Input: Following the rapid expanding knowledge on TMPKs and the rising interests in TMPKs as a drug target, in this review we try to describe current research on TMPKs in various organisms of eukaryotes, prokaryotes and viruses and to provide information for designing new potential inhibitors against TMPKs.


Input: Growth of highly fluorescent polyethylene glycol-and zwitterion-functionalized gold nanoclusters.

polyethylene glycol


Input: We have prepared and characterized a new set of highly fluorescent gold nanoclusters (AuNCs) using one-step aqueous reduction of a gold precursor in the presence of bidentate ligands made of lipoic acid anchoring groups, appended with either a poly (ethylene glycol) short chain or a zwitterion group.

lipoic acid

poly (ethylene glycol)


Input: The AuNCs fluoresce in the red to near-infrared region of the optical spectrum with emission centered at ~ 750 nm and a quantum yield of ~ 10-14%, and they exhibit long fluorescence lifetimes (up to ~ 300 ns).


Input: Dispersions of these AuNCs exhibit great long-term colloidal stability, over a wide range of pHs (2-13) and in the presence of high electrolyte concentrations, and a strong resistance to reducing agents such as glutathione.

glutathione


Input: The growth strategy further permitted the controlled, in situ functionalization of the NCs with reactive groups (e. g., carboxylic acid or amine), making these nanoclusters compatible with common and simple-to-implement coupling strategies, such as carbodiimide chemistry.

carboxylic acid

amine

carbodiimide


Input: These properties combined make these fluorescent NCs greatly promising for use in various imaging and sensing applications where NIR and long-lived excitations are desired.


Input: Correlating superlattice polymorphs to internanoparticle distance, packing density, and surface lattice in assemblies of PbS nanoparticles.

PbS


Input: Assemblies of 3. 5 nm PbS nanoparticles (NPs) nucleate in three dominant superlattice polymorphs: amorphous, body-centered-cubic (bcc) and face-centered-cubic (fcc) phase.

PbS


Input: This superlattice relationship can be controlled by the inter-NP distance without changing the NP size.


Input: Upon increase of inter-NP distance, the packing density decreases, and the capping molecules at NP surfaces change in structure and accordingly modify the surface energy.


Input: The driving force for NP assembly develops from an entropic maximization to a reduction of total free energy through multiple interactions between surface molecules and NPs and resulting variation of surface molecules.


Input: Upon long-term aging and additional thermal treatment, fcc undergoes a tetragonal distortion and subsequently transforms to bcc phase, and simultaneously, the NPs embedded in supercrystals reduce surface energy primarily in {200} facets.


Input: Linking molecule-NP interactions with a series of changes of packing density and surface lattice spacings of NPs allows for an interpretation of principles governing the nucleation, structure stability, and transformation of PbS NP-assembled supercrystals.

PbS


Input: Antiretroviral bioanalysis methods of tissues and body biofluids.


Input: Research in the many areas of HIV treatment, eradication and prevention has necessitated measurement of antiretroviral (ARV) concentrations in nontraditional specimen types.


Input: To determine the knowledgebase of critical details for accurate bioanalysis, a review of the literature was performed and summarized.


Input: Bioanalytical assays for 31 ARVs, including metabolites, were identified in 205 publications measuring various tissues and biofluids.


Input: 18 and 30% of tissue or biofluid methods, respectively, analyzed more than one specimen type; 35-37% of the tissue or biofluid methods quantitated more than one ARV.


Input: 20 and 76% of tissue or biofluid methods, respectively, were used for the analysis of human specimens.


Input: HPLC methods with UV detection predominated, but chronologically MS detection began to surpass.


Input: 40% of the assays provided complete intra-and inter-assay validation data, but only 9% of publications provided any stability data with even less for the prevalent ARV in treatments.


Input: Conundrum of angiotensin II and TGF-beta interactions in aortic aneurysms.


Input: Angiotensin II (AngII) has been invoked as a principal mediator for the development and progression of both thoracic and abdominal aortic aneurysms.


Input: While there is consistency in experimental and clinical studies that overactivation of the renin angiotensin system promotes aortic aneurysm development, there are many unknowns regarding the mechanistic basis underlying AngII-induced aneurysms.


Input: Interactions of AngII with TGF-beta in both thoracic and abdominal aortic aneurysms have been the focus of recent studies.


Input: While these studies have demonstrated profound effects of manipulating TGF-beta activity on AngII-induced aortic aneurysms, they have also led to more questions regarding the interactions between AngII and this multifunctional cytokine.


Input: This review compiled the recent literature to provide insights into understanding the potentially complex interactions between AngII and TGF-beta in the development of aortic aneurysms.


Input: Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist.

bile acid

tauro-beta-muricholic acid


Input: Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids.

Bile acids

cholesterol

bile acids


Input: Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver.

Bile acid


Input: Here we profiled the bile acid composition throughout the enterohepatic system in germ-free (GF) and conventionally raised (CONV-R) mice.

bile acid


Input: We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice.

muricholic acid

cholic acid


Input: Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7 alpha-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms.

cholesterol


Input: Importantly, we identified tauro-conjugated beta-and alpha-muricholic acids as FXR antagonists.

tauro-conjugated beta-and alpha-muricholic acids


Input: These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum.

bile acid

bile acid


Input: Tmem64 modulates calcium signaling during RANKL-mediated osteoclast differentiation.

calcium


Input: Osteoclast maturation and function primarily depend on receptor activator of NF-kappa B ligand (RANKL)-mediated induction of nuclear factor of activated T cells c1 (NFATc1), which is further activated via increased intracellular calcium ([Ca (2 +)] (i)) oscillation.

calcium

Ca (2 +)


Input: However, the coordination mechanism that mediates Ca (2 +) oscillation during osteoclastogenesis remains ill defined.

Ca (2 +)


Input: Here, we identified transmembrane protein 64 (Tmem64) as a regulator of Ca (2 +) oscillation during osteoclastogenesis.

Ca (2 +)


Input: We found that Tmem64-deficient mice exhibit increased bone mass due in part to impaired osteoclast formation.


Input: Using in vitro osteoclast culture systems, we show here that Tmem64 interacts with sarcoplasmic endoplasmic reticulum Ca (2 +) ATPase 2 (SERCA2) and modulates its activity.

Ca (2 +)


Input: Consequently, Tmem64 deficiency significantly diminishes RANKL-induced [Ca (2 +)] (i) oscillation, which results in reduced Ca (2 +)/calmodulin-dependent protein kinases (CaMK) IV and mitochondrial ROS, both of which contribute to achieving the CREB activity necessary for osteoclast formation.

Ca (2 +)

Ca (2 +)


Input: These data demonstrate that Tmem64 is a positive modulator of osteoclast differentiation via SERCA2-dependent Ca (2 +) signaling.

Ca (2 +)


Input: HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis.

heme


Input: Adult humans have about 25 trillion red blood cells (RBCs), and each second we recycle about 5 million RBCs by erythrophagocytosis (EP) in macrophages of the reticuloendothelial system.


Input: Despite the central role for EP in mammalian iron metabolism, the molecules and pathways responsible for heme trafficking during EP remain unknown.

iron

heme


Input: Here, we show that the mammalian homolog of HRG1, a transmembrane heme permease in C. elegans, is essential for macrophage iron homeostasis and transports heme from the phagolysosome to the cytoplasm during EP.

heme

iron

heme


Input: HRG1 is strongly expressed in macrophages of the reticuloendothelial system and specifically localizes to the phagolysosomal membranes during EP.


Input: Depletion of Hrg1 in mouse macrophages causes attenuation of heme transport from the phagolysosomal compartment.

heme


Input: Importantly, missense polymorphisms in human HRG1 are defective in heme transport.

heme


Input: Our results reveal HRG1 as the long-sought heme transporter for heme-iron recycling in macrophages and suggest that genetic variations in HRG1 could be modifiers of human iron metabolism.

heme

heme

iron

iron


Input: Sonication in combination with heat and low pressure as an alternative pasteurization treatment--effect on Escherichia coli K12 inactivation and quality of apple cider.


Input: Escherichia coli K12 cells suspended in apple cider were treated by manothermosonication (MTS, 400 kPa/59 degrees C), thermosonication (TS, 100 kPa/59 degrees C), and manosonication (MS, 400 kPa/55 degrees C) for up to 4 min.


Input: A 5-log reduction was achieved in 1. 4 min by MTS, 3. 8 min by TS, and 2. 5 min by MS.


Input: The inactivation curves of the E. coli exhibited a fast initial reduction followed by a slow inactivation section.


Input: The Weibull, log-logistic, and biphasic linear models showed a good fit of the inactivation data.


Input: Quality analyses were conducted with raw apple cider (control), thermally-pasteurized (TP), and MTS-, TS-, and MS-treated cider samples over a 3-week period at refrigeration temperature.


Input: Titratable acidity and pH did not differ among any of the samples.


Input: During storage, the turbidity value of the control was the highest, followed by TP, TS, MTS and MS.


Input: All color parameters of the TP sample were significantly different from those receiving the other treatments.


Input: The control and sonicated samples showed similar color parameters during storage.


Input: In total, 97 aroma compounds were identified in the control, TS-, MS-, and MTS-treated cider samples, while 95 aroma compounds were found in the TP at Week 0.


Input: Among all the aroma compounds, 9 key ones were identified in all samples, including ethyl 2-methylbutanoate, butyl acetate, 1-butanol, ethyl hexanoate, 1-hexanol, butanoic acid, beta-damascenone, hexanoic acid, and octanoic acid.

ethyl 2-methylbutanoate

butyl acetate

ethyl hexanoate

butanoic acid

beta-damascenone

hexanoic acid

octanoic acid


Input: The profiles of the key aroma compounds in all sonicated samples were more similar to the control than the TP sample at Weeks 0 and 3.


Input: Understanding metabolic regulation and its influence on cell physiology.


Input: Metabolism impacts all cellular functions and plays a fundamental role in biology.


Input: In the last century, our knowledge of metabolic pathway architecture and the genomic landscape of disease has increased exponentially.


Input: Combined with these insights, advances in analytical methods for quantifying metabolites and systems approaches to analyze these data now provide powerful tools to study metabolic regulation.


Input: Here we review the diverse mechanisms cells use to adapt metabolism to specific physiological states and discuss how metabolic flux analyses can be applied to identify important regulatory nodes to understand normal and pathological cell physiology.


Input: Biomedical applications of bisphosphonates.

bisphosphonates


Input: Since their discovery over 100 years ago, bisphosphonates have been used industrially as corrosion inhibitors and complexing agents.

bisphosphonates


Input: With the discovery of their pharmacological activity in the late 1960s, implicating their high affinity for hydroxyapatite, bisphosphonates have been employed in the treatment of bone diseases and as targeting agents for colloids and drugs.

hydroxyapatite

bisphosphonates


Input: They have notably been investigated for the treatment of Paget' s disease, osteoporosis, bone metastases, malignancy-associated hypercalcemia, and pediatric bone diseases.


Input: Currently, they are first-line medications for several of these diseases and are taken by millions of patients worldwide, mostly postmenopausal women.


Input: A major problem associated with their use is their low oral bioavailability.


Input: Several delivery systems have been proposed to improve their absorption and to direct them to sites other than bone tissues.


Input: Beyond their important pharmacological role, the medical applications of bisphosphonates are numerous.

bisphosphonates


Input: In addition, their metal-chelating properties have been exploited to coat and stabilize implants, nanoparticulates, and contrast agents.


Input: In this contribution, we review the pharmacological and clinical uses of bisphosphonates and highlight their novel applications in the pharmaceutical and biomedical fields.

bisphosphonates


Input: Sophocarpine alleviates hepatocyte steatosis through activating AMPK signaling pathway.

Sophocarpine


Input: Sophocarpine, an effective compound derived from foxtail-like sophora herb and seed, has been reported that it can alleviate non-alcoholic steatohepatitis (NASH) in rats and affect adipocytokine synthesis.

Sophocarpine


Input: Meanwhile, adipocytokines could adjust hepatic lipid metabolism through AMPK signaling pathway.


Input: In the work presented here, primary hepatocytes were isolated from specific pathogen-free male SD rats and incubated with 200 mu mol/L oleic acid for 24h to induce steatotic model, then treated with sophocarpine for 72 h.

oleic acid

sophocarpine


Input: Oil red staining was performed to evaluate steatosis, total RNA and protein of primary hepatocytes were extracted for real-time RT-PCR and western blot analysis.


Input: A cluster of aberrances were observed in the model group, including hepatocyte steatosis, increased leptin and decreased adiponectin mRNA expressions.


Input: While sophocarpine treatment resulted in: significant improvement of steatosis (> 50% decrease), decrease of leptin expression (< 0. 57-fold) and increase of adiponectin expression (> 1. 48-fold).

sophocarpine


Input: Moreover, compared with the model group, sophocarpine could significantly increase P-AMPK alpha (> 5. 82-fold), AMPK alpha (> 1. 29-fold) and ACC (> 3. 27-fold) protein expressions, and reduce P-ACC (< 0. 30-fold) and HNF-4 alpha (< 0. 20-fold) protein expression.

sophocarpine


Input: The mRNA expression of Srebp-1c was downregulated significantly simultaneously (< 0. 68-fold).


Input: We concluded that sophocarpine could alleviate hepatocyte steatosis and the potential mechanism might be the activated signaling pathway of AMPK.

sophocarpine


Input: Silymarin inhibits ultraviolet radiation-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells.


Input: Silymarin inhibits UVB-induced immunosuppression in mouse skin.


Input: To identify the molecular mechanisms underlying this effect, we used an adoptive transfer approach in which dendritic cells (DCs) from the draining lymph nodes of donor mice that had been UVB-exposed and sensitized to 2, 4,-dinitrofluorobenzene (DNFB) were transferred into na i ve recipient mice.

2, 4,-dinitrofluorobenzene

DNFB


Input: The contact hypersensitivity (CHS) response of the recipient mice to DNFB was then measured.

DNFB


Input: When DCs were obtained from UVB-exposed donor mice that were not treated with silymarin, the CHS response was suppressed confirming the role of DCs in the UVB-induced immunosuppression.


Input: Silymarin treatment of UVB-exposed donor mice relieved this suppression of the CHS response in the recipients.


Input: Silymarin treatment was associated with rapid repair of UVB-induced cyclobutane pyrimidine dimers (CPDs) in DCs and silymarin treatment did not prevent UV-induced immunosuppression in XPA-deficient mice which are unable to repair UV-induced DNA damage.

cyclobutane pyrimidine dimers

CPDs


Input: The CHS response in mice receiving DCs from silymarin-treated UV-exposed donor mice also was associated with enhanced secretion of Th1-type cytokines and stimulation of T cells.


Input: Adoptive transfer of T cells revealed that transfer of either CD8 (+) or CD4 (+) cells from silymarin-treated, UVB-exposed donors resulted in enhancement of the CHS response.


Input: Cell culture study showed enhanced secretion of IL-2 and IFN gamma by CD8 (+) T cells, and reduced secretion of Th2 cytokines by CD4 (+) T cells, obtained from silymarin-treated UVB-exposed mice.


Input: These data suggest that DNA repair-dependent functional activation of DCs, a reduction in CD4 (+) regulatory T-cell activity, and stimulation of CD8 (+) effector T cells contribute to silymarin-mediated inhibition of UVB-induced immunosuppression.


Input: Methods for oxysterol analysis: Past, present and future.

oxysterol


Input: Oxysterols are oxidised forms of cholesterol or its precursors.

Oxysterols

cholesterol


Input: In this article we will concentrate specifically on those formed in mammalian systems.


Input: Oxidation may be catalysed by endogenous enzymes or through reactive oxygen species forming a myriad of potential products.

oxygen


Input: A number of these products are biologically active, and oxysterols may have roles in cholesterol homeostasis, neurogenesis, protein prenylation and in the immune system.

oxysterols

cholesterol


Input: Oxysterols are also implicated in aetiology of disease states including atherosclerosis, neurodegenerative and inflammatory diseases.

Oxysterols


Input: Reports indicating the levels of oxysterols in plasma, cerebrospinal fluid and various tissues are in many cases unrealistic owing to a lack of attention to the possibility of autoxidation, a process by which oxysterols are formed from cholesterol by oxygen in air.

oxysterols

oxysterols

cholesterol

oxygen


Input: This article comprises a critical assessment of the technical difficulties of oxysterol analysis, highlights methodologies utilising best practise and discusses newer procedures.

oxysterol


Input: Prolactin regulates transcription of the ion uptake Na +/Cl-cotransporter (ncc) gene in zebrafish gill.

Na +

Cl-


Input: Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood.


Input: Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake.


Input: Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na (+)/Cl (-) cotransporter (ncc; slc12a10. 2), Na (+)/H (+) exchanger (nhe3b; slc9a3. 2), and epithelial Ca (2 +) channel (ecac; trpv6) transcripts within the gill.

Na (+)

Cl (-)

Na (+)

H (+)

Ca (2 +)


Input: Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac.


Input: Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Delta 1-9-G129R-hPRL).


Input: These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl (-) uptake in zebrafish for the first time.

Cl (-)


Input: Molecular design of a highly selective and strong protein inhibitor against matrix metalloproteinase-2 (MMP-2).


Input: Synthetic inhibitors of matrix metalloproteinases (MMPs), designed previously, as well as tissue inhibitors of metalloproteinases (TIMPs) lack enzyme selectivity, which has been a major obstacle for developing inhibitors into safe and effective MMP-targeted drugs.


Input: Here we designed a fusion protein named APP-IP-TIMP-2, in which the ten amino acid residue sequence of APP-derived MMP-2 selective inhibitory peptide (APP-IP) is added to the N terminus of TIMP-2.

amino acid

N


Input: The APP-IP and TIMP-2 regions of the fusion protein are designed to interact with the active site and the hemopexin-like domain of MMP-2, respectively.


Input: The reactive site of the TIMP-2 region, which has broad specificity against MMPs, is blocked by the APP-IP adduct.


Input: The recombinant APP-IP-TIMP-2 showed strong inhibitory activity toward MMP-2 (Ki (app) = 0. 68 pm), whereas its inhibitory activity toward MMP-1, MMP-3, MMP-7, MMP-8, MMP-9, or MT1-MMP was six orders of magnitude or more weaker (IC50 > 1 mu m).


Input: The fusion protein inhibited the activation of pro-MMP-2 in the concanavalin A-stimulated HT1080 cells, degradation of type IV collagen by the cells, and the migration of stimulated cells.


Input: Compared with the decapeptide APP-IP (t & frac12; = 30 min), APP-IP-TIMP-2 (t & frac12; >> 96 h) showed a much longer half-life in cultured tumor cells.

decapeptide


Input: Therefore, the fusion protein may be a useful tool to evaluate contributions of proteolytic activity of MMP-2 in various pathophysiological processes.


Input: It may also be developed as an effective anti-tumor drug with restricted side effects.


Input: In vitro activity of scorpiand-like azamacrocycle derivatives in promastigotes and intracellular amastigotes of Leishmania infantum and Leishmania braziliensis.


Input: The activity of a family scorpiand-like azamacrocycles against Leishmania infantum and Leishmania braziliensis was studied using promastigotes, axenic and intracellular amastigotes forms.


Input: All the compounds are more active and less toxic than meglumine antimoniate (Glucantime).

meglumine antimoniate

Glucantime


Input: Moreover, the data on infection rates and amastigotes showed that compounds P2Py, PN and P3Py are the most active against both species of Leishmania.


Input: On the other hand, studies on the inhibitory effect of these compounds on SOD enzymes showed that while the inhibition of the Fe-SOD enzyme of the promastigote forms of the parasites is remarkable, the inhibition of human CuZn-SOD and Mn-SOD from Escherichia coli is negligible.

Fe

CuZn

Mn


Input: The ultrastructural alterations observed in treated promastigote forms confirmed that the compounds having the highest activity were those causing the largest cell damage.


Input: The modifications observed by (1) H NMR, and the amounts of catabolites excreted by the parasites after treatment with the compounds, suggested that the catabolic mechanism could depend on the structure of the side chains linked to the aza-scorpiand macrocycles.

(1) H

aza


Input: Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts.

Alcohol

methyl CpG

CpG


Input: Fetal alcohol syndrome (FAS), presenting with a constellation of neuro-/psychological, craniofacial and cardiac abnormalities, occurs frequently in offspring of women who consume alcohol during pregnancy, with a prevalence of 1-3 per 1000 livebirths.

alcohol

alcohol


Input: The present study was designed to test the hypothesis that alcohol alters global DNA methylation, and modulates expression of the DNA methyltransferases (DNMTs) and various methyl CpG-binding proteins.

alcohol

methyl CpG


Input: Murine embryonic fibroblasts (MEFs), utilized as an in vitro embryonic model system, demonstrated ~ 5% reduction in global DNA methylation following exposure to 200mM ethanol.

ethanol


Input: In addition, ethanol induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway.

ethanol

methyl CpG


Input: Such degradation could be completely rescued by pretreatment of MEF cells with the proteasomal inhibitor, MG-132.


Input: These data support a potential epigenetic molecular mechanism underlying the pathogenesis of FAS during mammalian development.


Input: Functional expression and regulation of drug transporters in monolayer-and sandwich-cultured mouse hepatocytes.


Input: Primary hepatocyte cultures are now considered as convenient models for in vitro analyzing liver drug transport.


Input: However, if primary human and rat hepatocytes have been well-characterized with respect to drug transporter expression and regulation, much less is known for primary mouse hepatocytes.


Input: The present study was therefore designed to gain insights about this point.


Input: The profile of sinusoidal and canalicular drug transporter mRNA expression in short time (4h)-cultured mouse hepatocytes was found to be highly correlated with that of freshly isolated hepatocytes; by contrast, those of counterparts cultured for a longer time (until 4days) either in monolayer configurations on plastic or collagen or in sandwich configuration with matrigel were profoundly altered: uptake drug transporters such as Oct1, Oatps and Oat2 were thus down-regulated, whereas most of efflux transporters such as Mdr1a/b, Mrp3, Mrp4 and Bcrp were induced.


Input: Moreover, short time-cultured hepatocytes exhibited the highest levels of sinusoidal influx transporter activities.


Input: Transporter-mediated drug secretion into canalicular networks was however only observed in sandwich-cultured hepatocytes.


Input: Mouse hepatocytes cultured either in monolayer or sandwich configurations were finally shown to exhibit up-regulation of referent transporters in response to exposure to prototypical activators of the drug sensing receptors pregnane X receptor, aryl hydrocarbon receptor or constitutive androstane receptor.

pregnane

aryl hydrocarbon

androstane


Input: Taken together, these data demonstrate the feasibility of using primary mouse hepatocytes for investigating potential interactions of xenobiotics with hepatic transporter activity or regulation, provided that adequate culture conditions are retained.


Input: AhR-and NF-kappa B-dependent induction of interleukin-6 by co-exposure to the environmental contaminant benzanthracene and the cytokine tumor necrosis factor-alpha in human mammary MCF-7 cells.

benzanthracene


Input: Co-exposure to environmental polycyclic aromatic hydrocarbons (PAHs) and interleukin (IL)-1 beta induces expression of the tumor-promoting cytokine IL-6 in cancer cells.

polycyclic aromatic hydrocarbons

PAHs


Input: The present study was designed to determine whether such an IL-6 up-regulation also occurs in response to co-treatment by PAHs and tumor necrosis factor (TNF)-alpha, an inflammatory cytokine commonly found in tumor microenvironment.

PAHs


Input: Co-exposure to the prototypical PAH benzanthracene (BZA) and TNF-alpha was found to markedly induce mRNA expression and secretion of IL-6 in human breast cancer cells MCF-7, whereas exposure to either BZA or TNF-alpha alone was without significant effect.

PAH benzanthracene

BZA

BZA


Input: Co-treatment by BZA and TNF-alpha-containing conditioned media from human inflammatory macrophages similarly up-regulated IL-6 expression in MCF-7 cells.

BZA


Input: BZA/TNF-alpha-mediated IL-6 induction in MCF-7 cells was counteracted by silencing aryl hydrocarbon receptor (AhR), known to mediates most of PAH effects.

BZA

aryl hydrocarbon

PAH


Input: IL-6 up-regulation was moreover associated with NF-kappa B activation and was abolished by using chemical NF-kappa B inhibitors or knocking-down expression of the p65/RelA NF-kappa B subunit.


Input: Taken together, these data indicate that co-exposure to BZA/TNF-alpha induces IL-6 expression by AhR-and NF-kappa B-dependent pathways in MCF-7 cancer cells.

BZA


Input: This regulation of IL-6 by environmental PAHs, that is dependent of inflammatory cytokine microenvironment, may contribute to the well-known carcinogenic properties of these organic pollutants.

PAHs


Input: Quercetin prevents protein nitration and glycolytic block of proliferation in hydrogen peroxide insulted cultured neuronal precursor cells (NPCs): Implications on CNS regeneration.

Quercetin

hydrogen peroxide


Input: Survival along with optimal proliferation of neuronal precursors determines the outcomes of the endogenous cellular repair in CNS.


Input: Cellular-oxidation based cell death has been described in several neurodegenerative disorders.


Input: Therefore, this study was aimed at the identification of the potent targets of oxidative damage to the neuronal precursors and its effective prevention by a natural flavonoid, Quercetin.

Quercetin


Input: Neuronal precursor cells (NPCs), Nestin + and GFAP (Glial fibrillary acidic protein) + were isolated and cultured from adult rat SVZ (subventricular zone).


Input: These cells were challenged with a single dose of H2O2 (50 mu M) and/or pre-treated with different concentrations of Quercetin.

Quercetin


Input: H2O2 severely limited the cellular viability and expansion of the neurospheres.


Input: Cellular-oxidation studies revealed reduction in glutathione dependent redox buffering along with depletion of enzymatic cellular antioxidants that might potentiate the nitrite (NO2 (-)) and superoxide anion (O2 (-)) mediated peroxynitrite (ONOO (-)) formation and irreversible protein nitration.

glutathione

nitrite

NO2 (-)

superoxide

O2 (-)

peroxynitrite

ONOO (-)


Input: We identified depleted PK-M2 (M2 isoform of pyruvate kinase) activity and apoptosis of NPCs revealed by the genomic DNA fragmentation and elevated PARP (poly ADP ribose polymerase) activity along with increased Caspase activity initiated by severely depolarised mitochondrial membranes.

pyruvate

poly ADP ribose


Input: However, the pre-treatment of Quercetin in a dose-response manner prevented these changes and restored the expansion of neurospheres preferably by neutralizing the oxidative conditions and thereby reducing peroxynitrite formation, protein nitration and PK-M2 depletion.

Quercetin

peroxynitrite


Input: Our results unravel the potential interactions of oxidative environment and respiration in the survival and activation of precursors and offer a promise shown by a natural flavonoid in the protective strategy for neuronal precursors of adult brain.

flavonoid


Input: Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer.


Input: Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear.


Input: JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus.


Input: To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n = 30).


Input: Radiologists infused low-or high-dose JX-594 into liver tumors (days 1, 15 and 29); infusions resulted in acute detectable intravascular JX-594 genomes.


Input: Objective intrahepatic Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (15%) and Choi (62%) response rates and intrahepatic disease control (50%) were equivalent in injected and distant noninjected tumors at both doses.


Input: JX-594 replication and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression preceded the induction of anticancer immunity.


Input: In contrast to tumor response rate and immune endpoints, subject survival duration was significantly related to dose (median survival of 14. 1 months compared to 6. 7 months on the high and low dose, respectively; hazard ratio 0. 39; P = 0. 020).


Input: JX-594 demonstrated oncolytic and immunotherapy MOA, tumor responses and dose-related survival in individuals with HCC.


Input: Meta-immunological profiling of children with type 1 diabetes identifies new biomarkers to monitor disease progression.


Input: Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta-cells in genetically susceptible individuals.


Input: Triggers of islet autoimmunity, time course and the precise mechanisms responsible for the progressive beta-cell failure are not completely understood.


Input: The recent escalation of obesity in affluent countries has been suggested to contribute to the increased incidence of type 1 diabetes.


Input: Understanding the link between metabolism and immune tolerance could lead to the identification of new markers for the monitoring of disease onset and progression.


Input: We studied several immune cell subsets and factors with high metabolic impact as markers associated with disease progression in high-risk subjects, type 1 diabetes patients at onset, 12 and 24 months after diagnosis.


Input: A multiple correlation matrix among different parameters was evaluated statistically and assessed visually on two-dimensional graphs.


Input: Markers to predict residual beta-cell function up to one year after diagnosis were identified in multivariate logistic regression models.


Input: The metaimmunological profile changed significantly over time in patients and a specific signature that associated with worsening disease was identified.


Input: A multivariate logistic regression model measuring age, body mass index (BMI), fasting C-peptide, number of circulating CD3 (+) CD16 (+) CD56 (+) cells and the percentage of CD1c (+) CD19 (-) CD14 (-) CD303 (-) type 1 myeloid dendritic cells (mDC1s) at disease onset had a significant predictive value.


Input: The identification of a specific meta-immunological profile associated to disease status may contribute to understand the basis of diabetes progression.


Input: A non-enzymatic function of Golgi glycosyltransferases: Mediation of Golgi fragmentation by interaction with non-muscle myosin IIA.


Input: The Golgi apparatus undergoes morphological changes under stress or malignant transformation, but the precise mechanisms are not known.


Input: We recently showed that non-muscle myosin IIA (NMIIA) binds to the cytoplasmic tail of Core 2 N-acetylglucosaminyltransferase mucus-type (C2GnT-M) and transports it to the endoplasmic reticulum for recycling.

NMIIA


Input: Here, we report that Golgi fragmentation induced by brefeldin A (BFA) or coatomer protein (beta-COP) knockdown (KD) in Panc1-bC2GnT-M (c-Myc) cells is accompanied by the increased association of NMIIA with C2GnT-M and its degradation by proteasomes.

brefeldin A

BFA


Input: Golgi fragmentation is prevented by inhibition or KD of NMIIA.


Input: Using multiple approaches, we have shown that the speed of BFA-induced Golgi fragmentation is positively correlated with the levels of this enzyme in the Golgi.

BFA


Input: The observation is reproduced in LNCaP cells which express high levels of two endogenous glycosyltransferases-C2GnT-L and beta-galactoside alpha 2, 3 sialyltransferase 1.


Input: NMIIA is found to form complexes with these two enzymes but not Golgi matrix proteins.


Input: The KD of both enzymes or the prevention of Golgi glycosyltransferases from exiting endoplasmic reticulum reduced Golgi-associated NMIIA and decreased the BFA-induced fragmentation.

BFA


Input: Interestingly, the fragmented Golgi detected in colon cancer HT-29 cells can be restored to a compact morphology after inhibition or KD of NMIIA.


Input: The Golgi disorganization induced by the microtubule or actin destructive agent is NMIIA-independent and does not affect the levels of glycosyltransferases.


Input: We conclude that NMIIA interacts with Golgi residential but not matrix proteins, and this interaction is responsible for Golgi fragmentation induced by beta-COP KD or BFA treatment.

BFA


Input: This is a novel non-enzymatic function of Golgi glycosyltransferases.


Input: Saturable active efflux by p-glycoprotein and breast cancer resistance protein at the blood-brain barrier leads to nonlinear distribution of elacridar to the central nervous system.

elacridar


Input: The study objective was to investigate factors that affect the central nervous system (CNS) distribution of elacridar.

elacridar


Input: Elacridar inhibits transport mediated by P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) and has been used to study the influence of transporters on brain distribution of chemotherapeutics.

Elacridar


Input: Adequate distribution of elacridar across the blood-brain barrier (BBB) and into the brain parenchyma is necessary to target tumor cells in the brain that overexpress transporters and reside behind an intact BBB.

elacridar


Input: We examined the role of P-gp and Bcrp on brain penetration of elacridar using Friend leukemia virus strain B wild-type, Mdr1a/b (-/-), Bcrp1 (-/-), and Mdr1a/b (-/-) Bcrp1 (-/-) mice.

elacridar


Input: Initially, the mice were administered 2. 5 mg/kg of elacridar intravenously, and the plasma and brain concentrations were determined.

elacridar


Input: The brain-to-plasma partition coefficient of elacridar in the wild-type mice was 0. 82, as compared with 3. 5 in Mdr1a/b (-/-) mice, 6. 6 in Bcrp1 (-/-) mice, and 15 in Mdr1a/b (-/-) Bcrp1 (-/-) mice, indicating that both P-gp and Bcrp limit the brain distribution of elacridar.

elacridar

elacridar


Input: The four genotypes were then administered increasing doses of elacridar, and the CNS distribution of elacridar was determined.

elacridar

elacridar


Input: The observed and model predicted maximum brain-to-plasma ratios (Emax) at the highest dose were not significantly different in all genotypes.


Input: However, the ED50 was lower for Mdr1a/b (-/-) mice compared with Bcrp1 (-/-) mice.


Input: These findings correlate with the relative expression of P-gp and Bcrp at the BBB in these mice and demonstrate the quantitative enhancement in elacridar CNS distribution as a function of its dose.


Input: Overall, this study provides useful concepts for future applications of elacridar as an adjuvant therapy to improve targeting of chemotherapeutic agents to tumor cells in the brain parenchyma.

elacridar


Input: HepG2 cells simultaneously expressing five P450 enzymes for the screening of hepatotoxicity: identification of bioactivable drugs and the potential mechanism of toxicity involved.


Input: Use of the HepG2 cell line to assess hepatotoxicity induced by bioactivable compounds is hampered by their low cytochrome P450 expression.


Input: To overcome this limitation, we have used adenoviral transfection to develop upgraded HepG2 cells (ADV-HepG2) expressing the major P450 enzymes involved in drug metabolism (CYP1A2, CYP2D6, CYP2C9, CYP2C19, and CYP3A4) at levels comparable to those of human hepatocytes.


Input: The potential utility of this new cell model for the in vitro screening of bioactivable drugs was assessed using a high-content screening assay that we recently developed to simultaneously measure multiple parameters indicative of cell injury.


Input: To this end, ADV-HepG2 and HepG2 cells, cultured in 96-well plates, were exposed for 24 h to a wide range of concentrations of 12 bioactivable and 3 non-bioactivable compounds.


Input: The cell viability and parameters associated with nuclear morphology, mitochondrial function, intracellular calcium concentration, and oxidative stress indicative of prelethal cytotoxicity and representative of different mechanisms of toxicity were evaluated.


Input: Bioactivable compounds showed lower IC (50) values in ADV-HepG2 cells than in HepG2 cells.


Input: Moreover, significant differences in the other parameters analyzed were observed between both cell models, while similar effects were observed for non-bioactivable compounds (negative controls).


Input: The changes in cell parameters detected in our assay for a given compound are in good agreement with the previously reported toxicity mechanism.


Input: Overall, our results indicate that this assay may be a suitable new in vitro approach for early screening of compounds to identify bioactivable hepatotoxins and the mechanism (s) involved in their toxicity.


Input: Atomic layer deposition of a submonolayer catalyst for the enhanced photoelectrochemical performance of water oxidation with hematite.

hematite


Input: Hematite photoanodes were coated with an ultrathin cobalt oxide layer by atomic layer deposition (ALD).

Hematite

cobalt oxide


Input: The optimal coating-1 ALD cycle, which amounts to < 1 monolayer of Co (OH) 2/Co3O4-resulted in significantly enhanced photoelectrochemical water oxidation performance.

Co (OH) 2


Input: A stable, 100-200 mV cathodic shift in the photocurrent onset potential was observed that is correlated to an order of magnitude reduction in the resistance to charge transfer at the Fe2O3/H2O interface.


Input: Furthermore, the optical transparency of the ultrathin Co (OH) 2/Co3O4 coating establishes it as a particularly advantageous treatment for nanostructured water oxidation photoanodes.

Co (OH) 2


Input: The photocurrent of catalyst-coated nanostructured inverse opal scaffold hematite photoanodes reached 0. 81 and 2. 1 mA/cm (2) at 1. 23 and 1. 53 V, respectively.

hematite


Input: A detailed look at the reaction mechanisms of substituted carbenes with water.

carbenes


Input: Two competitive reaction mechanisms for the gas-phase chemical transformation of singlet chlorocarbene into chloromethanol in the presence of one and two water molecules are examined in detail.

chlorocarbene

chloromethanol


Input: An analysis of bond orders and bond order derivatives as well as of properties of bond critical points in the electron densities along the intrinsic reaction coordinates (IRCs for intermediates --> transition state (TS) --> products) suggests that, from the perspective of bond breaking/formation, both reactions should be considered to be highly nonsynchronous, concerted processes.


Input: Both transition states are early, resembling the intermediates, yielding rate constants whose magnitudes are mostly influenced by structural changes and to a lesser degree by bond breaking/formation.


Input: For the case of one water molecule, most of the energy in the reactants region of the IRC is used for structural changes, while the transition state region encompasses the majority of electron activity, except for the formation of the C-O bond, which extends well into the products region.

C-O


Input: In the case of two water molecules, very little electron flux and comparatively less work required for structural changes is noticed in the reactants region, leading to an earlier transition state and therefore to a smaller activation energy and to a larger rate constant.


Input: This, together with evidence gathered from other sources, allows us to provide plausible explanations for the observed difference in rate constants.


Input: Prediction of micelle/water and liposome/water partition coefficients based on molecular dynamics simulations, COSMO-RS, and COSMOmic.


Input: Liposomes and micelles find various applications as potential solubilizers in extraction processes or in drug delivery systems.


Input: Thermodynamic and transport processes governing the interactions of different kinds of solutes in liposomes or micelles can be analyzed regarding the free energy profiles of the solutes in the system.


Input: However, free energy profiles in heterogeneous systems such as micelles are experimentally almost not accessible.


Input: Therefore, the development of predictive methods is desirable.


Input: Molecular dynamics (MD) simulations reliably simulate the structure and dynamics of lipid membranes and micelles, whereas COSMO-RS accurately reproduces solvation free energies in different solvents.


Input: For the first time, free energy profiles in micellar systems, as well as mixed lipid bilayers, are investigated, taking advantage of both methods: MD simulations and COSMO-RS, referred to as COSMOmic (Klamt, A.; Huniar, U.; Spycher, S.; Keldenich, J. COSMOmic: A Mechanistic Approach to the Calculation of Membrane-Water Partition Coefficients and Internal Distributions within Membranes and Micelles. J. Phys. Chem. B 2008, 112, 12148-12157).


Input: All-atom molecular dynamics simulations of the system SDS/water and CTAB/water have been applied in order to retrieve representative micelle structures for further analysis with COSMOmic.

SDS

CTAB


Input: For the system CTAB/water, different surfactant concentrations were considered, which results in different micelle sizes.

CTAB


Input: Free energy profiles of more than 200 solutes were predicted and validated by means of experimental partition coefficients.


Input: To our knowledge, these are the first quantitative predictions of micelle/water partition coefficients, which are based on whole free energy profiles from molecular methods.


Input: Further, the partitioning in lipid bilayer systems containing different hydrophobic tail groups (DOPC (1, 2-dioleoyl-sn-glycero-3-phosphocholine), SOPC (stearoyl-oleoylphosphatidylcholine), DMPC (1, 2-dimyristoyl-sn-glycero-3-phosphocholine), and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)) as well as mixed bilayers was calculated.

DOPC

1, 2-dioleoyl-sn-glycero-3-phosphocholine

SOPC

stearoyl-oleoylphosphatidylcholine

DMPC

1, 2-dimyristoyl-sn-glycero-3-phosphocholine

POPC

1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine


Input: Experimental partition coefficients (log P) were reproduced with a root-mean-square error (RMSE) of 0. 62.


Input: To determine the influence of cholesterol as an important component of cellular membranes, free energy profiles in the presence of cholesterol were calculated and shown to be in good agreement with experimental data.

cholesterol

cholesterol


Input: Probing adsorption of polyacrylamide-based polymers on anisotropic Basal planes of kaolinite using quartz crystal microbalance.

polyacrylamide

kaolinite

quartz


Input: Quartz crystal microbalance with dissipation (QCM-D) was applied to investigate the adsorption characteristics of polyacrylamide-based polymers (PAMs) on anisotropic basal planes of kaolinite.

Quartz

polyacrylamide

PAMs

kaolinite


Input: Kaolinite basal planes were differentiated by depositing kaolinite nanoparticles (KNPs) on silica and alumina sensors in solutions of controlled pH values.

Kaolinite

kaolinite

silica

alumina


Input: Adsorption of an in-house synthesized organic-inorganic Al (OH) 3-PAM (Al-PAM) as an example of cationic hybrid PAM and a commercially available partially hydrolyzed polyacrylamide (MF1011) as an example of anionic PAM was studied.

Al (OH) 3-PAM

Al-PAM

PAM

polyacrylamide

anionic PAM


Input: Cationic Al-PAM was found to adsorb irreversibly and preferentially on tetrahedral silica basal planes of kaolinite.

Cationic Al-PAM

silica

kaolinite


Input: In contrast, anionic MF1011 adsorbed strongly on aluminum-hydroxy basal planes, while its adsorption on tetrahedral silica basal planes was weak and reversible.

anionic MF1011

aluminum-hydroxy

silica


Input: Adsorption study revealed that both electrostatic attraction and hydrogen-bonding mechanisms contribute to adsorption of PAMs on kaolinite.

hydrogen

PAMs

kaolinite


Input: The adsorbed Al-PAM layer was able to release trapped water overtime and became more compact, while MF1011 film became more dissipative as backbones stretched out from kaolinite surface with minimal overlapping.

Al-PAM

kaolinite


Input: Experimental results obtained from this study provide clear insights into the phenomenon that governs flocculation-based solid-liquid separation processes using multicomponent flocculants of anionic and cationic nature.


Input: Strong effects of cluster size and air exposure on oxygen reduction and carbon oxidation electrocatalysis by size-selected Pt (n) (n <= 11) on glassy carbon electrodes.

oxygen

carbon

Pt (n)

glassy carbon


Input: Model Pt (n)/glassy carbon electrodes (Pt (n)/GCE) were prepared by deposition of mass-selected Pt (n) (+) (n <= 11) on GCE substrates in ultrahigh vacuum.

Pt (n)

glassy carbon

Pt (n)

Pt (n) (+)


Input: Electrocatalysis under conditions appropriate for the oxygen reduction reaction (ORR) was studied, for samples both in situ with no exposure to laboratory air and with air exposure prior to electrochemical measurements.

oxygen


Input: Of the small clusters, only a few cluster sizes show the expected ORR activity, and in those cases, the activity per Pt atom is similar to that seen under identical conditions with a conventionally prepared electrode with Pt nanoparticles grown on a GCE.

Pt

Pt


Input: For other small Pt (n) on GCE, any ORR signal is overwhelmed by large oxidative currents attributed to catalysis of carbon oxidation by water.

Pt (n)

carbon


Input: If the samples are exposed to air prior to electrochemistry, both ORR and carbon oxidation signals are absent, and instead only small capacitive currents or currents attributed to redox chemistry of adventitious organic adsorbates are observed, indicating that air exposure results in passivation of the small Pt clusters.

carbon

Pt


Input: Effects of chronic dietary selenomethionine exposure on repeat swimming performance, aerobic metabolism and methionine catabolism in adult zebrafish (Danio rerio).

selenomethionine

methionine


Input: In a previous study we reported impaired swimming performance and greater stored energy in adult zebrafish (Danio rerio) after chronic dietary exposure to selenomethionine (SeMet).

selenomethionine

SeMet


Input: The goal of the present study was to further investigate effects of chronic exposure to dietary SeMet on repeat swimming performance, oxygen consumption (MO2), metabolic capacities (standard metabolic rate [SMR], active metabolic rate [AMR], factorial aerobic scope [F-AS] and cost of transport [COT]) and gene expression of energy metabolism and methionine catabolism enzymes in adult zebrafish.

SeMet

oxygen

methionine


Input: Fish were fed SeMet at measured concentrations of 1. 3, 3. 4, 9. 8 or 27. 5 mu g Se/g dry mass (d. m.) for 90 d.

SeMet

Se


Input: At the end of the exposure period, fish from each treatment group were divided into three subgroups: (a) no swim, (b) swim, and (c) repeat swim.


Input: Fish from the no swim group were euthanized immediately at 90 d and whole body triglycerides, glycogen and lactate, and gene expression of energy metabolism and methionine catabolism enzymes were determined.

triglycerides

lactate

methionine


Input: Individual fish from the swim group were placed in a swim tunnel respirometer and swimming performance was assessed by determining the critical swimming speed (U (crit)).


Input: After both Ucrit and MO2 analyses, fish were euthanized and whole body energy stores and lactate were determined.

lactate


Input: Similarly, individual fish from the repeat swim group were subjected to two U (crit) tests (U (crit-1) and U (crit-2)) performed with a 60 min recovery period between tests, followed by determination of energy stores and lactate.

lactate


Input: Impaired swim performance was observed in fish fed SeMet at concentrations greater than 3 mu g Se/g in the diet.

SeMet

Se


Input: However, within each dietary Se treatment group, no significant differences between single and repeat U (crits) were observed.

Se


Input: Oxygen consumption, SMR and COT were significantly greater, and F-AS was significantly lesser, in fish fed SeMet.

Oxygen

SeMet


Input: Whole body triglycerides were proportional to the concentration of SeMet in the diet.

triglycerides

SeMet


Input: While swimming resulted in lesser concentrations of glycogen in the body, exposure to SeMet in the diet had no significant effect on glycogen content.

SeMet


Input: Exposure to SeMet significantly down-regulated mRNA abundance of protein tyrosine phosphatase 1B (PTP 1B) in muscle, and beta-hydroxyacyl coenzyme A dehydrogenase (HOAD), sterol regulatory element binding protein 1 (SREBP 1) and methionine adenosyltransferase 1 alpha (MAT 1A) in liver of adult zebrafish.

SeMet

tyrosine

beta-hydroxyacyl coenzyme A

sterol

methionine


Input: Overall the results of this study suggest chronic exposure of adult zebrafish to SeMet in the diet can cause both cellular and organismal effects that could affect fitness and survivability of fish.

SeMet


Input: Electron attachment to the dipeptide dialanine: influence of methylation on site selective dissociation reactions.

dialanine


Input: Gas phase dissociative electron attachment (DEA) measurements with methyl-dialanine, C (7) H (14) N (2) O (3), are performed in a crossed electron-molecular beam experiment at high energy resolution (~ 120 meV).

methyl-dialanine

C (7) H (14) N (2) O (3)


Input: Anion efficiency yields as a function of the incident electron energy are obtained for the most abundant fragments up to electron energies of ~ 15 eV.


Input: There is no evidence of molecular anion formation whereas the dehydrogenated closed shell anion (M-H) (-) is one of the most dominant reaction products.


Input: Quantum chemical calculations are performed to investigate the electron attachment process and to elucidate site selective bond cleavage in the (M-H) (-) DEA-channel.


Input: Previous DEA studies on dialanine have shown that (M-H) (-) formation proceeds through abstraction of a hydrogen atom from the carboxyl and amide groups, contributing to two distinct resonances at 0. 81 and 1. 17 eV, respectively [D. Gschliesser, V. Vizcaino, M. Probst, P. Scheier and S. Denifl, Chem.-Eur. J., 2012, 18, 4613-4619].

dialanine

hydrogen

carboxyl

amide


Input: Here we show that by methylation of the carboxyl group, all (calculated) thresholds for H-loss from the different sites in the dialanine molecule are shifted up to a maximum of 1. 4 eV.

carboxyl

H

dialanine


Input: The lowest lying resonance observed experimentally for (M-H) (-) remains operative from the amide group at the electron energy of 2. 4 eV due to the methylation.

amide


Input: We further study methylation-induced effects on the unimolecular dissociation leading to a variety of negatively charged DEA products.


Input: Probing the dielectric response of graphene via dual-band plasmonic nanoresonators.

graphene


Input: In this article, we use optical transmission spectroscopy to measure the changes in the resonance features of a Au plasmonic nanoresonator array consisting of concentric ring/disc cavity elements, when graphene is introduced as an encapsulating medium.

Au


Input: We show that by using finite element modelling to best reproduce our experimental results the dielectric response of the graphene film can be determined.

graphene


Input: We discuss the potential of such structures for chemical sensing applications.


Input: Chromogenic and fluorogenic chemosensors and reagents for anions.


Input: A comprehensive review of the years 2010-2011.


Input: This review focuses on examples reported in the years 2010-2011 dealing with the design of chromogenic and fluorogenic chemosensors or reagents for anions.


Input: Feasibility of a breath test for monitoring adherence to vaginal administration of antiretroviral microbicide gels.


Input: Adherence to microbicide gel use is critical to optimizing effectiveness in preventing human immunodeficiency virus transmission.


Input: The authors hypothesized that ester taggants added to vaginal gels would generate exhaled alcohol and ketone metabolites and provide a " breath test " for vaginal gel use.

ester

alcohol

ketone


Input: This 2-arm (vaginal and dermal), randomized, participant-blinded, pilot study tested this hypothesis.


Input: On 8 visits, healthy women (n = 8) received intravaginal taggant (2-butyl acetate, 2-pentyl acetate, isopropyl butyrate, or 2-pentyl butyrate; 30 mg) formulated in hydroxyethylcellulose or tenofovir placebo gel.

2-butyl acetate

2-pentyl acetate

isopropyl butyrate

2-pentyl butyrate

tenofovir


Input: A second group (n = 4) of women received the same formulations administered dermally on the forearm to determine if skin administration might confound the system.


Input: Breath samples were collected using bags before and after taggant administration for 1 hour.


Input: Samples were measured using a miniature gas chromatograph and/or gas chromatography-mass spectroscopy for ester taggant, alcohol, and ketone concentrations.

alcohol

ketone


Input: After vaginal administration, 2-butyl acetate, 2-pentyl acetate, and metabolites were observed in breath, whereas isopropyl butyrate, 2-pentyl butyrate, and metabolites were not.

2-butyl acetate

2-pentyl acetate

isopropyl butyrate

2-pentyl butyrate


Input: Some women reported self-resolving, mild burning (24/64 visits) with vaginal administration or a " bubblegum " taste (7/64 visits).


Input: No taggants or metabolites were detected following dermal application.


Input: A " breath test " for adherence to antiretroviral vaginal gel application appears physiologically and technically feasible.


Input: Pharmacokinetics of intravenous voriconazole in obese patients: implications of CYP2C19 homozygous poor metabolizer genotype.

voriconazole


Input: There is a paucity of pharmacokinetic studies describing weight-based dosing of intravenous voriconazole in obese patients.

voriconazole


Input: In this case report, we describe the pharmacokinetics of intravenous voriconazole in an obese CYP2C19 homozygous poor metabolizer and review previously reported data regarding the use of intravenous voriconazole in obese patients.

voriconazole

voriconazole


Input: A 17-year-old obese Hispanic male patient (body mass index 35 kg/m (2)) received intravenous voriconazole for the treatment of suspected aspergillosis.

voriconazole


Input: After 2. 5 days of voriconazole 4 mg/kg intravenously every 12 hours based on adjusted body weight, the voriconazole area under the serum concentration-time curve over the course of a single (12-hr) dosing interval and trough concentration were 86, 100 ng. hr/ml and 6. 2 micro g/ml, respectively.

voriconazole

voriconazole


Input: Six days later, the voriconazole dosage was decreased.

voriconazole


Input: A trough concentration measured just before the dosage reduction (after 8. 5 days of voriconazole 4 mg/kg intravenously every 12 hours based on adjusted body weight) remained elevated at 5. 8 micro g/ml.

voriconazole


Input: Genotyping revealed a CYP2C19 homozygous poor metabolizer (CYP2C19 * 2/* 2).


Input: Voriconazole was subsequently discontinued due to QTc prolongation.

Voriconazole


Input: These data and those from two recent publications suggest that voriconazole does not distribute extensively into human adipose tissue and that obese patients should be dosed on an adjusted body weight basis.

voriconazole


Input: If an obese patient dosed on total body weight is also a CYP2C19 poor metabolizer, serum voriconazole concentrations will be further elevated, potentially leading to drug-induced toxicity.

voriconazole


Input: Key Articles and Guidelines in the Primary Prevention of Ischemic Stroke.


Input: Ischemic stroke is a prevalent disease with a large burden on the health system.


Input: Preventive strategies, therefore, are paramount.


Input: Primary prevention is aimed at reducing the risk of stroke in asymptomatic people.


Input: The most effective prevention is through control of modifiable risk factors.


Input: Due to the large amount of literature available on this topic, this bibliography (the first of a 2-part series) aims to provide a comprehensive resource for medical practitioners charged with caring for this population.


Input: Arsenic geochemistry in a biostimulated aquifer: An aqueous speciation study.

Arsenic


Input: Stimulating microbial growth through the use of acetate injection wells at the former uranium mill site in Rifle, Colorado, USA, has been shown to decrease dissolved uranium (VI) concentrations through bacterial reduction to immobile uranium (IV).

uranium (VI)

uranium (IV)


Input: Bioreduction also changed the redox chemistry of site groundwater, altering the mobility of several other redox-sensitive elements present in the subsurface, including iron, sulfur, and arsenic.

iron

sulfur

arsenic


Input: Following acetate amendment at the site, elevated concentrations of arsenic in the groundwater were observed.

acetate

arsenic


Input: Ion chromatography-inductively coupled plasma-mass spectrometry was used to determine the aqueous arsenic speciation.

arsenic


Input: Upgradient samples, unexposed to acetate, showed low levels of arsenic (=~ 1 mu M), with greater than 90% as arsenate (As [V]) and a small amount of arsenite (As [III]).

acetate

arsenic

arsenate

As [V]

arsenite

As [III]


Input: Downgradient acetate-stimulated water samples had much higher levels of arsenic (up to 8 mu M), and 4 additional thioarsenic species were present under sulfate-reducing conditions.

acetate

arsenic

thioarsenic

sulfate


Input: These thioarsenic species demonstrate a strong correlation between arsenic release and sulfide concentrations in groundwater, and their formation may explain the elevated total arsenic concentrations.

thioarsenic

arsenic

sulfide

arsenic


Input: An alternative remediation approach, enhanced flushing of uranium, was accomplished by addition of bicarbonate and did not result in highly elevated arsenic concentrations.

uranium

bicarbonate

arsenic


Input: Environ Toxicol Chem 2013; 32: 1216-1223.


Input: (c) 2013 SETAC.


Input: The Lignan (-)-Cubebin Inhibits Vascular Contraction and Induces Relaxation Via Nitric Oxide Activation in Isolated Rat Aorta.

Lignan (-)-Cubebin

Nitric Oxide


Input: Cubebin, the most abundant lignan in Piper cubeba, has been described as having several effects as trypanocidal, antimycobacterial, antispasmodic, antimicrobial, anti-inflammatory, and analgesic.

Cubebin

lignan


Input: This study investigated the vasorelaxant effect produced by (-)-cubebin in isolated rat aortic rings pre-contracted with phenylephrine (Phe), and the possible mechanism involved in this event was evaluated.

(-)-cubebin

phenylephrine

Phe


Input: Endothelium-dependent relaxation was evoked by acetylcholine and (-)-cubebin in intact aortic rings, while endothelium-independent vasorelaxation was elicited by sodium nitroprusside and (-)-cubebin in denuded rings.

acetylcholine

(-)-cubebin

sodium nitroprusside

(-)-cubebin


Input: Cumulative concentration-response curves for Phe (10 (-10)-10 (-5) M) were determined for endothelium-intact and endothelium-denuded aortic rings in either the presence or absence of (-)-cubebin.

Phe

(-)-cubebin


Input: Dose-response curves were also constructed for pre-incubation of vascular rings with N omega-nitro-L-arginine methyl ester (L-NAME) (a non-specific nitric oxide synthase inhibitor), indomethacin (an unspecific cyclooxygenase inhibitor), and 1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one (ODQ) (a guanylyl cyclase inhibitor).

N omega-nitro-L-arginine methyl ester

L-NAME

nitric oxide

indomethacin

1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one

ODQ


Input: (-)-Cubebin was found to exert a vasorelaxant effect irrespective of the presence of endothelium, which was abolished by pretreatment with L-NAME and ODQ, but not with indomethacin.

(-)-Cubebin

L-NAME

ODQ

indomethacin


Input: In addition, (-)-cubebin was able to reduce Phe contraction in the case of intact rings.

(-)-cubebin

Phe


Input: These results suggest that (-)-cubebin promotes vasorelaxation via NO/cGMP pathway in rat aorta, without prostacyclin involvement.

(-)-cubebin

NO

cGMP

prostacyclin


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


Input: [6]-Shogaol Attenuates Neuronal Apoptosis in Hydrogen Peroxide-Treated Astrocytes Through the Up-Regulation of Neurotrophic Factors.

Hydrogen Peroxide


Input: Neuronal apoptosis induced by oxidative stress is a prominent feature of neurodegenerative disorders.


Input: [6]-shogaol, a bio-active compound in ginger, possesses potent anti-inflammatory actions and has recently emerged as a potential therapeutic agent for neurodegenerative disorders.


Input: However, the effects of [6]-shogaol on astroglial apoptosis following exogenously induced oxidative stress has not yet been investigated.


Input: Here, we show that the anti-apoptotic activity of [6]-shogaol in astrocytes following exposure to hydrogen peroxide (H (2) O (2)) involves a marked up-regulation of neurotrophic factors such as nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor.

hydrogen peroxide

H (2) O (2)


Input: Astrocytes co-treated with [6]-shogaol and H (2) O (2) for 1 h showed decrease in reactive oxygen species production compared with those only treated with H (2) O (2).

H (2) O (2)

oxygen

H (2) O (2)


Input: Moreover, [6]-shogaol counteracted the reduced expression of ERK1/2 in H (2) O (2)-treated astrocytes and protected these cells from oxidative stress and apoptosis by attenuating the impairment of mitochondrial function proteins such as Bcl-2 and Bcl-xL.

H (2) O (2)


Input: Additionally, [6]-shogaol inhibits the expression of the apoptotic proteins Bax and caspase-3 in H (2) O (2)-treated astrocytes.

H (2) O (2)


Input: This data suggest that following oxidative stress, [6]-shogaol protects astrocytes from oxidative damage through the up-regulating levels of neurotrophic factors.


Input: These findings provide further support for the use of [6]-shogaol as a therapeutic agent in neurodegenerative disorders.


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


Input: In vivo Antimalarial Activity of a Labdane Diterpenoid from the Leaves of Otostegia integrifolia Benth.

Labdane Diterpenoid


Input: In Ethiopian traditional medicine, the leaves of Otostegia integrifolia Benth. are used for the treatment of several diseases including malaria.


Input: In an ongoing search for effective, safe and cheap antimalarial agents from plants, the 80% methanol leaf extract O. integrifolia was tested for its in vivo antimalarial activity, in a 4-day suppressive assay against Plasmodium berghei.

methanol


Input: Activity-guided fractionation of this extract which showed potent antiplasmodial activity resulted in the isolation of a labdane diterpenoid identified as otostegindiol.

labdane diterpenoid

otostegindiol


Input: Otostegindiol displayed a significant (P < 0. 001) antimalarial activity at doses of 25, 50 and 100 mg/kg with chemosuppression values of 50. 13, 65. 58 and 73. 16%, respectively.

Otostegindiol


Input: Acute toxicity studies revealed that the crude extract possesses no toxicity in mice up to a maximum dose of 5000 mg/kg suggesting the relative safety of the plant when administered orally.


Input: The results of the present study indicate that otostegindiol is among the antimalarial principles in this medicinal plant, and further support claims for the traditional medicinal use of the plant for the treatment of malaria.

otostegindiol


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


Input: Exploring the Interplay Between Ligand Derivatisation and Cation Type in the Assembly of Hybrid Polyoxometalate Mn-Andersons.

Polyoxometalate Mn


Input: Herein a library of hybrid Mn-Anderson polyoxometalates anions are presented: 1, [(MnMo (6) O (18)) ((OCH (2)) (3)-C-(CH (2)) (7) CHCH (2)) (2)] (3-); compound 2, [(MnMo (6) O (18)) ((OCH (2)) (3) C-NHCH (2) C (16) H (9)) (2)] (3-); compound 3, [(MnMo (6) O (18)) ((OCH (2)) (3) C-(CH (2)) (7) CHCH (2)) (1) ((OCH (2)) (3) C-NHCH (2) C (16) H (9)) (1)] (3-); compound 4, [(MnMo (6) O (18)) ((OCH (2)) (3) C-NHC (O) CH (2) CHCH (2)) (2)] (3-) and compounds 5-9, [(MnMo (6) O (18)) ((OCH (2)) (3) C-NHC (O) (CH (2)) (x) CH (3)) (2)]), where x = 4, 10, 12, 14, and 18 respectively.

Mn

polyoxometalates

[(MnMo (6) O (18)) ((OCH (2)) (3)-C-(CH (2)) (7) CHCH (2)) (2)] (3-)

[(MnMo (6) O (18)) ((OCH (2)) (3) C-NHCH (2) C (16) H (9)) (2)] (3-)

[(MnMo (6) O (18)) ((OCH (2)) (3) C-(CH (2)) (7) CHCH (2)) (1) ((OCH (2)) (3) C-NHCH (2) C (16) H (9)) (1)] (3-)

[(MnMo (6) O (18)) ((OCH (2)) (3) C-NHC (O) CH (2) CHCH (2)) (2)] (3-)

[(MnMo (6) O (18)) ((OCH (2)) (3) C-NHC (O) (CH (2)) (x) CH (3)) (2)])


Input: The compounds resulting from the cation exchange of the anions 1-9 to give TBA (a) and DMDOA (b) salts, and additionally for compounds 1, 2 and 3, tetraphenylphosphonium (PPh (4)) (c) salts, are explored at the air/water interface using scanning force microscopy, showing a range of architectures including hexagonal structures, nanofibers and other supramolecular forms.

TBA

DMDOA

tetraphenylphosphonium

PPh (4)


Input: Additionally the solid-state structures for compounds 1c, 2c, 4a, 6a, 9a, are presented for the first time and these investigations demonstrate the delicate interplay between the structure of the covalently derivatised hybrid organo-clusters as well as the ion-exchange cation types.


Input: Drug cocktail interaction study on the effect of the orally administered lavender oil preparation silexan on cytochrome p450 enzymes in healthy volunteers.


Input: This cocktail study evaluated the interaction potential of the oral lavender oil preparation silexan with major P450 (cytochrome P450) enzymes.


Input: Subjects and Methods: Sixteen healthy male or female Caucasians completed this double-blind, randomized, 2-fold crossover study.


Input: Silexan (160 mg) or placebo were administered once daily for 11 days.


Input: Additionally, on day 11 of both study periods, 150 mg caffeine (CYP1A2), 125 mg tolbutamide (CYP2C9), 20 mg omeprazole (CYP2C19), 30 mg dextromethorphan-HBr (CYP2D6), and 2 mg midazolam (CYP3A4) were administered orally.

caffeine

tolbutamide

omeprazole

dextromethorphan-HBr

midazolam


Input: Formal interaction was excluded if the 90% confidence interval (CI) for the silexan over placebo ratios for phenotyping metrics (primary: AUC0-t) was within a 0. 70-1. 43 range.


Input: Results: According to the AUC0-t comparisons, silexan had no relevant effect on CYP1A2, 2C9, 2D6, and 3A4 activity.


Input: Secondary phenotyping metrics confirmed this result.


Input: Mean ratios for all omeprazole-derived metrics were close to unity.

omeprazole


Input: The 90% CI for the AUC0-t ratio of omeprazole but not for omeprazole/5-OH-omeprazole plasma ratio 3 hours post-dose or omeprazole/5-OH-omeprazole AUC0-t ratio (secondary CYP2C19 metrics) was above the predefined threshold of 1. 43, probably caused by the inherent high variability of omeprazole pharmacokinetics.

omeprazole

omeprazole

omeprazole

omeprazole


Input: Silexan and the phenotyping drugs were well tolerated.


Input: Repeated silexan (160 mg/day) administration has no clinically relevant inhibitory or inducing effects on the CYP1A2, 2C9, 2C19, 2D6, and 3A4 enzymes in vivo.


Input: Tacticity-induced changes in the micellization and degradation properties of poly (lactic acid)-block-poly (ethylene glycol) copolymers.

poly (lactic acid)-block-poly (ethylene glycol)


Input: Poly (lactic acid)-block-poly (ethylene glycol) copolymers (PLA-b-PEG) featuring varying tacticities (atactic, heterotactic, isotactic) in the PLA block were synthesized and investigated for their micellar stability, degradation, and thermal properties.

Poly (lactic acid)-block-poly (ethylene glycol)

PLA-b-PEG

PLA


Input: Utilizing tin (II) bis (2-ethylhexanoate), aluminum salan, and aluminum salen catalysts, the copolymers were synthesized through the ring-opening polymerization of d-, l-, rac-, or a blend of l-and rac-lactide using monomethoxy-poly (ethylene glycol) as a macroinitiator.

tin (II) bis (2-ethylhexanoate)

aluminum salan

aluminum salen

l-and rac-lactide

monomethoxy-poly (ethylene glycol)


Input: The critical micelle concentration, which reflects the micellar stability, was probed using a fluorescence spectroscopic method with pyrene as the probe.

pyrene


Input: The copolymers were degraded in a methanolic solution of 1, 5, 7-triaza-bicyclo [4. 4. 0] dec-5-ene and the degradation was measured by (1) H NMR spectroscopic and gel permeation chromatographic analyses.

1, 5, 7-triaza-bicyclo [4. 4. 0] dec-5-ene

(1) H


Input: Differential scanning calorimetry and thermogravimetric analysis provided information on the thermal properties of the copolymers.


Input: Atactic and heterotactic microstructures in the PLA block resulted in lower micellar stability, as well as faster degradation and shorter erosion time compared to polymers with high isotactic enchainment (Pm).

PLA


Input: By modification of the Pm, micellar stability, degradation, and erosion rates of the copolymers can be tuned to specific biomedical applications.


Input: Interestingly, while tin (II) bis (2-ethylhexanoate) and aluminum salan-catalyzed PLA-b-PEG copolymers exhibited similar micellization behavior, the aluminum salen-catalyzed PLA-b-PEG exhibited unique behavior at high micelle concentration in the presence of the pyrene probe.

tin (II) bis (2-ethylhexanoate)

aluminum salan

PLA-b-PEG

aluminum salen

PLA-b-PEG

pyrene


Input: This unique behavior can be attributed to the disintegration of the micelles through the interactions of long isotactic stereoblock segments.


Input: Vitamin B12 and homocysteine status during pregnancy in the metformin in gestational diabetes trial: responses to maternal metformin compared with insulin treatment (+)

Vitamin B12

homocysteine

metformin

metformin


Input: AIM: The aim of the study is to compare the effects of metformin and insulin treatment for gestational diabetes mellitus (GDM) on vitamin B12 and homocysteine (Hcy) status.

metformin

vitamin B12

homocysteine

Hcy


Input: METHODS: Women with GDM, who met criteria for insulin treatment, were randomly assigned to metformin (n = 89) or insulin (n = 91) in the Adelaide cohort of the metformin in gestational diabetes (MiG) trial.

metformin

metformin


Input: Fasting serum total vitamin B12 (TB12), holotranscobalamin (HoloTC), a marker of functional B12 status and plasma Hcy concentrations were measured at 20-34 weeks (at randomization) and 36 weeks gestation, then at 6-8 weeks postpartum.

vitamin B12

Hcy


Input: RESULTS: Circulating TB12, HoloTC and Hcy were similar in both treatment groups at each time point.

Hcy


Input: Women who were taking dietary folate supplements at randomization had higher serum TB12 and HoloTC at randomization than those not taking folate.

folate

folate


Input: Overall, serum TB12 fell more between randomization and 36 weeks gestation in the metformin group than in the insulin group (metformin:-19. 7 +/- 4. 7 pmol/l, insulin:-6. 4 +/- 3. 6 pmol/l, p = 0. 004).

metformin

metformin


Input: The decrease in serum TB12 during treatment was greater with increasing treatment duration in metformin-treated (p < 0. 001), but not in insulin-treated women.

metformin


Input: CONCLUSIONS: Total, but not bioavailable, vitamin B12 stores were depleted during pregnancy to a greater extent in metformin-treated than in insulin-treated women with GDM, but neither analyte differed between groups at any stage.

vitamin B12

metformin


Input: This adds further evidence supporting metformin as a safe alternative treatment to insulin in GDM.

metformin


Input: Further investigation is needed to evaluate whether women treated with metformin for longer periods in pregnancy require additional B12 or other supplementation.

metformin


Input: Between superexchange and hopping: an intermediate charge-transfer mechanism in poly (A)-poly (T) DNA hairpins.


Input: We developed a model for hole migration along relatively short DNA hairpins with fewer that seven adenine (A): thymine (T) base pairs.

adenine

thymine


Input: The model was used to simulate hole migration along poly (A)-poly (T) sequences with a particular emphasis on the impact of partial hole localization on the different rate processes.


Input: The simulations, performed within the framework of the stochastic surrogate Hamiltonian approach, give values for the arrival rate in good agreement with experimental data.


Input: Theoretical results obtained for hairpins with fewer than three A: T base pairs suggest that hole transfer along short hairpins occurs via superexchange.


Input: This mechanism is characterized by the exponential distance dependence of the arrival rate on the donor/acceptor distance, k (a) ~ e (-beta R), with beta = 0. 9 A (-1).


Input: For longer systems, up to six A: T pairs, the distance dependence follows a power law k (a) ~ R (-eta) with eta = 2.


Input: Despite this seemingly clear signature of unbiased hopping, our simulations show the complete delocalization of the hole density along the entire hairpin.


Input: According to our analysis, the hole transfer along relatively long sequences may proceed through a mechanism which is distinct from both coherent single-step superexchange and incoherent multistep hopping.


Input: The criterion for the validity of this mechanism intermediate between superexchange and hopping is proposed.


Input: The impact of partial localization on the rate of hole transfer between neighboring A bases was also investigated.


Input: New insight into artifactual phenomena during in vitro toxicity assessment of engineered nanoparticles: study of TNF-alpha adsorption on alumina oxide nanoparticle.

alumina oxide


Input: Biomolecules can be adsorbed on nanoparticles (NPs) and degraded during in vitro toxicity assays.


Input: These artifactual phenomena could lead to misinterpretation of biological activity, such as false-negative results.


Input: To avoid possible underestimation of cytokine release after contact between NP and cells, we propose a methodology to account for these artifactual phenomena and lead to accurate measurements.


Input: We focused on the pro-inflammatory cytokine tumor necrosis factor TNF-alpha.


Input: We studied well-characterized boehmite engineered NP [aluminum oxide hydroxide, AlO (OH)].

boehmite

aluminum oxide hydroxide

AlO (OH)


Input: The rate of TNF-alpha degradation and its adsorption (on boehmite and on the walls of wells) were determined in cell-free conditions by adding a known TNF-alpha concentration (1500 pg/ml) under various experimental conditions.

boehmite


Input: After a 24-h incubation, we quantified that 7 wt.% of the initial TNF-alpha was degraded over time, 6 wt.% adsorbed on the walls of 96-well plates, and 13 wt.% adsorbed on the boehmite surface.

boehmite


Input: Finally, boehmite NP were incubated with murine macrophages (RAW 264. 7 cell line).

boehmite


Input: The release of TNF-alpha was assessed for boehmite NP and the experimental data were corrected considering the artifactual phenomena, which accounted for about 20-30% of the total.

boehmite


Input: Anti-atherosclerotic mechanisms of statin therapy.


Input: HMG-CoA-Reductase inhibitors, also known as statins, are currently the most powerful cholesterol-lowering drugs available on the market.

CoA

cholesterol


Input: Clinical trials and experimental evidence suggest that statins have anti-atherosclerotic effects.


Input: These are in part consequence of lipid lowering but also result from pleiotropic actions of the drugs.


Input: In this article, the anti-atherosclerotic actions of statins will be reviewed.


Input: Inhibition of mitochondrial carnitine/acylcarnitine transporter by H2O2: Molecular mechanism and possible implication in pathophysiology.

carnitine

acylcarnitine


Input: H2O2 inhibits the [(3) H] carnitine/carnitine antiport catalysed by the mitochondrial carnitine/acylcarnitine transporter reconstituted in proteoliposomes.

[(3) H] carnitine

carnitine

carnitine

acylcarnitine


Input: The inhibition was reversed by dithioerythritol, N-acetylcysteine and l-cysteine.

dithioerythritol

N-acetylcysteine

l-cysteine


Input: Inhibition time-dependence revealed a faster and a slower reaction stages with orders of reaction of 1. 0 and 1. 9, respectively.


Input: Inhibition was tested on mutants in which one or more of the six Cys residues had been substituted with Ser or with Val.

Cys

Ser

Val


Input: The four replacement mutant C23S/C58S/C89S/C283S containing C136 and C155 was inhibited as the wild-type.


Input: Mutants C23V/C58V/C155V/C89S/C283S and C23V/C58V/C136V/C89S/C283S containing only C136 or C155, respectively, were inhibited at a much lower extent respect to the wild-type, while the mutant C136S/C155S in which the two Cys were substituted and the C-less protein were virtually insensitive to inhibition.

Cys


Input: DTE reversed the inhibition of the H2O2 sensitive proteins except that in the case of the mutants containing only C136 or C155 after long time of incubation with H2O2.

DTE


Input: The IC50 values obtained by dose-response curves of H2O2 inhibition were 0. 17mM for the wild-type, 0. 39mM for the four replacement mutant containing C136 and C155, 2. 23 or 1. 8mM in the five replacement mutants containing the single C136 or C155, respectively.


Input: Carnitine and acetylcarnitine protected the protein from the inhibition by H2O2.

Carnitine

acetylcarnitine


Input: Inhibition kinetics showed a competitive behaviour of H2O2 respect to carnitine.

carnitine


Input: All the data concur to demonstrate that H2O2 interacts with C136 and C155 and completely inactivates the transporter by inducing the formation of a disulphide.

disulphide


Input: Hematologic and hepatic responses of the freshwater fish Hoplias malabaricus after saxitoxin exposure.

saxitoxin


Input: The bioaccumulation of saxitoxins (STX) in the trophic chain, mainly in freshwater, are not completely known.

saxitoxins

STX


Input: This work aimed to elucidate the effects of STX on Hoplias malabaricus through trophic bioassay.

STX


Input: The fish were fed once every five days with Astyanax sp. before being subjected to an intraperitoneal inoculation with the lysate of Cylindrospermopsis raciborskii culture containing 97% STX and 3% by neosaxitoxin and gonyautoxin during 20 days.

STX

neosaxitoxin

gonyautoxin


Input: The animal' s liver was assessed using biomarkers as activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx), and concentrations of reduced glutathione (GSH) and lipoperoxidation (LPO) and protein carbonylation (PCO).

superoxide

glutathione

glutathione

reduced glutathione

GSH


Input: In the blood was analyzed the genotoxic and hematological parameters.


Input: The hepatosomatic index and the relative condition factor did not show a significant difference between the exposed and control groups.


Input: The values of mean corpuscular hemoglobin concentration and mean corpuscular hemoglobin increased in the STX group.

STX


Input: The hepatic tissue from both groups exhibited a typical pattern that have been already described for most teleost fish.


Input: The results suggested the generation of reactive oxygen species, with increased activity of GPx and concentrations of LPO and GSH; whereas the specific activity of SOD decreased.

oxygen

GSH


Input: However, no changes were observed in the CAT, PCO, and DNA damage.


Input: Although the STX effects are known as neurotoxic, this cyanotoxin caused liver biochemical alterations that can be considered ecologically relevant.

STX


Input: Elemental composition of dog foods using nitric acid and simulated gastric digestions.

nitric acid


Input: Eighteen dry dog foods obtained commercially in the United States were digested using microwave assisted nitric acid digestion and a simulated gastric digestion.

nitric acid


Input: Digests were analysed for 23 elements using inductively coupled plasma-mass spectrometry.


Input: Data, expressed as dry matter concentrations, were compared to published nitric acid digestion results.

nitric acid


Input: Nitric acid data obtained in the present study were not statistically different from published data, with the exception of Mo, Sn, Sb, Tl and Th.

Nitric acid

Mo

Sn

Sb

Tl

Th


Input: However, significant differences in individual intra-sample results were observed between published studies and the present work.


Input: Simulated gastric digestions demonstrated lower extraction efficiencies (< 50% nitric acid digestions) that were statistically significant.


Input: Much lower bioavailability was observed for Al, Ba and Pb.

Al

Ba

Pb


Input: In general, elemental concentrations were determined to be lower than the appropriate Mineral Tolerance Limit or consistent with background concentrations in foodstuffs.


Input: Evaluation against Reference Doses (RfDs) showed concentrations for many elements obtained by nitric acid digestion to be above RfD levels.

nitric acid


Input: However, the respective simulated gastric digestion data were below or only moderately elevated above RfDs.


Input: Only arsenic displayed median and maximum concentrations at factors of five and ten above the relevant RfD.


Input: Biological clues to potent DNA-damaging activities in food and flavoring.


Input: Population differences in age-related diseases and cancer could stem from differences in diet.


Input: To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks.


Input: Substances testing positive included reference chemicals: quinacrine (peak response, 51 x) and etoposide (33 x); flavonoids: EGCG (19 x), curcumin (12 x), apigenin (9 x), and quercetin (7 x); beverages: chamomile (11 x), green (21 x), and black tea (26 x) and coffee (3-29 x); and liquid smoke (4-28 x).

quinacrine

etoposide

flavonoids

EGCG

curcumin

apigenin

quercetin


Input: Damage occurred at dietary concentrations: etoposide near 5 mu g/ml produced responses similar to a 1: 1000 dilution of liquid smoke, a 1: 20 dilution of coffee, and a 1: 5 dilution of tea.

etoposide


Input: Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30 x), 3-methoxycatechol (25 x), gallic acid (21 x), and 1, 2, 4-benzenetriol (21 x).

Pyrogallol

tannins

pyrogallol

gallic acid

1, 2, 4-benzenetriol


Input: From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring.

hydroxyls

benzene


Input: Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation.


Input: Breaks were also directly detected by comet assay.


Input: Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.


Input: The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates.

tyrosine


Input: Part 2.


Input: Various substituted indazole and benzoxazolone amino acids were investigated as d-tyrosine surrogates in highly potent CGRP receptor antagonists.

indazole

benzoxazolone amino acids

d-tyrosine


Input: Compound 3, derived from the 7-methylindazole core, afforded a 30-fold increase in CGRP binding potency compared with its unsubstituted indazole analog 1.

indazole


Input: When dosed at 0. 03mg/kg SC, compound 2 (a racemic mixture of 3 and its (S)-enantiomer) demonstrated robust inhibition of CGRP-induced increases in mamoset facial blood flow up to 105min.


Input: The compound possesses a favorable predictive in vitro toxicology profile, and good aqueous solubility.


Input: When dosed as a nasal spray in rabbits, 3 was rapidly absorbed and showed good intranasal bioavailability (42%).


Input: Production of dosage forms for oral drug delivery by laminar extrusion of wet masses.


Input: Laminar extrusion of wet masses was studied as a novel technology for the production of dosage forms for oral drug delivery.


Input: Extrusion was carried out with a ram extruder.


Input: Formulations contained either microcrystalline cellulose (MCC) or dicalcium phosphate (DCP) as diluent, hydroxypropyl methylcellulose (HPMC), lactose, and water.

dicalcium phosphate

DCP

lactose


Input: Extrudates were characterized for their tensile strength, Young' s modulus of elasticity, water absorption, gel forming capacity, and release of two model drugs, coumarin (COU) and propranolol hydrochloride (PRO).

coumarin

COU

propranolol hydrochloride

PRO


Input: Cohesive extrudates could be produced with both filling materials (MCC and DCP) when HPMC was included as a binder at low amounts (3. 3-4. 5% w/w dry weight).

DCP


Input: Employing more HPMC, the elasticity of the wet masses increased which resulted in distinct surface defects.


Input: For MCC, the maximum HPMC amount that could be included in the formulations (15% w/w dry weight) did not affect the mechanical properties or decrease the drug release significantly.


Input: For DCP extrudates, the maximally effective HPMC amount was 30% (w/w dry weight) with influence on both the mechanical properties and drug release.

DCP


Input: This study suggests that laminar extrusion of wet masses is a feasible technique for the production of dosage forms for oral drug delivery.


Input: Stabilisation of amorphous drugs under high humidity using pharmaceutical thin films.


Input: In this study, the stabilization effects of three polymers on four model drugs (felodipine, fenofibrate, carbamazepine, and celecoxib) under saturated humidity were investigated.

felodipine

fenofibrate

carbamazepine

celecoxib


Input: Three different types of thin films (solid dispersions, drug films with a polymer film coating and drug films laid on top of polymer coated surfaces) were prepared and compared with films containing the drug alone.


Input: ATR-FTIR spectroscopy, polarised light microscopy (PLM), scanning electron microscopy (SEM) and nano-thermal analysis (nano-TA) were performed on the model systems after storage under saturated humidity.


Input: The recrystallisation tendency of the drug in the drug containing thin films was found to be strongly related to the intrinsic crystallization tendency of the drug film alone and the strength of drug-polymer interactions.


Input: Additionally, under high humidity, the glass transition temperature of the polymer is no longer an indicator of its drug stabilization capability.


Input: Instead, it is the hygroscobicity of the polymer that appears to be the most important parameter.


Input: Amongst the polymers tested in this study, EUDRAGIT E PO was found to have the greatest inhibitory effect on crystallization, whilst PVP K30 was found to have the least protective effect; presumably because of its hygroscopic nature.

EUDRAGIT E PO

PVP K30


Input: Triethylenetetramine prevents insulin aggregation and fragmentation during copper catalyzed oxidation.

Triethylenetetramine

copper


Input: Metal catalyzed oxidation via the oxidative system Cu (2 +)/ascorbate is known to induce aggregation of therapeutic proteins, resulting in enhanced immunogenicity.

Cu (2 +)

ascorbate


Input: Hence, inclusion of antioxidants in protein formulations is of great interest.


Input: In this study, using recombinant human insulin (insulin) as a model, we investigated the ability of several excipients, in particular triethylenetetramine (TETA), reduced glutathione (GSH) and ethylenediamine tetraacetic acid (EDTA), for their ability to prevent protein oxidation, aggregation, and fragmentation.

triethylenetetramine

TETA

reduced glutathione

GSH

ethylenediamine tetraacetic acid

EDTA


Input: Insulin (1mg/ml) was oxidized with 40 mu M Cu (2 +) and 4mM ascorbic acid in absence or presence of excipients.

Cu (2 +)

ascorbic acid


Input: Among the excipients studied, 1mM of TETA, EDTA, or GSH prevented insulin aggregation upon metal catalyzed oxidation (MCO) for 3h at room temperature, based on size exclusion chromatography (SEC).

TETA

EDTA

GSH


Input: At lower concentration (100 mu M), for 72h at + 4 degrees C, TETA was the only one to inhibit almost completely oxidation-induced insulin aggregation, fragmentation, and structural changes, as indicated by SEC, nanoparticle tracking analysis, light obscuration particle counting, intrinsic/extrinsic fluorescence, circular dichroism, and chemical derivatization.

TETA


Input: In contrast, GSH had a slight pro-oxidant effect, as demonstrated by the higher percentage of aggregates and a more severe structural damage, whereas EDTA offered substantially less protection.

GSH

EDTA


Input: TETA also protected a monoclonal IgG1 against MCO-induced aggregation, suggesting its general applicability.

TETA


Input: In conclusion, TETA is a potential candidate excipient for inclusion in formulations of oxidation-sensitive proteins.

TETA


Input: Optimized glucocorticoid therapy: Teaching old drugs new tricks.


Input: Glucocorticoids (GCs) are commonly used in the treatment of a wide range of rheumatic and other inflammatory diseases.


Input: They exert their potent anti-inflammatory and immunosuppressive effects primarily via so called genomic mechanisms, mediated by the cytosolic glucocorticoid receptor (cGR).


Input: This mechanism of GC action can be divided into the transactivation and the transrepression processes.


Input: However, also rapid effects of GCs exist which are mediated by specific and unspecific non-genomic mechanisms.


Input: A clinical relevance of this mode of GC action is assumed for effects mediated by membrane-bound glucocorticoid receptors, but detailed knowledge on the underlying mechanisms is still missing.


Input: Great efforts have been made in the past to diminish GC-induced adverse effects, thus improving the benefit/risk ratio of the drugs.


Input: Besides approaches to improve the treatment with conventional glucocorticoids currently available to clinicians, new innovative GCs or GC receptor ligands are also being developed.


Input: Synthesis and Nrf2-inducing activity of the isothiocyanates iberverin, iberin and cheirolin.

isothiocyanates iberverin

iberin

cheirolin


Input: Numerous studies have reported a potent induction of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent gene expression by the isothiocyanate sulforaphane.

sulforaphane


Input: However, little is known regarding the Nrf2-inducing activities of the lower structure-related sulforaphane homologues, such as iberverin, iberin and cheirolin, which exhibit different sulfur oxidation states.

sulforaphane

iberverin

iberin

cheirolin


Input: Therefore, in this study we synthesized the isothiocyanates iberverin, iberin and cheirolin with a high yield and purity and determined their Nrf2-inducing activity in NIH3T3 fibroblasts.

isothiocyanates iberverin

iberin

cheirolin


Input: Iberverin, iberin and cheirolin significantly induced Nrf2 nuclear translocation.

Iberverin

iberin

cheirolin


Input: The increase in nuclear Nrf2 levels was accompanied by a significant increase in heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (gamma GCS) mRNA and protein levels.

gamma-glutamylcysteine


Input: Overall, iberverin, iberin and cheirolin exhibited a similar potency to sulforaphane in inducing Nrf2-dependent gene-expression.

iberverin

iberin

cheirolin

sulforaphane


Input: Furthermore, our data suggest that the induction of Nrf2 by iberverin, iberin and cheirolin may have occurred via an extracellular signal-related kinase (ERK)-dependent signal-transduction pathway.

iberverin

iberin

cheirolin


Input: The food contaminant deoxynivalenol activates the mitogen activated protein kinases in the intestine: interest of ex vivo models as an alternative to in vivo experiments.

deoxynivalenol


Input: Trichothecenes induce changes in the intestinal barrier function through decreased expression of cell junction proteins and apoptosis of enterocytes.

Trichothecenes


Input: The mitogen activated protein kinases (MAPK) play an important role in the signaling pathways of cell turnover and differentiation.


Input: Using ex vivo and in vivo approaches, the purpose of this study was to investigate the ability of low doses of DON to induce histological changes in the intestine and to activate the MAPK ERK 1/2, p38 and JNK.

DON


Input: Twelve weaning piglets received during four weeks a control diet or a DON-contaminated diet (2. 3 mg DON/kg feed).

DON

DON


Input: Six weaning piglets were used to prepare jejunal explants (ex vivo model).


Input: Explants were exposed during 4 h to vehicle, 5 or 10 mu M DON.

DON


Input: Intestinal changes were graded using a histological score.


Input: Pigs fed a DON-diet and explants exposed to DON showed a significant decrease in the jejunal score.

DON

DON


Input: In both models, the toxin significantly enhanced phosphorylation of ERK 1/2 and p38, whereas the increased phosphorylation of JNK was non significant.


Input: Taken together these results indicate that in vivo or ex vivo exposure of intestinal tissue to DON lead to similar intestinal lesions and activation of MAPK.

DON


Input: These effects could impair the homeostasis of intestinal tissue in the aspects of barrier function and immune protection.


Input: The similarity of the in vivo and ex vivo results provides also strong evidence that the jejunal explant model is a good alternative for toxicological studies in intestinal tissue.


Input: Antofine-induced connexin43 gap junction disassembly in rat astrocytes involves protein kinase C beta.

Antofine


Input: Antofine, a phenanthroindolizidine alkaloid derived from Cryptocaryachinensis and Ficusseptica in the Asclepiadaceae milkweed family, is cytotoxic for various cancer cell lines.

Antofine

phenanthroindolizidine alkaloid


Input: In this study, we demonstrated that treatment of rat primary astrocytes with antofine induced dose-dependent inhibition of gap junction intercellular communication (GJIC), as assessed by scrape-loading 6-carboxyfluorescein dye transfer.

antofine


Input: Levels of Cx43 protein were also decreased in a dose-and time-dependent manner following antofine treatment.

antofine


Input: Double-labeling immunofluorescence microscopy showed that antofine (10ng/ml) induced endocytosis of surface gap junctions into the cytoplasm, where Cx43 was co-localized with the early endosome marker EEA1.

antofine


Input: Inhibition of lysosomes or proteasomes by co-treatment with antofine and their respective specific inhibitors, NH4Cl or MG132, partially inhibited the antofine-induced decrease in Cx43 protein levels, but did not inhibit the antofine-induced inhibition of GJIC.

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