmarinus officinalis and Salvia officinalis extracts against cancer cells and to correlate this activity with their phytochemical profiles using liquid chromatography/diode array detection/electrospray ion trap tandem mass spectrometry (LC/DAD/ESI-MS (n)).


Input: For the quantitative estimation of triterpenic acids in the crude extracts an NMR based methodology was used and compared with the HPLC measurements, both applied for the first time, for the case of betulinic acid.

triterpenic acids

betulinic acid


Input: Both extracts exerted cytotoxic activity through dose-dependent impairment of viability and mitochondrial activity of rat insulinoma m5F (RINm5F) cells.


Input: Decrease of RINm5F viability was mediated by nitric oxide (NO)-induced apoptosis.

nitric oxide

NO


Input: Importantly, these extracts potentiated NO and TNF-alpha release from macrophages therefore enhancing their cytocidal action.

NO


Input: The rosemary extract developed more pronounced antioxidant, cytotoxic and immunomodifying activities, probably due to the presence of betulinic acid and a higher concentration of carnosic acid in its phytochemical profile.

betulinic acid

carnosic acid


Input: Phenylalanine ammonia lyase (PAL) enzyme activity and antioxidant properties of some cyanobacteria isolates.

Phenylalanine ammonia


Input: In the present study, six cyanobacteria isolates were evaluated for the PAL enzyme activity, and their methanol extracts were assessed for the total phenolic amount and other antioxidant parameters.

methanol

phenolic


Input: Synechocystis sp.


Input: BASO444 and Synechocystis sp.


Input: BASO673 isolates with high levels of total phenols (66. 0 +/- 1. 2 mu g/mg, 78. 1 +/- 1. 8 mu g/mg, respectively) also showed high levels of PAL activities (20. 5 +/- 3. 1U/mg protein, 17. 2 +/- 2. 3U/mg protein, respectively) and strong antioxidant activities.

phenols


Input: To understand the effect of l-phenylalanine (l-phe) on the PAL activity, total phenolic amount, and phenolic constituents, isolates were evaluated with 100mg/l l-phe.

l-phenylalanine

l-phe

phenolic

phenolic

l-phe


Input: While PAL activities exhibited no significant change with l-phe addition, total phenolic amount of the isolates significantly increased.

l-phe

phenolic


Input: HPLC analysis revealed gallic acid, trans-cinnamic acid, p-coumaric acid, and ferulic acid as the main compounds.

gallic acid

trans-cinnamic acid

p-coumaric acid

ferulic acid


Input: Results suggested that the two isolate mights be an important source for the l-phe inducible phenolic compounds.

l-phe

phenolic


Input: Ginger extract and zingerone ameliorated trinitrobenzene sulphonic acid-induced colitis in mice via modulation of nuclear factor-kappa B activity and interleukin-1 beta signalling pathway.

zingerone

trinitrobenzene sulphonic acid


Input: Ginger is a commonly used spice with anti-inflammatory potential.


Input: Colitis is the common pathological lesion of inflammatory bowel diseases.


Input: In this study, we investigated the therapeutic effects of ginger and its component zingerone in mice with 2, 4, 6-trinitrobenzene sulphonic acid (TNBS)-induced colitis.

zingerone

2, 4, 6-trinitrobenzene sulphonic acid

TNBS


Input: Ginger and zingerone ameliorated TNBS-induced colonic injury in a dose-dependent manner.

zingerone

TNBS


Input: Pathway analysis of ginger-and zingerone-regulated gene expression profiles showed that ginger and zingerone significantly regulated cytokine-related pathways.

zingerone

zingerone


Input: Network analysis showed that nuclear factor-kappa B (NF-kappa B) and interleukin-1 beta (IL-1 beta) were key molecules involved in the expression of ginger-and zingerone-affected genes.

zingerone


Input: Ex vivo imaging and immunohistochemical staining further verified that ginger and zingerone suppressed TNBS-induced NF-kappa B activation and IL-1 beta protein level in the colon.

zingerone

TNBS


Input: In conclusion, ginger improved TNBS-induced colitis via modulation of NF-kappa B activity and IL-1 beta signalling pathway.

TNBS


Input: Moreover, zingerone might be the active component of ginger responsible for the amelioration of colitis induced by TNBS.

zingerone

TNBS


Input: Metabolite profiling of phenolic and carotenoid contents in tomatoes after moderate-intensity pulsed electric field treatments.


Input: A metabolite profiling approach was used to study the effect of moderate-intensity pulsed electric field (MIPEF) treatments on the individual polyphenol and carotenoid contents of tomato fruit after refrigeration at 4 degrees C for 24h.

polyphenol


Input: The MIPEF processing variables studied were electric field strength (from 0. 4 to 2. 0kV/cm) and number of pulses (from 5 to 30).


Input: Twenty four hours after MIPEF treatments, an increase was observed in hydroxycinnamic acids and flavanones, whereas flavonols, coumaric and ferulic acid-O-glucoside were not affected.

hydroxycinnamic acids

flavanones

flavonols

coumaric and ferulic acid-O-glucoside


Input: Major changes were also observed for carotenoids, except for the 5-cis-lycopene isomer, which remain unchanged after 24h of MIPEF treatments.


Input: MIPEF treatments, conducted at 1. 2kV/cm and 30 pulses, led to the greatest increases in chlorogenic (152%), caffeic acid-O-glucoside (170%) and caffeic (140%) acids.

caffeic acid-O-glucoside

caffeic


Input: On the other hand, treatments at 1. 2kV/cm and 5 pulses led to maximum increases of alpha-carotene, 9-and 13-cis-lycopene, which increased by 93%, 94% and 140%, respectively.

alpha-carotene

9-and 13-cis-lycopene


Input: Therefore, MIPEF could stimulate synthesis of secondary metabolites and contribute to production of tomatoes with high individual polyphenol and carotenoid contents.

polyphenol


Input: Amino acid composition, antinutrients and allergens in the peanut protein fraction obtained by an aqueous enzymatic process.

Amino acid


Input: Enzyme-assisted aqueous extraction (EAE) of peanut kernel was used to extract oil and protein.


Input: The aqueous fraction (AF) obtained by EAE had a better essential amino acid profile than the residues obtained by solvent extraction (Rs) and cold pressing (Rc).

amino acid


Input: No major difference in the trypsin inhibitor activity among AF, Rs and Rc was observed; however, the trypsin inhibitor activity was drastically reduced in the residue obtained after EAE.


Input: AF was subjected to MALDI-TOF/MS, revealing it to be rich in peptides (107) with molecular masses from m/z 700 to 2369Da.


Input: AF had an extremely low phytate content and was rich in peptides, which could be used as a food supplement.

phytate


Input: ESI-MS/MS data were used for the identification of major peanut allergens, viz., Ara h1, h3, h6-8.


Input: Their allergenic potential needs to be established.


Input: Determination of volatile compounds in New Zealand Greenshell (TM) mussels (Perna canaliculus) during chilled storage using solid phase microextraction gas chromatography-mass spectrometry.


Input: Greenshell (TM) mussels (Perna canaliculus) were dry-stored at 6. 44 +/- 0. 54 degrees C for 8 days during which time volatile organic compounds (VOCs) were monitored using SPME GC-MS.


Input: Thirty-four VOCs were identified in homogenised mussel meat and 29 in the mussel liquor (i. e. the seawater enclosed in the mantle cavity).


Input: Of the 34 VOCs identified 20 were reliably identified throughout the storage treatment and 9 were found to change in relative concentration in homogenised mussel meat.


Input: Dimethyl sulphide, 1-penten-3-ol, 1-hexen-3-ol and 1-octen-3-ol increased during storage, whereas pentanal, hexanal, heptanal, octanal and 3-undecen-2-one decreased.

Dimethyl sulphide

pentanal

hexanal

heptanal

octanal


Input: In the mussel liquor, dimethyl sulphide was undetectable pre-storage, becoming detectable after 2 days, and a large increase was noted after 6 days.

dimethyl sulphide


Input: SPME GC-MS was a useful tool for monitoring VOC profiles of Greenshell (TM) mussels and could aid in the development of technologies that monitor and improve product quality and consistency.


Input: Phytochemical composition and in vitro antimicrobial and antioxidant activities of some medicinal plants.


Input: Different parts of three plants (Primula auriculata, Fumaria vaillantii and Falcaria vulgaris) were extracted with three different solvents to yield 72 crude extracts.


Input: The phytochemical analysis (chemical screening, GC-MS) of three plants was investigated for their antioxidant and antibacterial activity using nine Gram-positive and Gram-negative bacteria.


Input: The principal antioxidant and antimicrobial components were determined using HPLC with UV detection.


Input: All extracts possessed antibacterial activity especially methanolic extracts from flowers of P. auriculata.


Input: The DPPH-radical scavenging assay exhibited high antioxidant activities in three plants (more than 80% at 50 mu g).

DPPH


Input: The F. vulgaris showed high content of carvacrol (29. 8%) as main component.

carvacrol


Input: The contents of carvacrol and fumaric acid in the methanolic-water extracts were 1119 and 1966mg/l respectively.

carvacrol

fumaric acid


Input: Our results indicate that these plants would be able to promise sources of natural products with potential antibacterial and antioxidant activity.


Input: Hypocholesterolemic effects of low calorie structured lipids on rats and rabbits fed on normal and atherogenic diet.


Input: The hypocholesterolemic effects of two low calorie structured lipids (SL1 and SL2) containing essential fatty acids, prepared by lipase catalysed interesterification of ethyl behenate respectively with sunflower and soybean oils were studied in rats and rabbits.

fatty acids

ethyl behenate


Input: The feeding experiment conducted on rats as well as rabbits, fed on normal and atherogenic diet containing 10% of SL1 and SL2 (experimental) and sunflower oil (control) indicated no adverse effects on growth and food intake.


Input: However, the structured lipids beneficially lowered serum and liver lipids, particularly cholesterol, LDL cholesterol, triglycerides and also maintains the essential fatty acid status in serum and liver.

cholesterol

cholesterol

triglycerides

fatty acid


Input: The lipid deposition observed in the arteries of rabbits fed on atherogenic diets was significantly reduced when structured lipids were included in the diet.


Input: These observations coincided with reduced levels of serum cholesterol particularly LDL cholesterol observed in experimental groups.

cholesterol

cholesterol


Input: Therefore the structured lipids, designed to have low calorific value also beneficially lower serum lipids and lipid deposition in animals fed on atherogenic diets.


Input: Effects of solvent and alkaline earth metals on the heat-induced precipitation process of sodium caseinate.

alkaline earth metals

sodium


Input: The precipitation temperatures of sodium caseinate in H (2) O and D (2) O in the presence of Mg (2 +), Ca (2 +), Sr (2 +) and Ba (2 +) were investigated through fluorescence, turbidity and conductivity experiments.

sodium

H (2) O

D (2) O

Mg (2 +)

Ca (2 +)

Sr (2 +)

Ba (2 +)


Input: As for the ability of the divalent cations (1-17. 5mM) to induce the precipitation process in H (2) O, the sequence Ba (2 +) >= Ca (2 +) > Mg (2 +) > Sr (2 +) was found.

H (2) O

Ba (2 +)

Ca (2 +)

Mg (2 +)

Sr (2 +)


Input: Remarkably, while at low salt concentrations (< 10mM) precipitation temperatures (T (Ps)) were found to change significantly depending on the specific cation, at higher concentrations (> 10mM) the differences among the different cations were greatly reduced.


Input: By fitting these results with a modified Jones-Dole equation, we confirmed that the less hydrated ions possess a greater capacity to induce precipitation.


Input: In D (2) O, the order of ion ability to induce caseinate precipitation was Ba (2 +) > Ca (2 +) > Sr (2 +) > Mg (2 +).

D (2) O

Ba (2 +)

Ca (2 +)

Sr (2 +)

Mg (2 +)


Input: The different hydrophobicity between D (2) O and H (2) O was shown to affect significantly the T (Ps) of caseinate in the presence of calcium, strontium and barium.

D (2) O

H (2) O

calcium

strontium

barium


Input: Purification and characterisation of antibacterial peptide-containing compound derived from palm kernel cake.


Input: Palm kernel cake (PKC), the most useful by-product resulted from palm kernel oil production.


Input: In this study, PKC-derived protein product was found suitable for use as an antimicrobial agent with potent antibacterial activity, particularly against Bacillus species, after enzymatic hydrolysis with alcalase.


Input: The hydrolysate was further purified by gel filtration chromatography.


Input: The purified fraction was found to have 14. 63 +/- 0. 70% (w/w) protein, a molecular mass of 2. 4kDa and low hemolytic activity (< 50% hemolysis of human erythrocytes at concentration of 1000 mu g/ml).


Input: The presence of lysine and the major component lauric acid derivative, as indicated by electrospray ionisation-mass spectrometry (ESI-MS) direct infusion and nuclear magnetic resonance (NMR) spectroscopy, may have contributed to the antibacterial effect of purified PKC fraction.

lysine

lauric acid


Input: This study suggests that the antibacterial PKC compound may be not a pure peptide but instead a peptide-containing compound high in lauric acid derivative.

lauric acid


Input: Therapeutic modulation of intestinal dysbiosis.


Input: The human gastrointestinal tract is home to an extremely numerous and diverse collection of microbes, collectively termed the " intestinal microbiota ".


Input: This microbiota is considered to play a number of key roles in the maintenance of host health, including aiding digestion of otherwise indigestible dietary compounds, synthesis of vitamins and other beneficial metabolites, immune system regulation and enhanced resistance against colonisation by pathogenic microorganisms.


Input: Conversely, the intestinal microbiota is also a potent source of antigens and potentially harmful compounds.


Input: In health, humans can therefore be considered to exist in a state of natural balance with their microbial inhabitants.


Input: A shift in the balance of microbiota composition such that it may become deleterious to host health is termed " dysbiosis ".


Input: Dysbiosis of the gut microbiota has been implicated in numerous disorders, ranging from intestinal maladies such as inflammatory bowel diseases and colorectal cancer to disorders with more systemic effects such as diabetes, metabolic syndrome and atopy.


Input: Given the far reaching influence of the intestinal microbiota on human health a clear future goal must be to develop reliable means to alter the composition of the microbiota and restore a healthy balance of microbial species.


Input: While it is clear that much fundamental research remains to be done, potentially important therapeutic options include narrow spectrum antibiotics, novel probiotics, dietary interventions and more radical techniques such as faecal transplantation, all of which aim to suppress clinical dysbiosis, restore intestinal microbiota diversity and improve host health.


Input: A review on antioxidants, prooxidants and related controversy: natural and synthetic compounds, screening and analysis methodologies and future perspectives.


Input: Many studies have been conducted with regard to free radicals, oxidative stress and antioxidant activity of food, giving antioxidants a prominent beneficial role, but, recently many authors have questioned their importance, whilst trying to understand the mechanisms behind oxidative stress.


Input: Many scientists defend that regardless of the quantity of ingested antioxidants, the absorption is very limited, and that in some cases prooxidants are beneficial to human health.


Input: The detection of antioxidant activity as well as specific antioxidant compounds can be carried out with a large number of different assays, all of them with advantages and disadvantages.


Input: The controversy around antioxidant in vivo benefits has become intense in the past few decades and the present review tries to shed some light on research on antioxidants (natural and synthetic) and prooxidants, showing the potential benefits and adverse effects of these opposing events, as well as their mechanisms of action and detection methodologies.


Input: It also identifies the limitations of antioxidants and provides a perspective on the likely future trends in this field.


Input: Effects of vitamin D on antigen-specific and non-antigen-specific immune modulation: relevance for type 1 diabetes.

vitamin D


Input: Vitamin D is a fat-soluble precursor of the circulating 25-hydroxyvitamin D 3 (25 (OH) D 3) which can be converted by the 1 alpha-hydroxylase (1 alpha (OH) ase) enzyme into the bioactive hormonal metabolite 1, 25-dihydroxyvitamin D 3 (1, 25 (OH) 2 D 3), generally known to promote bone mineralization through its ability to enhance calcium absorption from the gut.

Vitamin D

25-hydroxyvitamin D 3

25 (OH) D 3

1, 25-dihydroxyvitamin D 3

1, 25 (OH) 2 D 3

calcium


Input: Importantly, in humans, vitamin D is mainly derived from endogenous production of vitamin D 3 from ultraviolet (UV) radiation exposure to the skin while a small part (< 10%) is obtained via dietary intake of dairy products and fatty fish (1).

vitamin D

vitamin D 3


Input: Taking these factors into account, geographic distribution and seasonality, skin pigmentation, age, and lifestyle may predispose certain populations to be at a higher risk of developing vitamin D insufficiency or deficiency (2).

vitamin D


Input: The first valid reports correlating the importance of an adequate vitamin D status to optimal human health originate from the early part of the 20th century, when vitamin D was described to prevent and treat the bone disease rickets.

vitamin D

vitamin D


Input: Since then, the findings that vitamin D receptors (VDR) are present in many body tissues and that vitamin D metabolizing enzymes can be found in various cells outside the kidney, including the intestine, prostate, immune cells, and within the skin itself (reviewed in reference 3), have revolutionized the vitamin D business.

vitamin D

vitamin D

vitamin D


Input: In this review, we will mainly focus on vitamin D as a component of immune regulation and on the role of vitamin D in antigen-specific and non-specific therapies with potential relevance for type 1 diabetes (T1D).

vitamin D

vitamin D


Input: Developmental effects of prenatal di-n-hexyl phthalate and dicyclohexyl phthalate exposure on reproductive tract of male rats: Postnatal outcomes.

di-n-hexyl phthalate

dicyclohexyl phthalate


Input: The present study is to investigate the effects of in utero di-n-hexyl phthalate (DHP) and dicyclohexyl phthalate exposure (DCHP) on the development of male reproductive tract at prepubertal, pubertal and adult stages.

di-n-hexyl phthalate

DHP

dicyclohexyl phthalate

DCHP


Input: Pregnant rats were exposed to DHP and DCHP at doses of 0, 20, 100 and 500mg/kg/day, by gavage, on gestational days (GD) 6-19.

DHP

DCHP


Input: Testosterone (T) levels of prepubertal rats diminished at high dose DHP and middle dose DCHP groups.

Testosterone

DHP

DCHP


Input: MIS/AMH levels elevated in DHP and DCHP groups.

DHP

DCHP


Input: T levels of pubertal rats decreased in low and high dose DHP and DCHP groups.

DHP

DCHP


Input: Inhibin B levels of adult rats diminished in DCHP groups.

DCHP


Input: Atrophic and amorphous tubules, spermatogenic cell debris, apoptotic cells, adherent tubules, Sertoli cell vacuolisation, prostatic atrophic tubules and prostatic intraepithelial neoplasia (PIN) were observed in the reproductive organs of treated animals at all developmental stages.


Input: There was an increase in immunoexpression of MIS/AMH in testes of treated rats.


Input: There were no changes in sperm head count but percentages of abnormal sperms increased.


Input: The diameters of seminiferous and epididymal tubules in treatment groups were significantly lower.


Input: This study shows that DHP and DCHP may have antiandrogenic effects on male reproductive development before and after birth.

DHP

DCHP


Input: Modeling the binding mechanism of Alzheimer' s A beta 1-4 2 to nicotinic acetylcholine receptors based on similarity with snake alpha-neurotoxins.

acetylcholine


Input: For over a decade, it has been known that amyloid beta (A beta) peptides of Alzheimer' s disease bind to the nicotinic alpha 7 acetylcholine receptor (AChR) with picomolar affinity, and that snake alpha-neurotoxins competitively inhibit this binding.

acetylcholine


Input: Here we propose a model of the binding mechanism of A beta peptides to alpha 7-AChR at atomic level.


Input: The binding mechanism is based on sequence and structure similarities of A beta residues with functional residues of snake alpha-neurotoxins (ATX) in complex with AChR.


Input: The binding mechanism involves residue (A beta) K28 (similar to (ATX) R32) which forms cation/pi interactions in the acetylcholine binding site, and residues (A beta) G29-(A beta) I32 [GAII] (similar to (ATX) G33-(ATX) I36 [GTII]) which form an intermolecular beta-sheet with residues (alpha 7) F189-(alpha 7) E191 of AChR.

acetylcholine


Input: Through these interactions, we propose that the AChR serves as a chaperone for A beta conformational changes from alpha-to beta-hairpin.


Input: The interactions which block channel opening provide fundamental insight into A beta neurotoxicity and cognition impairment, that could contribute to pathogenic processes in Alzheimer' s disease, thus paving the way for structure based therapies.


Input: Electrical detection of spin precession in freely suspended graphene spin valves on cross-linked poly (methyl methacrylate).

graphene

poly (methyl methacrylate)


Input: Spin injection and detection is achieved in freely suspended graphene using cobalt electrodes and a nonlocal spin-valve geometry.

graphene

cobalt


Input: The devices are fabricated with a single electron-beam-resist poly (methyl methacrylate) process that minimizes both the fabrication steps and the number of (aggressive) chemicals used, greatly reducing contamination and increasing the yield of high-quality, mechanically stable devices.

poly (methyl methacrylate)


Input: As-grown devices can present mobilities exceeding 10 (4) cm (2) V (-1) s (-1) at room temperature and, because the contacts deposited on graphene are only exposed to acetone and isopropanol, the method is compatible with almost any contacting material.

graphene

acetone

isopropanol


Input: Spin accumulation and spin precession are studied in these nonlocal spin valves.


Input: Fitting of Hanle spin precession data in bilayer and multilayer graphene yields a spin relaxation time of ~ 125-250 ps and a spin diffusion length of 1. 7-1. 9 mu m at room temperature.

graphene


Input: The organometallic chemistry of cycloheptatrienyl zirconium complexes.

cycloheptatrienyl zirconium


Input: This tutorial review summarizes the organometallic chemistry derived from the half-sandwich complex [(eta (7)-C (7) H (7)) ZrCl (tmeda)], which was used as an efficient and versatile starting material for the incorporation of monoanionic ligands into the cycloheptatrienyl zirconium coordination sphere by conventional salt metathesis reactions.

(eta (7)-C (7) H (7)) ZrCl (tmeda)

cycloheptatrienyl zirconium


Input: A broad variety of ligands was employed, affording novel and previously inaccessible cycloheptatrienyl (sandwich) complexes of the type [(eta (7)-C (7) H (7)) Zr (Y)]; Y comprises pentadienyl, cyclopentadienyl, allyl, phospholyl, boratabenzene, imidazolin-2-iminato and amido systems.

cycloheptatrienyl

(eta (7)-C (7) H (7)) Zr (Y)

pentadienyl

cyclopentadienyl

allyl

phospholyl

boratabenzene

amido


Input: The cycloheptatrienyl ring in these systems usually acts as an " innocent spectator ligand ", but reactivity can arise from the second ligand Y or the Lewis acidity of the, formally, Zr (+ iv) center, which was probed in selected examples and put in perspective to related studies.

cycloheptatrienyl

Zr (+ iv)


Input: The corresponding results emphasize why the use of [(eta (7)-C (7) H (7)) ZrCl (tmeda)] is clearly an advancement in the chemistry of the still fairly unexplored area of cycloheptatrienyl transition metal complexes.

(eta (7)-C (7) H (7)) ZrCl (tmeda)

cycloheptatrienyl transition metal complexes


Input: Portal vein glucose entry triggers a coordinated cellular response that potentiates hepatic glucose uptake and storage in normal but not high-fat/high-fructose-fed dogs.

glucose

glucose

fructose


Input: The cellular events mediating the pleiotropic actions of portal vein glucose (PoG) delivery on hepatic glucose disposition have not been clearly defined.

glucose

glucose


Input: Likewise, the molecular defects associated with postprandial hyperglycemia and impaired hepatic glucose uptake (HGU) following consumption of a high-fat, high-fructose diet (HFFD) are unknown.

glucose

fructose


Input: Our goal was to identify hepatocellular changes elicited by hyperinsulinemia, hyperglycemia, and PoG signaling in normal chow-fed (CTR) and HFFD-fed dogs.


Input: In CTR dogs, we demonstrated that PoG infusion in the presence of hyperinsulinemia and hyperglycemia triggered an increase in the activity of hepatic glucokinase (GK) and glycogen synthase (GS), which occurred in association with further augmentation in HGU and glycogen synthesis (GSYN) in vivo.


Input: In contrast, 4 weeks of HFFD feeding markedly reduced GK protein content and impaired the activation of GS in association with diminished HGU and GSYN in vivo.


Input: Furthermore, the enzymatic changes associated with PoG sensing in chow-fed animals were abolished in HFFD-fed animals, consistent with loss of the stimulatory effects of PoG delivery.


Input: These data reveal new insight into the molecular physiology of the portal glucose signaling mechanism under normal conditions and to the pathophysiology of aberrant postprandial hepatic glucose disposition evident under a diet-induced glucose-intolerant condition.

glucose

glucose

glucose


Input: Identification of the metabolites of lesogaberan using linear trap quadrupole orbitrap mass spectrometry and hydrophilic interaction liquid chromatography.

lesogaberan


Input: 1. In this study, hydrophilic interaction liquid chromatography (HILIC), radiochemical activity monitoring and linear trap quadrupole orbitrap mass spectrometry (MS) and tandem mass spectrometry (MS/MS) were used to identify the metabolites of a highly polar novel gamma-aminobutyric acid type-B receptor agonist, lesogaberan, in rats.

gamma-aminobutyric acid

lesogaberan


Input: 2. Urine was collected from three male Wistar rats for 24 h after dosing with (14) C-labelled lesogaberan (170 mg/kg, 10 MBq/kg); plasma samples were taken 2 and 24 h after dosing.

(14) C-labelled lesogaberan


Input: Pooled samples were separated by HILIC and eluents were analysed by radiochemical activity monitoring, MS and MS/MS.


Input: 3. Only the parent compound was detected in plasma, but six metabolites (M1-M6) were detected in urine.


Input: Analysis of MS and MS/MS data and comparison with synthetic reference standards enabled the identification of the structure of each metabolite.


Input: M1 was identified as the N-acetylated species [(2R)-3-acetamido-2-fluoropropyl]-phosphinic acid, and M6 as [(2R)-3-amino-2-fluoropropyl]-phosphonic acid.

N

[(2R)-3-acetamido-2-fluoropropyl]-phosphinic acid

[(2R)-3-amino-2-fluoropropyl]-phosphonic acid


Input: Metabolites M2 and M5 were the alcohol and carboxylic acid species 3-hydroxypropyl-phosphinic acid and 3-hydroxyphosphonoyl-propanoic acid, respectively, both of which had lost the fluorine atom present in the parent compound.

alcohol

carboxylic acid

3-hydroxypropyl-phosphinic acid

3-hydroxyphosphonoyl-propanoic acid

fluorine


Input: M3 was the corresponding carboxylic acid species retaining the fluorine atom, (2R)-2-fluoro-3-hydroxyphosphonoyl-propanoic acid.

carboxylic acid

fluorine

(2R)-2-fluoro-3-hydroxyphosphonoyl-propanoic acid


Input: Finally M4 was identified as [(2R)-2-fluoro-3-guanidino-propyl]-phosphinic acid.

[(2R)-2-fluoro-3-guanidino-propyl]-phosphinic acid


Input: Preparation and culture of precision-cut organ slices from human and animal.


Input: 1. Human and animal precision-cut organ slices are being widely used to obtain drug metabolism and toxicity profiles in vitro.


Input: These data are then used to predict what might be seen in human patients.


Input: The accuracy of this prediction and extrapolation of the findings based on human or animal in vitro systems to the findings that occur in vivo is dependent on both the quality of the tissue itself and the quality of the in vitro system.


Input: 2. The quality of human organs used in research is dependent on procurement methods, warm ischaemia time, preservation solutions, cold ischaemia time, and donor-specific factors.


Input: It is important to confirm that the organs being used are highly viable and fully functional before using them in scientific studies.


Input: 3. The optimal preparation and incubation of organ slices is also essential in maintaining slice viability and function.


Input: It is important to prepare the slices in a cold preservation solution, to prepare the slices at a correct thickness, and to incubate the slices in a system where the slice rotates in out of the oxygen atmosphere and medium.

oxygen


Input: 4. Meeting the criteria outlined here will lead to successful organ slice cultures for investigating drug-induced mechanisms and organ-specific toxicity.


Input: Wnt/beta-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts.


Input: The BMP and Wnt/beta-catenin signaling pathways cooperatively regulate osteoblast differentiation and bone formation.


Input: Although BMP signaling regulates gene expression of the Wnt pathway, much less is known about whether Wnt signaling modulates BMP expression in osteoblasts.


Input: Given the presence of putative Tcf/Lef response elements that bind beta-catenin/TCF transcription complex in the BMP2 promoter, we hypothesized that the Wnt/beta-catenin pathway stimulates BMP2 expression in osteogenic cells.


Input: In this study, we showed that Wnt/beta-catenin signaling is active in various osteoblast or osteoblast precursor cell lines, including MC3T3-E1, 2T3, C2C12, and C3H10T1/2 cells.


Input: Furthermore, crosstalk between the BMP and Wnt pathways affected BMP signaling activity, osteoblast differentiation, and bone formation, suggesting Wnt signaling is an upstream regulator of BMP signaling.


Input: Activation of Wnt signaling by Wnt3a or overexpression of beta-catenin/TCF4 both stimulated BMP2 transcription at promoter and mRNA levels.


Input: In contrast, transcription of BMP2 in osteogenic cells was decreased by either blocking the Wnt pathway with DKK1 and sFRP4, or inhibiting beta-catenin/TCF4 activity with FWD1/beta-TrCP, ICAT, or Delta TCF4.


Input: Using a site-directed mutagenesis approach, we confirmed that Wnt/beta-catenin transactivation of BMP2 transcription is directly mediated through the Tcf/Lef response elements in the BMP2 promoter.


Input: These results, which demonstrate that the Wnt/beta-catenin signaling pathway is an upstream activator of BMP2 expression in osteoblasts, provide novel insights into the nature of functional cross talk integrating the BMP and Wnt/beta-catenin pathways in osteoblastic differentiation and maintenance of skeletal homeostasis.


Input: Imaging in the cardiovascular and metabolic disease area.


Input: There is a widely held belief that the use of non-invasive imaging can reduce the gap between basic science and clinical proof-of-concept, ultimately improving decision-making and therefore the efficiency of the drug development process.


Input: Imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) are routinely used in oncology and neuroscience drug development.


Input: However, less attention has been paid to the systematic use of imaging in the cardiovascular and metabolic disease area.


Input: Here, with an emphasis on' early clinical' development, we discuss the application of imaging in those areas, highlighting opportunities and challenges.


Input: Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist into early childhood.

polychlorinated biphenyls

dioxins


Input: We investigated whether prenatal exposure from the maternal diet to the toxicants polychlorinated biphenyls (PCBs) and dioxins is associated with the development of immune-related diseases in childhood.

polychlorinated biphenyls

PCBs

dioxins


Input: Children participating in BraMat, a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), were followed in the three first years of life using annual questionnaires (0-3years; n = 162, 2-3years; n = 180), and blood parameters were examined at three years of age (n = 114).


Input: The maternal intake of the toxicants was calculated using a validated food frequency questionnaire from MoBa.


Input: Maternal exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze and more frequent upper respiratory tract infections.

PCBs

dioxins


Input: Furthermore, maternal exposure to PCBs and dioxins was found to be associated with reduced antibody response to a measles vaccine.

PCBs

dioxins


Input: No associations were found between prenatal exposure and immunophenotype data, allergic sensitization and vaccine-induced antibody responses other than measles.


Input: Our results suggest that prenatal dietary exposure to PCBs and dioxins may increase the risk of wheeze and the susceptibility to infectious diseases in early childhood.

PCBs

dioxins


Input: A subchronic dietary toxicity study of rice hull fiber in rats.


Input: We conducted a 90-day feeding study to investigate subchronic toxicity of rice hull fiber.


Input: Sprague Dawley rats were randomly divided into four groups; each received a diet containing 0%, 2. 5%, 3. 75% and 5. 0% (w/w) rice hull fiber for 90days.


Input: Clinical observations were carried out daily, with weekly measurements of body weight and food consumption.


Input: We performed ophthalmic and histological examinations at termination.


Input: Blood and urine samples were collected to measure hematology and clinical chemistry parameters.


Input: No mortality, ophthalmic abnormalities, or adverse treatment-related effects were seen during clinical observations, hematological tests, or analyses of urine.


Input: Macroscopic or microscopic examinations of organs revealed no treatment related abnormalities.


Input: The only treatment related significant changes were reduced concentrations of fasting blood glucose (up to 17. 6%) and cholesterol (up to 22. 0%), typical benefits of dietary fiber, in males treated with 3. 75 and 5% rice hull fiber.

glucose

cholesterol


Input: The no-observed-adverse-effect-level (NOAEL) for rice hull fiber was 5. 0% for both genders (females, 3. 80g/kg body weight/day; males, 4. 11g/kg body weight/day).


Input: PUB-NChIP--" in vivo biotinylation " approach to study chromatin in proximity to a protein of interest.


Input: We have developed an approach termed PUB-NChIP (proximity utilizing biotinylation with native ChIP) to purify and study the protein composition of chromatin in proximity to a nuclear protein of interest.


Input: It is based on coexpression of (1) a protein of interest, fused with the bacterial biotin ligase BirA, together with (2) a histone fused to a biotin acceptor peptide (BAP), which is specifically biotinylated by BirA-fusion in the proximity of the protein of interest.

biotin

biotin


Input: Using the RAD18 protein as a model, we demonstrate that the RAD18-proximal chromatin is enriched in some H4 acetylated species.


Input: Moreover, the RAD18-proximal chromatin containing a replacement histone H2AZ has a different pattern of H4 acetylation.


Input: Finally, biotin pulse-chase experiments show that the H4 acetylation pattern starts to resemble the acetylation pattern of total H4 after the proximity of chromatin to RAD18 has been lost.

biotin


Input: Anatomical and functional damage in experimental glaucoma.


Input: Glaucoma is a progressive neurodegenerative disease caused by retinal ganglion cell (RGC) loss.


Input: One important risk factor for glaucoma is elevated intraocular pressure and thus many animal models are based on spontaneous or induced ocular hypertension (OHT).


Input: Using these models it has been shown that RGCs initially suffer an impairment of the active axonal transport that progresses to a lack of passive diffusion along the axon.


Input: This axonal damage eventually causes the death of the parent RGCs in pie-shaped sectors of the retina, but there is also diffuse RGC loss, without involving displaced amacrine cells.


Input: Recent data show that OHT results in a protracted insult to the inner and outer retina that causes functional alterations and ultimately, degeneration and death of cones.


Input: Phlorotannin-rich Ecklonia cava reduces the production of beta-amyloid by modulating alpha-and gamma-secretase expression and activity.

Phlorotannin


Input: Beta-amyloid (A beta) is a major pathogenic peptide in Alzheimer' s disease (AD) and is generated by the processing of amyloid precursor protein (APP).


Input: We have previously reported that the brown algae Ecklonia cava, which has anti-oxidant and anti-inflammatory functions, decreased A beta production and further aggregation in HEK293 cells expressing the APP Swedish mutation.


Input: Here, we show the reduction mechanism of A beta production using the butanol extract of Ecklonia cava through the examination of expression and activity of alpha-, beta-, and gamma-secretase.

butanol


Input: Treatment with the extract resulted in the activation of alpha-secretase with a contrasting decrease in its mRNA and protein expression.


Input: This activation was consistent with the translocation of the extract into the plasma membrane of the secretase.


Input: Gamma-secretase activity was lowered by E. cava, and this effect may be due to the decreased expression of PSEN1 mRNA and protein.


Input: In addition, the basal nuclear location of PSEN1, which may affect chromosome missegregation in neurodegenerative disease, was reduced by the extract, despite the significance of this finding remains unclear.


Input: Taken together, these results led us to conclude that E. cava regulated the expression and activity of gamma-secretase and alpha-secretase, leading to a reduction in A beta production by the stable cells.


Input: Our data indicate that E. cava is a novel natural-product candidate for AD treatment, although further in vivo studies are needed.


Input: Apoptosis induced neurotoxicity of Di-n-butyl-di-(4-chlorobenzohydroxamato) Tin (IV) via mitochondria-mediated pathway in PC12 cells.

Di-n-butyl-di-(4-chlorobenzohydroxamato) Tin (IV)


Input: The severe toxicity of antitumor organotin (IV) compounds limits their application in clinic, however, the toxic mechanism is still unclear.

organotin (IV)


Input: Di-n-butyl-di-(4-chlorobenzohydroxamato) Tin (IV) (DBDCT), an antitumor agent with high activity and obvious neurotoxicity was chosen as a typical diorganotin (IV) compound to investigate its neurotoxic mechanism using PC12 cells and comprehensive methods.

Di-n-butyl-di-(4-chlorobenzohydroxamato) Tin (IV)

DBDCT

diorganotin (IV)


Input: Treatment with DBDCT resulted in a dose-and time-dependent growth inhibition of PC12 cells.

DBDCT


Input: The changes in cell morphology were observed using light microscopy, fluorescence microscopy and transmission electron microscopy.


Input: PC12 cell apoptosis induced by DBDCT was confirmed by annexin V/propidium iodide staining, and characterized by cleavage of caspase-9 and caspase-3 proteins.

DBDCT

propidium iodide


Input: DBDCT induced the release of cytochrome c from the mitochondria to the cytosol and the generation of reactive oxygen species.

DBDCT

oxygen


Input: DBDCT up-regulated the expression of Bax, down-regulated the expression of Bcl-2, and significantly increased the ratio of Bax/Bcl-2.

DBDCT


Input: DBDCT also caused the phosphorylation of JNK and p38 (MAPK).

DBDCT


Input: In rats exposed to DBDCT, apoptosis was also observed in brain, as shown by the detection of cleaved caspase-9 and caspase-3 proteins and increased TUNEL positive staining.

DBDCT


Input: In conclusion, the results demonstrated that DBDCT caused the neurotoxicity by inducing apoptosis via mitochondria-mediated pathway.

DBDCT


Input: Inclusion compound based approach to forming arrays of artificial dipolar molecular rotors: a search for optimal rotor structures.


Input: Hexagonal tris (o-phenylenedioxy) cyclotriphosphazene (TPP) is used as ahost for organizing dipolar molecular rotor guests into regular trigonal arrays.

tris (o-phenylenedioxy) cyclotriphosphazene

TPP


Input: Inclusion of molecular rotors with transversely dipolar rotators into TPP channels is followed by solid-state nuclear magnetic resonance, diifferential scanning calorimetry, X-ray diffraction, and dielectric spectroscopy.

TPP


Input: The more polar of the two rotors does not form an inclusion.


Input: The second rotor forms two different inclusions differing in crystallite size and the rotational barriers.


Input: Glycopolymers and glyco-nanoparticles in biomolecular recognition processes and vaccine development.


Input: With advances in polymerization techniques as well as selective chemical modification of carbohydrates, glycopolymers and glyco-nanoparticles are emerging as an important class of materials with tailored properties or novel nanotechnology-based platforms for a number of applications.

carbohydrates


Input: The field of the so-called glyco-nanotechnology is starting to show some promises for future clinical applications.


Input: Glyco-nanoparticles, due to their versatile nature, could offer a platform for the design of carbohydrate-based vaccines and possibly allow the development of new single-dose vaccines in disease areas of unmet need.

carbohydrate


Input: This paper surveys the emerging roles of carbohydrate-based polymeric and nanomaterials for biomolecular recognition processes and vaccine development.

carbohydrate


Input: Interactions between CYP2E1 and CYP2B4: effects on affinity for NADPH-cytochrome P450 reductase and substrate metabolism.

NADPH


Input: Studies in microsomal and reconstituted systems have shown that the presence of one cytochrome P450 isoform can significantly influence the catalytic activity of another isoform.


Input: In this study, we assessed whether CYP2E1 could influence the catalytic activity of CYP2B4 under steady-state turnover conditions.


Input: The results show that CYP2E1 inhibits CYP2B4-mediated metabolism of benzphetamine (BNZ) with a K (i) of 0. 04 micro M.

benzphetamine

BNZ


Input: However, CYP2B4 is not an inhibitor of CYP2E1-mediated p-nitrophenol hydroxylation.

p-nitrophenol


Input: When these inhibition studies were performed with the artificial oxidant tert-butyl hydroperoxide, CYP2E1 did not significantly inhibit CYP2B4 activity.

tert-butyl hydroperoxide


Input: Determinations of the apparent K (M) and k (cat) of CYP2B4 for CPR in the presence of increasing concentrations of CYP2E1 revealed a mixed inhibition of CYP2B4 by CYP2E1.


Input: At low concentrations of CYP2E1, the apparent K (M) of CYP2B4 for CPR increased up to 23-fold with virtually no change in the k (cat) for the reaction, however, at higher concentrations of CYP2E1, the apparent K (M) of CYP2B4 for CPR decreased to levels similar to those observed in the absence of CYP2E1 and the k (cat) also decreased by 11-fold.


Input: Additionally, CYP2E1 increased the apparent K (M) of CYP2B4 for BNZ by 8-fold and the apparent K (M) did not decrease to its original value when saturating concentrations of CPR were used.

BNZ