Input: Materials and methods: PLGA nanoparticles (NPs) were prepared by the solvent emulsification diffusion-evaporation technique and characterized for particle size, particle-size distribution, zeta potential, entrapment efficiency, drug loading and interaction studies and in vivo studies using gamma scintigraphy techniques.

PLGA


Input: Results and discussion: The size of drug-loaded NPs (drug polymer ratio 1: 1) was found to be 89. 67 +/- 6. 43 nm.


Input: The TEM and SEM images of the formulation suggested that particle size was within 20-100 nm and spherical in shape, smooth morphology and coating of Tween-80 on the NPs was clearly observed.


Input: The release behavior of donepezil exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous sustained release.

donepezil


Input: The biodistribution studies of donepezil-loaded PLGA NPs and drug solution via intravenous route revealed higher percentage of radioactivity per gram in the brain for the nanoparticulate formulation as compared with the drug solution (p < 0. 05).

donepezil

PLGA


Input: Conclusion: The high concentrations of donepezil uptake in brain due to coated NPs may help in a significant improvement for treating AD.

donepezil


Input: But further, more extensive clinical studies are needed to check and confirm the efficacy of the prepared drug delivery system.


Input: Synthesis and biological evaluation of nucleoside analogues than contain silatrane on the basis of the structure of acyclovir (ACV) as novel inhibitors of hepatitis B virus (HBV).

nucleoside

silatrane

acyclovir

ACV


Input: Hepatitis B virus (HBV) infection causes major public health problems worldwide.


Input: Acyclovir (ACV) is mainly used to inhibit herpes simplex virus (HSV) rather than HBV.

Acyclovir

ACV


Input: In this study, we used the combination principle to design and synthesize nucleoside analogues that contain silatrane on the basis of the structure of ACV.

nucleoside

silatrane

ACV


Input: We found that the compounds were effective inhibitors of HBV, both in vitro and in vivo.


Input: All of the compounds showed suppressive activity on the expression of HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the HepG2. 2. 15 cell line with low cytotoxicity.


Input: One of compounds was studied in HBV transgenic mice model, and the test results showed its ability to reduce the levels of HBsAg, HBeAg and HBV DNA by ELASE and qPCR.


Input: Furthermore, significant improvement of T lymphocyte was observed after treatment, as evaluated by flow cytometry (FCM).


Input: Serum amyloid A upsurge precedes standard biomarkers of hepatotoxicity in ritodrine-injected mice.

ritodrine


Input: The tocolytic agent ritodrine acts on the beta 2-adrenoceptor and is an effective treatment option for preterm labor.

ritodrine


Input: However, several adverse effects of ritodrine therapy, including liver damage, have been noted.

ritodrine


Input: To elucidate the underlying mechanisms of ritodrine-induced adverse effects, development of sensitive biomarkers of these adverse events is necessary.

ritodrine


Input: Here, we report the development and analysis of an animal model of ritodrine-induced liver damage.

ritodrine


Input: Female mice received daily ritodrine injections for 2 weeks; liver samples were then collected and subjected to DNA microarray analysis.

ritodrine


Input: Ritodrine significantly altered the expression of genes related to steroid and lipid metabolism, as well as the metabolism of ritodrine itself.

Ritodrine

steroid

ritodrine


Input: Importantly, expression of the acute-phase reactant serum amyloid A (SAA) significantly increased after ritodrine injection, with values indicating the largest fold-change.

ritodrine


Input: This large increase in blood SAA levels serves as a more sensitive biomarker than conventional liver enzymes, such as aspartate aminotransferase and alanine aminotransferase.

aspartate

alanine


Input: The increase in SAA expression is specific to ritodrine-induced liver damage, because SAA expression was not induced by other hepatotoxic drugs such as acetaminophen, valproic acid, or metformin.

ritodrine

acetaminophen

valproic acid

metformin


Input: Our in vitro studies showed that cyclic adenosine 3', 5'-monophosphate (cAMP) accumulation was not a primary cause of the ritodrine-induced SAA increase.

cyclic adenosine 3', 5'-monophosphate

cAMP

ritodrine


Input: Instead, SAA expression was enhanced by indirect phosphorylation of the signal transducer and activator of transcription-3 (STAT3) mediated by interleukin-6.


Input: Therefore, our study provides a method for sensitive and early detection of hepatic injury, and may thus help preclude serious liver damage due to ritodrine use in preterm labor.

ritodrine


Input: L-type voltage-dependent calcium channel is involved in the snake venom group IA secretory phospholipase A2-induced neuronal apoptosis.

calcium


Input: Snake venom group IA secretory phospholipase A2 (sPLA2-IA) is known as a neurotoxin.


Input: Snake venom sPLA2s are neurotoxic in vivo and in vitro, causing synergistic neurotoxicity to cortical cultures when applied with toxic concentrations of glutamate.

glutamate


Input: However, it has not yet been cleared sufficiently how sPLA2-IA exerts neurotoxicity.


Input: Here, we found sPLA2-IA induced neuronal cell death in a concentration-dependent manner.


Input: This death was a delayed response requiring a latent time for 6h.


Input: sPLA2-IA-induced neuronal cell death was accompanied with apoptotic blebbing, condensed chromatin, and fragmented DNA, exhibiting apoptotic features.


Input: NMDA receptor blockers suppressed the neurotoxicity of sPLA2-IA, but an AMPA receptor blocker did not.

NMDA

AMPA


Input: Interestingly, L-type voltage-dependent Ca (2 +) channel (L-VDCC) blocker significantly protected neurons from the sPLA2-IA-induced apoptosis.

Ca (2 +)


Input: On the other hand, neither N-VDCC blockers nor P/Q-VDCC blocker did.


Input: In conclusion, we demonstrated that sPLA2-IA induced neuronal cell death via apoptosis.


Input: Furthermore, the present study suggests that not only NMDA receptor but also L-VDCC contributed to the neurotoxicity of snake venom sPLA2-IA.

NMDA


Input: Chemo-responsive, self-oscillating gels that undergo biomimetic communication.


Input: Species ranging from single-cell organisms to social insects can undergo auto-chemotaxis, where the entities move towards a chemo-attractant that they themselves emit.


Input: Polymer gels undergoing the self-oscillating Belousov-Zhabotinsky (BZ) reaction exhibit autonomous, periodic pulsations, which produce chemical species collectively referred to as the activator.


Input: The diffusion of this activator into the surrounding solution affects the dynamic behavior of neighboring BZ gels and hence, the BZ gels not only emit, but also respond to self-generated chemical gradients.


Input: This review describes recent experimental and computational studies that reveal how this biomimetic behavior effectively allows neighboring BZ gels to undergo cooperative, self-propelled motion.


Input: These distinctive properties of the BZ gels provide a route for creating reconfigurable materials that autonomously communicate with neighboring units and thereby actively participate in constructing the desired structures.


Input: Mitogen-activated protein kinases as therapeutic targets for rheumatoid arthritis.


Input: Rheumatoid arthritis (RA) is a chronic autoimmune disease in which imbalances in pro-and anti-inflammatory cytokines promote the induction of autoimmunity, inflammation and joint destruction.


Input: Methotrexate, the standard disease-modifying anti-rheumatic drug (DMARD), has shown a gradual loss of efficacy in a significant proportion of patients, probably due to the onset of drug resistance, and thus it was hoped that the development of biologics would revolutionise RA management.

Methotrexate


Input: Even though biologics have improved the therapy of patients refractive to DMARDs, they require parenteral administration and may leave patients open to serious infection and cancer.


Input: Therefore, attention has also been focused on inhibitors of mitogen-activated protein kinases (MAPKs), signalling enzymes that play key roles in pathogenic cytokine production, and their downstream effector pathways, in order to create safe and effective oral drugs.


Input: This article therefore provides an overview of the structure and function of MAPKs and their role in the pathogenesis of RA as context to describing the advances in the development of specific, druggable MAPK inhibitors.


Input: Their potential as therapies in the management of RA is also discussed.


Input: Genotoxicity and carcinogenicity of the light emitted by artificial illumination systems.


Input: The light delivered by artificial illumination systems, and in particular by halogen quartz bulbs, contains UVA, UVB, and UVC radiation, is genotoxic to both bacterial and human cells and is potently carcinogenic to hairless mice.

halogen quartz


Input: Since IARC has classified UV radiation in Group 1, any source of UV light poses a carcinogenic hazard to humans.


Input: Suitable regulations would be needed in order to control the safety of the light emitted by artificial light sources.


Input: Impaired social behavior in chicks exposed to sodium valproate during the last week of embryogenesis.

sodium valproate


Input: RATIONALE AND OBJECTIVES: To evaluate direct exposure to sodium valproate (VPA) during embryogenesis, we administered VPA to chick embryos and examined their social behaviors after hatching.

sodium valproate

VPA

VPA


Input: METHODS AND RESULTS: Embryos treated with VPA (35 mu mol/egg) on day 14 were similar to controls for hatching date (day 21) and hatchlings' abilities, such as motor, imprinting, and surface righting.

VPA


Input: However, these VPA chicks on posthatching day 3 scored significantly low in the chick' s social separation stress (SSS) test as follows.

VPA


Input: Aggregation test evaluated the speed of four chicks, individually isolated by a cardboard in a box, to aggregate upon removal of the cardboards.


Input: Belongingness test evaluated the speed of a chick isolated at a corner to join the group of three chicks placed at the opposite corner.


Input: Vocalization test for each chick was performed in an isolated corner by using a sound level meter.


Input: The results demonstrated that compared with controls, VPA chicks were significantly slow in aggregation (12. 7 +/- 2. 5 s vs. 2. 9 +/- 0. 9 s, p = 0. 006) and belongingness (3. 6 +/- 0. 28 s/40 cm vs. 2. 6 +/- 0. 14 s/40 cm, P = 0. 003) and weak in vocalization (13. 4 +/- 2. 8 dB/30 s vs. 26. 7 +/- 1. 3 dB/30 s, P = 0. 001), respectively.

VPA


Input: Weight of cerebellum of VAP chick was 15% lighter than controls (P = 0. 004).

VAP


Input: CONCLUSIONS: Chick embryos exposed to VPA during the last week of embryogenesis had impaired social behaviors in spite of normal mortar and imprinting ability.

VPA


Input: The present method will be a useful animal model for assessing the effects of environment during embryogenesis on social behaviors in later life.


Input: Abstinence from repeated amphetamine treatment induces depressive-like behaviors and oxidative damage in rat brain.

amphetamine


Input: RATIONALE: Amphetamine has a significant potential for abuse and addiction.

Amphetamine


Input: Among prolonged abusers, amphetamine withdrawal-induced depressive symptoms are common; however, their pathophysiological mechanism is not fully understood.

amphetamine


Input: Previously, we found that repeated treatment with amphetamine for 2 weeks induced oxidative stress in rat brain.

amphetamine


Input: OBJECTIVES: The purpose of the current study is to analyze whether abstinence from repeated amphetamine treatment in rats induces depressive-like behaviors and if oxidative damage in the brain continues during abstinence.

amphetamine


Input: METHODS: Rats were given repeated treatment with amphetamine once daily at 1, 2, or 4 mg/kg for 14 days.

amphetamine


Input: From 10 to 14 days after final amphetamine treatment, behavioral changes were monitored using open field test, novel object recognition test, and forced swim test.

amphetamine


Input: Oxidative damage in the medial frontal cortex and hippocampus was analyzed by immunohistochemistry.


Input: RESULTS: We found that drug abstinence after repeated amphetamine stimulation decreased locomotor activity and exploratory behavior in the open field test, increased immobility in the forced swim test, and had no significant effect on the recognition index in the novel object recognition test.

amphetamine


Input: We also found that amphetamine abstinence increased levels of 4-hydroxynonenal-protein adducts and 8-hydroxyguanosine in rat medial frontal cortex and in CA3 and dentate gyrus regions of the hippocampus.

amphetamine


Input: CONCLUSIONS: These results suggest that amphetamine abstinence displays depressive-like behaviors in rats and induces oxidative damage to lipids and RNA in rat brain.

amphetamine


Input: Our findings indicate that the process of oxidative stress may play a role in pathophysiological changes during drug abstinence from repeated amphetamine stimulation.

amphetamine


Input: Oroxylin A improves attention deficit hyperactivity disorder-like behaviors in the spontaneously hypertensive rat and inhibits reuptake of dopamine in vitro.

Oroxylin A

dopamine


Input: In previous studies we have demonstrated that the gamma-aminobutryic acid-A (GABA-A) receptor antagonist oroxylin A has an awakening effect and it also represses ADHD-like behaviors (hyperactivity, impulsivity and inattention) in the spontaneously hypertensive rat (SHR) model of attention-deficit hyperactivity disorder (ADHD).

gamma-aminobutryic acid

GABA

oroxylin A


Input: We hypothesized that the effects of oroxylin A were exerted via the GABA-A receptor given the important role of the GABAergic system in ADHD.

oroxylin A

GABA


Input: However, it is possible that aside from the GABAergic system, oroxylin A may influence other systems especially those implicated in ADHD (e. g. DAergic, etc.).

oroxylin A


Input: To test this hypothesis, we evaluated the effects of GABA agonist, or dopamine (DA) antagonist in oroxylin A-induced alleviation of ADHD-like behaviors in SHR.

GABA

dopamine

oroxylin A


Input: SHR showed inattention and impulsivity as measured by the Y-maze and the electro-foot shock aversive water drinking tests, respectively.


Input: Oroxylin A significantly improved these behaviors, furthermore, its effect on SHR impulsivity was attenuated by haloperidol, a DA antagonist, but not by baicalein, an agonist of the GABA-A receptor.

Oroxylin A

haloperidol

baicalein

GABA


Input: In vitro studies showed that oroxylin A inhibited DA uptake similar to methylphenidate, a dopamine transporter blocker, but did not influence norepinephrine uptake unlike atomoxetine, a selective NE reuptake inhibitor.

oroxylin A

methylphenidate

dopamine

norepinephrine

atomoxetine


Input: Collectively, the present findings suggest that oroxylin A improves ADHD-like behaviors in SHR via enhancement of DA neurotransmission and not modulation of GABA pathway as previously reported.

oroxylin A

GABA


Input: Importantly, the present study indicates the potential therapeutic value of oroxylin A in the treatment of ADHD.

oroxylin A


Input: The toxicity of a ternary biocide mixture to two consecutive earthworm (Eisenia fetida) Generations.


Input: The aim of the present study was to determine the toxicity of a mixture containing the biocides picoxystrobin, esfenvalerate, and triclosan to the reproduction and adult survival of two consecutive generations of Eisenia fetida (Savigny, 1826).

picoxystrobin

esfenvalerate

triclosan


Input: Concentration addition and independent action were used to predict mixture toxicity.


Input: Due to degradation of mixture components during the course of the experiment, predictions were based both on the mixture composition at the beginning and the end of the exposure period.


Input: As degradations were dose-dependent, none of the calculated predictions were precise for the entire concentration range, although combining both predictions led us to conclude that lethal toxicity was well predicted by concentration addition and sublethal toxicity by independent action.


Input: Reproduction of the F1 generation was inhibited more (p < 0. 0001) than reproduction of the F0 generation.


Input: Adult survival did not differ between generations.


Input: The accuracy of the mixture toxicity predictions thus depended on both the time-dependent mixture composition and the earthworm generation.


Input: The results of this study underline the need for more advanced mixture toxicity prediction models that consider degradation kinetics and changes in toxic effects over time.


Input: Inadequate levothyroxine replacement for primary hypothyroidism is associated with poor health-related quality of life-a Brazilian multicentre study.

levothyroxine


Input: This study aimed to verify the impact of levothyroxine replacement on health-related quality of life (HRQoL) in a Brazilian sample of primary hypothyroidism patients.

levothyroxine


Input: A cross-sectional study was performed with 2, 057 consecutive primary hypothyroidism patients on levothyroxine (LT4) replacement at four referral centers in Brazil (median age = 53; 25th percentile = 43; 75th percentile = 61 years).

levothyroxine


Input: Patient biochemical data were acquired from medical records, and patients completed a questionnaire on socioeconomic issues and clinical signs and symptoms of hypothyroidism.


Input: HRQoL was assessed using the SF-36v2.


Input: Patients were divided into three groups according to TSH levels: overtreated (OvT; TSH < 0. 4 mU/L), appropriately treated (AT; TSH between 0. 4 and 4. 0 mU/L), and undertreated (UnT; TSH > 4. 0 mU/L).


Input: Patients were also analyzed by TSH and FT4 serum levels: overt hyperthyroidism (OHyper; TSH < 0. 4 mU/L and FT4 > 1. 9 ng/dL), subclinical hyperthyroidism (SHyper; TSH < 0. 4 mU/L and FT4 0. 8-1. 9 ng/dL), subclinical hypothyroidism (SHypo; TSH > 4. 0 mU/L and FT4 0. 8-1. 9 ng/dL), and overt hypothyroidism (OHypo; TSH > 4. 0 mU/L and FT4 < 0. 8 ng/dL).


Input: A total of 14. 4% of patients were OvT, with 13. 0% SHyper and 1. 4% OHyper.


Input: The prevalence of UnT was 25. 9%, with 21. 5% SHypo and 4. 4% OHypo.


Input: Overtreatment was not associated with HRQoL impairment.


Input: UnT patients had worse HRQoL than AT patients, especially for physical and emotional aspects, independent of SHypo or OHypo status.


Input: Hypothyroidism undertreatment is associated with poor patient HRQoL.


Input: Therefore, adequate LT4 therapy should be given to maintain serum TSH within the reference range.


Input: Novel locus including FGF21 is associated with dietary macronutrient intake.


Input: Dietary intake of macronutrients (carbohydrate, protein, and fat) has been associated with risk of chronic conditions such as obesity and diabetes.

carbohydrate


Input: Family studies have reported a moderate contribution of genetics to variation in macronutrient intake.


Input: In a genome-wide meta-analysis of a population-based discovery cohort (n = 33 533), rs838133 in FGF21 (19q13. 33), rs197273 near TRAF family member-associated NF-kappa-B activator (TANK) (2p24. 2), and rs10163409 in FTO (16q12. 2) were among the top associations (P < 10 (-5)) for percentage of total caloric intake from protein and carbohydrate.

carbohydrate


Input: rs838133 was replicated in silico in an independent sample from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) Nutrition Working Group (n = 38 360) and attained genome-wide significance in combined analysis (Pjoint = 7. 9 x 10 (-9)).


Input: A cytokine involved in cellular metabolism, FGF21 is a potential susceptibility gene for obesity and type 2 diabetes.


Input: Our results highlight the potential of genetic variation for determining dietary macronutrient intake.


Input: Effect of phospholipid composition and phase on nanodisc films at the solid-liquid interface as studied by neutron reflectivity.


Input: Nanodiscs are disc-like self-assembled structures formed by phospholipids and amphipatic proteins.


Input: The proteins wrap like a belt around the hydrophobic part of the lipids, basically producing nanometer-sized patches of lipid bilayers.


Input: The bilayer in the nanodisc constitutes a native-like model of the cell membrane and can act as a nanometer-sized container for functional single membrane proteins.


Input: In this study, we present a general nanodisc-based system, intended for structural and functional studies of membrane proteins.


Input: In this method, the nanodiscs are aligned at a solid surface, providing the ability to determine the average structure of the film along an axis perpendicular to the interface as measured by neutron reflectivity.


Input: The nanodisc film was optimized in terms of nanodisc coverage, reduced film roughness, and stability for time-consuming studies.


Input: This was achieved by a systematic variation of the lipid phase, charge, and length of lipid tails.


Input: Herein, we show that, although all studied nanodiscs align with their lipid bilayer parallel to the interface, gel-phase DMPC nanodiscs form the most suitable film for future membrane protein studies since they yield a dense irreversibly adsorbed film with low roughness and high stability over time.

DMPC


Input: This may be explained by the appropriate matching between the thickness of the hydrophobic lipid core of gel phase DMPC and the height of the belt protein.

DMPC


Input: Moreover, once formed the gel-phase DMPC nanodiscs film can be heated up to melt the lipid bilayer, thus providing a more biologically friendly environment for membrane proteins.

DMPC


Input: The GABA A receptor subunits heterologously expressed in Xenopus oocytes.

GABA


Input: The gamma-aminobutyric acid (GABA) A receptor is composed of a variety of subunits and combinations and shows a characteristic distribution in the CNS.

gamma-aminobutyric acid

GABA


Input: To date, 20 subunits of the GABA A receptor have been cloned: alpha 1-6, beta 1-4, gamma 1-3, delta, pi, epsilon, Theta, and rho 1-3.

GABA


Input: Oocyte of Xenopus laevis is one of the most frequently used heterologous expression systems, which are used to design and analyze specific combinations of GABA A receptor subunits.

GABA


Input: In oocytes, a certain GABA A receptor function is studied only by comparing the amplitude of the response to GABA and other drugs by physiological and pharmacological methods.

GABA

GABA


Input: According to the studies on Xenopus laevis oocytes, the alpha 1 beta 2 gamma 2S receptor combination is mostly used.


Input: The alpha 1-containing receptors mediate sedative and anticonvulsant acts.


Input: The results of studies on oocytes show that PKA, NKCC1, P2X3 receptors, and GABA A receptor-associated protein, etc., are existing systems that show different reactivity to the GABA A receptors.

GABA

GABA


Input: The GABA A receptor subunits contain distinct binding sites for BZDs, neurosteroids, general anesthetics, etc., which are responsible for the numerous functions of the GABA A receptor.

GABA

BZDs

neurosteroids

GABA


Input: A variety of other drugs, such as topiramate, TG41, (+)-and (-)-borneol, apigenin, and 6-methylflavone could also have modulatory effects on the GABA A receptors.

topiramate

(+)-and (-)-borneol

apigenin

GABA


Input: Some of the different models and hypotheses on GABA A receptor structure and function have been achieved by using the two-electrode voltage clamp method in oocytes.

GABA


Input: Bioactive natural products from the antarctic and arctic organisms.


Input: Polar regions are remote and challenging areas on the earth.


Input: In view of the unique environment and the severe competition in polar regions, it' s considered that the ecological system might be the producer of new compounds with diversity biological activities.


Input: This review is an attempt to consolidate the studies about 97 natural products isolated from Antarctic and Arctic organisms including microbes, algae, sponges, bryozoans, and tunicates and so on published in the recent years.


Input: The emphasis is mainly about the new compounds, source organisms and biological activities, which signifies the immense competence of Antarctic and Arctic organisms as bioactive natural products producers.


Input: Taxol: efficacy against oral squamous cell carcinoma.

Taxol


Input: In medicinal chemistry, one of the most studied molecules in recent history is taxol.

taxol


Input: Taxol is a versatile natural product that is used in various cancer treatment regimens.

Taxol


Input: It is administered to patients with breast, lung, and ovarian cancers, and is currently being studied for the treatment of squamous cell carcinoma of the oral cavity and tongue.


Input: Taxol has been tested in a number of research and clinical phase trials to determine feasibility, toxicity, and cytotoxicity against oral squamous cell carcinoma as a single drug regimen and as a contributing drug component in treatment plans.

Taxol


Input: This paper reviews over forty articles that examine cell lines, murine models, and human results for the response of taxol against squamous cell carcinoma (SCC) of the oral cavity and the tongue.

taxol


Input: The evolution of drugs on schistosoma treatment: looking to the past to improve the future.


Input: Schistosomiasis is a devastating worldwide widespread tropical disease that currently affects more than 230 million people, making it an issue of great socioeconomic and public health importance.


Input: Unfortunatelly there is a single drug for the treatment of all forms of schistosomiasis, praziquantel, which was introduced in therapy in 1980.

praziquantel


Input: The article goes by antimony compounds, emetine, hydantoin, nitrofurans, lucanthone, hycanthone, oxamniquine derivatives and organophosphates until it finally gets to praziquantel derivatives.

emetine

hydantoin

nitrofurans

lucanthone

hycanthone

oxamniquine

organophosphates

praziquantel


Input: The intent of this review is to provide a panorama of drugs that were and are being used in human chemotherapy looking to the past to improve rational design drugs in the future.


Input: Not only clinical used compounds will be shown but also synthesized and tested compounds in vitro and in vivo in animal models which haven' t yet to be used in humans.


Input: Prospects for drug discovery and vaccines to be used in the treatment and prevention of schistosomiasis, clinical trials, concerns about the resistance/decreased effectiveness of the treatment, and patent database will also be discussed.


Input: At the end of the review the reader will notice that much has been done but much still needs to be done yet.


Input: Electrochemiluminescence biosensor based on conducting poly (5-formylindole) for sensitive detection of Ramos cells.

poly (5-formylindole)


Input: A signal-on electrochemiluminescence (ECL) biosensor devoted to the detection of Ramos cells was fabricated based on a novel conducting polymer, poly (5-formylindole) (P5FIn), which was synthesized electrochemically by direct anodic oxidation of 5-formylindole (5FIn).

poly (5-formylindole)


Input: This ECL platform was presented by covalently coupling the 18-mer amino-substituted oligonucleotide (ODN) probes with aldehyde groups that are strongly reactive toward a variety of nucleophiles on the surface of solid substrates.

aldehyde


Input: The specific identification and high-affinity between aptamers and target cells, gold nanoparticles (AuNPs) enhanced ECL nanoprobes, along with P5FIn induced ECL quenching contributed greatly to the sensitivity and selectivity.


Input: The ECL signals were logarithmically linear with the concentration of Ramos cells in a wide determination range from 500 to 1. 0 x 10 (5) cells mL (-1), and the corresponding detection limit was 300 cells mL (-1).


Input: How the quantum efficiency of a highly emissive binuclear copper complex is enhanced by changing the processing solvent.

copper


Input: Polymorphism is often linked to the choice of processing solvents.


Input: Packing effects or the preference of one certain conformer as possible causes of this phenomenon are strongly dependent on solvents and especially on their polarity.


Input: Even in amorphous solids, the microstructure can be controlled by the choice of solvents.


Input: Polymorphs or amorphous solids featuring different packing densities can exhibit different properties in terms of stability or optical effects.


Input: The influence of these effects on a binuclear, strongly luminescent copper (I) complex was investigated.

copper (I)


Input: Many possible applications for luminescent, amorphous coordination compounds, such as organic light-emitting diodes, sensors, and organic lasers, rely on photophysical properties like quantum efficiency to be repeatable.


Input: The effect of processing solvents in this context is often underestimated, but very relevant for utilization in device manufacturing and should therefore be understood more deeply.


Input: In this work, theoretical derivations, DFT calculations, X-ray-diffraction, photoluminescence spectroscopy, and the time-dependent single-photon-counting-technique (TDSPC) were used to understand this phenomenon more deeply.


Input: The influence of five different solvents on Cu2I2 (MePyrPHOS) 3 was probed.

Cu2I2 (MePyrPHOS) 3


Input: This resulted in a modulation of the photoluminescence quantum yield phi between 0. 5 and 0. 9 in amorphous solid state.


Input: A new polymorph of the material with slightly reduced values for phi has been identified.


Input: The reduced efficiency could be correlated with a higher porosity and a reduced packing density.


Input: Dense packing reduces nonradiative decay by geometrical fixation and thus increases the quantum efficiency.


Input: The existence of similar effects on aluminum and iridium compounds has been confirmed by application of different processing solvents on Alq3 and Ir (ppy) 3.

aluminum

iridium

Ir (ppy) 3


Input: These results show that a tuning of the efficiency of a emissive metal complexes by choosing a proper processing solvent is possible.


Input: If highly efficient materials for practical applications are desired, an evaluation of multiple solvents has to be considered.


Input: Heavy-enzyme kinetic isotope effects on proton transfer in alanine racemase.

alanine


Input: The catalytic effects of perdeuterating the pyridoxal phosphate-dependent enzyme alanine racemase from Geobacillus stearothermophilus are reported.

pyridoxal phosphate

alanine


Input: The mass of the heavy perdeuterated form is ~ 5. 5% greater than that of the protiated form, causing kinetic isotope effects (KIEs) of ~ 1. 3 on k (cat) and k (cat)/K (M) for both L-and D-alanine.

L-and D-alanine


Input: These values increase when C alpha-deuterated alanine is used as the substrate.

C alpha-deuterated alanine


Input: The heavy-enzyme KIEs of ~ 3 on k (cat)/K (M) with deuterated substrates are greater than the product of the individual heavy-enzyme and primary substrate KIEs.


Input: This breakdown of the rule of the geometric mean is likely due to coupled motion between the protein and the proton-transfer reaction coordinate in the rate-limiting step.


Input: These data implicate a direct role for protein vibrational motions in barrier crossing for proton-transfer steps in alanine racemase.

alanine


Input: Gene copy-number alterations: a cost-benefit analysis.


Input: Changes in DNA copy number, whether confined to specific genes or affecting whole chromosomes, have been identified as causes of diseases and developmental abnormalities and as sources of adaptive potential.


Input: Here, we discuss the costs and benefits of DNA copy-number alterations.


Input: Changes in DNA copy number are largely detrimental.


Input: Amplifications or deletions of specific genes can elicit discrete defects.


Input: Large-scale changes in DNA copy number can also cause detrimental phenotypes that are due to the cumulative effects of copy-number alterations of many genes simultaneously.


Input: On the other hand, studies in microorganisms show that DNA copy-number alterations can be beneficial, increasing survival under selective pressure.


Input: As DNA copy-number alterations underlie many human diseases, we will end with a discussion of gene copy-number changes as therapeutic targets.


Input: Conformational coupling across the plasma membrane in activation of the EGF receptor.


Input: How the epidermal growth factor receptor (EGFR) activates is incompletely understood.


Input: The intracellular portion of the receptor is intrinsically active in solution, and to study its regulation, we measured autophosphorylation as a function of EGFR surface density in cells.


Input: Without EGF, intact EGFR escapes inhibition only at high surface densities.


Input: Although the transmembrane helix and the intracellular module together suffice for constitutive activity even at low densities, the intracellular module is inactivated when tethered on its own to the plasma membrane, and fluorescence cross-correlation shows that it fails to dimerize.


Input: NMR and functional data indicate that activation requires an N-terminal interaction between the transmembrane helices, which promotes an antiparallel interaction between juxtamembrane segments and release of inhibition by the membrane.

NMR


Input: We conclude that EGF binding removes steric constraints in the extracellular module, promoting activation through N-terminal association of the transmembrane helices.

N


Input: LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation.


Input: Eukaryotic cells have a layer of heterochromatin at the nuclear periphery.


Input: To investigate mechanisms regulating chromatin distribution, we analyzed heterochromatin organization in different tissues and species, including mice with mutations in the lamin B receptor (Lbr) and lamin A (Lmna) genes that encode nuclear envelope (NE) proteins.


Input: We identified LBR-and lamin-A/C-dependent mechanisms tethering heterochromatin to the NE.


Input: The two tethers are sequentially used during cellular differentiation and development: first the LBR-and then the lamin-A/C-dependent tether.


Input: The absence of both LBR and lamin A/C leads to loss of peripheral heterochromatin and an inverted architecture with heterochromatin localizing to the nuclear interior.


Input: Myoblast transcriptome analyses indicated that selective disruption of the LBR-or lamin-A-dependent heterochromatin tethers have opposite effects on muscle gene expression, either increasing or decreasing, respectively.


Input: These results show how changes in NE composition contribute to regulating heterochromatin positioning, gene expression, and cellular differentiation during development.


Input: Vitamin D metabolism in human bone marrow stromal (mesenchymal stem) cells.

Vitamin D


Input: There are many human extra-renal tissues and cells that biosynthesize 1 alpha, 25-dihydroxyvitamin D (1 alpha, 25 (OH) (2) D) by the action of CYP27B1/1 alpha-hydroxylase.

1 alpha, 25-dihydroxyvitamin D

1 alpha, 25 (OH) (2) D


Input: Human marrow stromal cells (hMSCs), also known as mesenchymal stem cells, were isolated from marrow discarded from well-characterized, consented subjects during common orthopedic procedures.


Input: Human MSCs can give rise to osteoblasts, chondrocytes, adipocytes, and other lineages.


Input: Their in vitro differentiation to osteoblasts is stimulated by 1 alpha, 25 (OH) (2) D, and recent evidence indicates that they have the capacity to metabolize vitamin D in a regulated manner.

1 alpha, 25 (OH) (2) D

vitamin D


Input: Human MSCs express the vitamin D receptor, 25-hydroxylases, 1 alpha-hydroxylase, and 24-hydroxylase; stimulation of in vitro osteoblastogenesis by 25 (OH) D depends on the activity of CYP27B1/1 alpha-hydroxylase.

vitamin D

25 (OH) D


Input: The finding that hMSCs are a both a producer and target of 1 alpha, 25 (OH) (2) D suggests a potential autocrine/paracrine role of vitamin D metabolism in osteoblast differentiation.

1 alpha, 25 (OH) (2) D

vitamin D


Input: Expression and enzyme activity of CYP27B1/1 alpha-hydroxylase are upregulated by substrate 25 (OH) D and Parathyroid Hormone (PTH) and are downregulated by 1 alpha, 25 (OH) (2) D.

25 (OH) D

1 alpha, 25 (OH) (2) D


Input: With subject age, there are decreases in basal osteoblast potential and in stimulation of osteoblastogenesis by 1 alpha, 25 (OH) (2) D, 25 (OH) D, and PTH.

1 alpha, 25 (OH) (2) D

25 (OH) D


Input: In vitro treatment with a combination of 25 (OH) D and PTH rejuvenated osteoblastogenesis with hMSCs from elders; this was attributable to increases in CYP27B1/1 alpha-hydroxylase and in receptor for each hormone by the reciprocal factor.

25 (OH) D


Input: Other clinical variables beside age, i. e. low serum 25 (OH) D or low estimated glomerular filtration rate, are correlated with reduced osteoblastogenesis.

25 (OH) D


Input: These studies suggest that osteoblastogenesis may not be optimal unless there is sufficient serum 25 (OH) D substrate for hMSCs to synthesize and respond to local 1 alpha, 25 (OH) (2) D.

25 (OH) D

1 alpha, 25 (OH) (2) D


Input: Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness.

amino acids


Input: OBJECTIVE: To identify novel biomarkers through metabolomic profiles that distinguish metabolically well (MW) from metabolically unwell (MUW) individuals, independent of body mass index (BMI).


Input: MATERIALS/METHODS: This study was conducted as part of the Measurement to Understand the Reclassification of Disease of Cabarrus/Kannapolis (MURDOCK) project.


Input: Individuals from 3 cohorts were classified as lean (BMI < 25kg/m (2)), overweight (BMI >= 25kg/m (2), BMI < 30kg/m (2)) or obese (BMI >= 30kg/m (2)).


Input: Cardiometabolic abnormalities were defined as: (1) impaired fasting glucose (>= 100mg/dL and <= 126mg/dL); (2) hypertension; (3) triglycerides >= 150mg/dL; (4) HDL-C < 40mg/dL in men, < 50mg/dL in women; and (5) insulin resistance (calculated Homeostatic Model Assessment (HOMA-IR) index of > 5. 13).

glucose

triglycerides


Input: MW individuals were defined as having < 2 cardiometabolic abnormalities and MUW individuals had >= two cardiometabolic abnormalities.


Input: Targeted profiling of 55 metabolites used mass-spectroscopy-based methods.


Input: Principal components analysis (PCA) was used to reduce the large number of correlated metabolites into clusters of fewer uncorrelated factors.


Input: RESULTS: Of 1872 individuals, 410 were lean, 610 were overweight, and 852 were obese.


Input: Of lean individuals, 67% were categorized as MUW, whereas 80% of overweight and 87% of obese individuals were MUW.


Input: PCA-derived factors with levels that differed the most between MW and MUW groups were factors 4 (branched chain amino acids [BCAA]) [p <. 0001], 8 (various metabolites) [p <. 0001], 9 (C4/Ci4, C3, C5 acylcarnitines) [p <. 0001] and 10 (amino acids) [p <. 0002].

amino acids

C4/Ci4, C3, C5 acylcarnitines

amino acids


Input: Further, Factor 4, distinguishes MW from MUW individuals independent of BMI.


Input: CONCLUSION: BCAA and related metabolites are promising biomarkers that may aid in understanding cardiometabolic health independent of BMI category.


Input: Critical role of a methyl group on the gamma-lactone ring of annonaceous acetogenins in the potent inhibition of mitochondrial complex I.

methyl

gamma-lactone

acetogenins


Input: C34-epi and C34-epi-C35-trifluoro analogues of solamin, a mono-THF annonaceous acetogenin, were synthesized.

solamin

mono-THF

acetogenin


Input: Their inhibitory activity, along with previously synthesized analogues (C35-fluoro, C35-difluoro, and C35-trifluorosolamins), against bovine mitochondrial NADH-ubiquinone oxidoreductase (complex I) was determined.

C35-fluoro, C35-difluoro, and C35-trifluorosolamins

NADH

ubiquinone


Input: The present study revealed that the methyl group on the gamma-lactone moiety is critical to the potent inhibition of complex I by natural acetogenins.

methyl

gamma-lactone

acetogenins


Input: Synthesis and antibacterial activity of 9-oxime ether non-ketolides, and novel binding mode of alkylides with bacterial rRNA.

9-oxime ether

ketolides

alkylides


Input: We report a series of new 9-oxime ether non-ketolides, including 3-hydroxyl, 3-O-acyl and 3-O-alkyl clarithromycin derivatives, and thiophene-containing ketolides 1b-1d.

9-oxime ether

ketolides

3-hydroxyl, 3-O-acyl and 3-O-alkyl clarithromycin

thiophene

ketolides


Input: Unlike previously reported ketolide 1a, none of them is comparable to telithromycin.

ketolide

telithromycin


Input: A molecular modeling study was performed to gain insight into the binding mode of alkylides 17-20 with bacterial rRNA and to rationalize the great disparity of their SAR.

alkylides


Input: The 3-O-sidechains of 19 and 20 point to the so-called hydrophilic side of the macrolide ring, as seen in clarithromycin.

O

macrolide

clarithromycin


Input: In contrast, the 3-O-sidechains of 17 and 18 bend to the backside, the so-called hydrophobic side of the macrolide ring.

O


Input: The results clearly indicated the alkylides with improved antibacterial activity might possess a novel binding mode, which is different from clarithromycin and the alkylides with poor activity.

alkylides

clarithromycin

alkylides


Input: Influence of GluN2 subunit identity on NMDA receptor function.

NMDA


Input: N-methyl-d-aspartate receptors (NMDARs) are ligand-gated ion channels (' ionotropic' receptors) activated by the major excitatory neurotransmitter, l-glutamate.

N-methyl-d-aspartate

l-glutamate


Input: While the term' the NMDAR' is often used it obscures the fact that this class of receptor contains within it members whose properties are as different as they are similar.


Input: This heterogeneity was evident from early electrophysiological, pharmacological and biochemical assessments of the functional properties of NMDARs and while the molecular basis of this heterogeneity has taken many years to elucidate, it indicated from the outset that the diversity of NMDAR phenotypes could allow this receptor family to subserve a variety of functions in the mammalian central nervous system.


Input: In this review we highlight some recent studies that have identified structural elements within GluN2 subunits that contribute to the heterogeneous biophysical properties of NMDARs, consider why some recently described novel pharmacological tools may permit better identification of native NMDAR subtypes, examine the evidence that NMDAR subtypes differentially contribute to the induction of long-term potentiation and long-term depression and discuss how through the use of chimeric proteins additional insights have been obtained that account for NMDAR subtype-dependency of physiological and pathophysiological signalling.


Input: This article is part of a Special Issue entitled' GluR-dep synaptic plasticity'.


Input: Arsenic induced neuronal apoptosis in guinea pigs is Ca2 + dependent and abrogated by chelation therapy: role of voltage gated calcium channels.

Arsenic

Ca2 +

calcium


Input: Arsenic contaminated drinking water has affected more than 200 million people globally.

Arsenic


Input: Chronic arsenicism has also been associated with numerous neurological diseases.


Input: One of the prime mechanisms postulated for arsenic toxicity is reactive oxygen species (ROS) mediated oxidative stress.

arsenic

oxygen


Input: In this study, we explored the kinetic relationship of ROS with calcium and attempted to dissect the calcium ion channels responsible for calcium imbalance after arsenic exposure.

calcium

calcium

calcium

arsenic


Input: We also explored if mono-or combinational chelation therapy prevents arsenic-induced (25ppm in drinking water for 4 months) neuronal apoptosis in a guinea pig animal model.

arsenic


Input: Results indicate that chronic arsenic exposure caused a significant increase in ROS followed by NO and calcium influx.

arsenic

NO

calcium


Input: This calcium influx is mainly dependent on L-type voltage gated channels that disrupt mitochondrial membrane potential, increase bax/bcl2 levels and caspase 3 activity leading to apoptosis.

calcium


Input: Interestingly, blocking of ROS could completely reduce calcium influx whereas calcium blockage partially reduced ROS increase.

calcium

calcium


Input: While in general mono-and combinational chelation therapies were effective in reversing arsenic induced alteration, combinational therapy of DMSA and MiADMSA was most effective.

arsenic

DMSA

MiADMSA


Input: Our results provide evidence for the role of L-type calcium channels in regulating arsenic-induced calcium influx and DMSA + MiADMSA combinational therapy may be a better protocol than monotherapy in mitigating chronic arsenicosis.

calcium

arsenic

calcium

DMSA

MiADMSA


Input: Gastrodin attenuation of the inflammatory response in H9c2 cardiomyocytes involves inhibition of NF-kappa B and MAPKs activation via the phosphatidylinositol 3-kinase signaling.

Gastrodin

phosphatidylinositol


Input: The phenolic glucoside gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties.

phenolic glucoside gastrodin


Input: However, the role and precise molecular mechanisms explaining how gastrodin suppresses the inflammatory response in septic cardiac dysfunction are unknown.

gastrodin


Input: To study this, rat H9c2 cardiomyocytes were treated with gastrodin and/or lipopolysaccharide (LPS).

gastrodin


Input: Our results showed that gastrodin treatment strongly suppressed nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinases (MAPKs) family activation and upregulation of the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in LPS-stimulated H9c2 cardiomyocytes.

gastrodin

nitric oxide


Input: Simultaneously, gastrodin obviously upregulated the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling in a dose-dependent manner.

gastrodin

phosphatidylinositol


Input: However, wortmannin, a specific PI3-K inhibitor, blocked the inhibitory effects of gastrodin on LPS-stimulated H9c2 cardiomyocytes.

wortmannin

gastrodin


Input: Furthermore, PI3-K/Akt inhibition partially abolished the inhibitory effects of gastrodin on the phosphorylation of inhibitor kappa B-alpha (I kappa B-alpha), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), and activity of NF-kappa B.

gastrodin

N


Input: Here we report activation of the PI3-K/Akt signaling by gastrodin and that inhibition of this pathway reverses the inhibitory effects of gastrodin on NF-kappa B and MAPKs activation in H9c2 cardiomyocytes.

gastrodin

gastrodin


Input: Catalytic-site conformational equilibrium in nerve-agent adducts of acetylcholinesterase: Possible implications for the HI-6 antidote substrate specificity.


Input: Nerve agents such as tabun, cyclosarin and Russian VX inhibit the essential enzyme acetylcholinesterase (AChE) by organophosphorylating the catalytic serine residue.

tabun

cyclosarin

Russian VX

serine


Input: Nucleophiles, such as oximes, are used as antidotes as they can reactivate and restore the function of the inhibited enzyme.

oximes


Input: The oxime HI-6 shows a notably low activity on tabun adducts but can effectively reactivate adducts of cyclosarin and Russian VX.

oxime HI-6

tabun

cyclosarin

Russian VX


Input: To examine the structural basis for the pronounced substrate specificity of HI-6, we determined the binary crystal structures of Mus musculus AChE (mAChE) conjugated by cyclosarin and Russian VX and found a conformational mobility of the side chains of Phe338 and His447.

cyclosarin

Russian VX


Input: The interaction between HI-6 and tabun-adducts of AChE were subsequently investigated using a combination of time resolved fluorescence spectroscopy and X-ray crystallography.

tabun


Input: Our findings show that HI-6 binds to tabun inhibited Homo sapiens AChE (hAChE) with an IC50 value of 300 mu M and suggest that the reactive nucleophilic moiety of HI-6 is excluded from the phosphorus atom of tabun.

tabun

phosphorus

tabun


Input: We propose that a conformational mobility of the side-chains of Phe338 and His447 is a common feature in nerve-agent adducts of AChE.


Input: We also suggest that the conformational mobility allow HI-6 to reactivate conjugates of cyclosarin and Russian VX while a reduced mobility in tabun conjugated AChE results in steric hindrance that prevents efficient reactivation.

cyclosarin

Russian VX

tabun


Input: Hepatocytes display a compensatory survival response against cadmium toxicity by a mechanism mediated by EGFR and Src.

cadmium


Input: Although the liver is a cadmium-target organ, hepatocyte response involved in its toxicity is not yet elucidated.

cadmium


Input: A link between this heavy metal treatment and Stat3 signaling pathways was examined in primary mouse hepatocytes.


Input: We provided evidence of a novel link among NADPH oxidase and Stat3 signaling, mediated by Src, EGFR, and Erk1/2.

NADPH


Input: Cadmium activates NADPH oxidase.

Cadmium

NADPH


Input: ROS produced by this oxidase activates Src, enable that in turn, transactivates EGFR that activates Stat3 in tyrosine, allowing its dimerization.

tyrosine


Input: Also, ROS from NADPH oxidase favors ERK1/2 activation that phosphorylates Stat3 in serine, resulting in a compensatory or adaptive survival response such as production of metallothionein-II in short Cd exposure times.

NADPH

serine

Cd


Input: However, after 12h CdCl2 treatment, cell viability diminished in 50%, accompanied by a drastic decrease of metallothionein-II production, and an increase in p53 activation and the pro-apoptotic protein Bax.


Input: Catalpol suppresses advanced glycation end-products-induced inflammatory responses through inhibition of reactive oxygen species in human monocytic THP-1 cells.

Catalpol

oxygen


Input: Advanced glycation end-products (AGEs) play a pivotal role in the development of diabetic complications by inducing inflammation.


Input: We previously reported that the fresh roots of Rehmannia glutinosa Libosch., which have been used for the treatment of diabetes in traditional Korean medicine, also have the potential to suppress AGE-mediated inflammatory response in THP-1 cells.


Input: In the present study, we isolated catalpol from R. glutinosa, and examined whether it has anti-inflammatory effects on AGE-stimulated THP-1 cells.

catalpol


Input: Catalpol reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), inducible NO synthase (iNOS), and receptor for AGE (RAGE).

Catalpol

NO


Input: Promoter and electromobility shift assays showed that transcriptional activation of NF-kappa B was significantly reduced by catalpol treatment, while AP-1 was not.

catalpol


Input: Catalpol also suppressed AGE-induced phosphorylation of mitogen activated protein (MAP) kinases, degradation of I kappa B alpha and the nuclear localization of NF-kappa B.

Catalpol


Input: Moreover, the production of intracellular reactive oxygen species (ROS) elicited by AGE was also suppressed by catalpol treatment, through dual action of reducing ROS itself and inhibiting NADPH oxidase activity.

oxygen

catalpol

NADPH


Input: Our findings indicate that catalpol suppresses AGE-mediated inflammation by inhibiting ROS production and NF-kappa B activity.

catalpol


Input: We suggest that catalpol, a major constituent of the fresh roots of R. glutinosa, contributes to the prevention of AGE-mediated diabetic complications.

catalpol


Input: New insights toward the discovery of antibacterial agents: multi-tasking QSBER model for the simultaneous prediction of anti-tuberculosis activity and toxicological profiles of drugs.


Input: Tuberculosis (TB) constitutes one of the most dangerous and serious health problems around the world.


Input: It is a very lethal disease caused by microorganisms of the genus mycobacterium, principally Mycobacterium tuberculosis (MTB) which affects humans.


Input: A very active field for the search of more efficient anti-TB chemotherapies is the use in silico methodologies for the discovery of potent anti-TB agents.


Input: The battle against MTB by using antimicrobial chemotherapies will depend on the design of new chemicals with high anti-TB activity and low toxicity as possible.


Input: Multi-target methodologies focused on quantitative-structure activity relationships (mt-QSAR) have played a very important role for the rationalization of drug design, providing a better understanding about the molecular patterns related with diverse pharmacological profiles including antimicrobial activity.


Input: Nowadays, almost all mt-QSAR models have considered the study of biological activity or toxicity separately.


Input: In the present study, we develop by the first time, a unified multitasking model based on quantitative-structure biological effect relationships (mtk-QSBER) for the simultaneous prediction of anti-TB activity and toxicity against Mus musculus and Rattus norvegicus.


Input: The mtk-QSBER model was created by using linear discriminant analysis (LDA) for the classification of compounds as positive (high biological activity and/or low toxicity) or negative (otherwise) under many experimental conditions.


Input: Our mtk-QSBER model, correctly classified more than 90% of the case in the whole database (more than 12, 000 cases), serving as a powerful tool for the computer-assisted screening of potent and safe anti-TB drugs.


Input: Excessive ethanol consumption under exposure to lead intensifies disorders in bone metabolism: A study in a rat model.

ethanol


Input: It was investigated whether ethanol (Et) modifies the damaging impact of lead (Pb) on bone metabolism in a rat model reflecting excessive alcohol consumption by humans exposed to relatively high levels of this metal.

ethanol

Pb

alcohol


Input: For this purpose, markers of bone formation (osteocalcin, procollagen I, osteoprotegerin, alkaline phosphatase) and resorption (telopeptides of collagen I, soluble receptor activator of nuclear factor-kappa B ligand), calciotropic hormones (parathormone, calcitonin, 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D) in the serum, and the femur content of mineral (including calcium-Ca and inorganic phosphorus-Pi) and organic components were estimated in the rats exposed to 500mg Pb/l (in drinking water) or/and Et (5g/kg b. wt./24h, by oral gavage) for 12weeks.

25-hydroxyvitamin D

1, 25-dihydroxyvitamin D

calcium

Ca

phosphorus

Pb


Input: Moreover, Ca and Pi in the serum and urine, alkaline phosphatase in the bone tissue and Pb in the blood and femur were determined.

Ca

Pb


Input: The exposure to Pb or/and Et decreased bone formation and increased its resorption resulting in the bone demineralization.

Pb


Input: These effects were accompanied by destroying the hormonal regulation of mineral metabolism, and Ca and Pi imbalance.

Ca


Input: The co-exposure to Pb and Et-induced disorders in bone metabolism were more advanced than those caused by Pb alone.

Pb

Pb


Input: Et co-administration increased Pb concentration in the blood and decreased its accumulation in the bone.

Pb


Input: This paper is the first report providing evidence that consumption of Et under exposure to Pb intensifies disorders in bone metabolism and that destroying of the receptor activator nuclear factor-kappa B (RANK)/RANK ligand/osteoprotegerin system is involved in the mechanisms of interactive action of these xenobiotics on the skeleton.

Pb


Input: The modifying impact of Et may be an effect of its independent osteotropic action and interaction with Pb.

Pb


Input: Based on the results it can be concluded that alcohol abuse by subjects excessively exposed to Pb considerably increases the risk of bone damage.

alcohol

Pb


Input: Cellular mechanisms of the cytotoxic effects of the zearalenone metabolites alpha-zearalenol and beta-zearalenol on RAW264. 7 macrophages.

zearalenone

alpha-zearalenol

beta-zearalenol


Input: Zearalenone (ZEN) and its metabolites are commonly found in many food commodities and are known to cause reproductive disorders and genotoxic effects.

Zearalenone

ZEN


Input: The major ZEN metabolites are alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL).

ZEN

alpha-zearalenol

alpha-ZOL

beta-zearalenol

beta-ZOL


Input: Although many studies have demonstrated the cytotoxic effects of these metabolites, the mechanisms by which alpha-ZOL or beta-ZOL mediates their cytotoxic effects appear to differ according to cell type and the exposed toxins.

alpha-ZOL

beta-ZOL


Input: We evaluated the toxicity of alpha-ZOL and beta-ZOL on RAW264. 7 macrophages and investigated the underlying mechanisms.

alpha-ZOL

beta-ZOL


Input: beta-ZOL not only more strongly reduced the viability of cells than did alpha-ZOL, but it also induced cell death mainly by apoptosis rather than necrosis.

beta-ZOL

alpha-ZOL


Input: The ZEN metabolites induced loss of mitochondrial membrane potential (MMP), mitochondrial changes in Bcl-2 and Bax proteins, and cytoplasmic release of cytochrome c and apoptosis-inducing factor (AIF).

ZEN


Input: Use of an inhibitor specific to c-Jun N-terminal kinase (JNK), p38 kinase or p53, but not pan-caspase or caspase-8, decreased the toxin-induced generation of reactive oxygen species (ROS) and also attenuated the alpha-ZOL-or beta-ZOL-induced decrease of cell viability.

N

oxygen

alpha-ZOL

beta-ZOL


Input: Antioxidative enzyme or compounds such as catalase, acteoside, and (E)-1-(3, 4-dihydroxyphenethyl)-3-(4-hydroxystyryl) urea suppressed the ZEN metabolite-mediated reduction of cell viability.

acteoside

(E)-1-(3, 4-dihydroxyphenethyl)-3-(4-hydroxystyryl) urea

ZEN


Input: Further, knockdown of AIF via siRNA transfection diminished the ZEN metabolite-induced cell death.

ZEN


Input: Collectively, these results suggest that the activation of p53, JNK or p38 kinase by ZEN metabolites is the main upstream signal required for the mitochondrial alteration of Bcl-2/Bax signaling pathways and intracellular ROS generation, while MMP loss and nuclear translocation of AIF are the critical downstream events for ZEN metabolite-mediated apoptosis in macrophages.

ZEN

ZEN


Input: Sodium arsenite induces cyclooxygenase-2 expression in human uroepithelial cells through MAPK pathway activation and reactive oxygen species induction.

Sodium arsenite


Input: Arsenic can induce reactive oxygen species (ROS) leading to oxidative stress and carcinogenesis.

Arsenic

oxygen


Input: Bladder is one of the major target organs of arsenic, and cyclooxygenase-2 (COX-2) may play an important role in arsenic-induced bladder cancer.

arsenic

arsenic


Input: However, the mechanism by which arsenic induces COX-2 in bladder cells remains unclear.

arsenic


Input: This study aimed at investigating arsenic-mediated intracellular redox status and signaling cascades leading to COX-2 induction in human uroepithelial cells (SV-HUC-1).

arsenic


Input: SV-HUC-1 cells were exposed to sodium arsenite and COX-2 expression, mitogen-activated protein kinase (MAPK) phosphorylation, glutathione (GSH) levels, ROS induction and Nrf2 expression were quantified.

sodium arsenite

glutathione

GSH


Input: Our results demonstrate that arsenite (1-10 mu M) elevates COX-2 expression, GSH levels, ROS and Nrf2 expression.

arsenite

GSH


Input: Arsenite treatment for 24h stimulates phosphorylation of ERK and p38, but not JNK in SV-HUC-1 cells.

Arsenite


Input: Induction of Cox-2 mRNA levels by arsenite was attenuated by inhibitors of ERK, p38 and JNK.

arsenite


Input: Arsenite-induced ROS generation and COX-2 expression were significantly attenuated by treatment with melatonin (a ROS scavenger), but enhanced by DL-buthionine-(S, R)-sulfoximine (BSO, an inhibitor of gamma-glutamylcysteine synthetase (gamma-GCS) resulting in lower GSH and increased ROS levels).

Arsenite

melatonin

DL-buthionine-(S, R)-sulfoximine

BSO

gamma-glutamylcysteine

GSH


Input: These data indicate that arsenite promotes an induction of ROS, which results in an induction of COX-2 expression through activation of the MAPK pathway.

arsenite


Input: OGG1 Ser326Cys polymorphism interacts with cigarette smoking to increase oxidative DNA damage in human sperm and the risk of male infertility.


Input: 8-Oxoguanine DNA glycosylase 1 (OGG1) plays an important role in repairing oxidative DNA damage induced by chemical agents, such as tobacco.


Input: This study examined the effects of OGG1 Ser326Cys polymorphism and cigarette smoking, alone or combined, on sperm oxidative DNA damage and the risk of male infertility.


Input: A total of 620 idiopathic infertile subjects and 480 fertile controls were recruited in this study.


Input: Sperm 8-hydroxydeoxyguanine (8-OHdG) was measured by immunofluorescent assay using flow cytometry and genotypes were determined by OpenArray platform with a chip-based Taq-Man genotyping technology.


Input: Our results demonstrated that both cigarette smoking and OGG1 polymorphism can affect the sperm 8-OHdG levels.


Input: Individuals with variant Cys/Cys homozygote showed higher levels of sperm 8-OHdG than wide-type homozygote carriers (Ser/Ser).

Cys

Cys

Ser

Ser


Input: Stratified analysis found that the association between OGG1 polymorphism and sperm 8-OHdG levels was only observed among smokers with pack-years >= 5 but not among those subjects with pack-years < 5 (pack-years = packs smoked per day x years as a smoker).


Input: Further analysis based on the case-control study revealed that variant allele (Cys) of OGG1 was significantly associated with male infertility risk in a dominant model (OR = 1. 35, 95% CI: 1. 01-1. 82; trend P < 0. 001).

Cys


Input: Furthermore, we found a significant gene-environment interaction between OGG1 Ser326Cys polymorphism and cigarette smoking in relation to male infertility risk (Pinteration = 0. 0003).


Input: These findings provided the first evidence about potential interactive effects of OGG1 polymorphism and cigarette smoking on male infertility risk.


Input: Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity.

Lycorine hydrochloride


Input: Uncontrolled tumor cell proliferation and robust neovascularization are prominent features of aggressive ovarian cancers.


Input: Although great efforts in anti-ovarian cancer therapy have been made in the past 4 decades, the 5-year survival rates for ovarian cancer patients are still poor, and effective drugs to cure ovarian cancer patients are absent.


Input: In this study, we evaluated the anti-cancer effects of lycorine hydrochloride (LH), a novel anti-ovarian cancer agent, using the highly-invasive ovarian cancer cell line, Hey1B, as a model.

lycorine hydrochloride


Input: Our data showed that LH effectively inhibited mitotic proliferation of Hey1B cells (half maximal inhibitory concentration = 1. 2 mu M) with very low toxicity, resulting in cell cycle arrest at the G2/M transition through enhanced expression of the cell cycle inhibitor p21 and marked down-regulation of cyclin D3 expression.


Input: Moreover, LH suppressed both the formation of capillary-like tubes by Hey1B cells cultured in vitro and the ovarian cancer cell-dominant neovascularization in vivo when administered to Hey1B-xenotransplanted mice.


Input: LH also suppressed the expression of several key angiogenic genes, including VE-cadherin, vascular endothelial growth factor, and Sema4D, and reduced Akt phosphorylation in Hey1B cells.


Input: These results suggest that LH selectively inhibits ovarian cancer cell proliferation and neovascularization and is a potential drug candidate for anti-ovarian cancer therapy.


Input: Catechins are not major components responsible for the beneficial effect of Camellia sinensis on the ovarian delta-ALA-D activity inhibited by cadmium.

Catechins

delta-ALA

cadmium


Input: Cadmium has been associated with a wide spectrum of deleterious effects on the reproductive tissues, including ovary.

Cadmium


Input: This investigation evaluated the protective role of Camellia sinensis (green, white and red teas) in the cadmium-induced inhibition of ovarian delta-aminolevulinate dehydratase (delta-ALA-D) activity in vitro and ex vivo.

cadmium

delta-aminolevulinate

delta-ALA


Input: This study demonstrated that green and white teas restored the cow ovary delta-ALA-D activity inhibited by cadmium whereas red tea had no effect in vitro.

delta-ALA

cadmium


Input: In addition, green tea was able to restore enzyme activity inhibited after acute cadmium exposure in mice ovary.

cadmium


Input: Teas infusions composition was assessed by HPLC in a quantitative assay for catechins, purine alkaloids and gallic acid as well as total polyphenol content.

catechins

purine alkaloids

gallic acid

polyphenol


Input: The greatest effect of green tea observed in vitro as well as the protective role presented in the ex vivo study could be attributed to the major content of phenols, but not catechins.

phenols

catechins


Input: In fact, catechins were not able to restore enzyme activity inhibited by cadmium, demonstrating that these compounds are not major components responsible for the beneficial effect of green tea observed in this study.

catechins

cadmium


Input: This study demonstrated the helpful effect of green tea infusion in ameliorating a marker protein of cadmium intoxication in ovarian tissue.

cadmium


Input: 4-Nerolidylcatechol and its synthetic analogues: Antioxidant activity and toxicity evaluation.


Input: 4-Nerolidylcatechol (1) is a secondary metabolite of plants and is described as a promising anti-inflammatory, antimalarial, antiulcerogenic, analgesic and cytotoxic compound possibly due to its antioxidant profile.


Input: In this study, we evaluated the pharmacologic activity and the antioxidant and toxicological profiles of compound (1) and its synthetic analogues (2-6).


Input: The synthetic analogues were designed from the lead compound, (1), using a molecular-simplification strategy.


Input: Compound 5 showed, by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and beta-carotene systems, similar antioxidant activity when compared to compound (1).

1, 1-diphenyl-2-picrylhydrazyl

DPPH

beta-carotene


Input: The oxidative stress in erythrocyte membrane demonstrated the highly protective effect of compounds (4), (5) and (6) and high antioxidant/pro-oxidant activity in relation to the concentrations of compounds (1) and (3).


Input: Compounds (2), (4), (5) and (6) were haemobiocompatible.


Input: All compounds (1-6) showed cytotoxic effects in 3T3 cells, but compounds (2) and (6) were highly cytotoxic in this lineage when compared to compound (1).


Input: Compound (5) had a lower myelosuppressive effect in haematopoietic progenitor cells compared to (1).


Input: Both compounds, (1) and (5), showed low genotoxic effects in vitro, on human lymphocyte cells.


Input: In addition, these compounds also showed low-toxicity in vivo as defined a LD50 > 2000 mg/kg.


Input: In this assay, we did not observe death in the animals exposed to treatment with (1) and (5) compound.


Input: In conclusion, the structural design of the analogues as validated once compound (5) was found to have an antioxidant profile that was as potent as the lead compound (1).


Input: In addition, considering the safety profile, these compounds are promising as preventive and/or therapeutic agents against oxidative damage.


Input: Isolation of a flavonoid, apigenin 7-O-glucoside, from Mentha longifolia (L.) Hudson subspecies longifolia and its genotoxic potency.

flavonoid

apigenin 7-O-glucoside


Input: Mentha is a medicinal and aromatic plant belonging to the Lamiaceae family, which is widely used in food, flavor, cosmetic and pharmaceutical industries.


Input: Recently, it has been found that the use of Mentha as a pharmaceutical source is based on its phytochemical constituents that have far been identified as tannins, saponins, phenolic acids and flavonoids.

tannins

saponins

phenolic acids

flavonoids


Input: This study was designed to evaluate the mutagenic and antimutagenic activities of apigenin 7-O-glucoside (A7G), a flavonoid isolated from Mentha longifolia (L.) Hudson subspecies longifolia (ML).

apigenin 7-O-glucoside

flavonoid


Input: The possible antimutagenic potential of A7G was examined against mutagens ethyl methanesulfonate and acridine in an eukaryotic cell system Saccharomyces cerevisiae and sodium azide in Salmonella typhimurium TA1535 and 9-aminoacridine in S. typhimurium TA1537.

ethyl methanesulfonate

acridine

sodium azide


Input: According to our findings, any concentrations of the A7G used did not show mutagenic activity but exerted strong antimutagenic activities at tested concentrations.


Input: The inhibition rates for the Ames test ranged from 27. 2% (S. typhimurium TA1535: 0. 4 mu M/plate) to 91. 1% (S. typhimurium TA1537: 0. 2 mu M/plate) and for the yeast deletion assay from 4% to 57. 7%.


Input: This genotoxicological study suggests that a flavonoid from ML owing to antimutagenic properties is of great pharmacological importance and might be beneficial to industries producing food additives, cosmetics and pharmaceuticals products.

flavonoid


Input: Influence of pesticide exposure on carbonic anhydrase II from sheep stomach.


Input: Carbonic anhydrase (CA) is a widely distributed enzyme and has a crucial role in the cells, tissues and organs of living organisms.


Input: It is found that CA-II is one of the most abundant CA isoenzymes in the gastrointestinal system.


Input: It plays an important role in the gastric acid secretion in stomach.


Input: In this study, we purified CA-II isoenzyme from sheep stomach with a 615. 2 purification fold, 78% purification yield and 5562. 02 specific activity.


Input: Moreover, the in vitro effects of some commonly used pesticides including chlorpyrifos, cypermethrin, dichlorvos, glyphosate isopropylamine and lambda cyhalomethrin on the enzyme activity were investigated.

chlorpyrifos

cypermethrin

dichlorvos

glyphosate isopropylamine

lambda cyhalomethrin


Input: Of these compounds, glyphosate isopropylamine and dichlorvos showed an inhibition on CA-II esterase activity.

glyphosate isopropylamine

dichlorvos


Input: They have IC (50) values of 0. 155 micro M and 2. 690 micro M and K (i) values of 0. 329 micro M and 3. 654 micro M, respectively.


Input: Both glyphosate isopropylamine and dichlorvos inhibited CA-II isoenzyme in a noncompetitive manner.

glyphosate isopropylamine

dichlorvos


Input: Trim24-repressed VL30 retrotransposons regulate gene expression by producing noncoding RNA.


Input: Trim24 (Tif1 alpha) and Trim33 (Tif1 gamma) interact to form a co-repressor complex that suppresses murine hepatocellular carcinoma.


Input: Here we show that Trim24 and Trim33 cooperatively repress retinoic acid receptor-dependent activity of VL30-class endogenous retroviruses (ERVs) in liver.

retinoic acid


Input: In Trim24-knockout hepatocytes, VL30 derepression leads to accumulation of reverse-transcribed VL30 cDNA in the cytoplasm that correlates with activation of the viral-defense interferon responses mimicking the preneoplastic inflammatory state seen in human liver following exogenous viral infection.


Input: Furthermore, upon derepression, VL30 long terminal repeats (LTRs) act as promoter and enhancer elements deregulating expression of neighboring genes and generating enhancer RNAs that are required for LTR enhancer activity in hepatocytes in vivo.


Input: These data reinforce the role of the TRIM family of proteins in retroviral restriction and antiviral defense and provide an example of an ERV-derived oncogenic regulatory network.


Input: Association between bisphenol A and abnormal free thyroxine level in men.

bisphenol A

thyroxine


Input: Bisphenol A (BPA) is a chemical that is used in a variety of consumer products, and exposure to BPA is widespread among the general population.

Bisphenol A

BPA

BPA


Input: Recent studies have suggested that BPA may affect the thyroid and related pathways.

BPA


Input: However, human studies are still limited.


Input: The aim of this study was to determine the relationship between BPA exposure and thyroid function.

BPA


Input: We obtained survey data and blood samples from The Thai National Health Examination Survey IV 2009, a nationally representative cross-sectional survey using a multistage, stratified sampling of the Thai population.


Input: A total of 2, 340 subjects aged 18-94 years were sampled for the present study.


Input: Serum BPA, TSH, FT (4), and related covariates were measured.

BPA


Input: BPA was log-transformed prior to analysis.

BPA


Input: BPA was detected in 52. 8% of serum samples with a median concentration of 0. 33 (range 0-66. 91) ng/mL.

BPA


Input: We excluded subjects who tested positive for thyroid autoantibody and then stratified the remaining subjects by gender; the analysis showed a significantly negative correlation between serum BPA and FT (4) levels in males (r =-0. 14, P < 0. 001).

BPA


Input: In contrast, no association was observed in females.


Input: BPA was not associated with TSH in either gender.

BPA


Input: This gender-related discrepancy is possibly related to androgen-related differences in the metabolism of BPA.

androgen

BPA


Input: Our preliminary results provide evidence of a negative association between BPA and FT (4) levels.

BPA


Input: Additional detailed studies are needed to investigate the temporal relationship and potential public health implications of such an association.


Input: Genetics of type 2 diabetes and potential clinical implications.


Input: Type 2 diabetes (T2DM) is a common complex metabolic disorder that has a strong genetic component.


Input: Recent advances in genome-wide association studies have revolutionized our knowledge regarding the genetics of T2DM.


Input: There are at least 64 common genetic variants that are strongly associated with T2DM.


Input: However, the pathophysiologic roles of these variants are mostly unknown and require further functional characterization.


Input: The variants identified so far have a small effect size and their added effect explains less than 10% of the T2DM heritability.


Input: The current ongoing whole exome and whole genome studies of T2DM are focused on identifying functionally important rare variants that have a stronger effect.


Input: Through these efforts, we will have a better understanding of the genetic architecture of T2DM and its pathophysiology.


Input: The potential clinical applications of genetic studies of T2DM include risk prediction, identification of novel therapeutic targets, genetic prediction of efficacy and toxicity of anti-diabetic medications, and eventually optimization of patient care through personalized genomic medicine.


Input: We hope further research in genetics of T2DM could aid patient care and improve outcomes of T2DM patients.


Input: Acute viral infections of the central nervous system in immunocompetent adults: diagnosis and management.


Input: Patients with viral infections of the central nervous system (CNS) may present with a variety of neurological symptoms, most commonly dominated by either encephalitis or meningitis.


Input: The aetiological panorama varies in different parts of the world as well as over time.


Input: Thus, virological first-line diagnostics must be adapted to the current epidemiological situation and to the individual patient history, including recent travels.


Input: This review focuses on the diagnostics and treatment of viral CNS infections in the immunocompetent host from a Northern European perspective.


Input: Effective vaccines are available for viruses such as poliovirus and tick-borne encephalitis virus (TBEV) and for the childhood diseases morbilli (measles), rubella (German measles), parotitis (mumps) and varicella (chickenpox).


Input: However, cases do appear due to suboptimal immunization rates.


Input: In viral CNS infections, epidemiological surveillance is essential for establishing preventive strategies and for detecting emerging viruses.


Input: Knowledge of the possibilities and limitations of diagnostic methods for specific viral CNS infections is vital.


Input: A positive cerebral spinal fluid (CSF) polymerase chain reaction (PCR) finding is usually reliable for aetiological diagnosis.


Input: The demonstration of intrathecal antibody synthesis is useful for confirming the aetiology in a later stage of disease, hitherto sufficiently evaluated in herpes simplex encephalitis (HSE) and tick-borne encephalitis (TBE).


Input: Despite improved virological and differential diagnostic methods, aetiology remains unknown in about half of the cases with suspected viral encephalitis.


Input: Antiviral treatment is available chiefly for infections caused by herpesviruses, and acyclovir (aciclovir) is the drug of choice for empirical therapy in suspected viral encephalitis.

acyclovir

aciclovir


Input: However, randomized, controlled antiviral trials have only been conducted for HSE, while such studies are lacking in other viral CNS infections.


Input: Viral cytolysis and immune-mediated mechanisms may contribute to varying extents to neurological damage.


Input: Although the brain damage is believed to depend, to a varying degree, on the intrathecal host immune response, the use of corticosteroids in viral CNS infections is scarcely studied, as is specific treatment for neuroinflammation.

corticosteroids


Input: Improved antiviral and immunomodulating treatment is desirable.


Input: Since neurological sequelae are still abundant, follow-up after severe viral CNS disease must include a neuropsychological assessment and an individually adapted rehabilitation plan.


Input: Sediment-associated pesticides in an urban stream in guangzhou, china: implication of a shift in pesticide use patterns.


Input: Pesticide use patterns in China have changed in recent years; however, the study of the environmental fate of current-use pesticides (CUPs) and their ecotoxicological significance in aquatic ecosystems is limited.


Input: In the present study, sediments were collected from an urban stream in the Chinese city of Guangzhou.


Input: Sediment-associated legacy organochlorine pesticides and CUPs-including organophosphates, pyrethroids, fipronil, and abamectin-were analyzed.

organochlorine

organophosphates

pyrethroids

fipronil

abamectin


Input: Additionally, the relative toxicity of the sediments was evaluated with 10-d bioassays using Chironomus dilutus.


Input: Fifteen of 16 sediments collected from the stream were acutely toxic to C. dilutus, with 81% of the samples causing 100% mortality.


Input: Abamectin, fipronil, and pyrethroids (mainly cypermethrin) were identified as the principal contributors to the noted toxicity in the midges, with median predicted toxic units of 1. 63, 1. 63, and 1. 03, respectively.

Abamectin

fipronil

pyrethroids

cypermethrin


Input: Sediments taken from downstream sites, where residential and industrial regions were located, had elevated CUP concentrations and sediment toxicity compared with upstream sites.


Input: The present study is the first of its kind to link sediment CUPs, fipronil, and abamectin concentrations with toxicity in urban streams in China with a focus on shifting pesticide usage patterns.

fipronil

abamectin


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 1040-1047.


Input: (c) 2013 SETAC.


Input: Pancreatic beta-Cell Dysfunction and Risk of New-Onset Diabetes After Kidney Transplantation.


Input: OBJECTIVEChronic exposure to calcineurin inhibitors and corticosteroids poses renal transplant recipients (RTR) at high risk for development of new-onset diabetes after transplantation (NODAT).


Input: Pancreatic beta-cell dysfunction may be crucial to the pathophysiology of NODAT and specific markers for beta-cell dysfunction may have additive value for predicting NODAT in this population.


Input: Therefore, we prospectively investigated whether proinsulin, as a marker of pancreatic beta-cell dysfunction, is associated with future development of NODAT and improves prediction of it. RESEARCH DESIGN AND METHODSAll RTR between 2001 and 2003 with a functioning graft for >= 1 year were considered eligible for inclusion, except for subjects with diabetes at baseline who were excluded.


Input: We recorded incidence of NODAT until April 2012. RESULTSA total of 487 RTR (age 50 +/- 12 years, 55% men) participated at a median time of 6. 0 (interquartile range [IQR], 2. 6-11. 5) years after transplantation.


Input: Median fasting proinsulin levels were 16. 6 (IQR, 11. 0-24. 2) pmol/L.


Input: During median follow-up for 10. 1 (IQR, 9. 1-10. 4) years, 42 (35%) RTR had development of NODAT in the highest quartile of the distribution of proinsulin versus 34 (9%) in the lowest three quartiles (P < 0. 001).


Input: In Cox regression analyses, proinsulin (hazard ratio, 2. 29; 95% confidence interval, 1. 85-2. 83; P < 0. 001) was strongly associated with NODAT development.


Input: This was independent of age, sex, calcineurine inhibitors, prednisolone use, components of the metabolic syndrome, or homeostasis model assessment. CONCLUSIONSIn conclusion, fasting proinsulin is strongly associated with NODAT development in RTR.

prednisolone


Input: Our results highlight the role of beta-cell dysfunction in the pathophysiology of NODAT and indicate the potential value of proinsulin for identification of RTR at increased risk for NODAT.


Input: Glycation Gap Is Associated With Macroproteinuria but Not With Other Complications in Patients With Type 2 Diabetes.


Input: OBJECTIVEWe investigated whether glycation gap (G-Gap), an index of intracellular glycation of proteins, was associated with diabetes complications. RESEARCH DESIGN AND METHODSWe measured concomitantly HbA (1c) and fructosamine in 925 patients with type 2 diabetes to calculate the G-Gap, defined as the difference between measured HbA (1c), and fructosamine-based predicted HbA (1c).

fructosamine

fructosamine


Input: Patients were explored for retinopathy, nephropathy, peripheral neuropathy, cardiac autonomic neuropathy (n = 512), and silent myocardial ischemia (n = 506). RESULTSMacroproteinuria was the only complication that was associated with G-Gap (prevalence in the first, second, and third tertile of G-Gap: 2. 9, 6. 2, and 11. 0%, respectively; P < 0. 001).


Input: The G-Gap was higher in patients with macroproteinuria than in those without (1. 06 +/- 1. 62 vs. 0. 03 +/- 1. 30%; P < 0. 0001).


Input: Because HbA (1c) was associated with both G-Gap (HbA (1c) 7. 0 +/- 1. 4, 7. 9 +/- 1. 4, and 10. 1 +/- 1. 8% in the first, second, and third G-Gap tertile, respectively; P < 0. 0001) and macroproteinuria (HbA (1c) 8. 8 +/- 2. 2% if macroproteinuria, 8. 3 +/- 2. 0% if none; P < 0. 05), and because it could have been a confounder, we matched 54 patients with macroproteinuria and 200 patients without for HbA (1c).


Input: Because macroproteinuria was associated with lower serum albumin and fructosamine levels, which might account for higher G-Gap, we calculated in this subpopulation albumin-indexed fructosamine and G-Gap; macroproteinuria was independently associated with male gender (odds ratio [OR], 3. 2; 95% CI, 1. 5-6. 7; P < 0. 01), hypertension (2. 9; [1. 1-7. 5]; P < 0. 05), and the third tertile of albumin-indexed G-Gap (2. 3; [1. 1-4. 4]; P < 0. 05) in multivariate analysis. CONCLUSIONIn type 2 diabetic patients, G-Gap was associated with macroproteinuria, independently of HbA (1c), albumin levels, and confounding factors, suggesting a specific role of intracellular glycation susceptibility on kidney glomerular changes.

fructosamine

fructosamine


Input: Activation of the anti-cancer agent upamostat by the mARC enzyme system.

upamostat


Input: Abstract 1.


Input: Upamostat (Mesupron (R)) is a new small molecule serine protease inhibitor.

Upamostat

Mesupron

serine


Input: The drug candidate was developed to inhibit the urokinase-type plasminogen activator (uPA) system, which plays a major role in tumor invasion and metastasis.


Input: Upamostat is currently in clinical development as an anti-metastatic and non-cytotoxic agent against pancreatic and breast cancer.

Upamostat


Input: Upamostat is the orally available amidoxime-(i. e. hydroxyamidine-) prodrug of the pharmacologically active form, WX-UK1.

Upamostat

amidoxime

hydroxyamidine


Input: In this study, the reductive enzymatic activation of upamostat to its corresponding amidine WX-UK1 was analyzed.

upamostat


Input: The recently discovered molybdenum enzyme " mitochondrial Amidoxime Reducing Component " (mARC) catalyses together with its electron transport proteins cytochrome b (5) and NADH cytochrome b (5) reductase the reduction of N-hydroxylated prodrugs.

molybdenum

Amidoxime

NADH

N


Input: In vitro biotransformation assays with porcine subcellular fractions and the reconstituted human enzymes demonstrate an mARC-dependent N-reduction of upamostat.

N

upamostat


Input: Nuclease-resistant DNA via high-density packing in polymeric micellar nanoparticle coronas.


Input: Herein, we describe a polymeric micellar nanoparticle capable of rendering nucleic acids resistant to nuclease digestion.


Input: This approach relies on utilizing DNA as the polar headgroup of a DNA-polymer amphiphile in order to assemble well-defined, discrete nanoparticles.


Input: Dense packing of DNA in the micelle corona allows for hybridization of complementary oligonucleotides while prohibiting enzymatic degradation.


Input: We demonstrate the preparation, purification, and characterization of the nanoparticles, then describe their resistance to treatment with endo-and exonucleases including snake-venom phosphodiesterase (SVP), a common, general DNA digestion enzyme.


Input: Diversification in a biodiversity hot spot: landscape correlates of phylogeographic patterns in the African spotted reed frog.


Input: The Eastern Afromontane Biodiversity Hotspot is known for microendemism and exceptional population genetic structure.


Input: The region' s landscape heterogeneity is thought to limit gene flow between fragmented populations and create opportunities for regional adaptation, but the processes involved are poorly understood.


Input: Using a combination of phylogeographic analyses and circuit theory, I investigate how characteristics of landscape heterogeneity including regional distributions of slope, rivers and streams, habitat and hydrological basins (drainages) impact genetic distance among populations of the endemic spotted reed frog (Hyperolius substriatus), identifying corridors of connectivity as well as barriers to dispersal.


Input: Results show that genetic distance among populations is most strongly correlated to regional and local hydrologic structure and the distribution of suitable habitat corridors, not isolation by distance.


Input: Contrary to expectations, phylogeographic structure is not coincident with the two montane systems, but instead corresponds to the split between the region' s two major hydrological basins (Zambezi and East Central Coastal).


Input: This results in a paraphyletic relationship for the Malawian Highlands populations with respect to the Eastern Arc Mountains and implies that the northern Malawian Highlands are the diversity centre for H. substriatus.


Input: Although the Malawian Highlands collectively hold the greatest genetic diversity, individual populations have lower diversity than their Eastern Arc counterparts, with an overall pattern of decreasing population diversity from north to south.


Input: Through the study of intraspecific differentiation across a mosaic of ecosystem and geographic heterogeneity, we gain insight into the processes of diversification and a broader understanding of the role of landscape in evolution.


Input: Multifunctional conducting fibres with electrically controlled release of ciprofloxacin.

ciprofloxacin


Input: We hereby present a new method of producing coaxial conducting polymer fibres loaded with an antibiotic drug that can then be subsequently released (or sustained) in response to electrical stimulation.


Input: The method involves wet-spinning of poly (3, 4-ethylenedioxythiophene) poly (styrenesulfonate) (PEDOT: PSS) fibre, which served as the inner core to the electropolymerised outer shell layer of polypyrrole (Ppy).

poly (3, 4-ethylenedioxythiophene) poly (styrenesulfonate)

PEDOT

PSS

polypyrrole

Ppy


Input: Ciprofloxacin hydrochloride (Cipro) was selected as the model drug and as the dopant in the Ppy synthesis.

Ciprofloxacin hydrochloride

Cipro

Ppy


Input: The release of Cipro in phosphate buffered saline (PBS) from the fibres was controlled by switching the redox state of Ppy. Cipro layer.

Cipro

phosphate

Ppy

Cipro


Input: Released Cipro under passive and stimulated conditions were tested against Gram positive (Streptococcus pyogenes) and Gram negative (Escherichia coli) bacteria.

Cipro


Input: Significant inhibition of bacterial growth was observed against both strains tested.


Input: These results confirm that Cipro retains antibacterial properties during fibre fabrication and electrochemically controlled release.

Cipro


Input: In vitro cytotoxicity testing utilising the neural B35 cell line confirmed the cytocompatibility of the drug loaded conducting fibres.


Input: Electrical conductivity, cytocompatibility and tuning release profile from this flexible fibre can lead to promising bionic applications such as neuroprosthetics and localised drug delivery.


Input: DNA delivery with hyperbranched polylysine: A comparative study with linear and dendritic polylysine.

polylysine

polylysine


Input: PEI and polylysine are among the most investigated synthetic polymeric carriers for DNA delivery.

PEI

polylysine


Input: Apart from their practical use, these 2 classes of polymers are also of interest from a fundamental point of view as they both can be prepared in different architectures (linear and branched/dendritic) and in a wide range of molecular weights, which is attractive to establish basic structure-activity relationships.


Input: This manuscript reports the results of an extensive study on the influence of molecular weight and architecture of a library of polylysine variants that includes linear, dendritic and hyperbranched polylysine.

polylysine

polylysine


Input: Hyperbranched polylysine is a new polylysine-based carrier that is structurally related to dendritic polylysine but possesses a randomly branched structure.

polylysine

polylysine

polylysine


Input: Hyperbranched polylysine is attractive as it can be prepared in a one-step process on a large scale.

polylysine


Input: The performance of these 3 classes of polylysine analogs was evaluated by assessing eGFP and IgG production in transient gene expression experiments with CHO DG44 cells, which revealed that protein production generally increased with increasing molecular weight and that at comparable molecular weight, the hyperbranched analogs were superior as compared to the dendritic and linear polylysines.

polylysine

polylysines


Input: To understand the differences between the gene delivery properties of the hyperbranched polylysine analogs on the one hand and the dendritic and linear polylysines on the other hand, the uptake and trafficking of the corresponding polyplexes were investigated.

polylysine

polylysines


Input: These experiments allowed us to identify (i) polyplex-external cell membrane binding, (ii) free, unbound polylysine coexisting with polyplexes as well as (iii) polymer buffer capacity as three possible factors that may contribute to the superior transfection properties of the hyperbranched polylysines as compared to their linear and dendritic analogs.

polylysine

polylysines


Input: Altogether, the results of this study indicate that hyperbranched polylysine is an interesting, alternative synthetic gene carrier.

polylysine


Input: Hyperbranched polylysine can be produced at low costs and in large quantities, is partially biodegradable, which may help to prevent cumulative cytotoxicity, and possesses transfection properties that can approach those of PEI.

polylysine

PEI


Input: Titanium dioxide nanoparticles increase inflammatory responses in vascular endothelial cells.

Titanium dioxide


Input: Atherosclerosis is a chronic inflammatory disease that remains the leading cause of death in the United States.


Input: Numerous risk factors for endothelial cell inflammation and the development of atherosclerosis have been identified, including inhalation of ultrafine particles.


Input: Recently, engineered nanoparticles (NPs) such as titanium (TiO2) NPs have attracted much attention due to their wide range of applications.

titanium


Input: However, there are also great concerns surrounding potential adverse health effects in vascular systems.


Input: Although TiO2 NPs are known to induce oxidative stress and inflammation, the associated signaling pathways have not been well studied.


Input: The focus of this work, therefore, deals with examination of the cellular signaling pathways responsible for TiO2 NP-induced endothelial oxidative stress and inflammation.


Input: In this study, primary vascular endothelial cells were treated with TiO2 NPs for 2-16h at concentrations of 0-50 mu g/mL.


Input: TiO2 NP exposure increased cellular oxidative stress and DNA binding of NF-kappa B.


Input: Further, phosphorylation of Akt, ERK, JNK and p38 was increased in cells exposed to TiO2 NPs.


Input: TiO2 NPs also significantly increased induction of mRNA and protein levels of vascular cell adhesion molecule-1 (VCAM-1) and mRNA levels of monocyte chemoattractant protein-1 (MCP-1).


Input: Pretreatment with inhibitors for NF-kappa B (pyrrolidine dithiocarbamate), oxidative stress (epigallocatechin gallate and apocynin), Akt (LY294002), ERK (PD98059), JNK (SP600125) and p38 (SB203580) significantly attenuated TiO2 NP-induced MCP-1 and VCAM-1 gene expression.

pyrrolidine dithiocarbamate

epigallocatechin gallate

apocynin


Input: These data indicate that TiO2 NPs can induce endothelial inflammatory responses via redox-sensitive cellular signaling pathways.


Input: Cinnamic acid derivatives as inhibitors for chorismatases and isochorismatases.

Cinnamic acid


Input: Chorismatases and isochorismatases catalyse the hydrolysis of chorismate or isochorismate leading to unsaturated cyclohexenoic acid derivatives.

chorismate

isochorismate

unsaturated cyclohexenoic acid


Input: Based on simplification of the physiological substrates, two cinnamic acid-derived compounds, differing in the saturation of the side chain, were developed.

cinnamic acid


Input: In contrast to earlier inhibitor studies, the compounds described here do not have an ether bond and therefore can be synthesised very easily in one or two steps without the need for protective groups.


Input: Both substances demonstrate inhibition of the isochorismatase EntB from Escherichia coli and the chorismatases FkbO and Hyg5 from Streptomyces.


Input: For chorismatases, the unsaturated compound shows IC (50) values in the millimolar range, while the saturated compound is the better inhibitor with IC (50) values in the micromolar/low millimolar range; for the isochorismatase tested both compounds inhibit in the micromolar range.


Input: Further, an analysis of the apparent K (m) values for FkbO and EntB was performed, showing that both inhibitors act in a competitive manner.


Input: Due to the ease of modifying these new inhibitors they are a suitable starting point for exploring further functionalised derivatives.


Input: Carbon monoxide protects against ovariectomy-induced bone loss by inhibiting osteoclastogenesis.

Carbon monoxide


Input: Carbon monoxide (CO) has been shown to have remarkable therapeutic value at low dosage by suppressing inflammation via inhibitory effects on macrophages, which are also precursors of osteoclasts (OC).

Carbon monoxide

CO


Input: The objective of the present study was to determine whether CO limits bone loss through its effects on osteoclastogenesis.

CO


Input: Intraperitoneal injection of CO-releasing molecule 2 (CORM2) into mice with reduced bone mass due to ovariectomy (OVX) resulted in significantly elevated bone mass.

CO


Input: Increased serum levels of collagen-type I fragments, tartrate-resistant acid phosphatase 5b, and reactive oxygen species (ROS) due to OVX were also decreased when treated with CORM2.

tartrate

oxygen


Input: In vitro, CORM2 inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-induced OC formation without affecting bone resorption.


Input: CORM2 reduced long-lasting ROS levels and nuclear factor-kappa B (NF-kappa B) activation in response to RANKL.


Input: Inhibition of NADPH oxidase partially reduced the inhibitory effect of CO.

NADPH

CO


Input: CO induced increase of peroxiredoxin 1 (PRX1) in BMM.

CO


Input: Down-regulation of PRX1 reduced the inhibitory effect of CO on OC formation and sustained the ROS levels induced by RANKL, suggesting that CO reduces generation of ROS and scavenges ROS to inhibit osteoclastogenesis.

CO

CO


Input: These data suggest that the inhibitory effect of CO on osteoclastogenesis is caused by impaired RANKL signaling through defective NF-kappa B activation and reduced levels of long-lasting ROS.

CO


Input: These changes result in decreased bone loss.


Input: Our data highlight the potential utility of CO for ameliorating bone loss induced by loss of ovarian function.

CO


Input: Rescue of hearing and vestibular function by antisense oligonucleotides in a mouse model of human deafness.


Input: Hearing impairment is the most common sensory disorder, with congenital hearing impairment present in approximately 1 in 1, 000 newborns.


Input: Hereditary deafness is often mediated by the improper development or degeneration of cochlear hair cells.


Input: Until now, it was not known whether such congenital failures could be mitigated by therapeutic intervention.