Molecularly imprinted polymers based stir bar sorptive extraction for determination of cefaclor and cefalexin in environmental water

Abstract

Although stir bar sportive extraction was thought to be a highly efficiency and simple pretreatment approach, its wide application was limited by low selectivity, short service life, and relatively high cost. In order to improve the performance of the stir bar, molecular imprinted polymers and magnetic carbon nanotubes were combined in the present study. In addition, two monomers were utilized to intensify the selectivity of molecularly imprinted polymers. Fourier transform infrared spectroscopy, scanning electron microscopy, and selectivity experiments showed that the molecularly imprinted polymeric stir bar was successfully prepared. Then micro-extraction based on the obtained stir bar was coupled with HPLC for determination of trace cefaclor and cefalexin in environmental water. This approach had the advantages of stir bar sportive extraction, high selectivity of molecular imprinted polymers, and high sorption efficiency of carbon nanotubes. To utilize this pretreatment approach, pH, extraction time, stirring speed, elution solvent, and elution time were optimized. The LOD and LOQ of cefaclor were found to be 3.5 ng · mL^–1 and 12.0 ng · mL^–1, respectively; the LOD and LOQ of cefalexin were found to be 3.0 ng · mL^–1 and 10.0 ng · mL^–1, respectively. The recoveries of cefaclor and cefalexin were 86.5 ~ 98.6%. The within-run precision and between-run precision were acceptable (relative standard deviation <7%). Even when utilized in more than 14 cycles, the performance of the stir bar did not decrease dramatically. This demonstrated that the molecularly imprinted polymeric stir bar based micro-extraction was a convenient, efficient, low-cost, and a specific method for enrichment of cefaclor and cefalexin in environmental samples.

http://ift.tt/2tfP7x9

In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone ( Haliotis rubra ) viscera hydrolysate

Abstract

Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti-coagulant activities. In this study, a hydrolysate was prepared from blacklip abalone (Haliotis rubra) viscera using papain and bromelain and fractionated using ion exchange and size exclusion chromatography. Hydrolysates and fractions were investigated for in vitro thrombin inhibition mediated through heparin cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5 μg/mL compared with 2.1 μg/mL for standard heparin. Fractionation concentrated HCII-mediated thrombin inhibition down to an IC50 of 1.8 μg/mL and improved anti-coagulant activities by significantly delaying clotting time. This study confirmed the presence of anti-thrombotic and anti-coagulant molecules in blacklip abalone viscera and demonstrated that these activities can be enriched with a simple chromatography regime. Blacklip abalone viscera warrant further investigation as a source of nutraceutical or functional food ingredients.

Graphical abstract

Schematic showing preparation of bioactive extracts and fractions from blacklip abalone

http://ift.tt/2si5TOJ

Solution to redox titration challenge

http://ift.tt/2siatMX

Optimization of an ultrasound-assisted derivatization for GC/MS analysis of oxygenated organic species in atmospheric aerosol

Abstract

A novel ultrasound-assisted derivatization followed by GC/MS analysis was developed for the quantification of oxygenated organic species in ambient aerosol. Derivatization parameters mostly influencing the analytical response were investigated, i.e., solvent type, reagent concentration, and reaction duration. Response surface methodology was used to design experiments and a quadratic model was utilized to predict the variables and establish the optimal conditions. The study was performed on standard solutions of 30 compounds representing the major classes of oxygenated compounds typically found in ambient aerosol, i.e., low molecular weight carboxylic acids, sugars, and phenols. In comparison with conventional methods, the optimized procedure uses mild reaction temperature (room temperature instead of 70 °C), reduces the amount of silyl reagent (24 vs. 40 μL), and shortens derivatization times (45 vs. 70 min), participating in the current trend of analytical chemistry towards clean, green methods that reduce costs and decrease pollution. Once optimized, the ultrasound procedure was validated by assessing for repeatability, linearity, detection limits, and derivative stability. For all oxygenated organic species, the proposed method showed a good reproducibility—as the relative standard deviations (RSDs%, n = 5) of intra-day analysis were ≤7% — a good linearity with the correlation coefficients of calibration curves R ² ≥ 99.8, and low detection limits, ranging from 0.34 to 6.50 ng μL⁻¹; thus it is suitable for its applicability in air quality monitoring. Finally, this method was successfully applied to determine 30 oxygenated organic species in three ambient PM_2.5 samples collected at an urban site in Northern Italy in three different seasons.

Graphical abstract

Ultrasound-assisted derivatization is a green alternative method for GC/MS analysis of oxygenated organic species in atmospheric aerosol towards reduction of energy and reactive consumption.

http://ift.tt/2tfHiHJ

Cobalt oxyhydroxide nanoflakes with intrinsic peroxidase catalytic activity and their application to serum glucose detection

Abstract

Cobalt oxyhydroxide (CoOOH) nanoflakes, an emerging type of two-dimensional nanomaterial, show great potential for use in molecular detection. Previous assays utilizing such materials have largely been based on their outstanding fluorescence quenching ability and oxidizing power. Herein, we report the intrinsic peroxidase-like activity of cobalt oxyhydroxide (CoOOH) nanoflakes, and we show how this activity can be employed for glucose detection. We found that, in the presence of hydrogen peroxide (H₂O₂), the nanoflakes accelerated the conversion of peroxidase substrates such as 3,3′,5,5′-tetramethylbenzidine (TMB) into colored products. By combining the CoOOH nanoflakes with the biological enzyme glucose oxidase (GOx), we developed a colorimetric method for the detection of glucose within the concentration range 5.3–500 μM. The proposed method was applied to detect elevated blood glucose levels in diabetic patients, and the intense color change induced by elevated glucose levels was found to be readily apparent to the naked eye, proving the utility of our assay for point-of-care testing.

Graphical abstract

The intrinsic peroxidase-like activity of cobalt oxyhydroxide (CoOOH) nanoflakes was exploited to enable the direct visualization of elevated glucose levels in sera from diabetic patients

http://ift.tt/2tfzFkH

Dual-mode immunoassay based on shape code and infrared absorption fingerprint signals of silica nanorods

Abstract

Silica nanorods were synthesized through a simple one-pot emulsion-droplet-based growth method, in which tetraethylorthosilicate (TEOS) was used as the silica source, ammonia as the catalyst, and polyvinylpyrrolidone (PVP) as the structure-directing agent and stabilizer. By controlling hydrolysis and condensation in the reaction process, we regulated the aspect ratios and the infrared (IR) absorption fingerprint signals (the transverse optical and the longitudinal optical phonon modes) of the silica nanorods. Based on this, a dual-mode immunoassay was performed for detecting model target analyte, human IgG. The shape code of the silica nanorods was used for simple, rapid qualitative, and sensitive semi-quantitative immunoassay by using a conventional optical microscope. The characteristic IR absorption fingerprint signals of the silica nanorods allowed for reliable quantitative immunoassay with good selectivity and high specificity. The detection limit and the linear range were found out to be 0.5 pM and 1 pM–10 nM, respectively. We expect that such dual-mode immunoassay could be applied for the detection of other analytes, such as protein, nucleic acids, bacteria, viruses, explosives, toxins, and so on.

Graphical abstract

A simple dual-mode immunoassay was performed using the shape code and infrared absorption fingerprint signals of silica nanorods as detection signals.

http://ift.tt/2tfsh8D

Design and development of amperometric biosensor for the detection of lead and mercury ions in water matrix—a permeability approach

Abstract

Intake of water contaminated with lead (Pb²⁺) and mercury (Hg²⁺) ions leads to various toxic effects and health issues. In this context, an amperometric urease inhibition-based biosensor was developed to detect Pb²⁺ and Hg²⁺ ions in water matrix. The modified Pt/CeO₂/urease electrode was fabricated by immobilizing CeO₂ nanoparticles and urease using a semi-permeable adsorption layer of nafion. With urea as a substrate, urease catalytic activity was examined through cyclic voltammetry. Further, maximum amperometric inhibitive response of the modified Pt/CeO₂/urease electrode was observed in the presence of Pb²⁺ and Hg²⁺ ions due to the urease inhibition at specific potentials of −0.03 and 0 V, respectively. The developed sensor exhibited a detection limit of 0.019 ± 0.001 μM with a sensitivity of 89.2 × 10⁻³ μA μM⁻¹ for Pb²⁺ ions. A detection limit of 0.018 ± 0.003 with a sensitivity of 94.1 × 10⁻³ μA μM⁻¹ was achieved in detecting Hg²⁺ ions. The developed biosensor showed a fast response time (<1 s) with a linear range of 0.5–2.2 and 0.02–0.8 μM for Pb²⁺ and Hg²⁺ ions, respectively. The modified electrode offered a good stability for 20 days with a good repeatability and reproducibility. The developed sensor was used to detect Pb²⁺ and Hg²⁺ ions contaminating Cauvery river water and the observed results were in good co-ordination with atomic absorption spectroscopic data.

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European analytical column number 45

http://ift.tt/2shPgmi

Pink tea challenge

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Rapid electrochemical quantification of Salmonella Pullorum and Salmonella Gallinarum based on glucose oxidase and antibody-modified silica nanoparticles

Abstract

In this article, a facile and sensitive electrochemical method for quantification of Salmonella Pullorum and Salmonella Gallinarum (S. Pullorum and S. Gallinarum) was established by monitoring glucose consumption with a personal glucose meter (PGM). Antibody-functionalized magnetic nanoparticles (IgG-MNPs) were used to capture and enrich S. Pullorum and S. Gallinarum, and IgG-MNPs-S. Pullorum and IgG-MNPs-S. Gallinarum complexes were magnetically separated from a sample using a permanent magnet. The trace tag was prepared by loading polyclonal antibodies and high-content glucose oxidase on amino-functionalized silica nanoparticles (IgG-SiNPs-GOx). With a sandwich-type immunoassay format, IgG-SiNPs-GOx were added into the above mixture solution and conjugated to the complexes, forming sandwich composites IgG-MNPs/S. Pullorum and S. Gallinarum/IgG-SiNPs-GOx. The above sandwich composites were dispersed in glucose solution. Before and after the hydrolysis of glucose, the concentration of glucose was measured using PGM. Under optimal conditions, a linear relationship between the decrease of glucose concentration and the logarithm of S. Pullorum and S. Gallinarum concentration was obtained in the concentration range from 1.27 × 10² to 1.27 × 10⁵ CFU mL⁻¹, with a detection limit of 7.2 × 10¹ CFU mL⁻¹ (S/N = 3). This study provides a portable, low-cost, and quantitative analytical method for bacteria detection; thus, it has a great potential in the prevention of disease caused by S. Pullorum and S. Gallinarum in poultry.

Graphical abstract

A schematic illustration of the fabrication process of IgG-SiNPs-GOD nanomaterials (A) and IgG-MNPs (B) and experimental procedure of detection of S. Pullorum and S. Gallinarum using GOD-functionalized silica nanospheres as trace tags based on PGM (C).

http://ift.tt/2siassn

Infrared laser ablation sample transfer of tissue DNA for genomic analysis

Abstract

Infrared (IR) laser ablation was used to remove material from tissue sections mounted on microscope slides, with subsequent capture in a solvent-containing microcentrifuge tube. Experiments conducted with a 3200-bp double-stranded plasmid DNA template demonstrated IR-laser ablation transfer of intact DNA. The transfer efficiency and the molecular integrity of the captured DNA were evaluated using Sanger sequencing, gel electrophoresis, and fluorimetric analysis. The plasmid DNA was reproducibly transferred with an efficiency of 59 ± 3% at laser fluences of between 10 and 20 kJ/m² at a wavelength of 3 μm. IR laser ablation sample transfer was then used to ablate and capture DNA from 50-μm-thick rat brain and kidney tissue sections. DNA was extracted from the captured material using five commercial DNA extraction kits that employed significantly divergent methodologies, with all kits recovering sufficient DNA for successful amplification by polymerase chain reaction (PCR). Four sets of primers were employed, targeting one region of the CYP 11b2 gene (376 bp) and three different regions of the Snn1g gene (298, 168, and 281 bp). The PCR results were not consistently reliable when using unpurified ablation samples; however, after extraction, all samples produced PCR products of the expected size. This work expands the sampling capabilities of IR laser ablation, demonstrating that DNA can be isolated from tissue samples for genomic assays. Due to the small size of the ablation regions (1 mm²), this technique will be useful for sampling discrete cell populations from tissue sections.

Graphical abstract

Infrared laser ablation transfer of intact DNA from a tissue section.

http://ift.tt/2si2WxY

Complexation-mediated electromembrane extraction of highly polar basic drugs—a fundamental study with catecholamines in urine as model system

Abstract

Complexation-mediated electromembrane extraction (EME) of highly polar basic drugs (log P < −1) was investigated for the first time with the catecholamines epinephrine, norepinephrine, and dopamine as model analytes. The model analytes were extracted as cationic species from urine samples (pH 4), through a supported liquid membrane (SLM) comprising 25 mM 4-(trifluoromethyl)phenylboronic acid (TFPBA) in bis(2-ethylhexyl) phosphite (DEHPi), and into 20 mM formic acid as acceptor solution. EME was performed for 15 min, and 50 V was used as extraction voltage across the SLM. TFPBA served as complexation reagent, and selectively formed boronate esters by reversible covalent binding with the model analytes at the sample/SLM interface. This enhanced the mass transfer of the highly polar model analytes across the SLM, and EME of basic drugs with log P in the range −1 to −2 was shown for the first time. Meanwhile, most matrix components in urine were unable to pass the SLM. Thus, the proposed concept provided highly efficient sample clean-up and the system current across the SLM was kept below 50 μA. Finally, the complexation-mediated EME concept was combined with ultra-high performance liquid chromatography coupled to tandem mass spectrometry and evaluated for quantification of epinephrine and dopamine. Standard addition calibration was applied to a pooled human urine sample. Calibration curves using standards between 25 and 125 μg L⁻¹ gave a high level of linearity with a correlation coefficient of 0.990 for epinephrine and 0.996 for dopamine (N = 5). The limit of detection, calculated as three times signal-to-noise ratio, was 5.0 μg L⁻¹ for epinephrine and 1.8 μg L⁻¹ for dopamine. The repeatability of the method, expressed as coefficient of variation, was 13% (n = 5). The proposed method was finally applied for the analysis of spiked pooled human urine sample, obtaining relative recoveries of 91 and 117% for epinephrine and dopamine, respectively.

http://ift.tt/2shZRxE

High-throughput analysis of sub-visible mAb aggregate particles using automated fluorescence microscopy imaging

Abstract

Aggregation of therapeutic proteins is a major concern as aggregates lower the yield and can impact the efficacy of the drug as well as the patient's safety. It can occur in all production stages; thus, it is essential to perform a detailed analysis for protein aggregates. Several methods such as size exclusion high-performance liquid chromatography (SE-HPLC), light scattering, turbidity, light obscuration, and microscopy-based approaches are used to analyze aggregates. None of these methods allows determination of all types of higher molecular weight (HMW) species due to a limited size range. Furthermore, quantification and specification of different HMW species are often not possible. Moreover, automation is a perspective challenge coming up with automated robotic laboratory systems. Hence, there is a need for a fast, high-throughput-compatible method, which can detect a broad size range and enable quantification and classification. We describe a novel approach for the detection of aggregates in the size range 1 to 1000 μm combining fluorescent dyes for protein aggregate labelling and automated fluorescence microscope imaging (aFMI). After appropriate selection of the dye and method optimization, our method enabled us to detect various types of HMW species of monoclonal antibodies (mAbs). Using 10 μmol L⁻¹ 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonate (Bis-ANS) in combination with aFMI allowed the analysis of mAb aggregates induced by different stresses occurring during downstream processing, storage, and administration. Validation of our results was performed by SE-HPLC, UV-Vis spectroscopy, and dynamic light scattering. With this new approach, we could not only reliably detect different HMW species but also quantify and classify them in an automated approach. Our method achieves high-throughput requirements and the selection of various fluorescent dyes enables a broad range of applications.

http://ift.tt/2tfsgS7

A new carbon-based magnetic material for the dispersive solid-phase extraction of UV filters from water samples before liquid chromatography–tandem mass spectrometry analysis

Abstract

Magnetic solid-phase extraction is one of the most promising new extraction methods for liquid samples before ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) analysis. Several types of materials, including carbonaceous ones, have been prepared for this purpose. In this paper, for the first time, the preparation, characterization, and sorption capability of Fe₃O₄-graphitized carbon black (mGCB) composite toward some compounds of environmental interest were investigated. The synthesized mGCB consisted of micrometric GCB particles with 55 m² g⁻¹ surface area bearing some carbonyl and hydroxyl functionalities and the surface partially decorated by Fe₃O₄ microparticles. The prepared mGCB was firstly tested as an adsorbent for the extraction from surface water of 50 pollutants, including estrogens, perfluoroalkyl compounds, UV filters, and quinolones. The material showed good affinity to many of the tested compounds, except carboxylates and glucoronates; however, some compounds were difficult to desorb. Ten UV filters belonging to the chemical classes of benzophenones and p-aminobenzoates were selected, and parameters were optimized for the extraction of these compounds from surface water before UHPLC–MS/MS determination. Then, the method was validated in terms of linearity, trueness, intra-laboratory precision, and detection and quantification limits. In summary, the method performance (trueness, expressed as analytical recovery, 85–114%; RSD 5–15%) appears suitable for the determination of the selected compounds at the level of 10–100 ng L⁻¹, with detection limits in the range of 1–5 ng L⁻¹. Finally, the new method was compared with a published one, based on conventional solid-phase extraction with GCB, showing similar performance in real sample analysis.

Graphical Abstract

Workflow of the analytical method based on magnetic solid-phase extraction followed by LC-MS/MS determination

http://ift.tt/2shOea0

Analysis of cellular autofluorescence in touch samples by flow cytometry: implications for front end separation of trace mixture evidence

Abstract

The goal of this study was to survey optical and biochemical variation in cell populations deposited onto a surface through touch or contact and identify specific features that may be used to distinguish and then sort cell populations from separate contributors in a trace biological mixture. Although we were not able to detect meaningful biochemical variation in touch samples deposited by different contributors through preliminary antibody surveys, we did observe distinct differences in red autofluorescence emissions (650–670 nm), with as much as a tenfold difference in mean fluorescence intensities observed between certain pairs of donors. Results indicate that the level of red autofluorescence in touch samples can be influenced by a donor's contact with specific material prior to handling the substrate from which cells were collected. In particular, we observed increased red autofluorescence in cells deposited subsequent to handling laboratory gloves, plant material, and certain types of marker ink, which could be easily visualized microscopically or using flow cytometry, and persisted after hand washing. To test whether these observed optical differences could potentially be used as the basis for a cell separation workflow, a controlled two-person touch mixture was separated into two fractions via fluorescence-activated cell sorting (FACS) using gating criteria based on intensity of 650–670 nm emissions and then subjected to DNA analysis. Genetic analysis of the sorted fractions provided partial DNA profiles that were consistent with separation of individual contributors from the mixture suggesting that variation in autofluorescence signatures, even if driven by extrinsic factors, may nonetheless be a useful means of isolating contributors to some touch mixtures.

Graphical Abstract

Conceptual workflow diagram. Trace biological mixtures containing cells from multiple individuals are analyzed by flow cytometry. Cells are then physically separated into two populations based on intensity of red autofluorescence using Fluorescence Activated Cell Sorting. Each isolated cell fraction is subjected to DNA analysis resulting in a DNA profile for each contributor.

http://ift.tt/2rpHYsP

Estimation of respiratory volume from thoracoabdominal breathing distances: comparison of two models of machine learning

Abstract

Purpose

The purposes of this study were to both improve the accuracy of respiratory volume (V) estimates using the respiratory magnetometer plethysmography (RMP) technique and facilitate the use of this technique.

Method

We compared two models of machine learning (ML) for estimating \(\widehat{V}_\mathrm{RMP}\) : a linear model (multiple linear regression—MLR) and a nonlinear model (artificial neural network—ANN), and we used cross-validation to validate these models. Fourteen healthy adults, aged \(24.1 \pm 3.4\) years participated in the present study. The protocol was conducted in a laboratory test room. The anteroposterior displacements of the rib cage and abdomen, and the axial displacements of the chest wall and spine were measured using two pairs of magnetometers. \(\widehat{V}_\mathrm{RMP}\) was estimated from these four signals, and the respiratory volume was simultaneously measured using a spirometer ( \(V_\mathrm{SP}\) ) under lying, sitting and standing conditions as well as various exercise conditions (working on computer, treadmill walking at 4 and 6 km \(\mathrm{ \ h}^{-1}\) , treadmill running at 9 and 12  km \(\mathrm{ \ h}^{-1}\) and ergometer cycling at 90 and 110 W).

Results

The results from the ANN model fitted the spirometer volume significantly better than those obtained through MLR. Considering all activities, the difference between \(\widehat{V}_\mathrm{RMP}\) and \(V_\mathrm{SP}\) (bias) was higher for the MLR model ( \(0.00191 \pm 0.141\) L) than for the ANN model ( \(0.00158 \pm 0.150\) L).

Conclusion

Our results demonstrate that this new processing approach for RMP seems to be a valid tool for estimating V with sufficient accuracy during lying, sitting and standing and under various exercise conditions.

http://ift.tt/2rpJs6g

Quality Colorectal Cancer Screening: Endoscopic Performance Measures and Beyond

Abstract

Purpose of Review

The rationale behind and implementation of quality measures around colonoscopy for colorectal (CRC) screening are important topics for endoscopists to understand to deliver exemplary care with the goal of decreasing the incidence of this disease. This article will evaluate recent data on this subject and summarize pertinent findings in the growing field of quality improvement research surrounding colonoscopy for CRC screening.

Recent Findings

Both pre- and intra-procedural metrics have been studied across a variety of practice models and patient populations. Contemporary metrics include adequate bowel preparation, cecal intubation rate, adenoma detection rate, polypectomy rate, proximal serrated polyp detection rate, withdrawal time, and patient satisfaction.

Summary

Multiple quality metrics have been formally evaluated regarding colonoscopy, and others have recently been proposed. Additional validation is necessary to determine which quality metrics serve as practical and implementable to improve endoscopic performance and overall delivery of care.

http://ift.tt/2smKepH

New Cantharellus species from the Republic of Korea

Abstract

In this first contribution on the genus Cantharellus in Korea, two new species are described. Cantharellus koreanus sp. nov. is extremely similar and closely related to the American C. appalachiensis, a species of subg. Parvocantharellus, while C. albovenosus sp. nov. is a new member of subg. Cinnabarinus and closely related to the Chinese C. phloginus. The new taxa are molecularly supported by phylogenetic analysis of sequences from the transcription elongation factor (TEF-1).

http://ift.tt/2rcp4GB

Quantitative Temporal Viromics of an Inducible HIV-1 Quantitative temporal viromics of an inducible HIV-1 model yields insight to global host targets and phospho-dynamics associated with Vpr [Research]

The mechanisms by which human immunodeficiency virus (HIV) circumvents and coopts cellular machinery to replicate and persist in cells are not fully understood. HIV accessory proteins play key roles in the HIV life cycle by altering host pathways that are often dependent on post-translational modifications (PTMs). Thus, the identification of HIV accessory protein host targets and their PTM status is critical to fully understand how HIV invades, avoids detection and replicates to spread infection. To date, a comprehensive characterization of HIV accessory protein host targets and modulation of their PTM status does not exist. The significant gap in knowledge regarding the identity and PTMs of HIV host targets is due, in part, to technological limitations. Here, we applied current mass spectrometry techniques to define mechanisms of viral protein action by identifying host proteins whose abundance is affected by the accessory protein Vpr and the corresponding modulation of down-stream signaling pathways, specifically those regulated by phosphorylation. By utilizing a novel, inducible HIV-1 CD4+ T-cell model system expressing either the wild type or a vpr-negative viral genome, we overcame challenges associated with synchronization and infection-levels present in other models. We report identification and abundance dynamics of over 7,000 proteins and 28,000 phospho-peptides. Consistent with Vprs ability to impair cell-cycle progression, we observed Vpr-mediated modulation of spindle and centromere proteins, as well as Aurora kinase A and cyclin-dependent kinase 4 (CDK4). Unexpectedly, we observed evidence of Vpr-mediated modulation of the activity of serine/arginine-rich protein-specific kinases (SRPKs), suggesting a possible role for Vpr in the regulation of RNA splicing. This study presents a new experimental system and provides a data-resource that lays the foundation for validating host proteins and phosphorylation-pathways affected by HIV-1 and its accessory protein Vpr.

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Editorial for EAIT Issue 4, 2017

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“It must not disturb, it’s as simple as that”: Students’ voices on mobile phones in the infrastructure for learning in Swedish upper secondary school

Abstract

Drawing from a survey and focus group interviews, this study explores how Swedish upper secondary students reason about the usage of their personal mobile phones in school. As a contribution to the debate around the mobile phone’s role in school, we present the students’ own voices relative to the question of regulating mobile phone use. We use the notion of infrastructure for learning (Guribye and Lindström 2009) to analytically approach the social and technological dimensions of the students’ narratives on their use of mobile phones in school practice. The students’ narratives present an intricate account of students’ awareness and concern of the implications of mobile phone presence in school. The students describe that the mobile phone is both a tool that facilitates their school work and a distraction that the teachers pursue. In school, the students are balancing their mobile phone usage with the teachers’ arbitrary enforcement of policy. Despite this process, the mobile phone is becoming a resource in the students’ infrastructure for learning. The findings from this study add to the limited body of research on the use of mobile phone in upper secondary school from a student perspective.

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Wnt3a Induces the Expression of Acetylcholinesterase during Osteoblast Differentiation via the Runx2 Transcription Factor [Cell Biology]

Acetylcholinesterase (AChE) hydrolyzes acetylcholine to terminate cholinergic transmission in neurons. Apart from this AChE activity, emerging evidence suggests that AChE could also function in other, nonneuronal cells. For instance, in bone, AChE exists as a proline-rich membrane anchor (PRiMA)-linked globular form in osteoblasts, in which it is proposed to play a noncholinergic role in differentiation. However, this hypothesis is untested. Here, we found that in cultured rat osteoblasts, AChE expression was increased in parallel with osteoblastic differentiation. Because several lines of evidence indicate that AChE activity in osteoblast could be triggered by Wnt/β-catenin signaling, we added recombinant human Wnt3a to cultured osteoblasts and found that this addition induced expression of the ACHE gene and protein product. This Wnt3a-induced AChE expression was blocked by the Wnt-signaling inhibitor Dickkopf protein-1 (DKK-1). We hypothesized that the Runt-related transcription factor 2 (Runx2), a downstream transcription factor in Wnt/β-catenin signaling, is involved in AChE regulation in osteoblasts, confirmed by the identification of a Runx2-binding site in the ACHE gene promoter, further corroborated by ChIP. Of note, Runx2 overexpression in osteoblasts induced AChE expression and activity of the ACHE promoter tagged with the luciferase gene. Moreover, deletion of the Runx2-binding site in the ACHE promoter reduced its activity during osteoblastic differentiation, and addition of 5-azacytidine (5-Aza) and trichostatin A (TSA) to differentiating osteoblasts affected AChE expression, suggesting epigenetic regulation of the ACHE gene. We conclude that AChE plays a role in osteoblastic differentiation and is regulated by both Wnt3a and Runx2.

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The transcriptional co-repressor TLE3 regulates myogenic differentiation by repressing the activity of the MyoD transcription factor [Gene Regulation]

Satellite cells are skeletal muscle stem cells that provide myonuclei for postnatal muscle growth, maintenance, and repair/regeneration in adults. Normally, satellite cells are mitotically quiescent, but they are activated in response to muscle injury, in which case they proliferate extensively and exhibit upregulated expression of the transcription factor MyoD, a master regulator of myogenesis. MyoD forms a heterodimer with E proteins through their basic helix-loophelix (bHLH) domain, binds to E boxes in the genome, and thereby activates transcription at muscle-specific promoters. MyoD's central role in muscle differentiation has increased interest in finding potential MyoD regulators. Here, we identified transducin-like enhancer of split (TLE3), one of the Groucho/TLE family members, as a regulator of MyoD function during myogenesis. TLE3 was expressed in activated and proliferative satellite cells in which increased TLE3 levels suppressed myogenic differentiation and, conversely, reduced TLE3 levels promoted myogenesis with a concomitant increase in proliferation. We found that, via its Q and SP domains, TLE3 interferes with MyoD function by disrupting the association between the bHLH domain of MyoD and E proteins. Our findings indicate that TLE3 participates in skeletal muscle homeostasis by dampening satellite cell differentiation via repression of MyoD transcriptional activity.

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Loss of the clock protein PER2 shortens the erythrocyte life span in mice [Signal Transduction]

Cell proliferation and release from the bone marrow have been demonstrated to be controlled by circadian rhythms in both humans and mice. However, it is unclear whether local circadian clocks in the bone marrow influence physiological functions and life span of erythrocytes. Here, we report that loss of the clock gene Per2 significantly decreased erythrocyte life span. Mice deficient in Per2 were more susceptible to acute stresses in the erythrocytes, becoming severely anemic upon phenylhydrazine, osmotic, and H2O2 challenges. 1H NMR-based metabolomics analysis revealed that the Per2 depletion causes significant changes in metabolic profiles of erythrocytes, including increased lactate and decreased ATP levels compared with wild-type mice. The lower ATP levels were associated with hyperfunction of Na+/K+-ATPase activity in Per2-null erythrocytes, and inhibition of Na+/K+-ATPase activity by ouabain efficiently rescued ATP levels. Per2-null mice displayed increased levels of Na+/K+-ATPase α1 (ATP1A1) in the erythrocyte membrane, and transfection of Per2 cDNA into the erythroleukemic cell line TF-1 inhibited Atp1a1 expression. Furthermore, we observed that PER2 regulates Atp1a1 transcription through interacting with trans-acting transcription factor 1 (SP1). Our findings reveal that Per2 function in the bone marrow is required for the regulation of lifespan in circulating erythrocytes.

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Polycomb repressive complex 2 in an autoinhibited state [Enzymology]

Polycomb-group proteins control many fundamental biological processes, such as anatomical development in mammals and vernalization in plants. Polycomb repressive complex 2 (PRC2) is responsible for methylation of histone H3 lysine 27 (H3K27), and trimethylated H3K27 (H3K27me3) is implicated in epigenetic gene silencing. Recent genomic, biochemical, and structural data indicate that PRC2 is broadly conserved from yeast to human in many aspects. Here, we determined the crystal structure of an apo PRC2 from the fungus Chaetomium thermophilum captured in a bona fide autoinhibited state, which represents a novel conformation of PRC2 associated with enzyme regulation in light of the basal and stimulated states that we reported previously. We found that binding by the cofactor SAM mitigates this autoinhibited structural state. Using steady-state enzyme kinetics, we also demonstrated that disrupting the autoinhibition results in a vastly activated enzyme complex. Autoinhibition provides a novel structural platform that may enable control of PRC2 activity in response to diverse transcriptional states and chromatin contexts and set a ground state to allow PRC2 activation by other cellular mechanisms as well.

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Autophagy downstream of endosomal Toll-like Receptors Signaling in Macrophages is a Key Mechanism for Resistance to Leishmania major Infection [Molecular Bases of Disease]

Leishmaniasis is caused by protozoan parasites of the genus Leishmania. In mammalians, these parasites survive and replicate in macrophages and parasite elimination by macrophages is critical for host resistance. Endosomal Toll-like receptors (TLRs) have been shown to be crucial for resistance to L. major in vivo. For example, mice in the resistant C57BL/6 genetic background that are triple-deficient for TLR3, -7 and -9 (Tlr3/7/9-/-) are highly susceptible to L. major infection. Tlr3/7/9-/- mice are as susceptible as mice deficient in MyD88 or UNC93B1, a chaperone required for appropriate localization of endosomal TLRs, but the mechanisms are unknown. Here we found that macrophages infected with L. major undergo autophagy, which effectively accounted for restriction of parasite replication. Signaling via endosomal TLRs was required for autophagy because macrophages deficient for TLR3, -7 and 9, UNC93B1 or MyD88 failed to undergo L. major-induced autophagy. We also confirmed that Myd88-/-, Tlr3/7/9-/-, and Unc93b1-/- cells were highly permissive to L. major replication. Accordingly, shRNA-mediated suppression of Atg5, an E3 ubiquitin ligase essential for autophagosome elongation, in macrophages impaired the restriction of L. major replication in C57BL/6, but did not affect parasite replication in Myd88-/- or Unc93b1-/- macrophages. Rapamycin treatment reduced inflammatory lesions formed in the ears of Leishmania-infected C57BL/6 and Tlr3/7/9-/- mice, indicating that autophagy operates downstream of TLR signaling and is relevant for disease development in vivo. Collectively, our results indicate that autophagy contributes to macrophage resistance to L. major replication, and mechanistically explain the previously described endosomal TLR mediated resistance to L. major infection.

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Auslagen

Die im Rahmen von Eingriffen und Operationen anfallenden Material- und Sachkosten werden in der Gebührenordnung für Ärzte (GOÄ) unterschiedlich behandelt. Der Beitrag klärt auf, welche Auslagen in welcher Form abrechenbar sind.

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Wischen statt blättern!

Was Sie gerade auf Papier gedruckt in den Händen halten, könnten Sie auch online auf Ihrem Tablet lesen, denn ab sofort gibt es Ihre „ästhetische dermatologie & kosmetologie" auch als ePaper: Es steht auf SpringerMedizin.de, dem Fachportal für Ärzte, kostenlos zum Download bereit. Dort finden Sie auch das Archiv der Zeitschrift und noch vieles mehr ...

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Molekulare Diagnostik entzündlicher Dermatosen

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Die neue Medizinprodukteverordnung EU

Spürbare Veränderungen gibt es derzeit im Medizinprodukterecht. Die Europäische Union hat mit der EU-Medizinprodukteverordnung 2017 (MDR) das Rechtsgebiet in wesentlichen Teilen novelliert. Betroffen von den Neuerungen sind in erster Linie die Hersteller von Medizinprodukten. Aber auch Anwender von Medizinprodukten, so auch niedergelassene Ärzte, die in ihrer Praxis Medizinprodukte zum Einsatz bringen, sollten über die neuen Regelungen Bescheid wissen.

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Zwischendurch bemerkt

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Narben wirksam behandeln

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Hautberuhigendes Reinigungserlebnis für Gesicht und Körper

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Ekzemen und Pickeln die Stirn bieten

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Dermatologen trafen sich zum zweiten Mal im CityCube in Berlin

Ende April 2017 fand die 49. Tagung der Deutschen Dermatologischen Gesellschaft (DDG) in Berlin statt. Die Vielzahl der vorgetragenen Themen und die Beteiligung zahlreicher Arbeitsgemeinschaften spiegelt die im Fachbereich vorhandene Innovationskraft wider. Eine Zusammenfassung über neue Ansätze bei der Behandlung der Psoriasis, die Lasertherapie beim malignen Melanom, die Fortschritte in der molekularen Diagnostik entzündlicher Erkrankungen sowie die Möglichkeiten und Grenzen der Off-Label-Medikation lesen Sie im folgenden Kongressbericht.

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Ästhetik-Konzept zur Verbesserung der Hautqualität

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Verbesserung in der Therapie von Krampfaderleiden

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Schutz vor UV-Strahlung lässt sich offenbar schlucken

Schlucken statt cremen: Karotinoide, wie sie in Tomaten und Grünkohl enthalten sind, schützen die Haut laut Ergebnissen einer Studie womöglich vor Schäden durch Sonnenlicht.

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Photodermatologie

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Ungleichgewicht im Mikrobiom

Mikrobiome sind beste Beispiele für gelungene Symbiosen — solang sich kein einzelnes Mitglied der Gemeinschaft in den Vordergrund drängt. Denn dann können sich bis dahin harmlose Kommensalen der Haut zu pathogenen Keimen aufschaukeln und Krankheiten wie Akne oder atopische Dermatitis begünstigen.

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Inhaltsverzeichnis

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Therapien jenseits der Zulassung

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Hyaluronidase unterstützt die Lokalanästhesie

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Supermodels verkörpern Typwandel

Der Modefotograf Peter Lindbergh richtete als Erster den Fokus auf die Persönlichkeit seiner Modelle: Statt menschlicher „Kleiderständer" zeigte er selbstbewusste, ausdrucksstarke Frauen und begründete damit das Supermodels-Phänomen der 1990er-Jahre. Sein ikonisches Werk in Bild und Film ist bis 27. August 2017 in der Kunsthalle München zu sehen.

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„Treat-to-target“ bei Psoriasis?

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Fraktioniertes Radiofrequenz-Microneedling

Die anspruchsvolle ästhetische Klientel von heute wünscht sich zur Hautverschönerung weitgehend schmerzfreie Behandlungen ohne große Nebenwirkungen oder lange Downtime, aber mit deutlich sichtbarem Ergebnis. Entsprechend steht der ästhetisch tätige Dermatologe heute vor der Qual der Wahl aus mehreren hunderten Laser-, IPL- und Radiofrequenz-Geräten, die am Markt zur nicht invasiven Hautverbesserung angeboten werden.

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Uneven cerebral hemodynamic change as a cause of neurological deterioration in the acute stage after direct revascularization for moyamoya disease: cerebral hyperperfusion and remote ischemia caused by the ‘watershed shift’

Abstract

Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard surgical treatment for moyamoya disease (MMD). The main potential complications of this treatment are cerebral hyperperfusion (CHP) syndrome and ischemia, and their managements are contradictory to each other. We retrospectively investigated the incidence of the simultaneous manifestation of CHP and infarction after surgery for MMD. Of the 162 consecutive direct revascularization surgeries performed for MMD, we encountered two adult cases (1.2%) manifesting the simultaneous occurrence of symptomatic CHP and remote infarction in the acute stage. A 47-year-old man initially presenting with infarction developed CHP syndrome (aphasia) 2 days after left STA-MCA anastomosis, as assessed by quantitative single-photon emission computed tomography (SPECT). Although lowering blood pressure ameliorated his symptoms, he developed cerebral infarction at a remote area in the acute stage. Another 63-year-old man, who initially had progressing stroke, presented with aphasia due to focal CHP in the left temporal lobe associated with acute infarction at the tip of the left frontal lobe 1 day after left STA-MCA anastomosis, when SPECT showed a paradoxical decrease in cerebral blood flow (CBF) in the left frontal lobe despite a marked increase in CBF at the site of anastomosis. Symptoms were ameliorated in both patients with the normalization of CBF, and there were no further cerebrovascular events during the follow-up period. CHP and cerebral infarction may occur simultaneously not only due to blood pressure lowering against CHP, but also to the 'watershed shift' phenomenon, which needs to be elucidated in future studies.

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Vertebral artery and osseous anomalies characteristic at the craniocervical junction diagnosed by CT and 3D CT angiography in normal Czech population: analysis of 511 consecutive patients

Abstract

There are numerous indications for stabilization using instrumentation of the upper cervical spine. This area is comprised of sophisticated anatomy. There is no study describing bony and vascular anomalies of this area in the middle European population. The main aim of this study was to investigate prevalence of any vertebral artery (VA) variations and osseous anomalies in the region of the craniocervical junction in a large sample of Czech patients based on three-dimensional computed tomographic angiography (3D CTA). The VA has a variable course through C2 before it passes above its groove on the posterior arch of C1. The artery can course more medially, more posteriorly or more superiorly, thus limiting the diameter of the bony elements used as landmarks for the safe insertion of metalwork. This is known as a high-riding VA (HRVA). The VA was considered HRVA in this study if the thickness of the C2 isthmus was less than 5 mm and/or the C2 internal height was less than 2 mm and/or the width of the C2 pedicle was less than 4 mm. The prevalence of ponticulus posticus (PP) was also identified. Following the VA variations in the V3 segment of the artery were persistent first intersegmental artery (FIA), fenestration (FEN) of the VA, and the posterior inferior cerebellar artery (PICA) branch originating from the C1/2 part of VA. Records of 511 patients from our institution were analyzed. The mean age of the patients was 63.6 years. One hundred and twenty-three (24.1 %) patients were identified to have HRVA, 30 (6 %) present on both sides. The age of patient over 70 years and female sex were found to be significant risk factors for HRVA presence. The prevalence of a nearby PICA branch was 4 %, FIA was 0.4 %, and FEN was 0.2 %. The presence of PP was identified in 14.3 % of patients. The HRVA and PP are common anomalies in the Czech population, and routine preoperative high-resolution CT evaluation is mandatory to prevent the VA injury when C1–C2 instrumentation is planned. The female sex and age over 70 years were found to be the most important factors for HRVA presence. The FIA and the FEN VA were rare in our study contrary to reports published from Asia, showing as many as a 10 % the VA presence over the starting point for C1 lateral screw. On the basis of the infrequent occurrence of these anomalies, we do not recommend routine CT angiography when upper cervical spine instrumentation in the normal population is planned.

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Out-of-office hours’ elective surgical intensive care admissions and their associated complications

Background

The 'weekend' effect is a controversial theory that links reduced staffing levels, staffing seniority and supportive services at hospitals during 'out-of-office hours' time periods with worsening patient outcomes. It is uncertain whether admitting elective surgery patients to intensive care units (ICU) during 'out-of-office hours' time periods mitigates this affect through higher staffing ratios and seniority.

Methods

Over a 3-year period in Western Australia's largest private hospital, this retrospective nested-cohort study compared all elective surgical patients admitted to the ICU based on whether their admission occurred 'in-office hours' (Monday–Friday 08.00–18.00 hours) or 'out-of-office hours' (all other times). The main outcomes were surgical complications using the Dindo-Clavien classification and length-of-stay data.

Results

Of the total 4363 ICU admissions, 3584 ICU admissions were planned following elective surgery resulting in 2515 (70.2%) in-office hours and 1069 (29.8%) out-of-office hours elective ICU surgical admissions. Out-of-office hours ICU admissions following elective surgery were associated with an increased risk of infection (P = 0.029), blood transfusion (P = 0.020), total parental nutrition (P < 0.001) and unplanned re-operations (P = 0.027). Out-of-office hours ICU admissions were also associated with an increased hospital length-of-stay, with (1.74 days longer, P < 0.0001) and without (2.8 days longer, P < 0.001) adjusting for severity of acute and chronic illnesses and inter-hospital transfers (12.3 versus 9.8%, P = 0.024). Hospital mortality (1.2 versus 0.7%, P = 0.111) was low and similar between both groups.

Conclusion

Out-of-office hours ICU admissions following elective surgery is common and associated with serious post-operative complications culminating in significantly longer hospital length-of-stays and greater transfers with important patient and health economic implications.

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Effects of two enzyme extracts of Aspergillus niger on green tea aromas

Abstract

Green tea was investigated in terms of its aroma changes induced by two enzyme extracts of Aspergillus niger, i.e., crude enzyme extracted from fermentation using tea stalk medium (CETSM) and crude enzyme yielded in potato dextrose medium. The result showed that the former had significant effects on sensory indexes and volatile constituents, with significant increases in toasty and mushroom notes, while the latter had little influence on the aforementioned indexes. In addition, the volatile constituents were significantly affected; in particular, the contents of cis-3-hexenol, 1-octen-3-ol, eucalyptol, hexanol, and benzaldehyde increased. Furthermore, gas chromatography–olfactometry (GC–O) analysis showed that an increase in 1-octen-3-ol strengthened the mushroom note. These results indicate that CETSM contains some novel enzymes that can modify the aroma profile of green tea. This study also provides valuable information and suggestions to use fermented enzymes to modify food aromas.

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The Role of Cold-inducible RNA binding protein (CIRP) in Cell Stress Response

Abstract

Cold-inducible RNA binding protein (CIRP) was discovered after the cells were exposed to a moderate cold shock because its production was induced. Other cellular stresses such as UV radiation and hypoxia also could increase its expression. Under stress conditions, CIRP could up regulate its own expression by self-transcriptional activation of alternative promoters. After relocating into cytoplasm from nucleus, CIRP assists cells in adapting to novel environmental conditions via stabilizing specific mRNAs and facilitating their translation. It not only participates in anti-apoptosis processes under mild hypothermia condition, but also protects cells from ultraviolet radiation and hypoxia induced senescence process. This article focuses on the possible mechanisms of its inducible expression, cytoprotective functions and carcinogenesis. In addition, extracellular CIRP has been shown to be a novel danger-associated molecular patter (DAMP) member and is able to induce inflammatory response. Finally, based on the distinct roles of CIRP in intracellular and extracellular conditions, a possible model of CIRP-mediated cell fate has been proposed. This article is protected by copyright. All rights reserved.

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Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF-1/IGF-1R signaling

Abstract

Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF-1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF-1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF-1/IGF-1R-induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF-1/IGF-1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies. This article is protected by copyright. All rights reserved.

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Biosimilars in the Treatment of Breast Cancer

Breast Care

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Prognostic factors and outcome of Liposarcoma patients: a retrospective evaluation over 15 years

Soft tissue sarcomas are rare entities with over 50 histological subtypes. Liposarcoma (LS) is the most common neoplasm in this group; it is a complex neoplasm that is divided into different histological subty...

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Antiangiogenic agents targeting different angiogenic pathways have opposite effects on tumor hypoxia in R-18 human melanoma xenografts

Studies comparing the effect of antiangiogenic agents targeting different angiogenic pathways are sparse. The purpose of this study was to compare the effect of properdistatin and sunitinib treatment in a prec...

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Pooled safety analyses of ALK-TKI inhibitor in ALK-positive NSCLC

The anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have been administered to patients with ALK-positive non-small cell lung cancer for a long period of time and show a promising response. How...

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Terre Haute Police Officer Looses Battle With Cancer - WIBQ

WIBQ

Terre Haute Police Officer Looses Battle With Cancer WIBQ Information posted on GoFundMe.com by Curt Pendergast says that McGuire was diagnosed with tonsil cancer in 2016. After much treatment, tests in January revealed that the cancer had spread from his throat to his chest. McGuire's patrol car will be ... and more »

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Robotics surgery giving patients another option for treatment - WRDW-TV

WRDW-TV

Robotics surgery giving patients another option for treatment WRDW-TV ENT Doctor Kenneth Byrd with the Georgia Cancer Center says it's extremely helpful in tight spaces like the mouth. "10 or 20 years ago before robotic technology, we would of had to split the jawbone to remove it fully" said Dr. Byrd. Byrd removed a ...

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JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin

Abstract

Purpose

Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells.

Methods

The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species.

Results

We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production.

Conclusions

JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

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Swelling of Graphene Oxide Membranes in Aqueous Solution: Characterization of Interlayer Spacing and Insight into Water Transport Mechanisms

ACS Nano

DOI: 10.1021/acsnano.7b02999

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JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin

Abstract

Purpose

Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells.

Methods

The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species.

Results

We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production.

Conclusions

JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

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Obesity and Obesity Shape Markedly Influence Spine Biomechanics: A Subject-Specific Risk Assessment Model

Abstract

Underlying mechanisms of obesity-related back pain remain unexplored. Thus, we aim to determine the effect of obesity and its shapes on the spinal loads and the associated risks of injury. Obesity shapes were initially constructed by principal component analysis based on datasets on 5852 obese individuals. Spinal loads, cycles to vertebral failure and trunk stability margin were estimated in a subject-specific trunk model taking account of personalized musculature, passive ligamentous spine, obesity shapes, segmental weights, spine kinematics and bone mineral density. Three obesity shapes (mean and extreme abdominal circumferences) at three body weights (BWs) of 86, 98 and 109 kg were analyzed. Additional BW (12 kg) increased spinal loads by ~11.8%. Higher waist circumferences at identical BW increased spinal forces to the tune of ~20 kg additional BW and the risk of vertebral fatigue compression fracture by 3–7 times when compared with smaller waist circumferences. Forward flexion, greater BW and load in hands increased the trunk stability margin. Spinal loads markedly increased with BW, especially at greater waist circumferences. The risk of vertebral fatigue fracture also substantially increased at greater waist circumferences though not at smaller ones. Obesity and its shape should be considered in spine biomechanics.

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Reduced Graphene Oxide/Alumina, A Good Accelerant for Cellulose-Based Artificial Nacre with Excellent Mechanical, Barrier, and Conductive Properties

ACS Nano

DOI: 10.1021/acsnano.7b01221

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Elastin-like Polypeptide Linkers for Single-Molecule Force Spectroscopy

ACS Nano

DOI: 10.1021/acsnano.7b02694

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Flow-Induced Shape Reconfiguration, Phase Separation, and Rupture of Bio-Inspired Vesicles

ACS Nano

DOI: 10.1021/acsnano.7b00753

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Applicability of a modified EFAST protocol (r-EFAST) to evaluate hemodynamically unstable patients after percutaneous cardiac intervention

Abstract

Percutaneous cardiac intervention is an invasive diagnostic and therapeutic technique which carries a significant complication rate. Although the usefulness of EFAST protocol is widely recognised, this paper will attempt to explore a modified approach involving a focused examination on the retroperitoneal (r-EFAST). We have provided examples of 3 cases where r-EFAST was used to detect retroperitoneal bleeding in critical situations.

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Epitaxial Templating of Two-Dimensional Metal Chloride Nanocrystals on Monolayer Molybdenum Disulfide

ACS Nano

DOI: 10.1021/acsnano.7b02838

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Your help changes the future of thyroid disease – Make a spring donation to the ATA!

This spring, we would like to extend a note of thanks to all the Friends of the American Thyroid Association (ATA.) We are grateful that you have chosen to be part of the ATA community.

It is our mission and privilege to provide reliable thyroid education and awareness information, patient care resources, and research grants to help you and all those patients and families who seek answers, information, and guidance on thyroid conditions and treatments. Read more

The post Your help changes the future of thyroid disease – Make a spring donation to the ATA! appeared first on American Thyroid Association.

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How long-lasting is the post-conflict slowing after incongruent trials? Evidence from the Stroop, Simon, and flanker tasks

Abstract

The purpose of the present study was to determine how long-lasting the post-conflict slowing following incongruent stimuli is. In previous research, incongruent stimuli have been used to induce a conflict because they have relevant features for two different response alternatives. So far, the post-conflict slowing following incongruent stimuli has mainly been assessed up to one trial. In the first two experiments, we assessed the persistence of the post-conflict slowing across several trials. To this end, we presented a few incongruent stimuli among non-conflict stimuli. The results showed a consistent slowing for the first few trials immediately following the incongruent trials. In addition, a sporadic slowing was still found on later trials. In two subsequent experiments, we investigated to what extent the infrequency of incongruent trials — rather than their conflict — induced this slowing. To determine this, we used the same design as in the first two experiments, but we presented non-conflict stimuli as infrequent stimuli. The results showed a slowing on one subsequent trial, ruling out the possibility that the post-conflict slowing following incongruent trials was only caused by infrequency. Together, the findings of the present study indicate that the conflict induced by incongruent trials can have a longer lasting impact on subsequent trials than previously thought.

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How long-lasting is the post-conflict slowing after incongruent trials? Evidence from the Stroop, Simon, and flanker tasks

Abstract

The purpose of the present study was to determine how long-lasting the post-conflict slowing following incongruent stimuli is. In previous research, incongruent stimuli have been used to induce a conflict because they have relevant features for two different response alternatives. So far, the post-conflict slowing following incongruent stimuli has mainly been assessed up to one trial. In the first two experiments, we assessed the persistence of the post-conflict slowing across several trials. To this end, we presented a few incongruent stimuli among non-conflict stimuli. The results showed a consistent slowing for the first few trials immediately following the incongruent trials. In addition, a sporadic slowing was still found on later trials. In two subsequent experiments, we investigated to what extent the infrequency of incongruent trials — rather than their conflict — induced this slowing. To determine this, we used the same design as in the first two experiments, but we presented non-conflict stimuli as infrequent stimuli. The results showed a slowing on one subsequent trial, ruling out the possibility that the post-conflict slowing following incongruent trials was only caused by infrequency. Together, the findings of the present study indicate that the conflict induced by incongruent trials can have a longer lasting impact on subsequent trials than previously thought.

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Microstructure and Shape Memory Behavior of Ti–Nb Shape Memory Alloy Thin Film

Abstract

Ti–Nb shape memory alloy (SMA) thin film is a promising candidate applied as microactuator in biomedical field. In this study, the microstructure and shape memory behavior of Ti–Nb SMA thin films in different heat treatment conditions have been investigated. Fine ω phases embedded in the β phase matrix suppress the martensitic transformation of the films. As a result, the as-deposited and most of the annealed films consist of the β and α″ dual phases. The annealed Ti–Nb thin film shows excellent superelasticity effect when deformed above the reverse martensitic transformation temperature, that is 3.5% total recovery strain can be obtained when 4% pre-strain is loaded.

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THE FOUR MAIN TYPES OF THYROID CANCER - Daily Mail

Daily Mail

THE FOUR MAIN TYPES OF THYROID CANCER Daily Mail She started researching the condition. 'That's when I realised all my vague symptoms had this underlying cause. I was later told that thyroid cancer had a high five-year survival rate of 91 per cent for women and 82 per cent for men, but that didn't ...

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Modification of oil palm fronds lignin by incorporation of m-cresol for improving structural and antioxidant properties

Publication date: November 2017
Source:International Journal of Biological Macromolecules, Volume 104, Part A
Author(s): Nurul Atiqah Sa’don, Afidah Abdul Rahim, Mohamad Nasir Mohamad Ibrahim, Nicolas Brosse, M. Hazwan Hussin
Lignin extracted from oil palm fronds (OPF) underwent chemical modification by incorporating m-cresol into the lignin matrix. This study reports on the physicochemical properties and antioxidant activity of unmodified autohydrolyzed ethanol organosolv lignin (AH EOL) and the modified autohydrolyzed ethanol organosolv lignin (AHC EOL). The lignin samples were analyzed by FTIR, ¹H and ¹³C NMR spectroscopy, 2D NMR: HSQC spectroscopy, CHN analysis, molecular weight distribution analysis; GPC and thermal analysis; DSC and TGA. The lignin modification has reduced the hydrophobicity of its complex structure by providing better quality lignin with smaller fragments and higher solubility rate in water (DAHCEOL: 42%>DAHEOL: 25%). It was revealed that the modification of lignin has improved their structural and antioxidant properties, thus venture their possible applications.



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Sequential IGF-1 and BMP-6 releasing chitosan/alginate/PLGA hybrid scaffolds for periodontal regeneration

Publication date: November 2017
Source:International Journal of Biological Macromolecules, Volume 104, Part A
Author(s): Tuğba Duruel, Anıl Sera Çakmak, Abdullah Akman, Rahime M. Nohutcu, Menemşe Gümüşderelioğlu
The goal of periodontal tissue engineering is to repair or regenerate the destructed or lost periodontium by improving functions of cells in the remaining tissue. For continuty of cell growth process, two group of growth factors, i.e. competence factors and progression factors, are needed to act together. However, the short biological half-life of these factors limits their effects on cells and their clinical efficacy. The purpose of this study is to develop different microparticles-loaded chitosan carriers/scaffolds for controlled and sequential delivery of a competence factor, insulin-like growth factor (IGF-1), and progression factor, bone morphogenetic factor-6 (BMP-6). Alginate and poly (lactic-co-glycolic acid) (PLGA) microparticles provided release of IGF-1 and BMP-6 for early short period and for long period, respectively. The cell culture studies showed that, chitosan/alginate/PLGA hybrid scaffolds induced proliferation and osteoblastic differentiation of cementoblasts when compared with IGF-1 and BMP-6 free chitosan scaffold.

Graphical abstract

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Phytochemical content, Fatty acids composition and antioxidant potential of different pomegranate parts: Comparison between edible and non edible varieties grown in Tunisia

Publication date: November 2017
Source:International Journal of Biological Macromolecules, Volume 104, Part A
Author(s): Zahra Amri, Faten Zaouay, Houda Lazreg-Aref, Hala Soltana, Amira Mneri, Messaoud Mars, Mohamed Hammami
Few comparative studies were interested between edible and non-edible pomegranate varieties. In the present study, flowers, leaves, juice and peel of two pomegranate varieties, ornamental variety “Nana” (NV) and sweet variety “Tounsi” (TV) were compared for their phenolic contents and antioxidant activity. Seeds oils were compared also for their fatty acids (FA) composition.Results showed that peel and juice of NV contained higher content in tannins, Flavonoids and anthocyanins. In contrast, peel and juice of TV were more concentrated in carotenoids and polyphenols. Flowers extracts of TV contained more polyphenols and flavonoids. However leaves from NV provided more polyphenols, flavonoids and anthocyanins. Flowers and leaves proved to be the strongest antioxidants for both varieties. For FA composition, NV was more concentrated in Mono-unsaturated FA (MUFA) however TV contained more Di-unsaturated FA (DiUFA). cis-γ-Linolenic acid was the major FA in NV. Contrariwise punicic acid was the predominant in TV.



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Mathematical modeling of gallic acid release from chitosan films with grape seed extract and carvacrol

Publication date: November 2017
Source:International Journal of Biological Macromolecules, Volume 104, Part A
Author(s): Javiera F. Rubilar, Rui M.S. Cruz, Rommy N. Zuñiga, Igor Khmelinskii, Margarida C. Vieira
Controlled release of antimicrobial and antioxidant compounds from packaging films is of utmost importance for extending the shelf-life of perishable foods. This study focused on the mathematical modeling of gallic acid release into an aqueous medium from three chitosan films, formulated with grape seed extract (GSE) and carvacrol. We quantified the release by HPLC technique during 30days at three temperatures (5, 25 and 45°C). The diffusion coefficients, varying with temperature according to an Arrhenius-type relationship, and the respective activation energies for Film-1 and Film-2 were, respectively Deff125°C=3.7×10−14m²s⁻¹ and Deff225°C=6.1×10−14m²s⁻¹, Ea1=58kJmol⁻¹ and Ea2=60kJmol⁻¹ as obtained from the Fickian fit. The low concentrations of gallic acid released by Film-3 could not be detected by HPLC, therefore the respective diffusion coefficient was not estimated. This study will help with the development and optimization of active packaging (AP) films aiming at improved food preservation and shelf-life extension.



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Fabrication of single and bundled filament-like tissues using biodegradable hyaluronic acid-based hollow hydrogel fibers

Publication date: November 2017
Source:International Journal of Biological Macromolecules, Volume 104, Part A
Author(s): Mehdi Khanmohammadi, Shinji Sakai, Masahito Taya
Hydrogel fibers with biodegradable and biocompatible features are useful for the fabrication of filament-like tissues. We developed cell-laden hyaluronic acid (HA)-based hollow hydrogel fibers to create single and bundled filament-like tissues. The cell-laden fibers were fabricated by crosslinking phenolic-substituted hyaluronic acid (HA-Ph) in an aqueous solution containing cells through a horseradish peroxidase (HRP)-catalyzed reaction in the presence of catalase by extruding the solution in ambient flow of an aqueous solution containing H2O2. The encapsulated cells proliferated and grew within the hollow core, and the cells formed filament-like constructs in both single and bundled fibers, which were obtained by collection on a rotating cylindrical tube. Single and bundled filament-like tissues covered with an additional heterogeneous cell layer were obtained by degrading the fiber membrane using hyaluronidase after covering the fiber surface with heterogeneous cells. Cellular viability was preserved during HA-Ph hydrogel fiber fabrication and filament-like tissue formation. These results demonstrate the feasibility of HA-based hollow hydrogel fibers obtained through HRP- and catalase-mediated reactions to engineer filament-like tissues.

Graphical abstract

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Thermal stability of red algal galactans: Effect of molecular structure and counterions

Publication date: November 2017
Source:International Journal of Biological Macromolecules, Volume 104, Part A
Author(s): Marju Robal, Kalle Truus, Olga Volobujeva, Enn Mellikov, Rando Tuvikene
Thermal degradation of κ-, ι-, λ-carrageenans, furcellaran, funoran and agarose samples in dry and sol states was investigated. The polysaccharides subjected to heat treatment were characterized by ¹H NMR, ¹³C NMR and FTIR spectroscopy, size exclusion chromatography and static rheometry methods. The microstructure of galactan gels was studied using a cryofixation method in combination with freeze-drying and SEM techniques. Thermal stability at high temperatures decreases in the order of agarose>furcellaran>funoran>κ-carrageenan>λ-carrageenan>ι-carrageenan for dry preparations. The respective sequence for sol state is ι-carrageenan>λ-carrageenan>κ-carrageenan>furcellaran>funoran>agarose. The presence of methoxy groups stabilizes algal polysaccharides whereas divalent cations as counterions increase the susceptibility towards thermal degradation. In dry state the thermal treatment leads to significant desulfation of the galactan before the complete depolymerization occurs. Depending on the sulfation degree and the presence of 3,6-anhydrogalactose residues in the galactan, a notable amount of 5-hydroxymethylfurfural (yield 0.7–21.8%) is formed during the decomposition in sol state.

Graphical abstract

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Tough chitosan hydrogel based on purified regeneration and alkaline solvent as biomaterials for tissue engineering applications

Publication date: November 2017
Source:International Journal of Biological Macromolecules, Volume 104, Part A
Author(s): Shichao Bi, Zixian Bao, Xiaoyu Bai, Shihao Hu, Xiaojie Cheng, Xiguang Chen
The chitosan based on purified regeneration could be dissolved in 6wt% aqueous NaOH without freeze-thawing cycles and acetylation processing, and such a solution system was effective and different from other dissolving methods Upon heating, a tough hydrogel was constructed from the chitosan (purified regeneration) alkaline solution. The results of XRD, TEM, SEM and rheology analysis proved that chitosan easily aggregated in the solution and formed a nanofibers network to gelate at elevated temperature and concentration. The merely chitosan hydrogel had a uniform network structure and its (5wt%) compressive fracture stress could reach 0.2MPa. Furthermore, the hydrogels exhibited excellent biodegradability, blood compatibility and cellular compatibility. Therefore, the tough chitosan hydrogels may have a wide range of applications in biomedicine.

Graphical abstract

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The Gut: A Key to the Pathogenesis of Type 2 Diabetes?

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


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Re: “Plasminogen Activator Inhibitor-1 and Pericardial Fat in Individuals with Type 2 Diabetes Mellitus” by Bayomi et al. (Metab Syndr Relat Disord DOI:10:1089/met.2017.0031)

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


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FREE IN-HOME WATER TEST

Free water test available by a licensed local water expert. Water Contaminants tested for include: Chlorine Calcium Iron Magnesium pH TDS (total dissolved solids) Additional water contaminants that can be tested for include: Aluminum Arsenic Barium Chloramines Chlorides Cryptosporidium Mercury N...

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A fourth bout of cancer isn't slowing this runner down - New York Post

New York Post

A fourth bout of cancer isn't slowing this runner down New York Post Grunewald, who's based in Minneapolis, Minn., was first diagnosed with adenoid cystic carcinoma — a rare form of cancer that had spread through one of her salivary glands — when she was a senior at the University of Minnesota in April 2009. Though ...

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RIP: North Beach Icon 'Captain Cool,' AKA Patrick LeBold - Hoodline

Hoodline

RIP: North Beach Icon 'Captain Cool,' AKA Patrick LeBold Hoodline Another memorable feature was the electro-larynx he used to communicate for the last decade, due to his ongoing struggle with throat cancer. “His voicebox echoed through the bar while I was trying to serve tourists” said former Vesuvio manager Michael ...

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i-motif structures in long cytosine-rich sequences found upstream of the promoter region of the SMARCA4 gene

Publication date: Available online 12 June 2017
Source:Biochimie
Author(s): Sanae Benabou, Anna Aviñó, S. Lyonnais, C. González, Ramon Eritja, Anna De Juan, Raimundo Gargallo
Cytosine-rich oligonucleotides are capable of forming complex structures known as i-motif with increasingly studied biological properties. The study of sequences prone to form i-motifs located near the promoter region of genes may be difficult because these sequences not only contain repeats of cytosine tracts of disparate length but also these may be separated by loops of varied nature and length. In this work, the formation of an intramolecular i-motif structures by a long sequence located upstream of the promoter region of the SMARCA4 gene has been demonstrated. Nuclear Magnetic Resonance, Circular Dichroism, Gel Electrophoresis, Size-Exclusion Chromatography, and multivariate analysis have been used. Not only the wild sequence (5‘-TC3T2GCTATC3TGTC2TGC2TCGC3T2G2TCATGA2C4-3’) has been studied but also several other truncated and mutated sequences. Despite the apparent complex sequence, the results showed that the wild sequence may form a relatively stable and homogeneous unimolecular i-motif structure, both in terms of pH or temperature. The model ligand TMPyP4 destabilizes the structure, whereas the presence of 20% (w/v) PEG200 stabilized it slightly. This finding opens the door to the study of the interaction of these kind of i-motif structures with stabilizing ligands or proteins.



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Peroxynitrite-modified histone as a pathophysiological biomarker in autoimmune diseases

Publication date: Available online 12 June 2017
Source:Biochimie
Author(s): Md. Asad Khan, Khursheed Alam, Md. Zafaryab, M. Moshahid A. Rizvi
Under physiological conditions, reactive nitrogen and oxygen species are produced continuously. However, excess of these radicals may damage biomolecules like lipids, proteins and nucleic acids. These reactive species have been implicated in many disease conditions including acute/chronic inflammation, rheumatoid arthritis (RA), neurodegenerative diseases and systemic lupus erythematosus (SLE). Peroxynitrite, an oxidant and nitrating molecule, formed in in vivo, when nitric oxide reacts with superoxide radical. The abnormal levels of nitrotyrosine detected in tissues affected by autoimmune diseases have been attributed to peroxynitrite-mediated enhanced nitration of tyrosine residues in proteins. The chromosomal histone proteins are conserved and weak immunogens. However, they exhibit strong immunogenicity after nitration. Rabbits challenged with peroxynitrite-modified histone induce high titre antibodies, indicating that peroxynitrite modification generated immunogenic epitopes. The preferential binding of peroxynitrite-modified histones by autoantibodies derived from SLE and RA sera shows oxidatively and nitrated modified histones involve in the initiation and progression of autoimmune diseases. This review article presents the literature review of the physicochemical and immunological studies on histone proteins modified with peroxynitrite with an objective of the possible role of oxidatively nitrated histones in the initiation/progression of autoimmune inflammatory diseases.



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On the Road to Development of an in Vitro Permeation Test (IVPT) Model to Compare Heat Effects on Transdermal Delivery Systems: Exploratory Studies with Nicotine and Fentanyl

Abstract

Purpose

At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT).

Methods

IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs. Both continuous and transient heat exposures were investigated by applying heat either for the maximum recommended TDS wear duration or for short duration.

Results

Continuous heat exposure for the two nicotine TDSs resulted in different effects, showing a prolonged heat effect for one product but not the other. The J_max enhancement ratio due to the continuous heat effect was comparable between the two nicotine TDS, but significantly different (p < 0.05) among the three fentanyl TDSs. The J_max enhancement ratios due to transient heat exposure were significantly different for the two nicotine TDSs, but not for the three fentanyl TDSs. Furthermore, the transient heat exposure affected the clearance of drug from the skin depot after TDS removal differently for two drugs, with fentanyl exhibiting a longer heat effect.

Conclusions

This exploratory work suggests that an IVPT study may be able to discriminate differences in transdermal drug delivery when different TDS are exposed to elevated temperatures. However, the clinical significance of IVPT heat effects studies should be further explored by conducting in vivo clinical studies with similar study designs.

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How Jupiter split the asteroid belt in two shows its great age

An analysis of meteorites shows that Jupiter divided the rocks of the asteroid belt into two families within the first million years of the solar system

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Eating a low carb breakfast may make you a more tolerant person

Diets low in carbohydrates may change your behaviour, making you less likely to punish people who split money unfairly

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Thymic large cell neuroendocrine carcinoma – a rare and aggressive tumor: a case report

Neuroendocrine tumors are a large group of tumors with a wide spectrum of behavior, affecting mainly the digestive system and the lung. The thymus is very rarely affected.

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Roles of purinergic P2X7 receptor in glioma and microglia in brain tumors

Publication date: 28 August 2017
Source:Cancer Letters, Volume 402
Author(s): James G. McLarnon
This review considers evidence suggesting that activation of the ionotropic purinergic receptor P2X7 (P2X7R) is a contributing factor in the growth of brain tumors. Importantly, expression of P2X7R may be upregulated in both glioma cells and in immune responding microglial cells with possible differential effects on tumor progression. The recruitment of immune cells into tumor regions may not only be involved in supporting an immunosuppressive environment aiding tumor growth but activated microglia could secrete inflammatory factors promoting neoangiogenesis in expanding tumors. The subtype P2X7R exhibits a number of unique properties including activation of the receptor in pathological conditions associated with developing brain tumors. In particular, the tumor microenvironment includes elevated levels of ATP required for activation of P2X7R and the sustained tumor and immune cell P2X7R-mediated responses which in total contribute to overall tumor growth and viability. Studies on cultured rat and human glioma show marked increases in expression of P2X7R and enhanced cell mobility relative to control. Glioma cell animal models demonstrate enhanced expression of P2X7R in both glioma and microglia with antagonism of receptor showing differential effects on tumor growth. Overall, P2X7R activation is associated with a complexity of modulatory actions on tumor growth in part due to ubiquitous expression of the receptor in glioma and immune responsive cells.



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Targeting of super-enhancers and mutant BRAF can suppress growth of BRAF-mutant colon cancer cells via repression of MAPK signaling pathway

Publication date: 28 August 2017
Source:Cancer Letters, Volume 402
Author(s): Yoshiaki Nakamura, Naoko Hattori, Naoko Iida, Satoshi Yamashita, Akiko Mori, Kana Kimura, Takayuki Yoshino, Toshikazu Ushijima
Bromodomain and extra-terminal (BET) inhibitors suppress super-enhancers and show cytotoxicity against multiple types of tumors. However, early clinical trials with BET inhibitors showed severe hematopoietic toxicities, highlighting the need for sensitive tumors and rational combination strategies to enhance their therapeutic potential. Here, we identified colon cancer-specific super-enhancers that were associated with multiple oncogenic pathways, including the mitogen-activated protein kinase (MAPK) signaling pathway. Among the 14 colon cancer cell lines tested, their sensitivity to JQ1, a BET inhibitor, was not correlated with c-MYC expression. Three of four BRAF^V600E-mutant cell lines were sensitive. Addition of JQ1 to vemurafenib, a specific mutant BRAF inhibitor, suppressed cell growth by arresting cell cycle progression and inducing apoptosis in the BRAF^V600E-mutant cells. Mechanistically, the feedback activation of MAPK signaling pathway by vemurafenib was repressed by JQ1. Further, the addition of JQ1 to a BRAF inhibitor enhanced the in vivo anti-tumor effect. Thus, this study indicates the therapeutic potential of targeting of super-enhancers and mutant BRAF in patients with BRAF^V600E-mutant colorectal cancer.



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Epigenetic effects of inhibition of heat shock protein 90 (HSP90) in human pancreatic and colon cancer

Publication date: 28 August 2017
Source:Cancer Letters, Volume 402
Author(s): Ganji Purnachandra Nagaraju, Christina Wu, Neha Merchant, Zhengjia Chen, Gregory B. Lesinski, Bassel F. El-Rayes
Silencing of tumor suppressor and DNA repair genes through methylation plays a role in cancer development, growth and response to therapy in colorectal and pancreatic cancers. Heat shock protein 90 (HSP90) regulates transcription of DNA methyltransferase enzymes (DNMT). In addition, DNMTs are client proteins of HSP90. The aim of this study is to evaluate the effects of HSP90 inhibition on DNA methylation in colorectal and pancreatic cancer cell lines. Our data shows that inhibition of HSP90 using ganetespib resulted in downregulation of mRNA and protein expression of DNMT1, DNMT3A, and DNMT3B in HT-29 and MIA PaCa-2 cell lines. This in turn was associated with a drop in the fraction of methylated cytosine residues and re-expression of silenced genes including MLH-1, P16 and SPARC. These effects were validated in HT-29 tumors implanted subcutaneously in mice following in vivo administration of ganetespib. This work demonstrates the effectiveness of ganetespib, an HSP90 inhibitor in modulating DNA methylation through downregulation of DNMT expression.



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Drs. Oz & Roizen: Trans fat ban; HPV vaccines for boys - Online Athens

Online Athens

Drs. Oz & Roizen: Trans fat ban; HPV vaccines for boys Online Athens That's a shame, because the vaccine provides effective protection from strains of HPV that lead to noncancerous genital warts, cancer of the penis in men and of the anus and throat, and base of the tongue and tonsils in both women and men. For women ... and more »

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Officer Mike McGuire dies after battle with cancer - Terre Haute Tribune Star

Terre Haute Tribune Star

Officer Mike McGuire dies after battle with cancer Terre Haute Tribune Star According to information posted by Curt Pendergast on GoFundMe.com, McGuire was diagnosed with tonsil cancer in summer 2016. He went through treatments, including chemotherapy and radiation, requiring multiple hospital stays and blood transfusions.

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How Jupiter split the asteroid belt in two shows its great age

An analysis of meteorites shows that Jupiter divided the rocks of the asteroid belt into two families within the first million years of the solar system

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Eating a low carb breakfast may make you a more tolerant person

Diets low in carbohydrates may change your behaviour, making you less likely to punish people who split money unfairly

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Elucidating Surface Ligand-Dependent Kinetic Enhancement of Proteolytic Activity at Surface-Modified Quantum Dots

ACS Nano

DOI: 10.1021/acsnano.7b01624

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The Distinct and Cooperative Roles of Toll-Like Receptor 9 and Receptor for Advanced Glycation End Products in Modulating In Vivo Inflammatory Responses to Select CpG and Non-CpG Oligonucleotides

Nucleic Acid Therapeutics , Vol. 0, No. 0.


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Toxic dust and asthma plague Salton Sea communities - Ventura County Star

Ventura County Star

Toxic dust and asthma plague Salton Sea communities Ventura County Star All three of her children have asthma, and many other people in the area suffer from allergies, chronic sinus infections and other respiratory illnesses. Eva said she hopes something gets done to combat the dust. “It should be taken care of .... The ... and more »

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