Input: Mechanisms of interaction comprise an upstream crosstalk at the level of pathway-activating ligands and their receptors, interrelations of cytosolic kinases involved in either pathways, as well as interaction in the nucleus related to the joint regulation of target gene transcription.


Input: Here, we present a comprehensive review of the current knowledge on the interaction of RAS/MAPK-and WNT/beta-catenin-driven signal transduction in mammalian cells.


Input: Progress and Developments in Tau Aggregation Inhibitors for Alzheimer Disease.


Input: Pharmacological approaches directed toward Alzheimer disease are diversifying in parallel with a growing number of promising targets.


Input: Investigations on the microtubule-associated protein tau yielded innovative targets backed by recent findings about the central role of tau in numerous neurodegenerative diseases.


Input: In this review, we summarize the recent evolution in the development of nonpeptidic small molecules tau aggregation inhibitors (TAGIs) and their advancement toward clinical trials.


Input: The compounds are classified according to their chemical structures, providing correlative insights into their pharmacology.


Input: Overall, shared structure-activity traits are emerging, as well as specific binding modes related to their ability to engage in hydrogen bonding.

hydrogen


Input: Medicinal chemistry efforts on TAGIs together with encouraging in vivo data argue for successful translation to the clinic.


Input: Optimization of Chloronitrobenzamides (CNBs) as Therapeutic Leads for Human African Trypanosomiasis (HAT).

Chloronitrobenzamides

CNBs


Input: We previously reported the discovery of the activity of chloronitrobenzamides (CNBs) against bloodstream forms of Trypanosoma brucei.

chloronitrobenzamides

CNBs


Input: Herein we disclose extensive structure-activity relationship and structure-property relationship studies aimed at identification of tractable early leads for clinical development.


Input: These studies revealed a promising lead compound, 17b, that exhibited nanomolar potency against T. brucei (EC50 = 27 nM for T. b. brucei, 7 nM for T. b. rhodesiense, and 2 nM for T. b. gambiense) with excellent selectivity for parasite cells relative to mammalian cell lines (EC50 > 25 mu M).


Input: In addition compound 17b displayed suitable physiochemical characteristics and microsomal stability (t1/2 > 4 h for human and mouse) to justify pursuing in vivo studies.


Input: Adsorption of Primary Substituted Hydrocarbons onto Solid Gallium Substrates.

Hydrocarbons

Gallium


Input: Adsorption of a series of primary substituted hydrocarbons (RX; C18H37PO (OH) 2 (ODPA), C17H35COOH, C18H37OH, C18H37NH2, and C18H37SH) onto solid gallium substrates with and without UV/ozone treatment was studied using contact angle goniometry, spectroscopic ellipsometry, and cyclic voltammetry (CV).

hydrocarbons

C18H37PO (OH) 2

ODPA

gallium

ozone


Input: UV/ozone treatment offered a hydrophilic surface (water contact angle (theta (water)) less than 10 degrees), reflecting the formation of a surface oxide layer with the maximum thickness of ca.

ozone

oxide


Input: 1 nm and possibly the removal of surface contaminants.


Input: Upon immersion in a toluene solution of a RX, theta (water) increased due to adsorption of the RX onto gallium substrates.

toluene

gallium


Input: In particular, UV/ozone-treated gallium substrates (UV-Ga) immersed in an ODPA solution exhibited theta (water) close to 105 degrees.

ozone

gallium

Ga

ODPA


Input: The ellipsometric thickness of the adsorbed ODPA layer was ca.

ODPA


Input: 2. 4 nm, and CV data measured in an acetonitrile solution showed significant inhibition of redox reaction on the substrate surface.

acetonitrile


Input: These results indicate the formation of a densely packed ODPA monolayer on UV-Ga.

ODPA

Ga


Input: The coverage of a C17H35COOH layer adsorbed onto UV-Ga was lower, as shown by smaller theta (water) (ca. 99 degrees), smaller ellipsometric thickness (ca. 1. 3 nm), and smaller electrode reaction inhibition.

Ga


Input: Adsorption of the other RX onto UV-Ga was weaker, as indicated by smaller theta (water) (82 degrees-92 degrees).

Ga


Input: ODPA did not strongly adsorb onto UV-untreated gallium substrates, suggesting that the ODPA adsorption mainly originates from hydrogen bond interaction of a phosphonate group with surface oxide.

ODPA

gallium

ODPA

hydrogen

phosphonate

oxide


Input: These results will provide a means for controlling the surface properties of oxide-coated gallium that play an essential role in monolayer conductivity measurements and electroanalytical applications.

oxide

gallium


Input: Diarylheptanoids and Flavonoids from Viscum album Inhibit LPS-Stimulated Production of Pro-inflammatory Cytokines in Bone Marrow-Derived Dendritic Cells.

Diarylheptanoids

Flavonoids


Input: Three new diarylheptanoids, (3S, 5R)-3-hydroxy-5-methoxy-1, 7-bis (4-hydroxyphenyl)-6E-heptene (1), (3S, 5S)-3-hydroxy-5-methoxy-1, 7-bis (4-hydroxyphenyl)-6E-heptene (2), and (3S)-3-hydroxy-1, 7-bis (4-hydroxyphenyl)-6E-hepten-5-one (3), four new flavonoid glycosides, 3, 7, 3'-tri-O-methylquercetin-4'-O-beta-d-apiofuranosyl-(1 --> 2)-O-beta-d-glucopyranoside (4), 7, 3'-di-O-methylquercetin-4'-O-beta-d-glucopyranosyl-3-O-[6'''-(3-hydroxy-3-methylglutaroyl)]-alpha-d-glucopyranoside (5), 7, 3'-di-O-methylquercetin-4'-O-beta-d-glucopyranosyl-3-O-[(6''''' --> 5'''')-O-1'''''-(sinap-4-yl)-beta-d-glucopyranosyl-6'''-(3-hydroxy-3-methylglutaroyl)]-alpha-d-glucopyranoside (6), and (2S)-5-hydroxy-7, 3'-dimethoxyflavanone-4'-O-beta-d-apiofuranosyl-(1 --> 5)-O-beta-d-apiofuranosyl-(1 --> 2)-O-beta-d-glucopyranoside (9), and 17 known compounds were isolated from the leaves and twigs of Viscum album.

diarylheptanoids

(3S, 5R)-3-hydroxy-5-methoxy-1, 7-bis (4-hydroxyphenyl)-6E-heptene

(3S, 5S)-3-hydroxy-5-methoxy-1, 7-bis (4-hydroxyphenyl)-6E-heptene

(3S)-3-hydroxy-1, 7-bis (4-hydroxyphenyl)-6E-hepten-5-one

flavonoid glycosides

3, 7, 3'-tri-O-methylquercetin-4'-O-beta-d-apiofuranosyl-(1 --> 2)-O-beta-d-glucopyranoside

7, 3'-di-O-methylquercetin-4'-O-beta-d-glucopyranosyl-3-O-[6'''-(3-hydroxy-3-methylglutaroyl)]-alpha-d-glucopyranoside

7, 3'-di-O-methylquercetin-4'-O-beta-d-glucopyranosyl-3-O-[(6''''' --> 5'''')-O-1'''''-(sinap-4-yl)-beta-d-glucopyranosyl-6'''-(3-hydroxy-3-methylglutaroyl)]-alpha-d-glucopyranoside

(2S)-5-hydroxy-7, 3'-dimethoxyflavanone-4'-O-beta-d-apiofuranosyl-(1 --> 5)-O-beta-d-apiofuranosyl-(1 --> 2)-O-beta-d-glucopyranoside


Input: Compounds 1, 4, and 19 significantly inhibited LPS-stimulated production of TNF-alpha, IL-6, and IL-12p40 with IC50 values ranging from 0. 09 +/- 0. 01 to 8. 96 +/- 0. 45 mu M.


Input: (+)-Medioresinol (13) showed inhibitory effects on LPS-stimulated production of IL-12p40 with an IC50 value of 2. 00 +/- 0. 15 mu M.

(+)-Medioresinol


Input: Ultrathin 2D Coordination Polymer Nanosheets by Surfactant-Mediated Synthesis.


Input: Low-dimensional nanostructures offer a host of intriguing properties which are distinct from those of the bulk material, owing to size-confinement effects and amplified surface areas.


Input: Here, we report on the scalable, bottom-up synthesis of ultrathin coordination polymer nanosheets via surfactant-mediated synthesis and subsequent exfoliation.


Input: Layers of a two-dimensional (2D) zinc coordination polymer are self-assembled in the interlamellar space of a reverse microemulsion mesophase into stacks of nanosheets interleaved with cethyltrimethylammonium bromide (CTAB) at regular intervals, thus giving rise to a lamellar hybrid mesostructure with a lattice period of ~ 8 nm and an underlying highly crystalline substructure.

zinc

cethyltrimethylammonium bromide

CTAB


Input: The basic structural motif is composed of 2D acetato-benzimidazolato-zinc layers of tetrahedrally coordinated zinc joined together by anionic acetate and benzimidazolate ligands.

acetato-benzimidazolato-zinc

zinc

acetate

benzimidazolate


Input: The hierarchical structure was studied by PXRD, TEM, EDX, EELS, AFM, and solid-state NMR spectroscopy, revealing a high level of order on both the atomic and mesoscale, suggesting fairly strong interactions along the organic-inorganic hybrid interface.


Input: Exfoliation of the hybrid material in organic solvents such as THF and chloroform yields sheet-and belt-like nanostructures with lateral sizes between 10' s and 100' s of nanometers and a height of about 10 nm measured by AFM, which precisely maps the basal spacing of the lamellar mesostructure; further exfoliation results in nanobelts with minimum sizes around 4 nm.

THF

chloroform


Input: Finally, the sheetlike nanostructures behave as morphological chameleons, transforming into highly regular multiwalled coordination polymer nanotubes upon treatment with organic solvents.


Input: Computational study of the coordination of methane to first row transition metal dication complexes.

methane

transition metal dication complexes


Input: The coordination of methane, the first step in methane activation, to coordinately unsaturated first row transition metal dication complexes has been studied computationally to determine the most stable metal-methane interaction.

methane

methane

transition metal dication complexes

methane


Input: The geometries and the vibrational frequencies of the encounter complexes [M (pyridine) 2 (CH4)] (2 +) have been determined using density functional theory with the omega B97XD hybrid functional and triple-zeta basis sets.

[M (pyridine) 2 (CH4)] (2 +)


Input: The structure is dependent on the metal center; for the early transition metals eta (3) coordination is favored, whereas eta (2) is more favorable for the later transition metals.

transition metals

transition metals


Input: The periodic trend in methane binding energies in the [M (pyridine) 2 (CH4)] (2 +) complexes follows the trend in electron affinity until the Mn complex but then exhibits decreasing energies from Fe to Zn.

methane

[M (pyridine) 2 (CH4)] (2 +)

Mn

Fe

Zn


Input: This is attributed to increasing Pauli repulsion and ligand-ligand repulsion.


Input: For the most stable complex, [Cr (pyridine) 2 (CH4)] (2 +), the structures, energies, and spin states of the key intermediates and products in the oxidative addition/reductive elimination pathway have been investigated.

[Cr (pyridine) 2 (CH4)] (2 +)


Input: It is found that the reaction is thermodynamically favorable and indicates that two-state reactivity may play an important role in lowering the energy of the hydridomethyl intermediate.

hydridomethyl


Input: Synergistic interactions of epigallocatechin gallate and oxytetracycline against various drug resistant Staphylococcus aureus strains in vitro.

epigallocatechin gallate

oxytetracycline


Input: Epigallocatechin gallate (EGCG), the major catechin contained in tea leaves, is known to possess the synergistic anti-staphylococcal activity in combination with various beta-lactam antibiotics and tetracycline.

Epigallocatechin gallate

EGCG

catechin

beta-lactam

tetracycline


Input: In the present study, we explored the in vitro combinatory effect of EGCG in combination with oxytetracycline against eight standard strains and clinical isolates of Staphylococcus aureus, including erythromycin, methicillin and tetracycline resistant strains.

EGCG

oxytetracycline

erythromycin

methicillin

tetracycline


Input: The minimum inhibitory concentrations were determined by the broth microdilution assay and the data were evaluated according to the sum of fractional inhibitory concentrations (sum FIC).


Input: Our results showed synergistic and additive interactions against all S. aureus strains tested (sum FIC 0. 288-0. 631), two of which were multidrug resistant.


Input: According to our best knowledge, it is the first report on the EGCG synergy with oxytetracycline.

EGCG

oxytetracycline


Input: Considering its significant synergistic antimicrobial effect and low toxicity, we suggest EGCG as a promising compound for the development of new anti-staphylococcal formulations.

EGCG


Input: Orally bioavailable and brain-penetrant pyridazine and pyridine-derived gamma-secretase modulators reduced amyloidogenic A beta peptides in vivo.

pyridazine

pyridine


Input: Accumulation of amyloid beta (A beta) in brain is a pathological hallmark of Alzheimer' s disease (AD).


Input: A beta is generated after sequential cleavage of its parental molecule, amyloid precursor protein (APP), by beta-and gamma-secretases.


Input: Inhibition of gamma-secretase activity is an effective approach for the reduction of A beta levels.


Input: Since gamma-secretase targets many different substrates, selective inhibition of its cleavage of APP is believed to be critical in order to avoid undesirable side effects.


Input: gamma-Secretase modulator (GSM) shifts the cleavage site on APP and production of amyloidogenic to non-amyloidogenic A beta fragments.


Input: Since GSMs only modulate and do not block cleavage of gamma-secretase substrates, they are believed less likely to produce untoward adverse reactions.


Input: Here, we report in vivo A beta-lowering profiles of a pyridazine and a pyridine-derived GSM: GSM-C (Wan et al., 2011a) and GSM-D (Wan et al., 2011b).

pyridazine

pyridine


Input: Both compounds reduced A beta 40 and A beta 42 productions, increased shorter A beta fragments, and had little effect on Notch signaling (~ 100-fold selective).


Input: They had excellent oral bioavailability (97. 8% for GSM-C, ~ 100% for GSM-D) and good brain permeability (free brain to free blood AUC ratio of 0. 41 and 1. 10 for GSM-C and GSM-D, respectively).


Input: Oral administration of these compounds in both acute and sub-chronic conditions reduced A beta levels in plasma and brain in rats in a dose-and time-dependent manner.


Input: Therefore, GSM-C and GSM-D represent two GSMs that are orally bioavailable and brain-permeable.


Input: They could serve as excellent tools in the investigation of the role of A beta peptides in AD pathogenesis.


Input: Research on cholinesterases in the Soviet Union and Russia: A historical perspective.


Input: Research on cholinesterases and effects of their inhibition in the USSR and Russia since 1930-1940s till present is exposed in historical aspects.


Input: The first physiological and toxicological effects of cholinesterase inhibition were reported by Alexander Ginetsinsky during World War II, when academic institutions were evacuated from Leningrad to Kazan.


Input: The main scientific schools that initiated research on chemistry, enzymology and physiology of cholinesterases and their inhibitors were leaded by Alexandr and Boris Arbuzovs, Victor Rozengart, Viktor Yakovlev, Michael Michelson, Martin Kabachnik, Mikhail Voronkov, Ivan Knunyants, Alexandr Bretskin and others.


Input: They investigated the main physiological effects of cholinesterase inhibitors, and analyzed the catalytic mechanisms of cholinesterases and related enzymes.


Input: Their contributions are landmarks in the history of cholinesterase research.


Input: At the present time revival of research on cholinesterases in different universities and institutes is vivid, in particular at the Moscow State University, research institutes of Russian Academy of Sciences and Kazan Scientific Center.


Input: Protective effect of bark and empty pod extracts from Acacia auriculiformis against paracetamol intoxicated liver injury and alloxan induced type II diabetes.

paracetamol

alloxan


Input: The present study is designed to decipher a clinical evidence and biochemical support for hepatoprotective and antidiabetic efficacy of Acacia auriculiformis by its bark and empty pods.


Input: Animal models with paracetamol intoxicated liver injury and alloxan induced diabetes were used in a 7 and 14days trial respectively.

paracetamol

alloxan


Input: The interventions were tested at 200 and 400mg/kg b. w. for bark extract; 100 and 200mg/kg b. w. for empty pod extract.


Input: Both interventions restored the liver function markers (alanine transaminase: ALT, aspartate transaminase: AST, alkaline phosphatase: ALP, total bilirubin and total protein) and hepatic antioxidants (superoxide dismutase: SOD, catalase: CAT, reduced glutathione: GSH and glutathione peroxidase: GPx) to the normal levels than elevated levels noticed on paracetamol control at P < 0. 001.

alanine

aspartate

bilirubin

superoxide

glutathione

GSH

glutathione

paracetamol


Input: Reversal of hepatoarchitecture has also been registered and the hepatoprotection is comparable to the reference drug silymarin.

silymarin


Input: Similarly, substantial elevations of blood glucose, distorted lipid profile (total cholesterol: TC, triglycerides: TGs, high density lipoprotein cholesterol: HDL-C and low density lipoprotein cholesterol: LDL-C) and kidney function signs (creatinine and urea) have been refurbished to the desirable levels on par with the standard antidiabetic glibenclamide.

glucose

cholesterol

triglycerides

cholesterol

cholesterol

creatinine

urea

glibenclamide


Input: The results signify the importance of bark and empty pod extracts of A. auriculiformis as good therapeutic candidates for liver injury and diabetes.


Input: The influence of study design and sex-differences on results from developmental neurotoxicity studies of bisphenol A, implications for toxicity testing.

bisphenol A


Input: Developmental neurotoxicity (DNT) of bisphenol A (BPA) has been investigated in a large number of studies.

bisphenol A

BPA


Input: However, there are discrepancies in the results reported between the studies.


Input: The aim of this study was to identify and analyze factors that may contribute to these differences and to assess whether there are sex-differences in the sensitivity of certain endpoints or tests used in DNT-studies.


Input: Forty-four DNT studies of BPA were identified from the open literature.

BPA


Input: Details about study design and results from each study, as well as the criteria for DNT testing according to the standardized OECD test guideline (TG) 426, were collected in a database.


Input: This enabled systematic and detailed comparisons between studies as well as to the criteria and recommendations stated in TG 426.


Input: Multivariate analyses were also used to investigate how different factors of the study design contributed to differences in study results.


Input: The analyses showed behavioral effects were often observed for endpoints that are not required according to OECD TG 426, such as anxiety-related, social and sexual behaviors, especially at very low doses and in female offspring.


Input: On the other hand relatively few studies observed any effects on motor activity, which is commonly used in screening for neurotoxic effects in regulatory testing.


Input: However, varied and to some extent seemingly contradictory results have been reported in these studies, especially for endpoints related to motor activity and anxiety and exploration.


Input: Many studies were also poorly reported, limiting these analyses.


Input: No strong conclusions could be drawn from the multivariate analyses.


Input: A few factors of study design, such as the size of the dose and number of dose levels used and the use of litter or individual pup as statistical unit seemed to have some influence on study results.


Input: In conclusion, this analysis suggests that DNT-studies conducted according to the standardized OECD TG 426 may overlook sensitive effects of BPA, and possibly other potential endocrine disruptors, especially in female offspring.

BPA


Input: High-throughput quantification of the mechanical competence of murine femora-A highly automated approach for large-scale genetic studies.


Input: Animal models are widely used to gain insight into the role of genetics on bone structure and function.


Input: One of the main strategies to map the genes regulating specific traits is called quantitative trait loci (QTL) analysis, which generally requires a very large number of animals (often more than 1000) to reach statistical significance.


Input: QTL analysis for mechanical traits has been mainly based on experimental mechanical testing, which, in view of the large number of animals, is time consuming.


Input: Hence, the goal of the present work was to introduce an automated method for large-scale high-throughput quantification of the mechanical properties of murine femora.


Input: Specifically, our aims were, first, to develop and validate an automated method to quantify murine femoral bone stiffness.


Input: Second, to test its high-throughput capabilities on murine femora from a large genetic study, more specifically, femora from two growth hormone (GH) deficient inbred strains of mice (B6-lit/lit and C3. B6-lit/lit) and their first (F1) and second (F2) filial offsprings.


Input: Automated routines were developed to convert micro-computed tomography (micro-CT) images of femora into micro-finite element (micro-FE) models.


Input: The method was experimentally validated on femora from C57BL/6J and C3H/HeJ mice: for both inbred strains the micro-FE models closely matched the experimentally measured bone stiffness when using a single tissue modulus of 13. 06GPa.


Input: The mechanical analysis of the entire dataset (n = 1990) took approximately 44 CPU hours on a supercomputer.


Input: In conclusion, our approach, in combination with QTL analysis could help to locate genes directly involved in controlling bone mechanical competence.


Input: Pediatric insecticide chalk exposures reported to Texas poison centers.


Input: The pesticide Miraculous Insecticide Chalk (TM) is illegal in the United States but can be obtained through a variety of sources.


Input: Because it is a stick similar in appearance to common blackboard chalk, children might play with it and put it in their mouths.


Input: All Miraculous Insecticide Chalk exposures involving children 5 years or younger reported to Texas poison centers during 2000-2010 were identified.


Input: The distribution by selected demographic and clinical factors was calculated.


Input: Of the total 188 exposures, the mean age was 1. 5 years (range 6 months-5 years) and 60. 6% were male.


Input: Ingestions were reported in 97. 3% of the exposures, and these were reported to involve at most one stick of the chalk.


Input: The lowest exposure rates per 100, 000 population of 5 years or younger were reported in the Public Health Regions in northern and eastern Texas (0. 00-2. 30) and the highest rates in the Public Health Regions in southern and western Texas (19. 08-39. 50).


Input: Of the 187 exposures not involving other substances, 96. 8% were known or expected to result in at most minor effects, and 71. 1% were managed on site (at residence).


Input: Synthesis and application of FePt/CNTs nanocomposite as a sensor and novel amide ligand as a mediator for simultaneous determination of glutathione, nicotinamide adenine dinucleotide and tryptophan.

FePt

amide

glutathione

nicotinamide adenine dinucleotide

tryptophan


Input: In this study, we report the synthesis and application of a FePt/CNTs nanocomposite as a highly sensitive sensor and novel amide ligand (9, 10-dihydro-9, 10-ethanoanthracene-11, 12-dicarboximido)-4-ethylbenzene-1, 2-diol as a mediator for the determination of glutathione (GSH), nicotinamide adenine dinucleotide (NADH) and tryptophan (Trp).

FePt

amide

(9, 10-dihydro-9, 10-ethanoanthracene-11, 12-dicarboximido)-4-ethylbenzene-1, 2-diol

glutathione

GSH

nicotinamide adenine dinucleotide

NADH

tryptophan

Trp


Input: The synthesized materials were characterized with different methods such as NMR, IR spectroscopy, TEM, XRD, FESEM, cyclic voltammetry, electrochemical impedance spectroscopy and square wave voltammetry (SWV).


Input: The modified electrode exhibited a potent and persistent electron mediating behavior followed by well-separated oxidation peaks of GSH, NADH and Trp.

GSH

NADH

Trp


Input: The peak currents were linearly dependent on GSH, NADH and Trp concentrations in the range of 0. 08-220, 1. 0-400 and 5. 0-500 mu mol L (-1), with detection limits of 0. 05, 0. 8 and 1. 0 mu mol L (-1), respectively.

GSH

NADH

Trp


Input: The modified electrode was used for the determination of these compounds in real samples.


Input: Channel Size Conversion of Phi29 DNA-Packaging Nanomotor for Discrimination of Single-and Double-Stranded Nucleic Acids.


Input: Nanopores have been utilized to detect the conformation and dynamics of polymers, including DNA and RNA.


Input: Biological pores are extremely reproducible at the atomic level with uniform channel sizes.


Input: The channel of the bacterial virus phi29 DNA-packaging motor is a natural conduit for the transportation of double-stranded DNA (dsDNA) and has the largest diameter among the well-studied biological channels.


Input: The larger channel facilitates translocation of dsDNA and offers more space for further channel modification and conjugation.


Input: Interestingly, the relatively large wild-type channel, which translocates dsDNA, cannot detect single-stranded nucleic acids (ssDNA or ssRNA) under the current experimental conditions.


Input: Herein, we reengineered this motor channel by removing the internal loop segment of the channel.


Input: The modification resulted in two classes of channels.


Input: One class was the same size as the wild-type channel, while the other class had a cross-sectional area about 60% of the wild-type.


Input: This smaller channel was able to detect the real-time translocation of single-stranded nucleic acids at single-molecule level.


Input: While the wild-type connector exhibited a one-way traffic property with respect to dsDNA translocation, the loop-deleted connector was able to translocate ssDNA and ssRNA with equal competencies from both termini.


Input: This finding of size alterations in reengineered motor channels expands the potential application of the phi29 DNA-packaging motor in nanomedicine, nanobiotechnology, and high-throughput single-pore DNA sequencing.


Input: Columnar Cell Variant of Papillary Thyroid Carcinoma: A Study of Ten Cases with Emphasis On CDX-2 Expression.


Input: Background: Columnar cell variant is a recognized rare variant of papillary thyroid carcinoma associated with an uncertain clinical course.


Input: This variant has two sub variants, and one is regarded as a more aggressive form in comparison to the more common classical and follicular variants.


Input: These tumors have morphological resemblance with endometrial or colonic adenocarcinoma.


Input: CDX2, a transcription factor of the caudal homeobox family, plays a key role in intestinal development and differentiation and it is widely used as a marker to detect adenocarcinoma of intestinal and colonic origin.


Input: CDX2 has been rarely reported in papillary thyroid carcinoma.


Input: Methods: We studied ten cases of columnar cell variant of papillary thyroid carcinoma.


Input: The histological, architectural, and cytological features fulfilled the diagnostic criteria of the columnar cell variant of papillary thyroid carcinoma as defined by the current WHO classification.


Input: Ten patients (6M: 4F) ranging from 32 to 90 years of age (mean 58. 3 years) presented with tumors classified as indolent (4 cases) or aggressive (6 cases); 3 with BRAFV600E mutation.


Input: All cases were-Catenin negative.


Input: The Ki-67 proliferative index was up to 50%.


Input: All cases were TTF-1 positive.


Input: Using paraffin embedded blocks, immunohistochemistry for CDX2 was performed to evaluate the reactivity of this antibody to this variant of papillary thyroid carcinoma.


Input: Results: Nuclear positivity for CDX2 was detected in one out of the ten cases studied (10%); the other nine cases did not express CDX2.


Input: Conclusion: Only one of our cases showed nuclear positivity for CDX2, therefore our study failed to confirm this as a marker for columnar cell variant of papillary thyroid carcinoma.


Input: The absence of CDX2 in the majority of the cases does not support the theory of CDX2 playing a role in the intestinal phenotype of these tumors.


Input: KEYWORDS: Papillary Thyroid Carcinoma, CDX-2, Columnar Cell, Immunohistochemistry.


Input: Iodine Status in Pregnant Women in the United States: National Children' s Study and National Health and Nutrition Examination Survey.

Iodine


Input: Background: This report presents iodine data from NHANES and from a sample of pregnant women in the National Children' s Study (NCS) Vanguard Study.

iodine


Input: Methods: UI was measured in a one third subsample of NHANES 2005-2006, and 2009-2010 participants and in all 2007-2008 participants age six years and older.


Input: These measurements are representative of the general U. S. population.


Input: UI was also measured in a convenience sample of 501 pregnant women enrolled in the NCS initial Vanguard Study from seven study sites across the U. S.


Input: Results: NHANES median UI concentration in 2009-2010 (144 micro g/L) was significantly lower than in 2007-2008 (164 micro g/L).


Input: Non-Hispanic blacks had the lowest UI concentrations (131 micro g/L) compared to non-Hispanic whites or Hispanics (147 and 148 micro g/L, respectively).


Input: The median for all pregnant women in NHANES 2005-2010 was less than adequate (129 micro g/L), the third trimester women had UI concentrations that were adequate (median UI 172 micro g/L).


Input: Third trimester women participating in the NCS study similarly had an adequate level of iodine intake, with a median UI concentration of 167 micro g/L.

iodine


Input: Furthermore, NCS median UI concentrations varied by geographic location.


Input: Conclusions: Dairy, but not salt, seafood or grain consumption, was significantly positively associated with median UI concentration in women of childbearing age.


Input: Pregnant women in their third trimester in the NHANES 2005-2010 had adequate median UI concentrations, but pregnant women in NHANES who were in their first or second trimesters had median UI concentrations that were less than adequate.


Input: Non-Hispanic black pregnant women from both the NHANES 2005-20010 and the NCS consistently had lower UI median concentrations than non-Hispanic whites or Hispanics.


Input: The use of U-500 regular insulin in the management of patients with obesity and insulin resistance.


Input: The rise in prevalence of obesity and diabetes has created a challenge in managing increasing numbers of patients who require high doses of insulin.


Input: This article reviews the published literature on the properties of U-500 insulin and its use in clinical practice.


Input: U-500 insulin is likely to have a longer time to peak effect and a longer duration of action than similar doses of U-100 insulin.


Input: Evidence for its use in clinical practice rests on retrospective case series, which suggests that the use of U-500 insulin either by multiple daily injections or a continuous subcutaneous insulin infusion is effective in improving glycaemic control.


Input: To prevent insulin dosing and administration errors, great care must be taken in providing staff and patient education, and in developing policies for the management of patients on U-500 insulin who are admitted to hospital.


Input: The use of insulin analogues in pregnancy.


Input: Excellent glycaemic control is essential in pregnancy to optimise maternal and foetal outcomes.


Input: The aim of this review is to assess the efficacy and safety of insulin analogues in pregnancy.


Input: Insulin lispro and insulin aspart are safe in pregnancy and may improve post-prandial glycaemic control in women with type 1 diabetes.


Input: However, a lack of data indicating improved foetal outcomes would suggest that there is no imperative to switch to a short-acting analogue where the woman' s diabetes is well controlled with human insulin.


Input: There are no reports of the use of insulin glulisine in pregnancy and so its use cannot be recommended.


Input: Most studies of insulin glargine in pregnancy are small, retrospective and include women with pre-existing diabetes and gestational diabetes.


Input: There appear to be no major safety concerns and so it seems reasonable to continue insulin glargine if required to achieve excellent glycaemic control.


Input: A head-to-head comparison between insulin detemir and NPH insulin in women with type 1 diabetes showed that while foetal outcomes did not differ, fasting plasma glucose improved with insulin detemir without an increased incidence of hypoglycaemia.

glucose


Input: The greater evidence base supports the use of insulin detemir as the first line long-acting analogue in pregnancy but the lack of definitive foetal benefits means that there is no strong need to switch a woman who is well controlled on NPH insulin.


Input: There seems little justification in using long acting insulin analogues in women with gestational diabetes or type 2 diabetes where the risk of hypoglycaemia is low.


Input: Synthesis and evaluation of cholecystokinin trimers: a multivalent approach to pancreatic cancer detection and treatment.


Input: In the quest for novel tools for early detection and treatment of cancer, we propose the use of multimers targeting overexpressed receptors at the cancer cell surface.


Input: Indeed, multimers are prone to create multivalent interactions, more potent and specific than their corresponding monovalent versions, thus enabling the potential for early detection.


Input: There is a lack of tools for early detection of pancreatic cancer, one of the deadliest forms of cancer, but CCK2-R overexpression on pancreatic cancer cells makes CCK based multimers potential markers for these cells.


Input: In this Letter, we describe the synthesis and evaluation of CCK trimers targeting overexpressed CCK2-R.


Input: Anti-influenza active and low toxic N-phenyl-substituted beta-amidoamidines structurally related to natural antibiotic amidinomycin.

N-phenyl-substituted beta-amidoamidines

amidinomycin


Input: A set of racemic N-phenyl-substituted beta-amidoamidines hydrochlorides 4, which are structurally related to natural antiviral agent amidinomycin (1), was synthesized in four steps starting from methacryloyl anilide (5).

racemic N-phenyl-substituted beta-amidoamidines hydrochlorides

amidinomycin

methacryloyl anilide


Input: In the final step of the synthetic route, an uncommon monoacylation of beta-aminoamidine 8 at the less reactive beta-phenylamino-group took place.

beta-aminoamidine

beta-phenylamino


Input: To rationalize this result, a mechanism which involves initial acylation at the more active amidine-function followed by intramolecular acyl-group transfer to beta-phenylamino-group was suggested.

amidine

acyl

beta-phenylamino


Input: All three beta-amidoamidines 4d-f bearing long linear aliphatic chain (from n-C8H17 to n-C12H25) revealed significant in vitro activity against influenza A virus (H3N2) and modest cytotoxicity.

beta-amidoamidines


Input: The in vitro antiviral potency of 4d, e is 6-20 times greater than that of commercial rimantadine with lower EC50 values and higher therapeutic index.

rimantadine


Input: The non-toxic in vivo compounds 4d-f showed a beneficial protective effect in influenza A (H3N2) infected mice.


Input: Peripubertal female athletes in high-impact sports show improved bone mass acquisition and bone geometry.


Input: OBJECTIVE: Intensive physical training may have a sport-dependent effect on bone mass acquisition.


Input: This cross-sectional study evaluated bone mass acquisition in girls practicing sports that put different mechanical loads on bone.


Input: MATERIALS/METHODS: Eighty girls from 10. 7 to 18. 0years old (mean 13. 83 +/- 1. 97) were recruited: 20 artistic gymnasts (AG; high-impact activity), 20 rhythmic gymnasts (RG; medium-impact activity), 20 swimmers (SW, no-impact activity), and 20 age-matched controls (CON; leisure physical activity < 3h/wk).


Input: Areal bone mineral density (aBMD) was determined using DEXA.


Input: Hip structural analysis applied at the femur evaluated cross-sectional area (CSA, cm (2)), section modulus (Z, cm (3)), and buckling ratio.


Input: Bone turnover markers and OPG/RANKL levels were analyzed.


Input: RESULTS: AG had higher aBMD than SW and CON at all bone sites and higher values than RG in the lumbar spine and radius.


Input: RG had higher aBMD than SW and CON only in the femoral region.


Input: CSA and mean cortical thickness were significantly higher and the buckling ratio was significantly lower in both gymnast groups compared with SW and CON.


Input: In RG only, endocortical diameter and width were reduced, while Z was only increased in AG compared with SW and CON.


Input: Reduced bone remodeling was observed in RG compared with AG only when groups were subdivided according to menarcheal status.


Input: All groups showed similar OPG concentrations, while RANKL concentrations increased with age and were decreased in SW.


Input: CONCLUSION: High-impact activity clearly had a favorable effect on aBMD and bone geometry during the growth period, although the bone health benefits seem to be more marked after menarche.


Input: Differential Expression of Human Cytochrome P450 Enzymes from the CYP3A Subfamily in the Brains of Alcoholics and Drug Free Controls.

Alcoholics


Input: Cytochrome P450 (P450, CYP) enzymes are responsible for the metabolism of most commonly used drugs.


Input: Amongst these enzymes, CYP3A forms mediate the clearance of around 40-50% of drugs and may also play roles in the biotransformation of endogenous compounds.


Input: CYP3A forms are expressed both in the liver and extrahepatically.


Input: However little is known about the expression of CYP3A proteins in specific regions of the human brain.


Input: In this study, form-selective antibodies raised to CYP3A4 and CYP3A5 were utilized to characterize the expression of these forms in the human brain.


Input: Both CYP3A4 and CYP3A5 immunoreactivity was found to varying extents in the microsomal fractions of cortex, hippocampus, basal ganglia, amygdala and cerebellum.


Input: However, only CYP3A4 expression was observed in the mitochondrial fractions of these brain regions.


Input: N-terminal sequencing confirmed the principal antigen detected by the anti-CYP3A4 antibody in cortical microsomes to be CYP3A4.

N


Input: Immunohistochemical analysis revealed that CYP3A4 and CYP3A5 expression was primarily localized in the soma and axonal hillock of neurons and varied according to cell type and cell layer within brain regions.


Input: Finally, analysis of the frontal cortex of chronic alcohol abusers revealed elevated expression of CYP3A4 in microsomal but not mitochondrial fractions; CYP3A5 expression was unchanged.

alcohol


Input: The site-specific expression of CYP3A4 and CYP3A5 in the human brain may have implications for the role of these enzymes in both normal brain physiology and the response to drugs.


Input: Polybrominated Dibenzo-p-dioxins (PBDDs), Dibenzofurans (PBDFs) and Biphenyls (PBBs)-Inclusion in the Toxicity Equivalency Factor Concept for Dioxin-like Compounds-

Polybrominated Dibenzo-p-dioxins

PBDDs

Dibenzofurans

PBDFs

Biphenyls

PBBs

Dioxin


Input: In 2011 a joint World Health Organization (WHO) and United Nations Environment Programme (UNEP) expert consultation took place, during which the possible inclusion of brominated analogues of the dioxin-like compounds in the WHO Toxicity Equivalency Factor (TEF) scheme were evaluated.

dioxin


Input: The expert panel concluded that polybrominated dibenzo-p-dioxins (PBDDs), dibenzofurans (PBDFs), and some dioxin-like biphenyls (dl-PBBs) may contribute significantly in daily human background exposure to the total dioxin toxic equivalencies (TEQs).

polybrominated dibenzo-p-dioxins

PBDDs

dibenzofurans

PBDFs

dioxin

biphenyls

PBBs

dioxin


Input: These compounds are also commonly found in the aquatic environment.


Input: Available data for fish toxicity were evaluated for possible inclusion in the WHO-UNEP TEF scheme (Van den Berg et al., 1998).


Input: Because of the limited database it was decided not to derive specific WHO-UNEP TEFs for fish, but for ecotoxicological risk assessment the use of specific relative effect potencies (REPs) from fish embryo assays is recommended.


Input: Based on the limited mammalian REP database for these brominated compounds, it was concluded that sufficient differentiation from the present TEF values of the chlorinated analogues (Van den Berg et al., 2005) was not possible.


Input: However, the REPs for PBDDs, PBDFs, and non-ortho dl-PBBs in mammals closely follow those of the chlorinated analogues, at least within one order of magnitude.

PBDDs

PBDFs

PBBs


Input: Therefore, the use of similar interim TEF values for brominated and chlorinated congeners for human risk assessment is recommended, pending more detailed information in the future.


Input: Yeast Proteome Variations Reveal Different Adaptive Responses to Grape Must Fermentation.


Input: Saccharomyces cerevisiae and S. uvarum are two domesticated species of the Saccharomyces sensu stricto clade that diverged around 100 Ma after whole-genome duplication.


Input: Both have retained many duplicated genes associated with glucose fermentation and are characterized by the ability to achieve grape must fermentation.

glucose


Input: Nevertheless, these two species differ for many other traits, indicating that they underwent different evolutionary histories.


Input: To determine how the evolutionary histories of S. cerevisiae and S. uvarum are mirrored on the proteome, we analyzed the genetic variability of the proteomes of domesticated strains of these two species by quantitative mass spectrometry.


Input: Overall, 445 proteins were quantified.


Input: Massive variations of protein abundances were found, that clearly differentiated the two species.


Input: Abundance variations in specific metabolic pathways could be related to phenotypic traits known to discriminate the two species.


Input: In addition, proteins encoded by duplicated genes were shown to be differently recruited in each species.


Input: Comparing the strain differentiation based on the proteome variability to those based on the phenotypic and genetic variations further revealed that the strains of S. uvarum and some strains of S. cerevisiae displayed similar fermentative performances despite strong proteomic and genomic differences.


Input: Altogether, these results indicate that the ability of S. cerevisae and S. uvarum to complete grape must fermentation arose through different evolutionary roads, involving different metabolic pathways and duplicated genes.


Input: Dexamethasone-mediated changes in adipose triacylglycerol metabolism are exaggerated, not diminished, in the absence of a functional GR dimerization domain.

Dexamethasone

triacylglycerol


Input: The glucocorticoid (GC) receptor (GR) has multiple effector mechanisms, including dimerization-mediated transactivation of target genes via DNA binding and transcriptional repression mediated by protein-protein interactions.


Input: Much attention has been focused on developing selective GR modulators that would dissociate adverse effects from therapeutic anti-inflammatory effects.


Input: The GR (dim/dim) mouse has a mutation in the dimerization domain of GR and has been shown to have attenuated transactivation with intact repression.


Input: To understand the role of GR dimerization-dependent targets in multiple tissues, we measured metabolic fluxes through several disease-relevant GC target pathways using heavy water labeling and mass spectrometry in wild-type and GR (dim/dim) mice administered the potent GC dexamethasone (DEX).

dexamethasone

DEX


Input: Absolute triglyceride synthesis was increased in both wild-type and GR (dim/dim) mice by DEX in the inguinal and epididymal fat depots.

triglyceride

DEX


Input: GR (dim/dim) mice showed an exaggerated response to DEX in both depots.

DEX


Input: De novo lipogenesis was also greatly increased in both depots in response to DEX in GR (dim/dim), but not wild-type mice.

DEX


Input: In contrast, the inhibitory effect of DEX on bone and skin collagen synthesis rates was greater in wild-type compared with GR (dim/dim) mice.

DEX


Input: Wild-type mice were more sensitive to DEX-dependent decreases in insulin sensitivity than GR (dim/dim) mice.

DEX


Input: Wild-type and GR (dim/dim) mice were equally sensitive to DEX-dependent decreases in muscle protein synthesis.

DEX


Input: Chronic elevation of GCs in GR (dim/dim) mice results in severe runting and lethality.


Input: In conclusion, some metabolic effects of GC treatment are exaggerated in adipose tissue of GR (dim/dim) mice, suggesting that selective GR modulators based on dissociating GR transactivation from repression should be evaluated carefully.


Input: X-box binding protein 1 is essential for insulin regulation of pancreatic alpha cell function.


Input: Type 2 diabetes mellitus (T2D) patients often exhibit hyperglucagonemia despite hyperglycemia suggesting defective alpha-cell function.


Input: While endoplasmic reticulum (ER) stress has been suggested to underlie beta-cell dysfunction in T2D, its role in alpha-cell biology remains unclear.


Input: X-box binding protein 1 (XBP1) is a transcription factor that plays a crucial role in the unfolded protein response (UPR) and its deficiency in beta-cells has been reported to impair insulin secretion leading to glucose intolerance.

glucose


Input: To evaluate the role of XBP1 in alpha-cells, we created complementary in vivo (alpha-cell specific XBP1 knockout (alpha XBPKO) mice) and in vitro (stable XBP1 knock down alpha-cell line, alpha XBPKD) models.


Input: alpha XBPKO mice exhibited glucose intolerance, mild insulin resistance and an inability to suppress glucagon secretion following glucose stimulation.

glucose

glucose


Input: alpha XBPKD cells exhibited activation of IRE1, an upstream activator of XBP1, leading to phosphorylation of JNK.


Input: Interestingly, insulin treatment of alpha XBPKD cells reduced tyrosine phosphorylation of IRS-1 (pY (896)), and phosphorylation of Akt, while enhancing serine phosphorylation (pS (307)) of IRS-1.

tyrosine

serine


Input: Consequently the alpha XBPKD cells exhibited blunted suppression of glucagon secretion following insulin treatment in the presence of high glucose.

glucose


Input: Together, these data indicate that XBP1 deficiency in pancreatic alpha-cells induces altered insulin signaling and dysfunctional glucagon secretion.


Input: Fabrication and multifunction integration of microfluidic chips by femtosecond laser direct writing.


Input: In the pursuit of modern microfluidic chips with multifunction integration, micronanofabrication techniques play an increasingly important role.


Input: Despite the fact that conventional fabrication approaches such as lithography, imprinting and soft lithography have been widely used for the preparation of microfluidic chips, it is still challenging to achieve complex microfluidic chips with multifunction integration.


Input: Therefore, novel micronanofabrication approaches that could be used to achieve this end are highly desired.


Input: As a powerful 3D processing tool, femtosecond laser fabrication shows great potential to endow general microfluidic chips with multifunctional units.


Input: In this review, we briefly introduce the fundamental principles of femtosecond laser micronanofabrication.


Input: With the help of laser techniques, both the preparation and functionalization of advanced microfluidic chips are summarized.


Input: Finally, the current challenges and future perspective of this dynamic field are discussed based on our own opinion.


Input: LDL Cholesterol Goals in High-Risk Patients: How Low Do We Go and How Do We Get There?

Cholesterol


Input: It is widely recognised that low-density lipoprotein cholesterol (LDL-C) is one of the most important and modifiable risk factors for cardiovascular disease (CVD).

cholesterol


Input: Statins (HMG-CoA reductase inhibitors) have consistently been shown to decrease both LDL-C and CVD risk in almost all patient categories, with the exception of heart and kidney failure as well as advanced aortic stenosis.

HMG-CoA


Input: As a consequence, statins have become the cornerstone in current prevention guidelines.


Input: In patients who do not reach the LDL-C target, combination therapy with additional LDL-C lowering drugs (e. g. ezetimibe, bile acid sequestrants or fibrates) should be considered.

ezetimibe

bile acid

fibrates


Input: Guidelines provide different LDL-C levels to strive for, depending on the CVD risk.


Input: In this review, we describe the rationale for these LDL-C targets and how these goals might be reached by current and future therapies.


Input: The clinical characteristics at diagnosis of type 2 diabetes in a multi-ethnic population: the South London Diabetes cohort (SOUL-D).


Input: AIMS/HYPOTHESIS: This study aimed to investigate the clinical features of newly diagnosed type 2 diabetes in an urban multi-ethnic cohort.


Input: METHODS: A population-based cross-sectional design was used.


Input: People diagnosed with type 2 diabetes in the preceding 6 months were recruited from primary care practices in three adjacent inner-city boroughs of South London, serving a population in which 20% of residents are of black African or Caribbean ethnicity.


Input: Sociodemographic and biomedical data were collected by standardised clinical assessment and from medical records.


Input: Multiple logistic regression methods were used to report associations between ethnicity and diabetes-complication status.


Input: RESULTS: From 96 general practices, 1, 506 patients were recruited.


Input: Their mean age was 55. 6 (+/- 11. 07) years, 55% were men, 60% were asymptomatic at diagnosis and 51%, 38% and 11% were of white, black and South Asian/other ethnicity, respectively.


Input: Compared with white participants, black and South Asian/other participants were: younger (mean age 58. 9 [+/- 10. 09], 52. 4 [+/- 11. 19] and 51. 5 [+/- 10. 42] years, respectively; p < 0. 0001); less likely to have neuropathy (10. 1%, 3. 6% and 4. 4%; p < 0. 0001) or report coronary artery disease (12. 7%, 4. 8% and 7. 3%; p < 0. 0001).


Input: In logistic regression, compared with white participants, black participants had lower levels of macrovascular complications (OR 0. 52, 95% CI 0. 32, 0. 84; p = 0. 01).


Input: Male sex was independently associated with microvascular disease (OR 1. 69, 95% CI 1. 26, 2. 28; p < 0. 0001).


Input: CONCLUSIONS/INTERPRETATION: The prevalence of complications at time of diagnosis was lower than expected, especially in black and South Asian/other ethnic groups.


Input: However, in multi-ethnic inner-city populations, onset of type 2 diabetes occurred almost 10 years earlier in non-white populations than in white participants, predicating a prolonged morbidity.


Input: Neuroprotection against neuroblastoma cell death induced by depletion of mitochondrial glutathione.

glutathione


Input: Mitochondrial glutathione pool is vital in protecting cells against oxidative stress as the majority of the cellular reactive oxygen species are generated in mitochondria.

glutathione

oxygen


Input: Oxidative stress is implicated as a causative factor in neuronal death in neurodegenerative disorders.


Input: We hypothesized that depletion of mitochondrial glutathione leads to mitochondrial dysfunction and apoptotic death of SK-N-SH (human neuroblastoma) cells and investigated the neuroprotective strategies against GSH depletion.

glutathione

GSH


Input: SK-N-SH cells were treated with two distinct inhibitors of glutathione metabolism: L-buthionine-(S, R)-sulfoximine (BSO) and ethacrynic acid (EA).

glutathione

L-buthionine-(S, R)-sulfoximine

BSO

ethacrynic acid


Input: EA treatment caused depletion of both the total and mitochondrial glutathione (while BSO had no effect on mitochondrial glutathione), enhanced rotenone-induced ROS production, and reduced the viability of SK-N-SH cells.

glutathione

BSO

glutathione

rotenone


Input: Glutathione depletion by BSO or EA demonstrated positive features of mitochondria-mediated apoptosis in neuroblastoma cell death.

Glutathione

BSO


Input: Prevention of apoptosis by Bcl2 overexpression or use of antioxidant ebselen did not confer neuroprotection.

ebselen


Input: Co-culture with U-87 (human glioblastoma) cells protected SK-N-SH cells from the cell death.


Input: Our data suggest that depletion of mitochondrial glutathione leads to mitochondrial dysfunction and apoptosis.

glutathione


Input: The study indicates that preventing mitochondrial glutathione depletion could become a novel strategy for the development of neuroprotective therapeutics in neurodegenerative disorders.

glutathione


Input: Structure of dipeptides having N-terminal selenocysteine residues: a DFT study in gas and aqueous phase.

dipeptides

N

selenocysteine


Input: Over the last few decades, dipeptides as well as their analogues have served as important model systems for the computational studies concerning the structure of protein and energetics of protein folding.

dipeptides


Input: Here, we present a density functional structural study on a set of seven dipeptides having N-terminal selenocysteine residues (the component in the C-terminus is varied with seven different combinations viz. Ala, Phe, Glu, Thr, Asn, Arg and Sec) in gas and simulated aqueous phase using a polarizable continuum model (PCM).

dipeptides

N

selenocysteine

C

Ala

Phe

Glu

Thr

Asn

Arg

Sec


Input: The molecular geometries of the dipeptides are fully optimized at B3LYP/6-311 + + G (d, p) level and subsequent frequency calculations confirm them as true minima.

dipeptides


Input: The effects of solvation and identity of the varying C-terminal residue on the energetics, structural features of the peptide planes, values of the psi and phi dihedrals, geometry around the alpha-carbon atoms and theoretically predicted vibrational spectra of the dipeptides are investigated.

C

alpha-carbon

dipeptides


Input: Two types of intramolecular H-bonds, namely N ... H-N and O ... H-C, are found to play important roles in influencing the planarity of the peptide planes and geometry around the alpha-carbon atoms of the dipeptides.

H

N

H-N

O

H-C

alpha-carbon

dipeptides


Input: The identity of the varying C-terminal residue influences the values of phi, planarity of the peptide planes and geometry around the C7 alpha-carbon atoms while the solvation effects are evident on the values of bond lengths and bond angles of the amide planes.

C

alpha-carbon

amide


Input: The Role of Traditional Chinese Medicines in Osteogenesis and Angiogenesis.


Input: The article aims to review various Traditional Chinese Medicines (TCMs) with both osteogenic and angiogenic effects, alone and in combination, and to consider whether these TCMs promote osteogenesis via angiogenesis and vascular endothelial growth factor (VEGF).


Input: Each of the TCMs involving in osteogenesis was searched through PubMed and CBMdisc using its Latin name and English name, and keywords such as' osteogenesis',' bone',' osteoblast',' angiogenesis',' VEGF' were used.


Input: A total of 241 articles were screened from PubMed and CBMdisc.


Input: The articles were only chosen if they discussed the relationship of the TCMs with bone formation and/or angiogenesis.


Input: Twenty-seven articles were chosen, of which 16 were in English and 11 were in Chinese with English abstract.


Input: As a result, the TCMs (Danshen or Salvia miltiorrhiza Bunge, Danggui or Angelica sinensis, Astragalus membranaceus Bunge or Huangqi, and Ge Gan or Puerarin radix) that have a relationship with both osteogenesis and angiogenesis were screened out.


Input: It is found that the aforementioned TCMs enhance angiogenesis and osteogenesis.


Input: They show a positive effect on bone formation, and the possible mechanisms may be related to their ability to promote angiogenesis via an effect on substances such as VEGF.


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


Input: Nickel sulfide/nitrogen-doped graphene composites: phase-controlled synthesis and high performance anode materials for lithium ion batteries.

Nickel sulfide

nitrogen-doped graphene

lithium


Input: Phase-controlled nickel sulfide (Ni3 S4 and NiS1. 03) nanoparticle (NP)/nitrogen-doped graphene (NG) composites are prepared through a facile one-pot hydrothermal process.

nickel sulfide

Ni3 S4

NiS1. 03

nitrogen-doped graphene


Input: The composites show ultrahigh capacity retentions of 98. 87% and 95. 94% for Ni3 S4/NG and NiS1. 03/NG electrodes, respectively, as anode materials for lithium ion batteries.

Ni3 S4

NiS1. 03

lithium


Input: (1) H and (13) C NMR analysis of 2-acetamido-3-mercapto-3-methyl-N-aryl-butanamides and 2-acetamido-3-methyl-3-nitrososulfanyl-N-aryl-butanamide derivatives.

(1) H

(13) C

2-acetamido-3-mercapto-3-methyl-N-aryl-butanamides

2-acetamido-3-methyl-3-nitrososulfanyl-N-aryl-butanamide


Input: The complete assignment of the (1) H and (13) C NMR spectra of various 2-acetamido-3-mercapto-3-methyl-N-aryl-butanamides and 2-acetamide-3-methyl-3-nitrososulfanyl-N-aryl-butanamides with p-methoxy, o-chloro and m-chloro substituents is reported.

(1) H

(13) C

2-acetamido-3-mercapto-3-methyl-N-aryl-butanamides

2-acetamide-3-methyl-3-nitrososulfanyl-N-aryl-butanamides

p-methoxy

o-chloro

m-chloro


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


Input: Targeting protein-protein interactions within the cyclic AMP signaling system as a therapeutic strategy for cardiovascular disease.

cyclic AMP


Input: The cAMP signaling system can trigger precise physiological cellular responses that depend on the fidelity of many protein-protein interactions, which act to bring together signaling intermediates at defined locations within cells.

cAMP


Input: In the heart, cAMP participates in the fine control of excitation-contraction coupling, hence, any disregulation of this signaling cascade can lead to cardiac disease.

cAMP


Input: Due to the ubiquitous nature of the cAMP pathway, general inhibitors of cAMP signaling proteins such as PKA, EPAC and PDEs would act non-specifically and universally, increasing the likelihood of serious' off target' effects.

cAMP

cAMP


Input: Recent advances in the discovery of peptides and small molecules that disrupt the protein-protein interactions that underpin cellular targeting of cAMP signaling proteins are described and discussed.

cAMP


Input: Identification of Transglutaminase Substrates from Porcine Nucleus Pulposus as Potential Amplifiers in Cross-Linking Cell Scaffolds.


Input: Nucleus pulposus from the porcine intervertebral disc was separated chromatographically to discover substrates of microbial transglutaminase.


Input: Highly purified proteins were prepared, among them type II collagen, the major protein of the nucleus pulposus.


Input: Determination of substrates was performed by transglutaminase-mediated incorporation of biotinylated probes displaying several glutamine and lysine donor proteins.

glutamine

lysine


Input: Type II collagen was only labeled if smaller nucleus pulposus proteins were present.


Input: One of the modulating proteins was serotransferrin, a lysine donor substrate of bacterial transglutaminase.

lysine


Input: An additional substrate was the carboxy-terminal propeptide of type II collagen, chondrocalcin.

carboxy


Input: Chondrocalcin, a regulator of type II collagen fibrillogenesis, occurs abundantly in juvenile cartilage and nucleus pulposus.


Input: Accordingly, the protein may be regarded as an excellent additive for the preparation of injectable stem cells in nucleus pulposus-like matrices cross-linked by microbial transglutaminase.


Input: From synaptic spines to nuclear signaling: nuclear and synaptic actions of the amyloid precursor protein.


Input: Despite intensive studies of the secretase-mediated processing of the amyloid precursor protein (APP) to form the amyloid beta-peptide (A beta), in relation to Alzheimer' s disease (AD), no new therapeutic agents have reached the clinics based on reducing A beta levels through the use of secretase inhibitors or immunotherapy.


Input: Furthermore, the normal neuronal functions of APP and its various metabolites still remain under-investigated and unclear.


Input: Here, we highlight emerging areas of APP function that may provide new insights into synaptic development, cognition, and gene regulation.


Input: By modulating expression levels of endogenous APP in primary cortical neurons, the frequency and amplitude of calcium oscillations is modified, implying a key role for APP in maintaining neuronal calcium homeostasis essential for synaptic transmission.

calcium

calcium


Input: Disruption of this homeostatic mechanism predisposes to aging and AD.


Input: Synaptic spine loss is a feature of neurogeneration resulting in learning and memory deficits, and emerging evidence indicates a role for APP, probably mediated via one or more of its metabolites, in spine structure and functions.


Input: The intracellular domain of APP (AICD) has also emerged as a key epigenetic regulator of gene expression controlling a diverse range of genes, including APP itself, the amyloid-degrading enzyme neprilysin, and aquaporin-1.


Input: A fuller understanding of the physiological and pathological actions of APP and its metabolic network could provide new opportunities for therapeutic intervention in AD.


Input: The effect of rituximab on thyroid function and autoimmunity.


Input: no abstract required.


Input: Pyridone Alkaloids from a Marine-Derived Fungus, Stagonosporopsis cucurbitacearum, and Their Activities against Azole-Resistant Candida albicans.

Pyridone Alkaloids

Azole


Input: Four new 4-hydroxy-2-pyridone alkaloids, didymellamides A-D (1-4), were isolated from the marine-derived fungus Stagonosporopsis cucurbitacearum.

4-hydroxy-2-pyridone alkaloids

didymellamides A-D


Input: The structures of 1-4 were elucidated from spectroscopic data (NMR, MS, and IR), and the absolute configuration of 1 was determined by X-ray diffraction analysis.


Input: Didymellamide A (1) exhibited antifungal activity against azole-resistant Candida albicans.

Didymellamide A

azole


Input: Chemical composition and antioxidant activity of dried powder formulations of Agaricus blazei and Lentinus edodes.


Input: Several mushroom species have been pointed out as sources of antioxidant compounds, in addition to their important nutritional value.


Input: Agaricus blazei and Lentinus edodes are among the most studied species all over the world, but those studies focused on their fruiting bodies instead of other presentations, such as powdered preparations, used as supplements.


Input: In the present work the chemical composition (nutrients and bioactive compounds) and antioxidant activity (free radical scavenging activity, reducing power and lipid peroxidation inhibition) of dried powder formulations of the mentioned mushroom species (APF and LPF, respectively) were evaluated.


Input: Powder formulations of both species revealed the presence of essential nutrients, such as proteins, carbohydrates and unsaturated fatty acids.

carbohydrates

unsaturated fatty acids


Input: Furthermore, they present a low fat content (< 2g/100g) and can be used in low-calorie diets, just like the mushrooms fruiting bodies.


Input: APF showed higher antioxidant activity and higher content of tocopherols and phenolic compounds (124 and 770 mu g/100g, respectively) than LPF (32 and 690 mu g/100g).

tocopherols

phenolic


Input: Both formulations could be used as antioxidant sources to prevent diseases related to oxidative stress.


Input: The antioxidants in oils heated at frying temperature, whether natural or added, could protect against postprandial oxidative stress in obese people.


Input: We have investigated the effects of the intake of oils heated at frying temperature in order to find an oil model for deep-frying that prevents postprandial oxidative stress.


Input: Twenty obese people received four breakfasts following a randomised crossover design consisting of different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)), which were subjected to 20 heating cycles.

dimethylpolysiloxane

SOX

SOP


Input: The intake of SFO-breakfast reduced plasma GSH levels and the GSH/GSSG ratio, increased protein carbonyl levels, and induced a higher gene expression of the different NADPH-oxidase subunits, Nrf2-Keap1 activation, gene expression of the antioxidant enzymes in peripheral blood mononuclear cells and antioxidant plasma activities than the intake of the breakfasts prepared with VOO, SOP and SOX.

GSH

GSH

GSSG

carbonyl

NADPH

SOP

SOX


Input: Oils with phenolic compounds, whether natural (VOO) or artificially added (SOP), or with artificial antioxidant (SOX), could reduce postprandial oxidative stress compared with sunflower oil.

phenolic

SOP

SOX


Input: Rapid monitoring of heat-accelerated reactions in vegetable oils using direct analysis in real time ionization coupled with high resolution mass spectrometry.


Input: Transmission-mode direct analysis in real time ionization coupled with high resolution mass spectrometry (TM-DART-HRMS) was used to monitor chemical changes in various vegetable oils (olive, rapeseed, soybean and sunflower oil) during their thermally-induced oxidation.


Input: This novel instrumental approach enabled rapid fingerprinting of examined samples and detection of numerous sample components, such as triacylglycerols (TAGs), phytosterols, free fatty acids (FFA), and their respective oxidation products.

triacylglycerols

TAGs

free fatty acids

FFA


Input: Mass spectra obtained from DART were processed with the use of principal component analysis (PCA) in order to assess the compositional differences between heated and non-heated samples.


Input: Good correlation was observed between the normalized intensities of the pre-selected ion corresponding to mono-oxidized TAG and' classic' criterion represented by the levels of TAG polymers determined by high performance-size exclusion chromatography with refractometric detection (HP-SEC-RID).

TAG

TAG


Input: Calcium hydroxy palmitate: possible precursor phase in calcium precipitation by palmitate.

Calcium hydroxy palmitate

calcium

palmitate


Input: Calcium (II) precipitates with palmitate (Pal (-)), a process affecting calcium absorption in the gut, in a first-order reaction, as followed by a calcium electrode in neutral aqueous solution for excess of calcium (II), with a rate constant showing a minimum at physiological ionic strength of 0. 32 +/- 0. 09 d (-1) at 25 degrees C with a stoichiometry of 1. 79 +/- 0. 03, lower than the expected 1: 2.

Calcium (II)

palmitate

Pal (-)

calcium

calcium

calcium (II)


Input: During ageing of precipitate, pH increases in the supernatant, while pH decreases for precipitation with excess of palmitate.

palmitate


Input: Increasing pH, as in some aged food products, decreases the solubility, and Ksp (') = [Ca (2 +)] [Pal (-)] [OH (-)] is found constant rather than Ksp = [Ca (2 +)] [Pal (-)] (2) in agreement with an initial precipitation of Ca (OH) (Pal), which slowly may convert into Ca (Pal) 2. Ca (OH) (Pal) has a solubility minimum at physiological ionic strength with Ksp (') = (1. 4 +/- 0. 4) 10 (-16) M (3).

Ca (2 +)] [Pal (-)] [OH (-)

[Ca (2 +)] [Pal (-)] (2)

Ca (OH) (Pal)

Ca (Pal) 2. Ca (OH) (Pal)


Input: X-ray diffraction showed a d-spacing of 44. 15 A (different from 45. 2 A reported for Ca (Pal) 2), and infrared spectroscopy confirmed the presence of a hydroxy group.

Ca (Pal) 2

hydroxy


Input: Sensory quality and compositional characteristics of blackcurrant juices produced by different processes.


Input: Effects of enzymatic and non-enzymatic juice pressing on key orosensory and chemical quality factors of blackcurrant juices were studied in laboratory scale using berries of five different cultivars (Mortti, Mikael, Marski, Ola and Breed15).


Input: Enzymatic processing increased the juice yield by 10-22% and the content of various phenolic compounds in juice by 4-10-fold as compared to the non-enzymatic process.

phenolic


Input: Higher intensity of the mouth-drying astringency of the enzyme-aided juice was the most significant orosensory difference between the processes.


Input: Juices of different blackcurrant cultivars varied in sweetness, sourness and bitterness.


Input: The most intensive sensory attributes of the juices were sourness and puckering astringency regardless of processing method.


Input: They correlated positively with each other and were contributed by acid content and pH.


Input: In enzyme-aided juices, the contents of flavonol glycosides and hydroxycinnamic acids were associated with mouth-drying astringency, and sugar/acid ratio correlated with sweetness.

flavonol glycosides

hydroxycinnamic acids

sugar


Input: These correlations were less clear in non-enzyme juices possibly due to lower content of phenolic compounds and the high content of pectin.

phenolic


Input: Nuclear positioning.


Input: The nucleus is the largest organelle and is commonly depicted in the center of the cell.


Input: Yet during cell division, migration, and differentiation, it frequently moves to an asymmetric position aligned with cell function.


Input: We consider the toolbox of proteins that move and anchor the nucleus within the cell and how forces generated by the cytoskeleton are coupled to the nucleus to move it.


Input: The significance of proper nuclear positioning is underscored by numerous diseases resulting from genetic alterations in the toolbox proteins.


Input: Finally, we discuss how nuclear position may influence cellular organization and signaling pathways.


Input: Antibodies targeting extracellular domain of connexins for studies of hemichannels.


Input: Hemichannels are transmembrane channels composed of either a connexin or pannexin hexamer.


Input: The docking of the extracellular domains of connexin hemichannels contributed by neighboring cells forms a gap junction channel that joins the cytoplasm of adjacent cells.


Input: Connexins are expressed ubiquitously in different organs, but some subtypes are expressed exclusively in certain tissues and tumors.


Input: Both gap junction channels and hemichannels participate in diverse physiological and pathological responses.


Input: However, the lack of specific reagents that inhibit only gap junction channels or hemichannels is a challenge that makes it different to discern the specific roles of either channel.


Input: Fortunately, the available information regarding the connexin sequence, secondary and tertiary structure, and their biochemical and physiological properties permits the development of strategies to block exclusively the hemichannel activity exclusively, with no effect on gap junction activity.


Input: This task is accomplished through the use of specifics antibodies that target the extracellular sites of desired connexin subtype.


Input: However, the underlying mechanism of how antibodies targeting extracellular connexin epitopes actually inhibit hemichannels remains unknown.


Input: Although these antibodies are being used for detecting and blocking of hemichannels in normal and tumor cells, they can also be potentially used for tissue-specific treatment and drug delivery in clinical applications.


Input: In this article, we will first review the literature concerning the structure of connexins and the unique properties of extracellular loop domains of the connexins.


Input: Furthermore, we will discuss briefly the development of connexin (Cx) 43 (E2) antibody, a specific antibody which detects the second extracellular loop of Cx43 and specifically prevents the opening of Cx43 hemichannels.


Input: We will then summarize the reported studies of specific reagents used for the inhibition of connexin hemichannels including antibodies developed against extracellular loop domains.


Input: This article is part of a Special Issue entitled' Connexin based channels'.


Input: Identification of pyrrolo [2, 3-g] indazoles as new Pim kinase inhibitors.

pyrrolo [2, 3-g] indazoles


Input: The synthesis and Pim kinase inhibition potency of a new series of pyrrolo [2, 3-g] indazole derivatives is described.

pyrrolo [2, 3-g] indazole


Input: The results obtained in this preliminary structure-activity relationship study pointed out that sub-micromolar Pim-1 and Pim-3 inhibitory potencies could be obtained in this series, more particularly for compounds 10 and 20, showing that pyrrolo [2, 3-g] indazole scaffold could be used for the development of new potent Pim kinase inhibitors.

pyrrolo [2, 3-g] indazole


Input: Molecular modeling experiments were also performed to study the binding mode of these compounds in Pim-3 ATP-binding pocket.

ATP


Input: The bizarre pharmacology of the ATP release channel pannexin1.

ATP


Input: Pannexins were originally thought to represent a second and redundant family of gap junction proteins in addition to the well characterized connexins.


Input: However, it is now evident that pannexins function as unapposed membrane channels and the major role of Panx1 is that of an ATP release channel.

ATP


Input: Despite the contrasting functional roles, connexins, innexins and pannexins share pharmacological properties.


Input: Most gap junction blockers also attenuate the function of Panx1, including carbenoxolone, mefloquine and flufenamic acid.

carbenoxolone

mefloquine

flufenamic acid


Input: However, in contrast to connexin based gap junction channels, Panx1 channel activity can be attenuated by several groups of drugs hitherto considered very specific for other proteins.


Input: The drugs affecting Panx1 channels include several transport inhibitors, chloride channel blockers, mitochondrial inhibitors, P2X7 receptor ligands, inflammasome inhibitors and malaria drugs.

chloride


Input: These observations indicate that Panx1 may play an extended role in a wider spectrum of physiological functions.


Input: Alternatively, Panx1 may share structural domains with other proteins, not readily revealed by sequence alignments.


Input: This article is part of a Special Issue entitled' Connexin based channels'


Input: Angiotensin-(1-7) inhibits autophagy in the brain of spontaneously hypertensive rats.


Input: Autophagy is an important cellular process that mediates lysosomal degradation of damaged organelles, which is activated in response to a variety of stress-related diseases, including hypertension.


Input: The basal level of autophagy plays an important role in the maintenance of cellular homeostasis, whereas excessive autophagic activity leads to cell death and is considered as a contributing factor to several disorders.


Input: Recent works have demonstrated that Angiotensin-(1-7) [Ang-(1-7)] exerted its neuroprotective effects by modulating classic components of renin-angiotensin system associated with reducing oxidative stress and apoptosis in brains of spontaneously hypertensive rats (SHRs).


Input: However, the effect of Ang-(1-7) on autophagic activity in brain of hypertensive individual remains unclear.


Input: In this study, Wistar-Kyoto rats received intracerebroventricular (I. C. V.) infusion of artificial cerebrospinal fluid (aCSF) while SHRs received I. C. V. infusion of aCSF, Ang-(1-7), Mas receptor antagonist A-779, or angiotensin II type 2 receptor antagonist PD123319 for 4 weeks.


Input: Brain tissues were collected and analyzed by western blotting analysis, immunofluorescence assay, and transmission electron microscopic examination.


Input: Our study showed that infusion of Ang-(1-7) for 4 weeks inhibited the increase of microtubule-associated protein 1 light chain 3 (LC3)-II and Beclin-1 levels, as well as the autophagosome formation in SHR brain.


Input: Meanwhile, the reduction of p62 expression in SHR brain was also reversed by Ang-(1-7).


Input: Of note, the anti-autophagic effects of Ang-(1-7) were independent of blood pressure reduction and can be inhibited by A-779 and PD123319.


Input: These findings suggest that treatment with Ang-(1-7) may be useful to prevent hypertension-induced excessive autophagic activation in brain.


Input: Steroidal glycosides from the bulbs of Fritillaria meleagris and their cytotoxic activities.

Steroidal glycosides


Input: Steroidal glycosides (1-18), including 10 new compounds (1-10), were isolated from the bulbs of Fritillaria meleagris (Liliaceae).

Steroidal glycosides


Input: The structures of the new compounds were determined by two-dimensional (2D) NMR analysis, and by hydrolytic cleavage followed by spectroscopic and chromatographic analysis.


Input: The isolated compounds and their aglycones were evaluated for cytotoxic activity against HL-60 human promyelocytic leukemia cells and A549 human lung adenocarcinoma cells.


Input: Morphological observation and flow cytometry analysis showed that 5 beta-spirostanol glycoside (2) and a cholestane derivative (17a) induced apoptotic cell death in HL-60 cells through different mechanisms of action.

5 beta-spirostanol glycoside

cholestane


Input: Furthermore, the (22R)-spirosolanol glycoside (11) selectively induced apoptosis in A549 cells without affecting the caspase-3 activity level.

(22R)-spirosolanol glycoside


Input: Arrhythmogenic effect of a crude extract from sea anemone Condylactis gigantea: Possible involvement of rErg1 channels.


Input: Sea anemones possess a number of peptide toxins that target ion channels which provide powerful tools to study the molecular basis of diverse signaling pathways.


Input: It is also acknowledged that currents through Erg1 K (+) channels in cardiac myocytes are important for electrical stability of the heart and alterations in its activity has been linked to the onset of a potentially life-threatening heart condition named long QT syndrome type 2.

K (+)


Input: Here, we report that a crude extract from sea anemone Condylactis gigantea significantly increases the QT interval and has arrhythmogenic effects in the rat heart.


Input: Furthermore, a bioassay-guided purification procedure allowed the isolation of a chromatographic fraction containing a major component with a molecular mass of 4478 Da from the crude extract, which causes a significant inhibition of whole-cell patch-clamp currents through recombinant Erg1 channels, responsible of the rapid delayed rectifying current crucial for electrical activity in the heart.


Input: Further studies could provide relevant information on the molecular mechanism of C. gigantea peptide toxins which represent promising tools in studying the physiology of diverse ion channels.


Input: Delivery of definable number of drug or growth factor loaded poly (dl-lactic acid-co-glycolic acid) microparticles within human embryonic stem cell derived aggregates.

poly (dl-lactic acid-co-glycolic acid)


Input: Embryoid bodies (EBs) generated from embryonic stem cells are used to study processes of differentiation within a three dimensional (3D) cell environment.


Input: In many instances however, EBs are dispersed to single cell suspensions with a subsequent monolayer culture.


Input: Moreover, where the 3D integrity of an EB is maintained, cytokines or drugs of interest to stimulate differentiation are often added directly to the culture medium at fixed concentrations and effects are usually limited to the outer layers of the EB.


Input: The aim of this study was to create an EB model with localised drug and or growth factor delivery directly within the EB.


Input: Using poly (DL-lactic acid-co-glycolic acid) microparticles (MPs) with an average diameter of 13 mu m, we have demonstrated controllable incorporation of defined numbers of MPs within human ES cell derived EBs, down to 1 MP per EB.

poly (DL-lactic acid-co-glycolic acid)


Input: This was achieved by coating MPs with human ES cell lysate and centrifugation of specific ratios of ES cells and MPs to form 3D aggregates.


Input: Using MPs loaded with simvastatin (pro or active drug) or BMP-2, we have demonstrated osteogenic differentiation within the 3D aggregates, maintained in culture for up to 21days, and quantified by real time QPCR for osteocalcin.

simvastatin


Input: Immunostaining for RUNX2 and osteocalcin, and also histochemical staining with picrosirius red to demonstrate collage type 1 and Alizarin red to demonstrate calcium/mineralisation further demonstrated osteogenic differentiation and revealed regional staining associated with the locations of MPs within the aggregates.

Alizarin red

calcium


Input: We also demonstrated endothelial differentiation within human ES cell-derived aggregates using VEGF loaded MPs.


Input: In conclusion, we demonstrate an effective and reliable approach for engineering stem aggregates with definable number of MPs within the 3D cellular structure.


Input: We also achieved localised osteogenic and endothelial differentiation associated with MPs releasing encapsulated drug molecules or cytokines directly within the cell aggregate.


Input: This provides a powerful tool for controlling and investigating differentiation within 3D cell cultures and has applications to drug delivery, drug discovery, stem cell biology, tissue engineering and regenerative medicine.


Input: Raft forming system-An upcoming approach of gastroretentive drug delivery system.


Input: In recent era various technologies have been made in research and development of controlled release oral drug delivery system to overcome various physiological difficulties such as variation in gastric retention and emptying time.


Input: To overcome this drawback and to maximize the oral absorption of various drugs, novel drug delivery systems have been developed.


Input: Gastroretentive drug delivery system is facing many challenges which can be overcome by upcoming newly emerging approach i. e. raft forming system.


Input: The purpose of writing this review is to focus on recent development of stomach specific floating drug delivery system to circumvent the difficulties associated with formulation design.


Input: Various gastroretentive approaches that have been developed till now are also discussed.


Input: The present study provides valuable information & highlights advances in this raft forming system.


Input: This review attempts to discuss various factors like physiological factors, physicochemical factors and formulation factors to be considered in the development of the raft forming system.


Input: Different types of smart polymers used for their formulation have also been summarized.


Input: The review focuses on the mechanism, formulation and development of the raft forming system.


Input: This review also summarizes the studies to evaluate the performance and application of these systems.


Input: The study finally highlights advantages, disadvantages, and marketed preparation of the raft forming system.


Input: Analysis of the enhanced oral bioavailability of fenofibrate lipid formulations in fasted humans using an in vitro-in silico-in vivo approach.

fenofibrate


Input: Lipid-based formulations have established a significant role in the formulation of poorly soluble drugs for oral administration.


Input: In order to better understand their potential advantages over solid oral dosage forms, we studied the solubility and dissolution/precipitation characteristics of three self-microemulsifying drug delivery system (SMEDDS) formulations and one suspension of micronized fenofibrate in lipid excipients, for which pharmacokinetic studies had already been reported in the open literature.

fenofibrate


Input: The in vitro dispersion/dissolution studies were carried out in biorelevant media using USP II apparatus.


Input: These were followed up by in silico simulations using STELLA (R) software, in which not only dispersion/dissolution, but also the precipitation and re-dissolution of fenofibrate was taken into account.

fenofibrate


Input: While unformulated drug exhibited poor solubility (0. 22 mu g/mL in FaSSGF and 4. 31 mu g/mL in FaSSIF-V2 (PO4)) and dissolved less than 2% in dissolution tests, the solubility of fenofibrate in the presence of the lipid excipients increased dramatically (e. g., to 65. 44 mu g/mL in the presence of the Myritol 318/TPGS/Tween 80 SMEDDS) and there was an attendant increase in the dissolution (over 80% from capsules containing the Myritol 318/TPGS/Tween 80 SMEDDS and about 20% from the dispersion of fenofibrate in lipid excipients).

V2 (PO4)

fenofibrate

Myritol 318

TPGS

Tween 80

Myritol 318

TPGS

Tween 80

fenofibrate


Input: For the four lipid-based fenofibrate formulations studied, combining in vitro data in biorelevant media with in silico simulation resulted in accurate prediction of the in vivo human plasma profiles.

fenofibrate


Input: The point estimates of Cmax and AUC ratio calculated from the in silico and in vivo plasma profiles fell within the 0. 8-1. 25 range for the SMEDDS solution and capsule formulations, suggesting an accurate simulation of the in vivo profiles.


Input: This similarity was confirmed by calculation of the respective f2 factors.


Input: Sensitivity analysis of the simulation profiles revealed that the SMEDDS formulations had virtually removed any dependency of absorption on the dissolution rate in the small intestine, whereas for the dispersion in lipid excipients, this barrier remained.


Input: Such results pave the way to optimizing the performance of oral lipid-based formulations via an in vitro-in silico-in vivo approach.


Input: Evaluation of the pharmacodynamics and pharmacokinetics of brucine following transdermal administration.

brucine


Input: Before the design of brucine-containing transdermal formulations, the pharmacodynamics and pharmacokinetics of brucine following transdermal administration should be evaluated.

brucine

brucine


Input: In this study, the effect of addition of ethanol on solubility of bruicne was investigated and 20% ethanol was added into PBS to obtain 10mg/mL brucine solution.

ethanol

bruicne

ethanol

brucine


Input: Then three transdermal doses (10, 20 and 40mg/kg) were administered to mice to evaluate pharmacological activity.


Input: It had been demonstrated that brucine possessed analgesic and anti-inflammatory activity in a dose-dependent manner.

brucine


Input: Cytotoxicities of brucine against various tumor cells including skin tumor cell were also compared in vitro.

brucine


Input: Brucine was found to possess antitumor activity in a concentration and time-dependent manner and gastrointestinal tumor cells seemed to be more sensitive to brucine.

Brucine

brucine


Input: Then in vitro skin permeation behavior and in vivo pharmacokinetics following transdermal administration were further investigated.


Input: The cumulative amounts of brucine across mouse skin in vitro were found to be higher than 90%.

brucine


Input: The absolute bioavailability of brucine was determined to be 40. 83%.

brucine


Input: And compared with intravenous administration, MRT and T1/2 values were increased about 8 ~ 12-fold by transdermal route.


Input: Moreover, fluctuations of drug levels were found to be significantly decreased in tissues, especially in brain.


Input: Finally, no dermal toxicity of brucine was observed.

brucine


Input: The results of this study indicated that transdermal administration might be beneficial for the sustained efficacy and reduced toxicity of brucine.

brucine


Input: The vascular protective properties of kinsenoside isolated from Anoectochilus roxburghii under high glucose condition.

kinsenoside

glucose


Input: Anoectochilus roxburghii is a traditional Chinese herb used for the treatment of diabetes and some other diseases.


Input: The vascular protective effect of its major active ingredient, kinsenoside, in high glucose conditions was investigated in in vivo and in vitro experiments.

kinsenoside

glucose


Input: In in vivo tests, kinsenoside (50 and 100mg/kg) efficiently lowered blood glucose and cholesterol levels and it enhanced the oxidation resistance of diabetic mice induced by streptozotocin.

kinsenoside

glucose

cholesterol

streptozotocin


Input: In the in vitro assay, kinsenoside (20 and 50 mu g/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system.

kinsenoside

nitric oxide

NO

lactic

superoxide

glucose


Input: The vascular protective effects of kinsenoside were speculated to be attributed to oxidative stress inhibition and the reduction of nuclear factor kappa B (NF-kappa B) mRNA expression levels in high glucose conditions.

kinsenoside

glucose


Input: Moreover, histological examination, including hematoxylin-eosin (H & E) staining, masson trichrome (Masson) staining, and periodic Schiff-methenamine (PASM) staining, greatly supported the morphological and functional amelioration of diabetes-related changes in mice aortas after kinsenoside (20 and 50 mu g/mL) treatment.

hematoxylin

eosin

methenamine

kinsenoside


Input: These results indicated that kinsenoside might be a promising agent for the treatment of diabetic vascular disease.

kinsenoside


Input: The application of a DNA-based identification technique to over-the-counter herbal medicines.


Input: Reliable methods to identify medicinal plant material are becoming more important in an increasingly regulated market place.


Input: DNA-based methods have been recognised as a valuable tool in this area with benefits such as being unaffected by the age of the plant material, growth conditions and harvesting techniques.


Input: It is possible that the methods of production used for medicinal plant products will degrade or remove DNA.


Input: So how applicable are these techniques to processed medicinal plant products?


Input: A simple PCR-based identification technique has been developed for St.


Input: John' s Wort, Hypericum perforatum L.


Input: Thirteen St.


Input: John' s Wort products were purchased including capsules, tablets and tinctures.


Input: DNA was extracted from each product, and the species specific PCR test conducted.


Input: DNA was successfully extracted from all thirteen products, using a fast and efficient modified method for extracting DNA from tinctures.


Input: Only four products yielded the full length ITS region (850bp) due to the quality of the DNA.


Input: All of the products tested positive for H. perforatum DNA.


Input: DNA-based identification methods can complement existing methods of authentication.


Input: This paper shows that these methods are applicable to a wide range of processed products, provided that they are designed to account for the possibility of DNA degradation.


Input: Bioactive carbazole alkaloids from Murraya koenigii (L.) Spreng.

carbazole alkaloids


Input: Four new carbazole alkaloids (1-4) and fourteen known carbazole alkaloids (5-18) were isolated from Murraya koenigii.

carbazole alkaloids

carbazole alkaloids


Input: Their structures were elucidated on the basis of extensive spectroscopic analysis.


Input: Compounds 4, 6, 16, and 17 (10 mu M) had moderate hepatoprotective activities against d-galactosamine-induced HL-7702 cell damage.

d-galactosamine


Input: Compounds 11, 12 and 18 showed significant PTP1B inhibitory activity with IC50 values of 1. 773, 1. 875 and 2. 286 mu M, respectively.


Input: Curcumin attenuates allergic airway inflammation by regulation of CD4 (+) CD25 (+) regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice.

Curcumin


Input: The present study aimed to determine the protective effects and the underlying mechanisms of curcumin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma.

curcumin


Input: Asthma mice model was established by ovalbumin.


Input: A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2mg/kg), and curcumin (50mg/kg, 100mg/kg, 200mg/kg).

dexamethasone

curcumin


Input: Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright-Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Treg/Th17 cytokines were measured by enzyme-linked immunosorbent assay, Treg cells and Th17 cells were evaluated by flow cytometry (FCM).

hematoxylin

eosin


Input: Our study demonstrated that curcumin inhibited OVA-induced increases in eosinophil count; interleukin (IL)-17A level were recovered in bronchoalveolar lavage fluid increased IL-10 level in bronchoalveolar lavage fluid.

curcumin


Input: Histological studies demonstrated that curcumin substantially inhibited OVA-induced eosinophilia in lung tissue.

curcumin


Input: Flow cytometry (FCM) studies demonstrated that curcumin remarkably inhibited Th17 cells and significantly increased Treg cells.

curcumin


Input: The results in vivo show ovalbumin-induced significantly broke Treg/Th17 balance; curcumin treatments markedly attenuated the inflammatory in asthma model by regulating Treg/Th17 balance.

curcumin


Input: Our findings support the possible use of curcumin as a therapeutic drug for patients with allergic asthma.

curcumin


Input: Identification, assessment and management of " endocrine disruptors " in wildlife in the EU substance legislation-Discussion paper from the German Federal Environment Agency (UBA).


Input: A discussion paper was developed by a panel of experts of the German Federal Environment Agency (UBA) contributing to the on-going debate on the identification, assessment and management of endocrine disruptors with a view to protect wildlife according to the EU substance legislation (plant protection products, biocides, industrial chemicals).


Input: Based on a critical synthesis of the state-of-the-art regarding regulatory requirements, testing methods, assessment schemes, decision-making criteria and risk management options, we advise an appropriate and consistent implementation of this important subject into existing chemicals legislation in Europe.


Input: Our proposal for a balanced risk management of endocrine disruptors essentially advocates transparent regulatory decision making based on a scientifically robust weight of evidence approach and an adequate risk management consistent across different legislations.


Input: With respect to the latter, a more explicit consideration of the principle of proportionality of regulatory decision making and socio-economic benefits in the on-going debate is further encouraged.


Input: The C-Terminal Region of Cytoplasmic Polyadenylation Element Binding Protein Is a ZZ Domain with Potential for Protein-Protein Interactions.

C


Input: Cytoplasmic polyadenylation element binding protein (CPEB) provides temporal and spatial control of protein synthesis required for early development and neuronal synaptic plasticity.


Input: CPEB regulates protein expression by inhibiting polyadenylation of selected mRNA transcripts, which prevents binding of the ribosome for protein synthesis.


Input: Two RNA recognition motif domains and a C-terminal binuclear zinc-binding domain are required for mRNA binding, but the zinc-binding domain is not required for sequence-specific recognition of the targeted mRNA transcript.

C

zinc

zinc


Input: The structure and function of the zinc-binding domain of CPEB are unknown.

zinc


Input: The C-terminal region of CPEB may participate in assembly of the ribonucleoprotein complex that includes the scaffold protein, Symplekin, and the cleavage and polyadenylation specificity factor.

C


Input: Sumoylation of Symplekin is required for polyadenylation, and both cleavage and polyadenylation specificity factor and poly (A) polymerase are sumoylated.


Input: The foreshortened poly (A) tail is maintained by poly (A) ribonuclease, which associates with CPEB.


Input: While zinc-binding domains are renowned for nucleic acid recognition, binuclear zinc-binding structural motifs, such as LIM (Lin-11, Isl-1, Mec-3), RING (really interesting new gene), PHD (plant homeodomain) and ZZ (ZZ-type zinc finger) domains, participate in protein-protein interactions.

zinc

zinc

zinc


Input: Here, we report the solution structure of the C-terminal zinc-binding domain of CPEB1 (CPEB1-ZZ), which has a cross-braced zinc binding topology.

C

zinc

zinc


Input: The structural similarity to other ZZ domains suggests that the CPEB1-ZZ domain recruits sumoylated proteins during assembly of the ribonucleoprotein complex prior to mRNA export from the nucleus.


Input: Characterization of monomeric and multimeric snake neurotoxins and other bioactive proteins from the venom of the lethal Australian common copperhead (Austrelaps superbus).


Input: Envenomation by Australian copperheads results mainly in muscle paralysis largely attributed to the presence of postsynaptic alpha-neurotoxins.


Input: However, poorly reversible neurotoxic effects suggest that these venoms may contain snake presynaptic phospholipase A2 neurotoxins (SPANs) that irreversibly inhibit neurotransmitter release.


Input: Using size-exclusion liquid chromatography, the present study isolated the first multimeric SPAN complex from the venom of the Australian common copperhead, Austrelaps superbus.


Input: The multimeric SPAN P-elapitoxin-As1a (P-EPTX-As1a) along with two novel monomeric SPANs and a new postsynaptic alpha-neurotoxin were then pharmacologically characterized using the chick biventer cervicis nerve-muscle preparation.


Input: All SPANs inhibited nerve-evoked twitch contractions at the neuromuscular junction without inhibiting contractile responses to cholinergic agonists or KCl.

KCl


Input: These actions are consistent with a prejunctional action to inhibit neurotransmitter release, without direct myotoxicity.


Input: Furthermore, the multimeric P-EPTX-As1a caused tetanic' fade' in muscle tension under high frequency nerve stimulation, and produced a triphasic alteration to neurotransmitter release.


Input: These actions have been previously noted with other multimeric SPAN complexes such as taipoxin.


Input: Moreover, the neurotoxic alpha-subunit of P-EPTX-As1a shows high homology to taipoxin alpha-chain.