Input: Chromatin immunoprecipitation (ChIP) and nuclease hypersensitivity assays showed that Chd4, interacting with Hdac1/2, cooperates with its related proteins Kap1 and Cbx1 to bind at-207/-148 of the Sox9 promoter.


Input: We also provided evidence that let-7a targets the 3' UTR of Chd4 to promote chondrogenesis of MEFs.


Input: Together, our findings indicate that BMP-2 induced the upregulation of let-7a, targeting Chd4 and positively controlling the chondrogenic differentiation of MEFs.


Input: These findings illustrate epigenetic regulation of the chondrogenic differentiation process and also expand the understanding of the involved intracellular mechanisms.


Input: (c) 2013 American Society for Bone and Mineral Research.


Input: Positive Regulation of Insulin Signaling by Neuraminidase 1.


Input: Neuraminidases (sialidases) catalyze the removal of sialic acid residues from sialylated glycoconjugates.

sialic acid


Input: We now report that mammalian neuraminidase 1 (Neu1), in addition to its catabolic function in lysosomes, is transported to the cell surface where it is involved in regulation of insulin signaling.


Input: Insulin binding to its receptor rapidly induces interaction of the receptor with Neu1, which hydrolyzes sialic acid residues in the glycan chains of the receptor and, consequently, induces its activation.

sialic acid


Input: Cells from sialidosis patients with a genetic deficiency of Neu1 show impairment of insulin-induced phosphorylation of downstream protein kinase AKT, while treatment of these cells with purified Neu1 restores signaling.


Input: Genetically-modified mice with ~ 10% of the normal Neu1 activity exposed to a high-fat diet develop hyperglycemia and insulin resistance twice as fast as their wild type counterparts.


Input: Together, these studies identify Neu1 as a novel component of the signaling pathways of energy metabolism and glucose uptake.

glucose


Input: Specific Transport of Target Molecules by Motor Proteins in Microfluidic Channels.


Input: Direct transport powered by motor proteins can alleviate the challenges presented by miniaturization of microfluidic systems.


Input: There have been several recent attempts to build motor-protein-driven transport systems based on simple capturing or transport mechanisms.


Input: However, to achieve a multifunctional device for practical applications, a more complex sorting/transport system should be realized.


Input: Herein, the proof of concept of a sorting device employing selective capture of distinct target molecules and transport of the sorted molecules to different predefined directions is presented.


Input: By combining the bottom-up functionality of biological systems with the top-down handling capabilities of micro-electromechanical systems technology, highly selective molecular recognition and motor-protein-based transport is integrated in a microfluidic channel network.


Input: Peak forces in high-resolution imaging of soft matter in liquid.


Input: The maximum force exerted by the tip of a force microscope on the sample surface is a critical factor that determines the spatial resolution and the degree of invasiveness of the measurement, in particular, on soft materials.


Input: Here we determine the conditions needed to image soft matter in the 30-500 MPa range while applying very small forces.


Input: Imaging at sub-50 pN in the elastic regime can only be achieved under strict conditions in terms of force constant values (below 0. 1 N/m) and free amplitudes (below 2 nm).


Input: The peak force depends on the operational parameters, probe properties, the elastic and/or viscoelastic response of the sample, and the contact mechanics model.


Input: Images of heterogeneous samples are never taken at a constant peak force.


Input: Under the same operational conditions, smaller forces are obtained on the more compliant materials.


Input: We also find that the viscoelastic response reduces the peak force with respect to the purely elastic regions.


Input: Our findings are summarized in three-dimensional maps that contain the operational conditions for imaging at low forces.


Input: Potent fibrinolysis inhibitor discovered by shape and electrostatic complementarity to the drug tranexamic Acid.

tranexamic Acid


Input: Protein-protein interfaces provide an important class of drug targets currently receiving increased attention.


Input: The typical design strategy to inhibit protein-protein interactions usually involves large molecules such as peptides and macrocycles.


Input: One exception is tranexamic acid (TXA), which, as a lysine mimetic, inhibits binding of plasminogen to fibrin.

tranexamic acid

TXA

lysine


Input: However, the daily dose of TXA is high due to its modest potency and pharmacokinetic properties.

TXA


Input: In this study, we report a computational approach, where the focus was on finding electrostatic potential similarities to TXA.

TXA


Input: Coupling this computational technique with a high-quality low-throughput screen identified 5-(4-piperidyl)-3-isoxazolol (4-PIOL) as a potent plasminogen binding inhibitor with the potential for the treatment of various bleeding disorders.


Input: Remarkably, 4-PIOL was found to be more than four times as potent as the drug TXA.

TXA


Input: Scutellarin from Scutellaria baicalensis Suppresses Adipogenesis by Upregulating PPAR alpha in 3T3-L1 Cells.

Scutellarin


Input: Adipocyte dysfunction is a major cause of obesity, which is associated strongly with many disorders including psychological and medical morbidities, metabolic abnormalities, and cardiovascular diseases as well as a series of cancers.


Input: This study investigated the antiadipogenic activity of scutellarin (1) in 3T3-L1 preadipocytes as well as the underlying molecular mechanisms.

scutellarin


Input: It was observed that 1 reduced adipocyte differentiation of 3T3-L1 cells potently, as evidenced by a decrease in cellular lipid accumulation.


Input: At the molecular level, mRNA expression of the master adipogenic transcription factors, PPAR gamma and C/EBP alpha, was decreased markedly.


Input: However, mRNA levels of C/EBP beta, the upstream regulator of PPAR gamma and C/EBP alpha, were not decreased by 1.


Input: Moreover, a dose-dependent upregulation of PPAR alpha was observed for 1.


Input: Computational modeling indicated that 1 can bind to PPAR alpha, gamma, and delta each in a distinct manner, while it can activate PPAR alpha only by forming a hydrogen bond with Y464, thus stabilizing the AF-2 helix and activating PPAR alpha.

hydrogen


Input: Therefore, these results suggest that 1, a major component of Scutellaria baicalensis, attenuates fat cell differentiation by upregulating PPAR alpha as well as downregulating the expression of PPAR gamma and C/EBP alpha, thus showing therapeutic potential for obesity-related diseases.


Input: A Redox Responsive, Fluorescent Supramolecular Metallohydrogel Consists of Nanofibers with Single-Molecule Width.


Input: The integration of a tripeptide derivative, which is a versatile self-assembly motif, with a ruthenium (II) tris (bipyridine) complex affords the first supramolecular metallo-hydrogelator that not only self assembles in water to form a hydrogel but also exhibits gel-sol transition upon oxidation of the metal center.

tripeptide

ruthenium (II) tris (bipyridine)


Input: Surprisingly, the incorporation of the metal complex in the hydrogelator results in the nanofibers, formed by the self-assembly of the hydrogelator in water, to have the width of a single molecule of the hydrogelator.


Input: These results illustrate that metal complexes, besides being able to impart rich optical, electronic, redox, or magnetic properties to supramolecular hydrogels, also offer a unique geometrical control to prearrange the self-assembly motif prior to self-assembling.


Input: The use of metal complexes to modulate the dimensionality of intermolecular interactions may also help elucidate the interactions of the molecular nanofibers with other molecules, thus facilitating the development of supramolecular hydrogel materials for a wide range of applications.


Input: Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors.


Input: Polo-like kinase-2 (Plk-2) is a potential therapeutic target for Parkinson' s disease and this Letter describes the SAR of a series of dihydropteridinone based Plk-2 inhibitors.

dihydropteridinone


Input: By optimizing both the N-8 substituent and the biaryl region of the inhibitors we obtained single digit nanomolar compounds such as 37 with excellent selectivity for Plk-2 over Plk-1.


Input: When dosed orally in rats, compound 37 demonstrated a 41-45% reduction of pS129-alpha-synuclein levels in the cerebral cortex.


Input: Phellinus linteus mushroom protects against tacrine-induced mitochondrial impairment and oxidative stress in HepG2 cells.

tacrine


Input: Tacrine (THA) was the first drug licensed for the treatment of Alzheimer' s disease.

Tacrine

THA


Input: Unfortunately, reversible hepatotoxicity is evident in about 30% of patients and limits its clinical use.


Input: The intracellular mechanisms have not yet been elucidated.


Input: Phellinus linteus (PL) is a mushroom that has long been used as a folk medicine.


Input: In our previous study, we found that PL could decrease the reactive oxygen species (ROS) formation in HepG2 cells.

oxygen


Input: Presently, protective effects of PL on tacrine-induced ROS formation and mitochondria dysfunction were evaluated.

tacrine


Input: The results showed that PL significantly reduced tacrine-induced ROS production, disruption of Delta Psi m, 8-OHdG formation in mitochondrial DNA, and cytotoxicity in HepG2 cells.

tacrine


Input: These data suggest that PL could attenuate the cytotoxicity and mitochondria dysfunction induced by tacrine in HepG2 cells.

tacrine


Input: The protection is probably mediated by an antioxidant protective mechanism.


Input: Consumption of PL may be a plausible way to prevent tacrine-induced hepatotoxicity.

tacrine


Input: System-wide hybrid MPC-PID control of a continuous pharmaceutical tablet manufacturing process via direct compaction.


Input: The next generation of QbD based pharmaceutical products will be manufactured through continuous processing.


Input: This will allow the integration of online/inline monitoring tools, coupled with an efficient advanced model-based feedback control systems, to achieve precise control of process variables, so that the predefined product quality can be achieved consistently.


Input: The direct compaction process considered in this study is highly interactive and involves time delays for a number of process variables due to sensor placements, process equipment dimensions, and the flow characteristics of the solid material.


Input: A simple feedback regulatory control system (e. g., PI (D)) by itself may not be sufficient to achieve the tight process control that is mandated by regulatory authorities.


Input: The process presented herein comprises of coupled dynamics involving slow and fast responses, indicating the requirement of a hybrid control scheme such as a combined MPC-PID control scheme.


Input: In this manuscript, an efficient system-wide hybrid control strategy for an integrated continuous pharmaceutical tablet manufacturing process via direct compaction has been designed.


Input: The designed control system is a hybrid scheme of MPC-PID control.


Input: An effective controller parameter tuning strategy involving an ITAE method coupled with an optimization strategy has been used for tuning of both MPC and PID parameters.


Input: The designed hybrid control system has been implemented in a first-principles model-based flowsheet that was simulated in gPROMS (Process System Enterprise).


Input: Results demonstrate enhanced performance of critical quality attributes (CQAs) under the hybrid control scheme compared to only PID or MPC control schemes, illustrating the potential of a hybrid control scheme in improving pharmaceutical manufacturing operations.


Input: Biodegradation and heart retention of polymeric microparticles in a rat model of myocardial ischemia.


Input: Poly-lactide-co-glycolide (PLGA) microparticles emerged as one of the most promising strategies to achieve site-specific drug delivery.

Poly-lactide-co-glycolide

PLGA


Input: Although these microparticles have been demonstrated to be effective in several wound healing models, their potential in cardiac regeneration has not yet been fully assessed.


Input: The present work sought to explore PLGA microparticles as cardiac drug delivery systems.

PLGA


Input: PLGA microparticles were prepared by Total Recirculation One-Machine System (TROMS) after the formation of a multiple emulsion.

PLGA


Input: Microparticles of different size were prepared and characterized to select the most suitable size for intramyocardial administration.


Input: Next, the potential of PLGA microparticles for administration in the heart was assessed in a MI rat model.

PLGA


Input: Particle biodegradation over time and myocardial tissue reaction were studied by routine staining and confocal microscopy.


Input: Results showed that microparticles with a diameter of 5 mu m were the most compatible with intramyocardial administration in terms of injectability through a 29-gauge needle and tissue response.


Input: Particles were present in the heart tissue for up to 3months post-implantation and no particle migration toward other solid organs was observed, demonstrating good myocardial retention.


Input: CD68 immunolabeling revealed 31%, 47% and below 4% microparticle uptake by macrophages 1week, 1month, and 3months after injection, respectively (P < 0. 001).


Input: Taken together, these findings support the feasibility of the developed PLGA microparticles as vehicles for delivering growth factors in the infarcted myocardium.

PLGA


Input: Inhibition of the renin-angiotensin system for lowering coronary artery disease risk.


Input: The renin-angiotensin system when activated exerts proliferative and pro-inflammatory actions and thereby contributes to progression of atherosclerosis, including that occurring in the coronary arteries.


Input: It thus contributes as well to coronary artery disease (CAD).


Input: Several clinical trials have examined effects of renin-angiotensin system inhibition for primary and secondary prevention of coronary heart disease.


Input: These include important trials such as HOPE, EUROPA and PEACE using angiotensin converting enzyme inhibitors, VALIANT, OPTIMAAL and TRANSCEND using angiotensin receptor blockers, and the ongoing TOPCAT study in patients with preserved ejection fraction heart failure, many of who also have coronary artery disease.


Input: Data are unavailable as yet of effects of either direct renin inhibitors or the new angiotensin receptor/neprilysin inhibitor agents.


Input: Today, inhibition of the renin-angiotensin system is standard-of-care therapy for lowering cardiovascular risk in secondary prevention in high cardiovascular risk subjects.


Input: GLPG0492, a novel selective androgen receptor modulator, improves muscle performance in the exercised-mdx mouse model of muscular dystrophy.

androgen


Input: Anabolic drugs may counteract muscle wasting and dysfunction in Duchenne muscular dystrophy (DMD); however, steroids have unwanted side effects.

steroids


Input: We focused on GLPG0492, a new non-steroidal selective androgen receptor modulator that is currently under development for musculo-skeletal diseases such as sarcopenia and cachexia.

androgen


Input: GLPG0492 was tested in the exercised mdx mouse model of DMD in a 4-week trial at a single high dose (30mg/kg, 6 day/week s. c.), and the results were compared with those from the administration of alpha-methylprednisolone (PDN; 1mg/kg, i. p.) and nandrolone (NAND, 5mg/kg, s. c.).

alpha-methylprednisolone

PDN

nandrolone

NAND


Input: This assessment was followed by a 12-week dose-dependence study (0. 3-30mg/kg s. c.).


Input: The outcomes were evaluated in vivo and ex vivo on functional, histological and biochemical parameters.


Input: Similar to PDN and NAND, GLPG0492 significantly increased mouse strength.

PDN

NAND


Input: In acute exhaustion tests, a surrogate of the 6-min walking test used in DMD patients, GLPG0492 preserved running performance, whereas vehicle-or comparator-treated animals showed a significant increase in fatigue (30-50%).


Input: Ex vivo, all drugs resulted in a modest but significant increase of diaphragm force.


Input: In parallel, a decrease in the non-muscle area and markers of fibrosis was observed in GLPG0492-and NAND-treated mice.

NAND


Input: The drugs exerted minor effects on limb muscles; however, electrophysiological biomarkers were ameliorated in extensor digitorum longus muscle.


Input: The longer dose-dependence study confirmed the effect on mdx mouse strength and resistance to fatigue and demonstrated the efficacy of lower drug doses on in vivo and ex vivo functional parameters.


Input: These results support the interest of further studies of GLPG0492 as a potential treatment for DMD.


Input: Cytoprotective dibenzoylmethane derivatives protect cells from oxidative stress-induced necrotic cell death.

dibenzoylmethane


Input: Screening of a small in-house library of 1863 compounds identified 29 compounds that protected Jurkat cells from hydrogen peroxide-induced cytotoxicity.

hydrogen peroxide


Input: From the cytoprotective compounds eleven proved to possess antioxidant activity (ABTS radical scavenger effect) and two were found to inhibit poly (ADP-ribosyl) ation (PARylation), a cytotoxic pathway operating in severely injured cells.

ABTS

poly (ADP-ribosyl)


Input: Four cytoprotective dibenzoylmethane (DBM) derivatives were investigated in more detail as they did not scavenge hydrogen peroxide nor did they inhibit PARylation.

dibenzoylmethane

DBM

hydrogen peroxide


Input: These compounds protected cells from necrotic cell death while caspase activation, a parameter of apoptotic cell death was not affected.


Input: Hydrogen peroxide activated extracellular signal regulated kinase (ERK1/2) and p38 MAP kinases but not c-Jun N-terminal kinase (JNK).

Hydrogen peroxide

N


Input: The cytoprotective DBMs suppressed the activation of Erk1/2 but not that of p38.

DBMs


Input: Cytoprotection was confirmed in another cell type (A549 lung epithelial cells), indicating that the cytoprotective effect is not cell type specific.


Input: In conclusion we identified DBM analogs as a novel class of cytoprotective compounds inhibiting ERK1/2 kinase and protecting from necrotic cell death by a mechanism independent of poly (ADP-ribose) polymerase inhibition.

DBM

poly (ADP-ribose)


Input: Avermectin induces P-glycoprotein expression in S2 cells via the calcium/calmodulin/NF-kappa B pathway.

Avermectin

calcium


Input: Avermectin (AVM) is a macrocyclic lactone agent widely used as a nematicide, acaricide and insecticide in veterinary medicine and plant protection.

Avermectin

AVM

lactone


Input: P-glycoprotein (P-gp) is an ATP-dependent drug efflux pump for xenobiotic compounds, and is involved in multidrug resistance.

ATP


Input: To understand the development of AVM resistance in invertebrates, we investigated the mechanisms by which AVM affected P-gp expression in Drosophila S2 cells.

AVM

AVM


Input: We found that AVM induced upregulation of P-gp protein expression, increased P-gp ATPase activity and enhanced cellular efflux of the P-gp substrate rhodamine 123 from cells.

AVM

rhodamine 123


Input: Furthermore, we observed that AVM-induced expression of P-gp was due to elevation of intracellular calcium concentration ([Ca (2 +)] i).

AVM

calcium

Ca (2 +)


Input: This occurred both directly, by activating calcium ion channels, and indirectly, by activating chloride ion channels.

calcium

chloride


Input: These results are supported by our observations that verapamil, a Ca (2 +) channel blocker, and niflumic acid, a chloride channel antagonist, significantly attenuated AVM-induced [Ca (2 +)] i elevation, thereby reducing P-gp expression.

verapamil

Ca (2 +)

niflumic acid

chloride

AVM

Ca (2 +)


Input: Inhibition of P-gp with anti-P-gp antibody or cyclosporine A (a P-gp inhibitor) reduced the AVM-induced elevation of [Ca (2 +)] i, implying that P-gp and [Ca (2 +)] i regulate each other.

cyclosporine A

AVM

Ca (2 +)

Ca (2 +)


Input: Finally, we found that trifluoperazine, a calmodulin inhibitor, and pyrrolidine dithiocarbamic acid, an NF-kappa B inhibitor, attenuated the AVM-induced expression of P-gp, suggesting that AVM induces P-gp protein expression via the calmodulin/Relish (NF-kappa B) signaling pathway.

trifluoperazine

pyrrolidine dithiocarbamic acid

AVM

AVM


Input: Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells.

gefitinib


Input: Gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), has been used to treat numerous cancers; however, evidence has shown that cancer cells can become resistant to gefitinib during therapy.

Gefitinib

tyrosine

gefitinib


Input: Here, we report a human proto-oncogene, securin, which displays resistance to death in cancer cells.


Input: Gefitinib treatment decreases securin levels at the protein level by inducing protein instability but did not affect on the securin gene expression.

Gefitinib


Input: Treatment with gefitinib induced cytotoxicity in various human cancer cell types, including RKO (colon cancer), A549 (lung cancer), BFTC905 (bladder cancer), MCF7 (breast cancer) and A375 (skin cancer).

gefitinib


Input: BFTC905 and A549 cells expressed relatively high levels of the phosphorylated and total EGFR proteins; however, A375, MCF7 and RKO cells did not markedly express these proteins.


Input: Moreover, following treatment with gefitinib, the securin-wild type cancer cells were more resistant to apoptotic induction than the securin-null cancer cells.

gefitinib


Input: Surprisingly, both the securin-wild type and securin-null cancer cells expressed the EGFR protein at similar levels.


Input: Treatment with gefitinib induced mitochondrial dysfunction, cytochrome c release, caspase-3 activation and poly (ADP-ribose) polymerase protein cleavage, indicating that apoptosis occurred in these cancer cells.

gefitinib

poly (ADP-ribose)


Input: The transfection of a GPF-securin expression vector increased both the proliferation rates and resistance to gefitinib-induced death in these cancer cells.

gefitinib


Input: Taken together, these findings demonstrate that the presence of securin promotes resistance to gefitinib-induced apoptosis via an EGFR-independent pathway in human cancer cells.

gefitinib


Input: Copper induces apoptotic cell death through reactive oxygen species-triggered oxidative stress in the intertidal copepod Tigriopus japonicus.

Copper

oxygen


Input: The copepod, Tigriopus japonicus is an important model for toxicity testing.


Input: However, no attempt has been made in analyzing the effect of toxicants at the level of the ROS-mediated signal transduction pathway.


Input: To understand copper-induced cytotoxicity at the molecular level, we employed several cellular and biochemical assays after exposure to copper, and found a significant induction of enzyme activities of antioxidant proteins with increased intracellular reactive oxygen species (ROS) as well as an increase of TUNEL-positive cells, but a decrease of BrdU-positive cells.

copper

copper

oxygen

BrdU


Input: In addition, several important genes such as p38 MAPK, antioxidant-related genes, Hsps, and apoptosis-related genes were significantly modulated by copper exposure.

copper


Input: Taken together, we suggest that copper-induced cytotoxicity is mediated by the formation of intracellular ROS and oxidative stress in T. japonicus.

copper


Input: Whole body biochemical assays such as TUNEL-and BrdU-assay will provide a better understanding of cellular responses such as apoptosis and cell death upon cytotoxic exposure of copper in T. japonicus.

BrdU

copper


Input: Efficient synthesis of new (R)-2-amino-1-butanol derived ureas, thioureas and acylthioureas and in vitro evaluation of their antimycobacterial activity.

ureas

thioureas

acylthioureas


Input: The synthesis of 22 structurally diverse urea, thiourea and acylthiourea derivatives containing the (R)-2-amino-1-butanol motif has been performed.

urea

thiourea

acylthiourea


Input: The evaluation of their in vitro activity against Mycobacterium tuberculosis (H37Rv and strain 43) showed promising results in the case of the acylthiourea derivatives (MIC range 0. 36-7. 46 mu M for H37Rv strain).

acylthiourea


Input: The Crystal Structure of the Lumenal Domain of Erv41p, a Protein Involved in Transport between the Endoplasmic Reticulum and Golgi Apparatus.


Input: Erv41p is a conserved integral membrane protein that is known to play a role in transport between the endoplasmic reticulum and Golgi apparatus, part of the early secretory pathway of eukaryotes.


Input: However, the exact function of the protein is not known, and it shares very low sequence identity with proteins of known structure or function.


Input: Here we present the structure of the full lumenal domain of Erv41p from Saccharomyces cerevisiae, determined by X-ray crystallography to a resolution of 2. 0 A.


Input: The structure reveals the protein to be composed predominantly of two large beta-sheets that form a twisted beta-sandwich.


Input: Comparison to structures in the Protein Data Bank shows that the Erv41p lumenal domain displays only limited similarity to beta-sandwich domains of other proteins.


Input: Analysis of the surface properties of the protein identifies an extensive patch of negative electrostatic potential on the exposed surface of one of the beta-sheets, which likely forms a binding site for a ligand or interaction partner.


Input: A predominantly hydrophobic region close to the membrane interface is identified as a likely site for protein-protein interaction.


Input: This structure, the first of Erv41p or any of its homologues, provides a new starting point for studies of the roles of Erv41p and its interaction partners in the eukaryotic secretory pathway.


Input: Placental ABC transporters, cellular toxicity and stress in pregnancy.


Input: The human placenta, in addition to its roles as a nutrient transfer and endocrine organ, functions as a selective barrier to protect the fetus against the harmful effects of exogenous and endogenous toxins.


Input: Members of the ATP-binding cassette (ABC) family of transport proteins limit the entry of xenobiotics into the fetal circulation via vectorial efflux from the placenta to the maternal circulation.


Input: Several members of the ABC family, including proteins from the ABCA, ABCB, ABCC and ABCG subfamilies, have been shown to be functional in the placenta with clinically significant roles in xenobiotic efflux.


Input: However, recent findings suggest that these transporters also protect placental tissue by preventing the cellular accumulation of cytotoxic compounds such as lipids, sterols and their derivatives.


Input: Such protective functions are likely to be particularly important in pregnancies complicated by inflammatory or oxidative stress, where the generation of toxic metabolites is enhanced.


Input: For example, ABC transporters have been shown to protect against the harmful effects of hypoxia and oxidative stress through increased expression and efflux of oxysterols and glutathione conjugated xenobiotics.

oxysterols

glutathione


Input: However, this protective capacity may be diminished in response to the same stressors.


Input: Several studies in primary human trophoblast cells and animal models have demonstrated decreased expression and activity of placental ABC transporters with inflammatory, oxidative or metabolic stress.


Input: Several clinical studies in pregnancies complicated by inflammatory conditions such as preeclampsia and gestational diabetes support these findings, although further studies are required to determine the clinical relevance of the relationships between placental ABC transporter expression and activity, and placental function in stressed pregnancies.


Input: Such studies are necessary to fully understand the consequences of pregnancy disorders on placental function and viability in order to optimise pregnancy care and maximise fetal growth and health.


Input: Thermoreversible in situ gelling poloxamer-based systems with chitosan nanocomplexes for prolonged subcutaneous delivery of heparin: Design and in vitro evaluation.


Input: In situ forming systems including thermoreversible hydrogels, which undergo sol-gel transition upon an increase in temperature have been used for various biomedical applications.


Input: Heparins are the standard of anticoagulation in the prophylaxis and treatment of deep vein thrombosis and pulmonary embolism.


Input: Both conditions require long-lasting treatment with frequent subcutaneous administrations of heparin.


Input: The objective of this study was to prepare and evaluate in situ forming gel systems designed by combination of two poloxamers (P407 and P188) and hydroxypropylmethylcellulose (HPMC) for prolonged release of heparin.

poloxamers (P407 and P188)


Input: Thermoreversible hydrogels were prepared with heparin solution and dispersion of heparin/chitosan nanocomplexes.


Input: Nanocomplexes formed by self-assembly of heparin with chitosan at various mass ratios were thoroughly characterized.


Input: A heparin/chitosan mass ratio of 1: 1 with pH 5. 20 was the most appropriate for preparation of small, homogenous and stable nanocomplexes (mean diameter 123nm; polydispersity index 0. 22 and zeta potential + 35. 5mV).


Input: Thermoreversible hydrogels were evaluated by gelation temperature, viscosity over the temperature range 20-40 degrees C, rate of hydrogel dissolution, and heparin release in vitro.


Input: The addition of P188 to P407 gel formulations resulted in an increase in gelation temperature, decrease in viscosity at room temperature and faster gel dissolution.


Input: The opposite effects were observed with formulations containing HPMC which demonstrated 18-day-long gel dissolution and complete heparin release in 9days from gels containing heparin solution.


Input: Considerable prolongation of heparin release was achieved with incorporation of heparin/chitosan nanocomplexes into the gelling systems.


Input: It may be concluded that with poloxamer mixtures at specific concentrations, addition of HPMC and use of heparin/chitosan nanocomplexes dispersions, thermoreversible formulations for prolonged subcutaneous release of heparin are feasible.


Input: Polymer coated liposomes for dental drug delivery-Interactions with parotid saliva and dental enamel.


Input: The interactions between pectin coated liposomes and parotid saliva and dental enamel were studied to investigate their potential to mimic the protective biofilm formed naturally on tooth surfaces.


Input: Different pectin coated liposomes with respect to pectin type (LM-, HM-and AM-pectin) and concentration (0. 05% and 0. 2%) were prepared.


Input: Interactions between the pectin coated liposomes and parotid saliva were studied by turbidimetry and imaging by atomic force microscopy.


Input: The liposomes were adsorbed to hydroxyapatite (HA) and human dental enamel using phosphate buffer and parotid saliva as adsorption media.

hydroxyapatite

phosphate


Input: A continuous flow was imposed on the enamel surfaces for various time intervals to examine their retention on the dental enamel.


Input: The results were compared to uncoated, charged liposomes.


Input: No aggregation tendencies for the pectin coated liposomes and parotid saliva were revealed.


Input: This makes them promising as drug delivery systems to be used in the oral cavity.


Input: In phosphate buffer the adsorption to HA of pectin coated liposomes was significantly lower than the negative liposomes.

phosphate


Input: The difference diminished in parotid saliva.


Input: Positive liposomes adsorbed better to the dental enamel than the pectin coated liposomes.


Input: However, when subjected to flow for 1h, no significant differences in the retention levels on the enamel were found between the formulations.


Input: For all formulations, more than 40% of the liposomes still remained on the enamel surfaces.


Input: At time point 20min the retention of HM-pectin coated and positive liposomes were significantly higher.


Input: It was concluded that pectin coated liposomes can adsorb to HA as well as to the dental enamel.


Input: Their ability to retain on the enamel surfaces promotes the concept of using them as protective structures for the teeth.


Input: Effect of quercetin-rich onion peel extracts on arterial thrombosis in rats.

quercetin


Input: The aim of this study was to examine whether oral supplementation of quercetin-rich onion peel extract (OPE) influences blood coagulation and arterial thrombosis in Sprague-Dawley (SD) rats.

quercetin


Input: 24 male rats, 5weeks old, were divided into three groups with different diets (C: control, 2mg OPE: chow diet with 2mg OPE supplementation, 10mg OPE: chow diet with 10mg OPE supplementation) for 6weeks.


Input: Blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet aggregation were examined.


Input: The OPE did not affect blood cholesterol levels but significantly decreased blood triglyceride and glucose levels.

cholesterol

triglyceride

glucose


Input: PT, aPTT and platelet aggregation were not significantly different among all tested groups.


Input: However, in vivo arterial thrombosis was significantly delayed in groups that were fed 2mg and 10mg OPE diets compared to the control group.


Input: In addition, the OPE greatly diminished thrombin-induced expression of tissue factor in human umbilical vein endothelial cells (HUVECs), a coagulation initiator.


Input: In addition, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways activated by thrombin treatment were prevented by the OPE pre-treatment.

N


Input: These results indicate that OPE may have anti-thrombotic effects through restricting the induced expression of tissue factor via down-regulating mitogen-activated protein kinase (MAPK) activation upon coagulation stimulus, leading to the prolongation of time for arterial thrombosis.


Input: FGFR4 genetic polymorphisms determine the chemotherapy response of Chinese patients with non-small cell lung cancer.


Input: Aim: To investigate the relationship of fibroblast growth factor receptor 4 (FGFR4) gene polymorphisms with the response of Chinese patients with non-small cell lung cancer (NSCLC) to chemotherapy. Methods: A total of 629 patients with Stage III (A + B) or IV NSCLC, as well as 729 age-and gender-matched healthy controls were recruited.


Input: All the patients received platinum-based chemotherapy, and the therapeutic effects were evaluated.

platinum


Input: Three polymorphisms in the FGFR4 gene (rs351855G/A, rs145302848C/G, and rs147603016G/A) were genotyped, and the association between the 3 polymorphisms and the chemotherapy effect was analyzed using SPSS software, version 16. 0. Results: The genotype frequencies of rs145302848C/G and rs147603016G/A were not significantly different between NSCLC patients and healthy controls on one hand, and between the responders and non-responders to the chemotherapy on the other hand.


Input: The distribution of AA genotype and A-allele of rs351855G/A was significantly lower in NSCLC patients than in healthy controls.


Input: Using patients with the GG genotype as a reference, the AA carrier had a significantly reduced risk for the development of NSCLC after normalizing to age, sex and smoking habits.


Input: In NSCLC patients, this genotype occurred more frequently in the responders to the chemotherapy than in non-responders.


Input: The chance of being a responder was significantly increased with the AA genotype as compared to G genotype.


Input: The AA genotype of rs351855G/A had a better prognosis compared with GA and GG genotype carriers: the overall survival of patients with the AA genotype of rs351855G/A was significantly longer than those with the GG + GA genotype (21. 1 vs 16. 5 months). Conclusion: The rs351855G/A polymorphisms of FGFR4 gene can be used to predict the occurrence, chemotherapy response and prognosis of NSCLC.


Input: Amelioration of iron overload-induced liver toxicity by a potent antioxidant and iron chelator, Emblica officinalis Gaertn.

iron

iron


Input: In liver, the major site of iron storage, iron overload is associated with oxidative damage of protein, lipid, and DNA and causes protein oxidation, lipid peroxidation, and rupture of hepatocytes, leading to cell death.

iron

iron


Input: Serum ferritin and liver iron content are the main forecasters of moderate to severe iron overload in the liver.

iron

iron


Input: The sequels of excess iron deposition in the liver are fibrosis and enhanced levels of serum enzymes and bilirubin markers.

iron

bilirubin


Input: Emblica officinalis (EO) fruit extract was found efficient in lessening intraperitoneally injected iron dextran-induced liver toxicity in Swiss albino mice.

iron


Input: Mice administered with different doses of 70% methanol extract of EO (50, 100, and 200 mg kg (-1) body weight) showed significant decrease in liver iron, serum ferritin, and serum enzyme levels, along with the decrease in lipid peroxidation, protein oxidation, and collagen content.

methanol

iron


Input: The activity was further supported by its considerable iron chelation with half-maximal inhibitory concentration of 70. 24 +/- 2. 74 mu g ml (-1) and the protection on ferrous ion-mediated DNA breakdown with 50% protection ([P] 50) of 1. 04 +/- 0. 01 mu g ml (-1).

iron

ferrous


Input: Simultaneously, the extract effectively induced the antioxidant enzyme levels and also exhibited the potential activity of reductive release of ferritin iron.

iron


Input: These findings suggest that the EO extract may be used as a potent drug for the treatment of pathological sequences arisen in the iron overload-induced liver damage.

iron


Input: Ophthalmic findings in acute mercury poisoning in adults: A case series study.

mercury


Input: The aim of this study is to report ophthalmic findings of acute mercury poisoning in 48 adults referred to emergency department.

mercury


Input: Full ophthalmologic examination including the best corrected visual acuity, external eye examination, reaction to light, a slit-lamp examination, funduscopy, intraocular pressure measurements, and visual field (VF) and color vision (CV) tests were performed at the presentation and repeated after 6 months.


Input: The parametric values of VF test, the mean deviation (MD), and pattern standard deviation (PSD) were recorded in order to compare patients and the 30 healthy controls.


Input: The mean parameter of color confusion index in patients was found to be statistically different than controls (p < 0. 01).


Input: The MD and PSD in patients were different from controls statistically significant (p < 0. 01 and p < 0. 01, respectively).


Input: There was no correlation between the ocular findings and the urine and blood mercury levels.

mercury


Input: Methyl mercury, held in the school laboratory for experimental purpose, may be a source of poisoning.

Methyl mercury


Input: In this case series, we showed that acute exposure to mercury had hazardous effect on the visual system, especially CV and VF.

mercury


Input: We propose that emphasizing the public education on the potential hazards of mercury is crucial for preventive community health.

mercury


Input: dNTP-dependent conformational transitions in the fingers subdomain of Klentaq1 DNA polymerase: insights into the role of the " nucleotide binding " state.

dNTP

nucleotide


Input: DNA polymerases are responsible for the accurate replication of DNA.


Input: Kinetic, single molecule and X-ray studies show that multiple conformational states are important for DNA polymerase fidelity.


Input: Using high-precision FRET we show that Klentaq1 (the Klenow fragment of Thermus aquaticus DNA polymerase 1) is in equilibrium between three structurally distinct states.


Input: In the absence of nucleotide, the enzyme is mostly open, whereas in the presence of DNA and a correctly base-pairing dNTP it re-equilibrates to a closed state.

nucleotide

dNTP


Input: In the presence of a dNTP alone, with DNA and an incorrect dNTP, or in elevated MgCl2 concentrations, an intermediate state termed'' nucleotide binding'' state predominates.

dNTP

dNTP

nucleotide


Input: Photon distribution and hidden Markov analysis revealed fast dynamic and slow conformational processes occurring between all three states in a complex energy landscape suggesting a mechanism in which dNTP delivery is mediated by the'' nucleotide binding'' state: After nucleotide binding, correct dNTPs are transported to the closed state while incorrect dNTPs are delivered to the open state.

dNTP

nucleotide

nucleotide

dNTPs

dNTPs


Input: One-pot formation of multifunctional Pt-conducting polymer intercalated nanostructures.

Pt


Input: A novel multifunctional Pt nanoparticle @PPy nanofiber intercalated structure (Pt NP @PPy NF) has been synthesized facilely in one-pot.

Pt

PPy

Pt

PPy


Input: Pt NPs, with size and facet control, were nicely assembled and embedded into the polymer nanofiber network.

Pt


Input: Polyvinylpyrrolidone (PVP) was used during the synthesis process which would assist the self-assembly of the metal nanoparticles and polymer backbones into the intercalated structure.

Polyvinylpyrrolidone

PVP


Input: Space-confined distribution of the Pt NPs was achieved within the large dimension PPy nanofiber network, which could enhance the interfacial electron transfer process as well as diminish the catalyst deformation.

Pt

PPy


Input: The as-formed Pt NPs have a cluster-like structure and are mainly composed of 3. 5 nm primary Pt particles with (100) surface atoms.

Pt

Pt


Input: Enhanced electrocatalytic properties were shown by the Pt NP @PPy NF intercalated structure, with sufficiently high enzyme-less glucose biosensitivity and a long linear range from 1-30 mM (R = 0. 9995).

Pt

PPy

glucose


Input: High electrochemical cycling stability, chloride (Cl (-)) tolerance and good selectivity are also obtained for the Pt NP @PPy NF structure, as the electrode showed no obvious response to the common interfering agents, such as ascorbic acid (AA), uric acid (UA), and 4-acetamidophenol (AP).

chloride

Cl (-)

Pt

PPy

ascorbic acid

uric acid


Input: Furthermore, the Pt NP @PPy NF showed excellent catalytic activity for the methanol oxidation reaction (MOR) and oxygen reduction reaction (ORR), which displayed sufficient CO tolerance, and higher activity compared to the commercial Pt/C catalyst.

Pt

PPy

methanol

oxygen

CO

Pt

C


Input: This intrinsically multifunctional Pt NP @PPy NF with well-controlled Pt facets thus could serve as an advanced electrocatalyst for biosensing and fuel cell applications, surpassing the performance of many existing materials.

Pt

PPy

Pt


Input: Testicular Growth and Regression Are Not Correlated With Dio2 Expression in a Wild Male Songbird, Sturnus vulgaris, Exposed to Natural Changes in Photoperiod.


Input: Timing of seasonal breeding in birds and mammals is regulated by changing the day length and is dependent on the presence of thyroid hormones.


Input: A mechanism for thyroid-dependent control of seasonality has been proposed, in which exposure to long day lengths induces rapid local conversion of T4 to its bioactive form, T3, via the up-regulation of the enzyme type 2 iodothyronine deiodinase (Dio2) in the brain, and the down-regulation of Dio3 (which inactivates T3).


Input: Such changes were correlated with gonadotropin release and gonadal growth in quail.


Input: This mechanism was elucidated in a domesticated species (quail) exposed to unnatural acute changes in day length.


Input: Here we investigated the Dio2/Dio3 mechanism in a wild species, the European starling, under naturally changing day length.


Input: Although Dio2 expression varied seasonally, Dio3 did not.


Input: We found no correlation of Dio2 with photoperiod, seasonal regulation of GnRH, or testicular volume.


Input: The observed differences in data from starlings and quail could be a result of phylogeny, genetic drift from founder populations, or differences in reproductive seasonality in addition to or instead of arising from domestication or use of artificially changing photoperiods.


Input: Overall, the data indicate that in a wild species exposed to natural changes in day length, the current proposed mechanism for photoperiodic timing is less straightforward than is generally accepted and might not be as universally applicable as previously thought.


Input: Free fatty acids induce Lhb mRNA but suppress Fshb mRNA in pituitary L beta T2 gonadotropes and diet-induced obesity reduces FSH levels in male mice and disrupts the proestrus LH/FSH surge in female mice.

fatty acids


Input: Female obesity is associated with insulin resistance, hyperandrogenemia, and reproductive dysfunction.


Input: We hypothesized that elevated free fatty acids (FFAs) might directly modulate pituitary gonadotropin production.

fatty acids


Input: FFAs caused a time and dose-dependent increase in phosphorylation of the MAP kinases p38MAPK, JNK1/2 and ERK1/2 in L beta T2 gonadotrope cells.


Input: Furthermore, FFAs upregulated Lhb mRNA expression acutely, an effect that was blocked by JNK inhibition, but suppressed Fshb mRNA expression, an effect that was independent of MAPK signaling.


Input: FFAs enhanced the activation of the MAPKs in the presence of GnRH although the cotreatment did not alter Lhb induction, but did eliminate the GnRH induction of Fshb.

GnRH

GnRH


Input: FFAs also suppressed activin-induced Fshb expression.


Input: Knockdown experiments showed that the FFA effect on the inflammatory kinases p38MAPK and JNK and on Lhb, but not Fshb, mRNA expression is mediated via TLR2 and TLR4 and was mimicked by LPS stimulation.


Input: In vivo, male C57BL/6 mice on a high-fat diet (HFD) showed reduced FSH levels consistent with the suppression of Fshb seen in vitro.


Input: Histological analysis of the testes showed an increased number of abnormal seminiferous tubules.


Input: Female mice on HFD lacked the expected proestrus LH and FSH surge, exhibited an increase in the number of days at estrus and a reduced number of days at proestrus, and ovaries had significantly fewer corpora lutea.


Input: Taken together, our findings suggest that lipid excess can lead to reproductive defects in both male and female mice.


Input: Doped quantum dots for chemo/biosensing and bioimaging.


Input: Quantum dots (QDs) have received great interest for diverse applications due to their distinct advantages, such as narrow and symmetric emission with tunable colors, broad and strong absorption, reasonable stability, and solution processibility.


Input: Doped QDs not only potentially retain almost all of the above advantages, but also avoid the self-quenching problem due to their substantial ensemble Stokes shift.


Input: Two obvious advantages of doped QDs, especially doped ZnS QDs, over typical CdSe @ZnS and CdTe QDs are longer dopant emission lifetime and potentially lower cytotoxicity.

ZnS

CdSe

ZnS

CdTe


Input: The lifetime of dopant emission from transition-metal ion or lanthanide ion-doped QDs is generally longer than that of the bandgap or defect-related emission of host, and that of biological background fluorescence, providing great opportunities to eliminate background fluorescence for biosensing and bioimaging.

lanthanide


Input: For bioimaging applications, fluorescent dopants may mitigate toxicity problems by producing visible or infrared emission in nanocrystals made from less-harmful elements than those currently used.


Input: In this review, recent advances in utilizing doped QDs for chemo/biosensing and bioimaging are discussed, and the synthetic routes and optical properties of doped QDs that make them excellent probes for various strategies in chemo/biosensing and bioimaging are highlighted.


Input: Moreover, perspectives on future exploration of doped QDs for chemo/biosensing and bioimaging are also given.


Input: High-throughput identification of long-range regulatory elements and their target promoters in the human genome.


Input: Enhancer elements are essential for tissue-specific gene regulation during mammalian development.


Input: Although these regulatory elements are often distant from their target genes, they affect gene expression by recruiting transcription factors to specific promoter regions.


Input: Because of this long-range action, the annotation of enhancer element-target promoter pairs remains elusive.


Input: Here, we developed a novel analysis methodology that takes advantage of Hi-C data to comprehensively identify these interactions throughout the human genome.


Input: To do this, we used a geometric distribution-based model to identify DNA-DNA interaction hotspots that contact gene promoters with high confidence.


Input: We observed that these promoter-interacting hotspots significantly overlap with known enhancer-associated histone modifications and DNase I hypersensitive sites.


Input: Thus, we defined thousands of candidate enhancer elements by incorporating these features, and found that they have a significant propensity to be bound by p300, an enhancer binding transcription factor.


Input: Furthermore, we revealed that their target genes are significantly bound by RNA Polymerase II and demonstrate tissue-specific expression.


Input: Finally, we uncovered that these elements are generally found within 1 Mb of their targets, and often regulate multiple genes.


Input: In total, our study presents a novel high-throughput workflow for confident, genome-wide discovery of enhancer-target promoter pairs, which will significantly improve our understanding of these regulatory interactions.


Input: Modelling the surface free energy parameters of polyurethane coats-part 1.

polyurethane


Input: Solvent-based coats obtained from linear polyurethane elastomers.

polyurethane


Input: Polyurethane elastomers coating were synthesised by using typical diisocyanates, polyether and polyester polyols and HO-tertiary amines or diols as a chain extenders.

Polyurethane

diisocyanates

polyether

polyester polyols

HO

tertiary amines

diols


Input: Mole fractions of structural fragments (kappa exp) responsible for the polar interactions within polyurethane chains were calculated by (1) H NMR method.

polyurethane

(1) H


Input: Obtained results were confronted with the analogous parameter values (kappa theor) calculated on the basis of process stoichiometry, considering the stage of the production of isocyanate prepolymers and reaction of their extension for polyurethanes.

isocyanate

polyurethanes


Input: Trials of linear correlation between the kappa exp parameters and surface free energy (SFE) values of investigated coatings were presented.


Input: SFE values were determined by Owens-Wendt method, using contact angles measured with the goniometric method.


Input: Based on achieved results, another empirical models, allowing for prediction the influence of the kind of polyurethane raw materials on SFE values of received coatings were determined.

polyurethane


Input: It was found that it is possible to regulate the SFE in the range millijoules per cubic metre by the selection of appropriate substrates.


Input: It has been found that use of 2, 2, 3, 3-tetrafluoro-1, 4-butanediol as a fluorinated extender of prepolymer chains is essential to obtain coatings with increased hydrophobicity, applied among others as biomaterials-next to diphenylmethane diisocyanate and polyoxyethylene glycol.

2, 2, 3, 3-tetrafluoro-1, 4-butanediol

diphenylmethane diisocyanate

polyoxyethylene glycol


Input: Biocomposites of pHEMA with HA/beta-TCP (60/40) for bone tissue engineering: Swelling, hydrolytic degradation, and in vitro behavior.

pHEMA

beta-TCP


Input: The field of bone and cartilage tissue engineering has a pressing need for novel, biocompatible, biodegradable biocomposites comprising polymers with bioceramics or bioglasses to meet numerous requirements for these applications.


Input: We created hydrolytically degradable hydrogel/bioceramic biocomposites, comprising poly (2-hydroxyethyl methacrylate) (pHEMA) hydrogels and 50 wt% biphasic hydroxyapatite/beta-tricalcium phosphate (60/40) through in situ polymerization.

poly (2-hydroxyethyl methacrylate)

pHEMA

hydroxyapatite

beta-tricalcium phosphate


Input: The hydrolytic degradation starts with hydrolysis of the cross-linker, N, O-dimethacryloyl hydroxylamine, which was synthesized in house.

N, O-dimethacryloyl hydroxylamine


Input: Swelling and degradation were examined in details at a phosphate buffered saline solution at 37 degrees C over a 12-week period of time.

phosphate


Input: To vary degradability, a co-monomer, acrylic acid (AA) or 2-hydroxypropyl methacrylamide (HPMA), was introduced, coupled with altering the concentration of the cross-linker and of the bioceramic.

acrylic acid

2-hydroxypropyl methacrylamide

HPMA


Input: The co-monomer HPMA was found to be more effective than AA in enhancing degradation, though AA led to greater swelling ratios.

HPMA


Input: 33% of weight loss was achieved in some of the biocomposites containing HPMA.

HPMA


Input: Porous structures were developed during swelling and degradation in biocomposites with AA but not in those containing HPMA, suggesting different degradation mechanisms: bulk erosion vs. bulk degradation.

HPMA


Input: Good biocompatibility, as evidenced by attachment and proliferation of mouse-derived osteoblast precursor cells from the MC3T3-E1 lineage, was observed on these biomaterials, regardless of the type of the co-monomer.


Input: The rationale and approaches employed here open up new opportunities for creating novel, complex organic-inorganic biomaterials in orthopedic tissue engineering.


Input: Use of magnetic forces to promote stem cell aggregation during differentiation, and cartilage tissue modeling.


Input: Magnetic forces induce cell condensation necessary for stem cell differentiation into cartilage and elicit the formation of a tissue-like structure: Magnetically driven fusion of aggregates assembled by micromagnets results in the formation of a continuous tissue layer containing abundant cartilage matrix.


Input: Nicotinic Acid and Nicotinamide: A Review of Their Use for Hyperphosphatemia in Dialysis Patients.

Nicotinic Acid

Nicotinamide


Input: Phosphate binders have traditionally been used to treat hyperphosphatemia, a common complication in patients with end stage renal disease (ESRD).

Phosphate


Input: New evidence suggests that nicotinic acid and its metabolites may effectively decrease phosphorus absorption in the gastrointestinal tract, thereby reducing serum phosphorus concentrations.

nicotinic acid

phosphorus

phosphorus


Input: We conducted a literature search to identify studies of patients with ESRD on dialysis that evaluated the role of niacin and related compounds in decreasing serum phosphorus levels.

niacin

phosphorus


Input: We searched PubMed using the search terms niacin, nicotinic acid, niacinamide, nicotinamide and hyperphosphatemia.

niacin

nicotinic acid

niacinamide

nicotinamide


Input: Limits were set to include only those articles published since 2002, conducted in human subjects, and written in the English language.


Input: Review articles captured through this process were mined for references to other primary literature that may not have been returned through the initial search.


Input: All studies were included if they met the search criteria and were conducted in patients with ESRD who received either hemodialysis or peritoneal dialysis.


Input: To identify current, ongoing studies, another search was conducted through clinicaltrials. gov.


Input: Among the seven studies that met our exclusion criteria, three used nicotinic acid as the therapeutic intervention and four used nicotinamide.

nicotinic acid

nicotinamide


Input: Both nicotinic acid and nicotinamide were effective in significantly reducing serum phosphorus concentrations in patients with ESRD on either hemodialysis or peritoneal dialysis.

nicotinic acid

nicotinamide

phosphorus


Input: Additional, large-scale studies that assess the appropriate dose as well as long-term safety and efficacy are recommended before clinicians can confirm their place in therapy.


Input: Multiple Phytoestrogens Inhibit Cell Growth and Confer Cytoprotection By Inducing Manganese Superoxide Dismutase Expression.

Manganese Superoxide


Input: Phytoestrogens are of interest because of their reported beneficial effects on many human maladies including cancer, neurodegeneration, cardiovascular disease and diabetes.


Input: As data on phytoestrogens continues to accumulate, it is clear that there is significant overlap in the cellular effects elicited by these various compounds.


Input: Here, we show that one mechanism by which a number of phytoestrogens achieve their growth inhibitory and cytoprotective effects is via induction of the mitochondrial manganese superoxide dismutase (MnSOD).

manganese superoxide


Input: Eight phytoestrogens, including resveratrol, coumestrol, kaempferol, genistein, daidzein, apigenin, isoliquirtigenin and glycitin, were tested for their ability to induce MnSOD expression in mouse C2C12 and primary myoblasts.

resveratrol

coumestrol

kaempferol

genistein

daidzein

apigenin

isoliquirtigenin

glycitin


Input: Five of these, resveratrol, coumestrol, kaempferol, genistein and daidzein, significantly increased MnSOD expression, slowed proliferative growth and enhanced stress resistance (hydrogen peroxide LD50).

resveratrol

coumestrol

kaempferol

genistein

daidzein

hydrogen peroxide


Input: When siRNA was used to prevent the MnSOD induction by genistein, coumestrol or daidzein, none of these compounds exerted any effect on proliferative growth, and only the effect of coumestrol on stress resistance persisted.

genistein

coumestrol

daidzein

coumestrol


Input: The estrogen antagonist ICI182780 prevented the increased MnSOD expression and also the changes in cell growth and stress resistance, indicating that these effects are mediated by estrogen receptors (ER).

estrogen

estrogen


Input: The absence of effects of resveratrol or coumestrol, but not genistein, in ER beta-null cells further indicated that this ER in particular is important in mediating these effects.

resveratrol

coumestrol

genistein


Input: Thus, an ER-mediated induction of MnSOD expression appears to underlie the growth inhibitory and cytoprotective activities of multiple phytoestrogens.


Input: Copyright (c) 2013 John Wiley & Sons, Ltd.


Input: The pre-clinical absorption, distribution, metabolism and excretion properties of IPI-926, an orally bioavailable antagonist of the hedgehog signal transduction pathway.


Input: Abstract 1.


Input: IPI-926 is a novel semisynthetic cyclopamine derivative that is a potent and selective Smoothened inhibitor that blocks the hedgehog signal transduction pathway.

cyclopamine


Input: The in vivo clearance of IPI-926 is low in mouse and dog and moderate in monkey.


Input: The volume of distribution is high across species.


Input: Oral bioavailability ranges from moderate in monkey to high in mouse and dog.


Input: Predicted human clearance using simple allometry is low (24 L h (-1)), predicted volume of distribution is high (469 L) and predicted half-life is long (20 h).


Input: IPI-926 is highly bound to plasma proteins and has minimal interaction with human alpha-1-acid glycoprotein.


Input: In vitro metabolic stability ranges from stable to moderately stable.


Input: Twelve oxidative metabolites were detected in mouse, rat, dog, monkey and human liver microsome incubations and none were unique to human.


Input: IPI-926 is not a potent reversible inhibitor of CYP1A2, 2C8, 2C9 or 3A4 (testosterone).

testosterone


Input: IPI-926 is a moderate inhibitor of CYP2C19, 2D6 and 3A4 (midazolam) with KI values of 19, 16 and 4. 5 micro M, respectively.

midazolam


Input: IPI-926 is both a substrate and inhibitor (IC50 = 1. 9 micro M) of P-glycoprotein.


Input: In summary, IPI-926 has desirable pre-clinical absorption, distribution, metabolism and excretion properties.


Input: A multiple perspectives on atypical polypoid adenomyoma of uterus.


Input: Abstract Atypical polypoid adenomyoma (APA) is a rare benign uterine tumor, with less than 200 cases have been reported in English literature.


Input: Although, it is considered as a benign lesion and treated conservatively previously, more and more cases show that APA has a high rate of recurrence or residual, and is found to precede the development of carcinoma.


Input: Given the data from present research on APA, the therapy of APA becomes more complex and must be cautious, especially for the nulliparous and premenopausal patients.


Input: In addition, because of the low incidence, studies on this disease are less, and the etiology and pathogenesis of APA is still unclear.


Input: In this review, we aim to summarize recent researches concerning APA from multiple perspectives, including clinical presentation, histogenesis, immunohistochemistry and molecular features, diagnosis and differential diagnosis, treatment opinion and prognosis, which may provide theory and clinical basis for the future clinical treatment and research of this rare disease.


Input: Path-Branching Representation for Nonadiabatic Electron Dynamics in Conical Intersection.


Input: Path-branching representation (or phase-space averaging and natural branching method (PSANB) as its approximation) of nonadiabatic electron wavepacket dynamics is now known to work well for avoided crossings in many dimensional nonadiabatic transitions [Yonehara, T.; Hanasaki, K.; Takatsuka, K. Chem. Rev. 2012, 112, 499].


Input: In this paper we examine feasibility of the path-branching representation in the theoretical studies of conical intersection (CI).


Input: The most characteristic feature of CI is the Herzberg-Longuet-Higgins phase (or the Berry phase) arising from the electronic part of the total wave function, and accordingly quantum phases of both electronic and nuclear dynamics should be taken into account in a balanced manner.


Input: We first show the PSANB can well capture the essential feature of the phase dynamics of CI.


Input: However, the nuclear phases, the wavelength of which is far shorter than that of the electronic phases, make the computation of nonadiabatic transition extremely oscillatory, resulting in very slow convergence with respect to the number of sampling paths.


Input: A similar difficulty quite often takes place in theoretical chemical dynamics.


Input: To cope with this situation, we devise a simple and tractable approximation in the application of PSANB resting on the fact that a small number of PSANB paths already reproduce accurate nonadiabatic transition probability.


Input: Thiolactone Sulfoxides as New Reactive Metabolites Acting as Bis-Electrophiles: Implication in Clopidogrel and Prasugrel Bioactivation.

Thiolactone Sulfoxides

Clopidogrel

Prasugrel


Input: The antithrombotics of the tetrahydrothienopyridine series, clopidogrel and prasugrel, are prodrugs that must be metabolized in two steps to become pharmacologically active.

tetrahydrothienopyridine

clopidogrel

prasugrel


Input: The first step is the formation of a thiolactone metabolite.

thiolactone


Input: The second step is a cytochrome P450 (P450)-dependent oxidation of this thiolactone resulting in the formation of a sulfenic acid that is eventually reduced into the corresponding active thiol.

thiolactone

sulfenic acid

thiol


Input: It has been postulated that the sulfenic acid metabolite resulted from a nucleophilic attack of water on a highly reactive thiolactone sulfoxide derived from P450-dependent oxidation of the thiolactone primary metabolite.

sulfenic acid

thiolactone sulfoxide

thiolactone


Input: The data described in the present article are in complete agreement with this proposition as they show that it was possible to trap these thiolactone sulfoxides by a series of nucleophiles such as amines, thiols, or cyclopentane-1, 3-dione (CPDH), an equivalent of dimedone that is used as a sulfenic acid trapping agent.

thiolactone sulfoxides

amines

thiols

cyclopentane-1, 3-dione

CPDH

dimedone

sulfenic acid


Input: HPLC-MS studies showed that various bis-adducts having incorporated two nucleophile molecules were formed in these reactions.


Input: One of them that resulted from the oxidation of 2-oxo-prasugrel by human liver microsomes in the presence of ethanolamine and CPDH was isolated and completely characterized by (1) H and (13) C NMR spectroscopy in addition to MS and MS (2) spectrometry.

ethanolamine

CPDH

(1) H

(13) C


Input: All metabolites derived from an attack of H2O or an amine at the CO carbon of the intermediate thiolactone sulfoxide existed as a mixture of two diastereomers having a cis configuration of the double bond, whereas those formed in the presence of thiols appeared as a mixture of four diastereomers with a cis or trans configuration of the double bond.

amine

CO carbon

thiolactone sulfoxide

thiols


Input: This led us to propose tentative mechanisms for the previously reported formation of trans isomers of the active thiol metabolite of clopidogrel upon microsomal metabolism of this antithrombotic in the presence of thiols.

thiol

clopidogrel

thiols


Input: The results described in this article showed that thiolactone sulfoxides are formed as reactive metabolites during the metabolism of clopidogrel and prasugrel and are able to react as bis-electrophiles with a variety of nucleophiles.

thiolactone sulfoxides

clopidogrel

prasugrel


Input: The possible implications of the formation of these reactive metabolites in the pharmacological and/or secondary toxic effects of these drugs remain to be studied.


Input: Tensile Lattice Strain Accelerates Oxygen Surface Exchange and Diffusion in La1-xSrxCoO3-delta Thin Films.

Oxygen


Input: The influence of lattice strain on the oxygen exchange kinetics and diffusion in oxides was investigated on (100) epitaxial La1-xSrxCoO3-delta (LSC) thin films grown by pulsed laser deposition.

oxygen

oxides

LSC


Input: Planar tensile and compressively strained LSC films were obtained on single-crystalline SrTiO3 and LaAlO3.

LSC


Input: (18) O isotope exchange depth profiling with ToF-SIMS was employed to simultaneously measure the tracer surface exchange coefficient k * and the tracer diffusion coefficient D * in the temperature range 280-475 degrees C.

(18) O


Input: In accordance with recent theoretical findings, much faster surface exchange (~ 4 times) and diffusion (~ 10 times) were observed for the tensile strained films compared to the compressively strained films in the entire temperature range.


Input: The same strain effect-tensile strain leading to higher k * and D *-was found for different LSC compositions (x = 0. 2 and x = 0. 4) and for surface-etched films.

LSC


Input: The temperature dependence of k * and D * is discussed with respect to the contributions of strain states, formation enthalpy of oxygen vacancies, and vacancy mobility at different temperatures.

oxygen


Input: Our findings point toward the control of oxygen surface exchange and diffusion kinetics by means of lattice strain in existing mixed conducting oxides for energy conversion applications.

oxygen

oxides


Input: Exciton Coupling Mechanisms Analyzed with Subsystem TDDFT: Direct vs Pseudo Exchange Effects.


Input: The dominant effect in exciton coupling is usually the so-called Coulomb coupling contribution, that is the Coulomb interaction between transition densities of localized excitations.


Input: At short distances, Dexter-type exchange effects are discussed to play a role, which are not well described by (semi) local functionals in time-dependent density functional theory (TDDFT) calculations.


Input: Overall, a large effect of the percentage of exact exchange on the resulting exciton splittings is known.


Input: Subsystem TDDFT allows one to analyze the exciton coupling mechanism by distinguishing direct from indirect effects, that is, changes in the actual coupling mechanism from modifications in the underlying local excitations.


Input: Our analysis shows that the strong influence of exact exchange is not due to a direct Dexter-type (exchange) coupling, but rather to an increased Coulomb (or pseudo-exchange) coupling triggered by a change in transition densities.


Input: This is demonstrated in calculations for 2-pyridone and chlorophyll dimers.


Input: We finally propose a route to efficient calculations of excited states of large pigment aggregates with hybrid functionals, which so far has been out of reach for quantum chemical methods.


Input: Arylpiperazines as fatty acid transport protein 1 (FATP1) inhibitors with improved potency and pharmacokinetic properties.

Arylpiperazines

fatty acid


Input: The discovery and optimization of a novel series of FATP1 inhibitors are described.


Input: Through the derivatization process, arylpiperazine derivatives 5k and 12a were identified as possessing potent in vitro activity against human and mouse FATP1s as well as excellent pharmacokinetic properties.

arylpiperazine


Input: In vivo evaluation of triglyceride accumulation in the liver, white gastrocnemius muscle and soleus is also described.

triglyceride


Input: Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors.

cyclic imides

benzenesulfonamide


Input: Part 2.


Input: A group of cyclic imides (1-10) was designed for evaluation as a selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activity.

cyclic imides


Input: Compounds 6a, 6b, 8a, 8b, 9a, 9b, 10a and 10b were proved to be potent COX-2 inhibitors with IC50 range of 0. 1-4. 0 mu M.


Input: In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 8a as a highly potent (IC50 = 0. 1 mu M), and an extremely selective [COX-2 (SI) > 1000] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 72. 4mg/kg) relative to diclofenac (ED50 = 114mg/kg).

celecoxib

diclofenac


Input: Molecular modeling was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors.


Input: The study showed that the homosulfonamide fragment of 8a inserted deep inside the 2 degrees-pocket of the COX-2 active site, where the SO2NH2 group underwent H-bonding interaction with Gln (192) (2. 95 A), Phe (518) (2. 82 A) and Arg (513) (2. 63 and 2. 73 A).

homosulfonamide

H

Gln

Phe

Arg


Input: Docking study of the synthesized compound 8a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.


Input: Protection of glycyrrhizic acid against AGEs-induced endothelial dysfunction through inhibiting RAGE/NF-kappa B pathway activation in human umbilical vein endothelial cells.

glycyrrhizic acid


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Licorice (Glycyrrhiza uralensis roots) is used as a traditional medicine for the treatment of diabetes mellitus and its vascular complications.


Input: Glycyrrhizic acid (GA, also known as Glycyrrhizin), a triterpenoid saponin glycoside, is considered to be a bioactive component in Licorice and is beneficial to diabetic vascular complications.

Glycyrrhizic acid

Glycyrrhizin

triterpenoid saponin glycoside


Input: AIM OF STUDY: The present study was conducted to evaluate the potential protective activities on AGEs-induced endothelial dysfunction, including anti-apoptosis, antioxidant stress and anti-proinflammatory responses, and explore the underlying mechanism.


Input: MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were incubated and pre-treated with GA (10 (-9)-10 (-6) M) or RAGE-Ab (5 mu g/ml) in the presence or absence of 200 mu g/ml AGEs.


Input: AO/EB fluorescence staining assay was performed to evaluate anti-apoptosis activity.


Input: The superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in cell supernatant were detected by kits while the intracellular reactive oxygen species (ROS) generation was determined by 2, 7-dichlorodihydrofluorescin diacetate (DCFH-DA) kit.

superoxide

malondialdehyde

MDA

oxygen

2, 7-dichlorodihydrofluorescin diacetate

DCFH-DA


Input: Immunocytochemistry analysis was designed to determine transforming growth factor beta1 (TGF-beta 1) protein expression while immunofluorescence analysis for RAGE and NF-kB.


Input: The protein expressions of TGF-beta 1, RAGE and NF-kB were analyzed by Western blot analysis.


Input: RESULTS: Pretreatment with GA at a concentration of 10 (-8)-10 (-6) M significantly reduced the AGEs-induced apoptosis in HUVECs.


Input: GA significantly increased antioxidant enzyme SOD activity and decreased peroxide degradation product MDA level in a dose-dependent manner.

MDA


Input: Furthermore, GA also remarkably inhibited the overgeneration of AGEs-induced ROS.


Input: Both immunocytochemistry analysis and western blot analysis showed that GA significantly decreased the protein expression of poinflammatory cytokine TGF-beta 1 in a similar manner which RAGE-Ab did.


Input: Additionally, AGEs-induced RAGE and NF-kB protein expressions were down-regulated significantly by the pretreatment with GA or RAGE-Ab.


Input: CONCLUSION: These findings provide evidences that GA possesses protective activity on AGEs-induced endothelial dysfunction, including anti-apoptosis, anti-inflammation and antioxidant stress, via inhibiting RAGE/NF-kB pathway.


Input: GA might be an alternative for the prevention and treatment of diabetic vascular complications in an appropriate dosage.


Input: Complement activation by PEGylated liposomes containing prednisolone.

prednisolone


Input: Infusion of PEGylated liposomes can give rise to hypersensitivity reactions (HSRs) in a relatively large number of patients.


Input: Previously it has been shown that these reactions can be caused by activation of the complement (C) system by a negative charge on the anchor molecule of PEG at the liposomal surface.

PEG


Input: In this study it is tested whether the activation of the C system by PEG-liposomes could be significantly reduced to values comparable to nonreactive liposomal formulations, by changing the PEGylation-profile on the liposomal surface.

PEG


Input: Therefore, the formation of C activation markers SC5b-9, C3a, C4d and Bb in normal human serum by both prednisolone loaded and empty liposomes with a variation of PEG chain length, PEG surface concentration, PEG anchor molecule and liposomal size was determined using in vitro assays.

prednisolone

PEG

PEG

PEG


Input: The tested liposomes caused no or only mild (30%) activation of C except for one formulation wherein the PEG2000 was anchored to cholesterol (CHOL-PEG2000).

cholesterol


Input: The latter liposomes caused paralleling rises in SC5b-9 and Bb levels, suggesting excess activation of the alternative pathway.


Input: While the relative safety of weak C activator liposomes remains to be confirmed in vivo, the unique, non-charge and non-antibody-mediated direct conversion of C3 by CHOL-PEG2000 liposomes (although argues against the clinical development of these vesicles) opens new opportunities to understand liposomal C activation at the molecular level.


Input: Technological and biopharmaceutical optimization of nystatin release from a multiparticulate based bioadhesive drug delivery system.

nystatin


Input: Formulation considerations of a new drug delivery system include controlling the site of release of the active ingredient, maintaining drug level for a suitable time and decreasing dosage frequency.


Input: In research and development practice, these therapeutic benefits can be attained by selecting suitable active ingredients and optimizing procedure parameters, determining the composition of the medicine, and dissolution properties.


Input: The aim of our study was to design a pharmaceutical preparation with increased local therapeutic effect in the therapy of gastrointestinal candidiasis.


Input: The polyene antibiotic nystatin may be an optimal choice for active agent, incorporated in a bioadhesive multiparticulate system.

polyene

nystatin


Input: Choosing the proper excipients in the proper dosage form and ensuring prolonged residence time may further improve the optimal treatment.


Input: Using an experimental design, the micropellets were prepared with 5% nystatin content, taking the factors average pellet size (~ 200 to ~ 800 mu m) and the amount of applied carbomer and hydroxyethylcellulose (0-5%) into consideration.

nystatin


Input: Dissolution of the active ingredient was detected by UV spectrophotometric and microbiological assay.


Input: The bioadhesive character of the multiparticulate dosage form was examined by ex vivo wash-off test.


Input: The only factor which significantly influenced the examined parameters was average pellet size.


Input: The proportion of applied bioadhesive excipients had significance mostly in interactions with average pellet size.


Input: Eventually, optimized drug release (5-10min mean dissolution time, 50-55% bioadhesion retention) could be achieved with 550 mu m pellet size, containing carbomer and hydroxyethylcellulose in 85: 15 ratio.


Input: The molecular fingerprint of high grade serous ovarian cancer reflects its fallopian tube origin.


Input: High grade serous ovarian cancer (HGSC), the most lethal and frequent type of epithelial ovarian cancer (EOC), has poor long term prognosis due to a combination of factors: late detection, great metastatic potential and the capacity to develop resistance to available therapeutic drugs.


Input: Furthermore, there has been considerable controversy concerning the etiology of this malignancy.


Input: New studies, both clinical and molecular, strongly suggest that HGSC originates not from the surface of the ovary, but from the epithelial layer of the neighboring fallopian tube fimbriae.


Input: In this paper we summarize data supporting the central role of fallopian tube epithelium in the development of HGSC.


Input: Specifically, we address cellular pathways and regulatory mechanisms which are modulated in the process of transformation, but also genetic changes which accumulate during disease progression.


Input: Similarities between fallopian tube mucosa and the malignant tissue of HGSC warrant a closer analysis of homeostatic mechanisms in healthy epithelium in order to elucidate key steps in disease development.


Input: Finally, we highlight the importance of the cancer stem cell (CSC) identification and understanding of its niche regulation for improvement of therapeutic strategies.


Input: Systematic review of anticholinergic risk scales in older adults.


Input: BACKGROUND: Anticholinergic drugs are often involved in explicit criteria for inappropriate prescribing in older adults.


Input: Several scales were developed for screening of anticholinergic drugs and estimation of the anticholinergic burden.


Input: However, variation exists in scale development, in the selection of anticholinergic drugs, and the evaluation of their anticholinergic load.


Input: This study aims to systematically review existing anticholinergic risk scales, and to develop a uniform list of anticholinergic drugs differentiating for anticholinergic potency.


Input: METHODS: We performed a systematic search in MEDLINE.


Input: Studies were included if provided (1) a finite list of anticholinergic drugs; (2) a grading score of anticholinergic potency and, (3) a validation in a clinical or experimental setting.


Input: We listed anticholinergic drugs for which there was agreement in the different scales.


Input: In case of discrepancies between scores we used a reputed reference source (Martindale: The Complete Drug Reference (R)) to take a final decision about the anticholinergic activity of the drug.


Input: RESULTS: We included seven risk scales, and evaluated 225 different drugs.


Input: Hundred drugs were listed as having clinically relevant anticholinergic properties (47 high potency and 53 low potency), to be included in screening software for anticholinergic burden.


Input: CONCLUSION: Considerable variation exists among anticholinergic risk scales, in terms of selection of specific drugs, as well as of grading of anticholinergic potency.


Input: Our selection of 100 drugs with clinically relevant anticholinergic properties needs to be supplemented with validated information on dosing and route of administration for a full estimation of the anticholinergic burden in poly-medicated older adults.


Input: Everolimus in Combination with Exemestane: A Review of its Use in the Treatment of Patients with Postmenopausal Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer.

Everolimus

Exemestane


Input: Oral everolimus (Afinitor ((R))) in combination with exemestane is indicated for the treatment of hormone receptor-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer in postmenopausal women after failure of treatment with letrozole or anastrozole (in the USA) or after recurrence of progression following a nonsteroidal aromatase inhibitor (AI) in women without symptomatic visceral disease (in the EU).

everolimus

Afinitor

exemestane

letrozole

anastrozole


Input: Everolimus, a selective inhibitor of mammalian target of rapamycin (mTOR), inhibits the downstream signalling events of the mTOR pathway.

Everolimus

rapamycin


Input: This review summarizes the pharmacology of everolimus and reviews its efficacy and tolerability when administered in combination with exemestane in postmenopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer refractory to nonsteroidal AIs.

everolimus

exemestane

oestrogen


Input: In the well-designed BOLERO-2 study, the addition of everolimus to exemestane was shown to significantly prolong progression-free survival in this patient population.

everolimus

exemestane


Input: However, treatment-emergent adverse events and treatment discontinuations occurred more frequently with combination therapy than with exemestane alone, suggesting a need for careful benefit/risk assessment prior to initiating therapy.

exemestane


Input: Mature survival data from this study are awaited and additional studies would help to further demonstrate the benefit of combination therapy.


Input: Nevertheless, current evidence suggests that everolimus plus exemestane combination therapy may be a useful treatment option in patients with postmenopausal hormone receptor-positive, HER2-negative, advanced breast cancer refractory to nonsteroidal AIs.

everolimus

exemestane


Input: Lorcaserin: a review of its use in chronic weight management.

Lorcaserin


Input: Oral lorcaserin (BELVIQ ((R))), a selective serotonin 5-HT2C receptor agonist, is indicated in the US as an adjunct to diet and exercise in the chronic weight management of obese adults, or overweight adults with at least one weight-related comorbidity (e. g. dyslipidaemia, hypertension, type 2 diabetes).

lorcaserin

BELVIQ

serotonin


Input: This article reviews the pharmacological properties, therapeutic efficacy and tolerability of oral lorcaserin in this patient population.

lorcaserin


Input: In three large randomized, double-blind, multicentre studies, oral lorcaserin was more effective than placebo in the management of obese and overweight adults with or without type 2 diabetes mellitus.

lorcaserin


Input: Following 12 months' therapy, significantly higher proportions of lorcaserin than placebo recipients achieved a >= 5 and >= 10% reduction from baseline in their bodyweight and a significant between-group difference favouring lorcaserin over placebo was observed for the change from baseline in bodyweight.

lorcaserin

lorcaserin


Input: Moreover, among patients who had achieved a >= 5% reduction in their bodyweight after 12 months' therapy with lorcaserin, a significantly higher proportion who received lorcaserin for a further 12 months than those who switched to placebo maintained >= 5% weight loss at 24 months.

lorcaserin

lorcaserin


Input: In general, oral lorcaserin was well tolerated in clinical studies, with hypoglycaemia and headache the most frequently reported adverse events in those with or without type 2 diabetes, respectively.

lorcaserin


Input: According to a pooled analysis, the risk of US-FDA-defined valvulopathy with lorcaserin is generally low and not statistically significantly different from placebo.

lorcaserin


Input: From these and other data, the FDA has concluded that lorcaserin is unlikely to elevate the risk of valvulopathy.

lorcaserin


Input: Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1.


Input: COL1A1 haploinsufficiency mutations lead to the mildest form of osteogenesis imperfecta (OI), OI type I.


Input: The skeletal clinical characteristics resulting from such mutations have not been characterized in detail.


Input: In this study we assessed 86 patients (36 male, 50 female; mean age 13. 3 years; range 0. 6 to 54 years) with COL1A1 haploinsufficiency mutations, of whom 70 were aged 21 years or less (' pediatric' patients).


Input: Birth history was positive for fracture or long-bone deformity in 12% of patients.


Input: The average rate of long-bone fracture (femur, tibia/fibula, humerus, radius/ulna) in pediatric patients was 0. 62 fractures per year, half of which affected the tibia/fibula.


Input: Long-bone fracture rate was negatively associated with age and lumbar spine areal bone mineral density.


Input: Vertebral compression fractures were observed in 71% of the 58 pediatric patients who had lateral spine radiographs.


Input: The median number of vertebral fractures was higher for females (median 4; range 0 to 14) than for males (median 1, range 0 to 8) (P = 0. 03).


Input: Lumbar spine areal bone mineral density was negatively associated with the severity of vertebral compression fractures, as reflected in the spine deformity index.


Input: Scoliosis was present in about 30% of pediatric patients but the Cobb angle was < 30 degrees in all cases.


Input: The average final height z-score was-1. 1, representing a deficit of 8 to 10 cm compared to the general population.


Input: In summary, OI patients with COL1A1 haploinsufficiency mutations have high rates of significant skeletal involvement.


Input: Systematic follow up of growing patients with COL1A1 haploinsufficiency mutations including radiographic screening for vertebral compression fractures and scoliosis is warranted.


Input: (c) 2013 American Society for Bone and Mineral Research.


Input: Broadband Light-Trapping Enhancement in an Ultrathin Film a-Si Absorber Using Whispering Gallery Modes and Guided Wave Modes with Dielectric Surface-Textured Structures.

Si


Input: An embedded nanosphere dielectric structure on an a-Si ultrathin film improves weighted absorption from 23. 8% to 39. 9%.

Si


Input: The PMMA embedding layer offers a guided wave mode as well as mechanical robustness, in addition to the resonant whispering gallery modes coupling.

PMMA


Input: Broadband light-trapping enhancements are observed by dielectric surface textured structures of hemispheres, nanocones, nanospheres, or embedded nanospheres.


Input: Carotid body denervation prevents the development of insulin resistance and hypertension induced by hypercaloric diets.


Input: Increased sympathetic activity is a well-known pathophysiological mechanism in insulin resistance (IR) and hypertension (HT).


Input: The carotid bodies (CB) are peripheral chemoreceptors that classically respond to hypoxia by increasing chemosensory activity in the carotid sinus nerve (CSN), causing hyperventilation and activation of the sympathoadrenal system.


Input: Besides its role in the control of ventilation, the CB has been proposed as a glucose sensor being implicated in the control of energy homeostasis.

glucose


Input: However, to date no studies have anticipated its role in the development of IR.


Input: Herein we propose that CB overstimulation is involved in the aetiology of IR and HT, core metabolic and hemodynamic disturbances of highly prevalent diseases like the metabolic syndrome, type 2 diabetes and obstructive sleep apnoea.


Input: We demonstrated CB activity is increased in IR animal models and that CSN resection prevents CB-overactivation and diet-induced IR and HT.


Input: Moreover we showed that insulin triggers CB, highlighting a new role for hyperinsulinemia as a stimulus for CB-overactivation.


Input: We propose that CB is implicated in the pathogenesis of metabolic and hemodynamic disturbances through sympathoadrenal overactivation and may represent a novel therapeutic target in these diseases.


Input: Universal rule on chirality-dependent bandgaps in graphene antidot lattices.

graphene


Input: Graphene with periodically patterned antidots has attracted intense research attention as it represents a facile route to open a bandgap for graphene electronics.

Graphene

graphene


Input: However, not all graphene antidot lattices (GALs) can open a bandgap and a guiding rule is missing.

graphene


Input: Here, through systematic first-principles calculations, it is found that bandgaps in triangular GALs are surprisingly well defined by a chirality vector R = n a1 + ma2 connecting two neighboring antidots, where a1 and a2 are the basis vectors of graphene.

graphene


Input: The bandgap opens in the GALs with (n-m) mod3 = 0 but remains closed in those with (n-m) mod3 = +/- 1, reminiscent of the gap-chirality rule in carbon nanotubes.

carbon


Input: Remarkably, the gap value in GALs allows ample modulation by adjusting the length of chirality vectors, shape and size of the antidots.


Input: The gap-chirality relation in GALs stems from the chirality-dependent atomic structures of GALs as revealed by a super-atom model as well as Clar sextet analyses.


Input: This chirality-dependent bandgap is further shown to be a generic behavior in any parallelogram GAL and thus serves as an essential stepping stone for experimenters to realize graphene devices by antidot engineering.

graphene


Input: Circulating Vitamin D Metabolites and Subclinical Atherosclerosis in Type 1 Diabetes.

Vitamin D


Input: OBJECTIVEPeople with type 1 diabetes are at high risk of premature atherosclerosis.


Input: Existing evidence suggests that impaired vitamin D metabolism may contribute to the development of atherosclerosis.

vitamin D


Input: We tested associations of circulating vitamin D metabolite concentrations with subclinical atherosclerosis among 1, 193 participants with type 1 diabetes in the DCCT/EDIC study. RESEARCH DESIGN AND METHODSWe measured plasma concentrations of 25-hydroxyvitamin D [25 (OH) D], 1, 25-dihydroxyvitamin D, and 24, 25-dihydroxyvitamin D by mass spectrometry at the end of the DCCT.

vitamin D

25-hydroxyvitamin D

25 (OH) D

1, 25-dihydroxyvitamin D

24, 25-dihydroxyvitamin D


Input: In a staggered cross-sectional design, we tested associations with coronary artery calcium (CAC), measured by computed tomography a median of 10 years later, and with common and internal carotid intima-media thickness (IMT), measured by B-mode ultrasonography on two occasions a median of 4 years later and a median of 10 years later.

calcium


Input: We hypothesized that lower concentrations of each vitamin D metabolite would be associated with increased risk of CAC and greater carotid IMT. RESULTSAt the time metabolites were measured, mean age was 32. 4 years and mean duration of diabetes was 7. 5 years.

vitamin D


Input: The prevalence and severity of CAC tended to be lower-not higher-with lower concentrations of each vitamin D metabolite.

vitamin D


Input: For instance, in a fully adjusted multinomial logistic model, a 25 nmol/L lower 25-hydroxyvitamin D was associated with a 0. 8-fold decrease in the odds of having higher CAC (95% CI 0. 68-0. 96, P = 0. 01).

25-hydroxyvitamin D


Input: No vitamin D metabolite was associated with either common or internal mean IMT. CONCLUSIONSWe did not find evidence linking impaired vitamin D metabolism with increased subclinical atherosclerosis in type 1 diabetes.

vitamin D

vitamin D


Input: Regulation of the Bone-restricted ifitm-like (Bril) gene transcription by Sp and Gli family members and CpG methylation.

CpG


Input: Bril encodes a small membrane protein present in osteoblasts.


Input: In humans, a single recurrent mutation in the 5' UTR of BRIL causes osteogenesis imperfecta type V.


Input: The exact function of BRIL and the mechanism by which it contributes to disease are still unknown.


Input: The goal of the current study was to characterize the mechanisms governing Bril transcription in the human, rat and mouse.


Input: In the three species, as detected by luciferase reporter assays in UMR106 cells, we found that most of the baseline regulatory activity was localized within =~ 250bp upstream of the coding ATG.


Input: Co-transfection experiments indicated that Sp1 and Sp3 were potent inducers of the promoter activity, through the binding several GC-rich boxes.


Input: Osterix was a weak activator but acted cooperatively with Sp1 and GLI2 to synergistically induce the BRIL promoter.


Input: GLI2, a mediator of hedgehog signaling pathway, was also a potent activator of BRIL through a single GLI binding site.


Input: Correspondingly, agonists of the Hedgehog pathway (purmorphamine and Indian hedgehog) in MC3T3 osteoblasts led to increased BRIL levels.

purmorphamine


Input: The BRIL promoter activity was also found to be negatively modulated through two different mechanisms.


Input: First, the ZFP354C zinc finger protein repressed basal and Sp1-induced activity.


Input: Second, CpG methylation of the promoter region correlated with an inactive state, and prevented Sp1 activation.

CpG


Input: The data provide the very first analyses of the cis-and trans-acting factors regulating Bril transcription.


Input: They revealed key roles for the Sp members and GLI2 that possibly cooperate to activate Bril when the promoter becomes demethylated.


Input: E-cadherin polarity is determined by a multi-function motif mediating lateral membrane retention through ankyrin-G and apical-lateral transcytosis through clathrin.


Input: We report a highly conserved motif in the E-cadherin juxtamembrane domain that determines apical-lateral polarity by conferring both restricted mobility at the lateral membrane and transcytosis of apically mis-sorted protein to the lateral membrane.


Input: Mutations causing either increased lateral membrane mobility or loss of apical-lateral transcytosis result in partial mis-sorting of E-cadherin in MDCK cells.


Input: However, loss of both activities results in complete loss of polarity.


Input: We present evidence that residues required for restricted mobility mediate retention at the lateral membrane through interaction with ankyrin-G, while dileucine residues conferring apical-lateral transcytosis act through a clathrin-dependent process and function in an editing pathway.

dileucine


Input: Ankyrin-G interaction with E-cadherin is abolished by the same mutations resulting in increased E-cadherin mobility.


Input: Clathrin heavy chain knockdown and dileucine mutation of E-cadherin both cause the same partial loss of polarity of E-cadherin.

dileucine


Input: Moreover, clathrin knockdown causes no further change in polarity of E-cadherin with dileucine mutation, but does completely randomize E-cadherin mutants lacking ankyrin-binding.

dileucine


Input: Dileucine mutation, but not loss of ankyrin-binding, prevented transcytosis of apically mis-sorted E-cadherin to the lateral membrane.

Dileucine


Input: Finally, neurofascin, which binds ankyrin but lacks dileucine residues, exhibited partial apical-lateral polarity that was abolished by mutation of its ankyrin-binding site but was not affected by clathrin knockdown.

dileucine


Input: The polarity motif thus integrates complementary activities of lateral membrane retention through ankyrin-G and apical-lateral transcytosis of mis-localized protein through clathrin.


Input: Together, the combination of retention and editing function to ensure a high fidelity steady state localization of E-cadherin at the lateral membrane.


Input: Biomimetic cryptic site surfaces for reversible chemo-and cyto-mechanoresponsive substrates.


Input: Chemo-mechanotransduction, the way by which mechanical forces are transformed into chemical signals, plays a fundamental role in many biological processes.


Input: The first step of mechanotransduction often relies on exposure, under stretching, of cryptic sites buried in adhesion proteins.


Input: Likewise, here we report the first example of synthetic surfaces allowing for specific and fully reversible adhesion of proteins or cells promoted by mechanical action.


Input: Silicone sheets are first plasma treated and then functionalized by grafting sequentially under stretching poly (ethylene glycol) (PEG) chains and biotin or arginine-glycine-aspartic acid (RGD) peptides.

poly (ethylene glycol)

PEG

biotin

arginine

glycine

aspartic acid


Input: At unstretched position, these ligands are not accessible for their receptors.


Input: Under a mechanical deformation, the surface becomes specifically interactive to streptavidin, biotin antibodies, or adherent for cells, the interactions both for proteins and cells being fully reversible by stretching/unstretching, revealing a reversible exposure process of the ligands.

biotin


Input: By varying the degree of stretching, the amount of interacting proteins can be varied continuously.


Input: Self-assembly of DNA rings from scaffold-free DNA tiles.


Input: We report a scaffold-free approach in which four-and six-helix DNA bundle units, assembled from a small number of single stranded DNA oligonucleotides precisely arranged in networks of contiguous and semicrossover strands, are connected into DNA nano rings.


Input: Nearly uniform structures with well-defined diameters of 53 +/- 7, 81 +/- 9, 85 +/- 8, and 166 +/- 13 nm were achieved by introducing uniform, in-plane curvature to the repeating units.