Screening program in ovarian cancer: A logical step in clinical management? A meta-analysis

Publication date: Available online 5 January 2018
Source:Current Problems in Cancer
Author(s): Claudia Marchetti, Francesca De Felice, Giorgia Perniola, Francesca Lecce, Laura Vertechy, Marco Monti, Daniela Musio, Ludovico Muzii, Vincenzo Tombolini, Pierluigi Benedetti Panici
ObjectiveTreatment of ovarian cancer is a challenge and its poor prognosis still remains a problem of major importance. Due to the lack of early and specific symptoms, the vast majority of women are diagnosed with an advanced stage disease. The aim of this meta-analysis is to evaluate the impact of ovarian cancer screening program in asymptomatic women on clinical outcomes.Methods and materialA systematic literature electronic search was conducted in Pubmed, Medline, Scopus and ClinicalTrials.gov databases. Articles were selected with a systematic approach. Clinical trials concerning screening strategy compared with usual care in asymptomatic ovarian cancer women were considered, without any restrictions on the publication date. Trials were eligible if participants were asymptomatic and post-menopausal women. Outcomes included ovarian cancer diagnosis and disease specific mortality. The pooled relative risk was calculated using a fixed-effects model.ResultsOverall, three randomized controlled trials met inclusion criteria, totaling 353,590 asymptomatic women. In total 177,188 women were assigned to screening program, and 176,402 women were assigned to usual care. The risk of ovarian cancer diagnosis, both overall and at an early stage, was higher in screening group (relative risk 1.07, 95% confidence interval, 0.98–1.18; and relative risk 1.30, 95% confidence interval, 1.14–1.49, respectively). The relative risk for disease specific mortality was 0.96 (95% confidence interval, 0.85–1.10).ConclusionOur results suggest the possible benefit of ovarian cancer screening program in term of early stage diagnosis and reduced specific ovarian cancer mortality. Further studies of environmental and/or constitutional factors may lead to the identification of patient populations that could benefit from a screening program.



http://ift.tt/2CLveGE

Insights into insulin resistance, lifestyle and anthropometric measures of patients with prior colorectal cancer compared to controls: A National Health and Nutrition Examination Survey (NHANES) Study

Publication date: Available online 5 January 2018
Source:Current Problems in Cancer
Author(s): Kenneth Obi, Ramsey Mitchell, Alice Hinton, Peter Stanich, Darrell M. Gray, Somashekar Krishna, Samer El-Dika, Hisham Hussan
BackgroundInsulin resistance (IR) increases the risk of index colorectal cancer (CRC) development. Limited data exist on IR values, lifestyle and anthropometric alterations of patients after CRC diagnosis, a population at high risk for CRC recurrence.MethodsThis is a retrospective cohort study using the National Health and Nutrition Examination Survey (NHANES), 1999–2010. We identified patients with and without prior CRC above age 50. Our outcomes were lifestyle, anthropometric measures and insulin resistance measured using the triglyceride to high-density lipoprotein (TG/HDL) ratio and the homeostasis model assessment (HOMA-IR).ResultsThere were 146,841 patients with prior CRC and 26,979,507 without prior cancer (controls) in our cohort. Prior CRC patients were significantly older than controls (75.8 vs 62.3, p<0.01), however there were no significant differences in gender, ethnicity, income, caloric intake, tobacco use or alcohol consumption between both groups. Multivariate analysis revealed no difference between prior CRC patients and controls in TG/HDL ratio (Adjusted percent change = -2.17; 95% confidence interval [CI]: -27.96, 18.43) or HOMA-IR (Adjusted percent change = -6.85; 95% CI: -35.74, 15.90). Despite similar weight at age 25, prior CRC subjects had lower weights compared to controls (at time of NHANES survey, one and 10 years prior to survey and greatest weight). Furthermore prior CRC subjects gained less weight in the 10 years prior to survey.ConclusionPatients with prior CRC above age 50 have no conclusive evidence of increased insulin resistance compared to non-CRC controls. This is possibly due to lesser weight gain in the peri-CRC diagnosis or treatment period. Future efforts should focus on alternate etiologies for the increased CRC recurrence in this high risk group.



http://ift.tt/2CKanmZ

Emerging facets in the treatment of patients with hepatopancreaticobiliary malignancies

Publication date: Available online 5 January 2018
Source:Current Problems in Cancer
Author(s): M.G. McNamara




http://ift.tt/2m2sWbV

Preliminary Clinical Experience with a Combined Automated Breast Ultrasound and Digital Breast Tomosynthesis System

Publication date: Available online 5 January 2018
Source:Ultrasound in Medicine & Biology
Author(s): Eric D. Larson, Won-Mean Lee, Marilyn A. Roubidoux, Mitchell M. Goodsitt, Chris Lashbrook, Cynthia E. Davis, Oliver D. Kripfgans, Paul L. Carson
We analyzed the performance of a mammographically configured, automated breast ultrasound (McABUS) scanner combined with a digital breast tomosynthesis (DBT) system. The GE Invenia ultrasound system was modified for integration with GE DBT systems. Ultrasound and DBT imaging were performed in the same mammographic compression. Our small preliminary study included 13 cases, six of whom had contained invasive cancers. From analysis of these cases, current limitations and corresponding potential improvements of the system were determined. A registration analysis was performed to compare the ease of McABUS to DBT registration for this system with that of two systems designed previously. It was observed that in comparison to data from an earlier study, the McABUS-to-DBT registration alignment errors for both this system and a previously built combined system were smaller than those for a previously built standalone McABUS system.



http://ift.tt/2lZtpve

MiR-449a suppresses cell migration and invasion by targeting PLAGL2 in breast cancer

Publication date: Available online 5 January 2018
Source:Pathology - Research and Practice
Author(s): Bin Xu, Xiping Zhang, Shanshan Wang, Bailing Shi
BackgroundBreast cancer is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying breast cancer metastasis are still incompletely clear. MicroRNAs (miRNAs) play a crucial role in cancer metastasis. In this study, we aimed to analyze the expression and function of miR-449a in breast cancer.Material and MethodsA total of 15 human primary breast cancer tissues and adjacent non-cancerous tissues (10 pairs) were obtained. MiR-449a was examined in tumor tissues and adjacent nontumorous tissues of breast cancer patients and cell lines by real-time PCR. The protein expression levels were analyzed by western blot and immunohistochemistry staining. Luciferase reporter assays was used to validate the target of miR-449a. The effect of miR-449a on breast cancer cell migration and invasion were studied in vitro and in vivo.ResultsThe expression levels of miR-449a were significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-449a suppressed breast cancer cell proliferation, clone formation, migration, invasion and metastasis in vitro and in vivo. Pleomorphic adenoma gene like-2 (PLAGL2) was identified as a major target of miR-449a. Both overexpression of miR-449a inhibited the expression of PLAGL2 significantly and the knockdown of PLAGL2 expression inhibited the breast cancer cell proliferation and metastasis.ConclusionWe demonstrate the miR-449a tumor suppressor role in breast cancer cell migration and invasion via targeting PLAGL2. These findings suggesting that miR-449a/PLAGL2 could serve as a therapeutic strategy for targeting breast cancer.



http://ift.tt/2EdZk2p

Process-induced morphology and mechanical properties of high-density polyethylene

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Regine Boldt, Uwe Gohs, Udo Wagenknecht, Manfred Stamm
Electron induced reactive processing (EIReP) is an emerging technology for the development of high performance polymer materials. It simultaneously combines the traditional electron beam (EB) treatment of polymers and their melt mixing in the presence of shear stresses and/or rates of deformation. In comparison to traditional EB treatment of high-density polyethylene (HD-PE) at room temperature, EIReP modified HD-PE shows an inhomogeneous morphology, a self-nucleation effect as well as a significant increased tensile strength and decreased elongation at break. In order to identify the reason of these changed properties and the working principle of EIReP, HD-PE has been modified by EB treatment in solid and molten state as well as before and after the presence of shear stresses and/or rates of deformation. Shear stresses and/or rates of deformation were applied during injection moulding of tensile specimens. Based on results of previous work the EB treatments and EIReP of HD-PE were performed under nitrogen atmosphere in order to reduce oxygen induced side reactions. The process induced morphological and mechanical properties have been investigated using optical light microscopy, transmission electron microscopy as well as thermal analysis and tensile tests. Changes of molecular mass were measured with size exclusion chromatography and confirmed by rheological measurements. The results demonstrate that the morphology and specific tensile properties of HD-PE were only changed by an EB treatment before the influence of shear stresses and/or rates of deformation on EB modified HD-PE during injection moulding. In addition, the state of aggregate during EB treatment has no influence on morphology and tensile properties. Consequently, the EIReP induced effect based on electron induced changes of HD-PE molecular structure and the subsequent influence of shear stresses and/or rates of deformation.

Graphical abstract

http://ift.tt/2CIY9uL

Screening of GLE1 mutations in Chinese amyotrophic lateral sclerosis patients

Publication date: Available online 5 January 2018
Source:Neurobiology of Aging
Author(s): Kang Zhang, Qing Liu, Dongchao Shen, Hongfei Tai, Hanhui Fu, Shuangwu Liu, Jinyi Chen, Xiaoguang Li, Mingsheng Liu, Xue Zhang, Liying Cui
Amyotrophic lateral sclerosis (ALS) is a lethal neurological disease primarily involving the spinal cord, brainstem, and corticospinal tract. Recently, mutations in the GLE1 gene were reported in Caucasian ALS patients. To inquire whether Chinese ALS patients carried causal mutations in the gene, we screened all 16 coding exons of GLE1 with Sanger sequencing in a Han Chinese cohort of 250 ALS cases. No nonsynonymous coding variants was detected. Our results suggest that pathogenic variants in the GLE1 gene are rare in Chinese ALS patients.



http://ift.tt/2F5XhP8

Interdependence of bacterial cell division and genome segregation and its potential in drug development

Publication date: Available online 5 January 2018
Source:Microbiological Research
Author(s): Hari S. Misra, Ganesh K. Maurya, Reema Chaudhary, Chitra S. Misra
Cell division and genome segregation are mutually interdependent processes, which are tightly linked with bacterial multiplication. Mechanisms underlying cell division and the cellular machinery involved are largely conserved across bacteria. Segregation of genome elements on the other hand, follows different pathways depending upon its type and the functional components encoded on these elements. Small molecules, that are known to inhibit cell division and/or resolution of intertwined circular chromosome and maintenace of DNA topology have earlier been tested as antibacterial agents. The utility of such drugs in controlling bacterial infections has witnessed only partial success, possibly due to functional redundancy associated with targeted components. However, in due course, literature has grown with newer information. This review has brought forth some recent findings on bacterial cell division with special emphasis on crosstalk between cell division and genome segregation that could be explored as novel targets in drug development.



http://ift.tt/2EdItgi

TMS of primary motor cortex with a biphasic pulse activates two independent sets of excitable neurones

Publication date: Available online 5 January 2018
Source:Brain Stimulation
Author(s): Martin Sommer, Matteo Ciocca, Raffaella Chieffo, Paul Hammond, Andreas Neef, Walter Paulus, John C. Rothwell, Ricci Hannah
BackgroundBiphasic pulses produced by most commercially available TMS machines have a cosine waveform, which makes it difficult to study the interaction between the two phases of stimulation.ObjectiveWe used a controllable pulse TMS (cTMS) device delivering quasi-rectangular pulse outputs to investigate whether monophasic are more effective than biphasic pulses.MethodsTemporally symmetric ("biphasic") or highly asymmetric ("monophasic") charge-balanced biphasic stimuli were used to target the hand area of motor cortex in the anterior-posterior (AP) or posterior-anterior (PA) initial current direction.ResultsWe observed the lowest motor thresholds and shortest motor evoked potential (MEP) latencies with initial PA pulses, and highest thresholds and longest latencies with AP pulses. Increasing pulse symmetry tended to increase threshold with a PA direction whereas it lowered thresholds and shortened latencies with an AP direction. Furthermore, it steepened the MEP input-output curve with both directions.Conclusions"Biphasic" TMS pulses can be viewed as two monophasic pulses of opposite directions, each stimulating a different set of interneurons with different thresholds (PA < AP). At threshold, the reverse phase of an initially PA pulse increases threshold compared with "monophasic" stimulation. At higher intensities, the reverse phase begins to activate AP-sensitive neurones and increase the effectiveness of stimulation above that of a "monophasic" PA pulse. "Biphasic" stimulation with initially AP pulses is dominated at threshold by activation produced by the lower threshold reverse (PA) phase.SignificanceThe effects of biphasic stimulation are best understood as the summed output of two independent sets of directionally selective neural populations.



http://ift.tt/2F4eB7v

Silver ions enhanced AuNCs fluorescence as a turn-off nanoprobe for ultrasensitive detection of iodide

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Wenli Hou, Yuan Chen, Qiujun Lu, Meiling Liu, Youyu Zhang, Shouzhuo Yao
Fluorescence nanoprobes are frequently employed to construct sensitive biosensors via turn-on and turn-off strategy. In this paper, a novel strategy for ultrasensitive detection of iodide was firstly constructed based on Ag⁺ regulated photoluminescence enhancement of gold nanoclusters (AuNCs) as a turn-off nanoplatform. In the presence of Ag⁺, the fluorescence (FL) intensity of AuNCs can be enhanced obviously. When adding iodide ions (I^-) in the Ag⁺-AuNCs, Ag⁺ can be pulled down from AuNCs and results in quenching of the fluorescent effectively owing to the combination between Ag⁺ and I^-. Compared with that of I^- directly reaction with AuNCs, the introducing of Ag⁺ shows improved quenching efficiency from 32% to 66% since I^- can react with Ag⁺ as well as AuNCs. Therefore, the platform could be applied to assay Ag⁺ and I^-, on the basis of the FL enhancement and the further FL quenching. The detection ranges and detection limits were 0.2–12μM and 0.06μM for Ag⁺, 0.001–6μM and 0.3nM for I^-, respectively. The new sensing method based on ion regulation to enhance the detection sensitivity can extend to the appliance of other fluorescent materials in biosensing and biomedical field.

Graphical abstract

http://ift.tt/2Ee4gEL

Sensitive fluorescence sensing of T4 polynucleotide kinase activity and inhibition based on DNA/polydopamine nanospheres platform

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Yao Cen, Wen-Jing Deng, Ru-Qin Yu, Xia Chu
5′-Polynucleotide kinase (PNK) is a crucial enzyme that catalyzes the phosphorylation of nucleic acid with 5′-OH termini and this phosphorylation reaction has been involved in many important cellular activities. The evaluation of PNK activity has received an increasing attention due to the significance of PNK. Here, the polydopamine nanospheres (PDANS) could adsorb single-stranded DNA (ssDNA) through π–π stacking or hydrogen bonding between nucleobases and aromatic groups of PDANS, while the interaction between double-stranded DNA (dsDNA) with PDANS was weakened due to the changed conformation. Hence, a novel DNA/PDANS platform was constructed for the sensitive and selective determination of T4 PNK activity based on the preferential binding properties of PDANS for ssDNA over dsDNA and the excellent fluorescence quenching property of PDANS. The dye-labeled dsDNA was phosphorylated by T4 PNK and then digested by λ exonuclease, yielding dye-labeled ssDNA, which would be adsorbed on the surface of the PDANS and the fluorescence was greatly quenched by PDANS. Because of the preferential binding properties of PDANS for ssDNA over dsDNA and the high quenching property of PDANS, the developed DNA/PDANS platform exhibited good analytical performance for T4 PNK sensing in complex biological matrix and applied to screening inhibitors. The proposed DNA/PDANS based platform is promising in developing high-throughput assays for drug screening and clinical diagnostics.

Graphical abstract

http://ift.tt/2EbW9s8

A highly selective, colorimetric and ratiometric fluorescent probe for NH2NH2 and its bioimaging

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Hai Xu, Biao Gu, Yaqian Li, Zhen Huang, Wei Su, Xiaoli Duan, Peng Yin, Haitao Li, Shouzhuo Yao
In this work, we report a novel approach which employed substrate-triggered intramolecular addition-cyclization cascade to develop a highly selective fluorescent probe E)-3-(4-(1H-phenanthro[9,10-d]imidazol-2-yl)phenyl)-1-(2-hydroxylphenyl) prop-2-en-1-one (P-OH) for NH2NH2. The new sensing mechanism of P-OH for NH2NH2 was investigated in detail by fluorescence spectroscopy, ¹H NMR titration, mass spectrometry and control experiments. The synthesized probe showed ratiometric fluorescent response to NH2NH2 with naked-eye color changes from yellow to colorless. It's noteworthy that this probe displayed high sensitivity and selectivity to NH2NH2 over other species, including primary amines, Cys, Hcy, GSH, HS^- and HSO3^-. Furthermore, the probe can not only detect NH2NH2 in real water samples but also image NH2NH2 in living cells, indicating its potential utility for NH2NH2 sensing in environmental and biological samples.

Graphical abstract

http://ift.tt/2EdBQL9

Rapid and interference-free analysis of nine B-group vitamins in energy drinks using trilinear component modeling of liquid chromatography-mass spectrometry data

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Yong Hu, Hai-Long Wu, Xiao-Li Yin, Hui-Wen Gu, Rong Xiao, Li-Xia Xie, Zhi Liu, Huan Fang, Li Wang, Ru-Qin Yu
The aim of the present work was to develop a rapid and interference-free method based on liquid chromatography-mass spectrometry (LC-MS) for the simultaneous determination of nine B-group vitamins in various energy drinks. A smart and green strategy that modeled the three-way data array of LC-MS with second-order calibration methods based on alternating trilinear decomposition (ATLD) and alternating penalty trilinear decomposition (APTLD) algorithms was developed. By virtue of "mathematical separation" and "second-order advantage", the proposed strategy successfully solved the co-eluted peaks and unknown interferents in LC-MS analysis with the elution time less than 4.5min and simple sample preparation. Satisfactory quantitative results were obtained by the ATLD-LC-MS and APTLD-LC-MS methods for the spiked recovery assays, with the average spiked recoveries ranging from 87.2–113.9% to 92.0–111.7%, respectively. These results acquired from the proposed methods were confirmed by the LC-MS/MS method, which shows a quite good consistency with each other. All these results demonstrated that the developed chemometrics-assisted LC-MS strategy had advantages of being rapid, green, accurate and low-cost, and it could be an attractive alternative for the determination of multiple vitamins in complex food matrices, which required no laborious sample preparation, tedious condition optimization or more sophisticated instrumentations.

Graphical abstract

http://ift.tt/2EcMzp7

Direct olive oil analysis by mass spectrometry: A comparison of different ambient ionization methods

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Felipe J. Lara-Ortega, Miriam Beneito-Cambra, José Robles-Molina, Juan F. García-Reyes, Bienvenida Gilbert-López, Antonio Molina-Díaz
Analytical methods based on ambient ionization mass spectrometry (AIMS) combine the classic outstanding performance of mass spectrometry in terms of sensitivity and selectivity along with convenient features related to the lack of sample workup required. In this work, the performance of different mass spectrometry-based methods has been assessed for the direct analyses of virgin olive oil for quality purposes. Two sets of experiments have been setup: (1) direct analysis of untreated olive oil using AIMS methods such as Low-Temperature Plasma Mass Spectrometry (LTP-MS) or paper spray mass spectrometry (PS-MS); or alternatively (2) the use of atmospheric pressure ionization (API) mass spectrometry by direct infusion of a diluted sample through either atmospheric pressure chemical ionization (APCI) or electrospray (ESI) ionization sources. The second strategy involved a minimum sample work-up consisting of a simple olive oil dilution (from 1:10 to 1:1000) with appropriate solvents, which originated critical carry over effects in ESI, making unreliable its use in routine; thus, ESI required the use of a liquid-liquid extraction to shift the measurement towards a specific part of the composition of the edible oil (i.e. polyphenol rich fraction or lipid/fatty acid profile). On the other hand, LTP-MS enabled direct undiluted mass analysis of olive oil. The use of PS-MS provided additional advantages such as an extended ionization coverage/molecular weight range (compared to LTP-MS) and the possibility to increase the ionization efficiency towards nonpolar compounds such as squalene through the formation of Ag⁺ adducts with carbon-carbon double bounds, an attractive feature to discriminate between oils with different degree of unsaturation.

Graphical abstract

http://ift.tt/2EbW6ws

Trends of non-destructive analytical methods for identification of biodiesel feedstock in diesel-biodiesel blend according to European Commission Directive 2012/0288/EC and detecting diesel-biodiesel blend adulteration: A brief review

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Sarmento Júnior Mazivila
Discrimination of biodiesel feedstock present in diesel-biodiesel blend is challenging due to the great similarity in the spectral profile as well as digital image profile of each type of feedstock employed in biodiesel production. Once the marketed diesel-biodiesel blend is subsidized, in which motivates adulteration in biofuel blend by cheaper supplies with high solubility to obtain profits associated with the subsidies involved in biodiesel production. Non-destructive analytical methods based on qualitative and quantitative analysis for detecting marketed diesel-biodiesel blend adulteration are reviewed. Therefore, at the end is discussed the advantage of the qualitative analysis over quantitative analysis, when the systems require immediate decisions such as to know if the marketed diesel-biodiesel blend is unadulterated or adulterated in order to aid the analyst in selecting the most appropriate green analytical procedure for detecting diesel-biodiesel blend adulteration proceeding in fast way. This critical review provides a brief review on the non-destructive analytical methods reported in scientific literature based on different first-order multivariate calibration models coupled with spectroscopy data and digital image data to identify the type of biodiesel feedstock present in diesel-biodiesel blend in order to meets the strategies adopted by European Commission Directive 2012/0288/EC as well as to monitoring diesel-biodiesel adulteration. According to that Directive, from 2020 biodiesel produced from first-generation feedstock, that is, oils employed in human food such as sunflower, soybean, rapeseed, palm oil, among other oils should not be subsidized. Therefore, those non-destructive analytical methods here reviewed are helpful for discrimination of biodiesel feedstock present in diesel-biodiesel blend according to European Commission Directive 2012/0288/EC as well as for detecting diesel-biodiesel blend adulteration.

Graphical abstract

http://ift.tt/2F1Fnxf

Ultrasensitive electrochemical detection of poly (ADP-ribose) polymerase-1 via polyaniline deposition

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Yong Liu, Jiahui Fan, Li Shangguan, Yuanjian Liu, Yuanqing Wei, Wei Wei, Songqin Liu
Recent findings have thrust poly ADP (ADP: adenosine diphosphate)-ribose polymerase-1 (PARP-1) into the limelight as potential chemotherapeutic target because it is closely related to the development of tumor. So, studies on its detection and inhibitors evaluation have attracted more attention. It is interesting that poly (ADP-ribose) (PAR), the catalytic product of PARP-1 in the existence of nicotinamide adenine dinucleotide (NAD⁺), possess twice charge density of DNA strands. PAR contain 200 units, i.e., about 400bp bases, and multiple branched strands. So, plentiful negative charges on PAR supplied exquisite environment for PANI deposition, which was triggered by horseradish peroxidase (HRP). Because of the unique electrochemical property of PANI, ultrasensitive electrochemical detection of PARP-1 was proposed. Under optimum conditions, DPV intensity linearly increased with the increment of PARP-1 in the range of 0.005–1.0 U. The detection limit was 0.002 U, which was comparable or more sensitive than that obtained from previously reported strategies.

Graphical abstract

http://ift.tt/2F6qj15

Silica nanoparticles coated by poly(acrylic acid) brushes via host-guest interactions for detecting DNA sequence of Hepatitis B virus

Publication date: 1 May 2018
Source:Talanta, Volume 181
Author(s): Lu Ding, Chunlan Xiang, Gang Zhou
Poly(acrylic acid) (PAA) brushes coated onto silica nanoparticles have been widely utilized in bioassays due to their abilities of providing favorable microenvironments and ensuring good biological activities for biomolecules. However, traditional PAA brushes are synthesized by reversible addition–fragmentation chain transfer polymerization. Hence, it is generally difficult to control and characterize the molecular weight of the PAA brushes, which may depress the reproducibility and bring more uncertain results. Herein, atom transfer radical polymerization method is employed to synthesize β-cyclodextrin-cored PAA with uniform and controllable molecular weight. After loading on the surfaces of adamantane-functionalized silica nanoparticles via host-guest interactions, glucose oxidase and probe single strand DNA (ssDNA) are further immobilized on the as-prepared nanoparticles. Meanwhile, capture ssDNA is functionalized on amino modified magnetic beads. In the presence of ssDNA sequence of Hepatitis B Virus (HBV) containing completely matched sequence of both probe and capture ssDNA, a bioconjugate is formed and can be separated by an external magnet. The isolated glucose oxidase can further catalyze glucose into gluconic acid and H2O2, and then reduce HAuCl4 on Au seeds. By monitoring the absorption intensity change of the Au NPs at 530nm, the proposed biosensor with novel signal amplification probes can be used to detect DNA sequence of HBV with high sensitivity and selectivity in both buffer and serum samples. This developed strategy has presented a new way to construct silica nanoparticles coated by PAA brushes for the fields of clinical diagnosis and other life sciences.

Graphical abstract

http://ift.tt/2F1FkBz

A sensitive SPR biosensor based on hollow gold nanospheres and improved sandwich assay with PDA-Ag@Fe3O4/rGO

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Shuo Li, Qiong Wu, Pinyi Ma, Yue Zhang, Daqian Song, Xinghua Wang, Ying Sun
A novel surface plasmon resonance (SPR) biosensor based on hollow gold nanospheres (HGNPs) and an improved sandwich assay was developed to detect rabbit IgG. The electromagnetic coupling between the HGNPs and Au film, and the notable plasmonic fields spread over the inner and outer surfaces of HGNPs, led to the considerable amplification of the SPR signal. Polydopamine-Ag@Fe3O4/reduced graphene oxide (PDA-Ag@Fe3O4/rGO) was introduced to bind detection antibody (Ab2) to form the improved sandwich structure. Ag nanoparticles were excited to produce SPR and their hot electrons were doped on graphene thin films, which amplified the response of biomolecules. Magnetic nanoparticles (Fe3O4) simplified the collection of Ab2-PDA-Ag@Fe3O4/rGO. An external layer of polydopamine (PDA) permitted the efficient immobilization of Ab2 without activation via abundant functional groups and protected the nanoparticles from etching or agglomeration. In addition, because of its large mass, Ab2-PDA-Ag@Fe3O4/rGO also played a key role in the further amplification of the SPR response signals. This novel SPR biosensor exhibited an effective response to the rabbit IgG at the different concentrations ranging from 0.019 to 40.00μgmL⁻¹. This value is 132 times lower than that observed for a traditional SPR biosensor based on Au-3-mercaptopropionic acid and 8 times lower than that obtained from an Ab2 sandwich assay, which indicates that the SPR sensor has high sensitivity. In addition, the designed biosensor showed satisfactory recoveries to detect the rabbit IgG spiked in serum samples. Therefore, the novel SPR biosensor with high sensitivity and acceptable recovery has potential for practical applications.

Graphical abstract

http://ift.tt/2F2P52e

The synthesis of a smart streptavidin-functionalized poly(N-isopropylacrylamide) composite and its application in the separation and detection of virus nucleic acid

Publication date: 1 May 2018
Source:Talanta, Volume 181
Author(s): Xinxin Wang, Mingyuan Du, Guobin Mao, Jiao Zheng, Jinyang Chen, Xinghu Ji, Zhike He
A new kind of polymeric material (PNIPAAm-co-SA) was prepared by conjugating a thermosensitive polymer, Poly (N-isopropylacrylamide) (PNIPAAm) with streptavidin (SA). This smart prepared composite displayed a controllable conformation change between an expanded and a collapsed form, below or above its lower critical solution temperature (LCST). Differential scanning calorimetry (DSC) analysis demonstrated that the PNIPAAm-co-SA bioconjugate showed the same LCST as the original synthetic polymer, PNIPAAm, which was also 32°C. Based on the specific interaction between SA and biotin, a higher capture efficiency of PNIPAAm-co-SA, which was almost 100% in PBS buffer solution and above 70% in serum was obtained, respectively. And the high affinity between PNIPAAm-co-SA and biotin was still maintained after three heating cycles. Subsequently, the variola virus (small pox, VV) oligonucleotide sequence was chosen as a model to demonstrate the sensitivity of the biosensor which was fabricated based on PNIPAAm-co-SA. The biosensor exhibited the ability to separate and enrich targets from complicated system with its phase transition ability, and high sensitivity toward VV-targets were achieved. Moreover, other types of targets such as proteins and cells, could be detected by changing the biotin-captures, which indicated the broad applicability of biosensors based on this smart polymer material.

Graphical abstract

http://ift.tt/2F3o52J

Rapid identification of regulated organic chemical compounds in toys using ambient ionization and a miniature mass spectrometry system

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Xiangyu Guo, Hua Bai, Yueguang Lv, Guangcheng Xi, Junfang Li, Xiaoxiao Ma, Yue Ren, Zheng Ouyang, Qiang Ma
Rapid, on-site analysis was achieved through significantly simplified operation procedures for a wide variety of toy samples (crayon, temporary tattoo sticker, finger paint, modeling clay, and bubble solution) using a miniature mass spectrometry system with ambient ionization capability. The labor-intensive analytical protocols involving sample workup and chemical separation, traditionally required for MS-based analysis, were replaced by direct sampling analysis using ambient ionization methods. A Mini β ion trap miniature mass spectrometer was coupled with versatile ambient ionization methods, e.g. paper spray, extraction spray and slug-flow microextraction nanoESI for direct identification of prohibited colorants, carcinogenic primary aromatic amines, allergenic fragrances, preservatives and plasticizers from raw toy samples. The use of paper substrates coated with Co3O4 nanoparticles allowed a great increase in sensitivity for paper spray. Limits of detection as low as 5μgkg^-1 were obtained for target analytes. The methods being developed based on the integration of ambient ionization with miniature mass spectrometer represent alternatives to current in-lab MS analysis operation, and would enable fast, outside-the-lab screening of toy products to ensure children's safety and health.

Graphical abstract

http://ift.tt/2F6YUwj

An electrochemical sensor based on copper-based metal-organic frameworks-graphene composites for determination of dihydroxybenzene isomers in water

Publication date: 1 May 2018
Source:Talanta, Volume 181
Author(s): Jun Li, Jianfei Xia, Feifei Zhang, Zonghua Wang, Qingyun Liu
A highly and simply sensitive electrochemical sensor was presented for the simultaneous determination of hydroquinone (HQ) and catechol (CT) in the water based on copper centered metal-organic framework-graphene composites (Cu-MOF-GN) [Cu-MOF = Cu3(BTC)2 (BTC = 1, 3, 5-benzenetricarboxylicacid)] modified glassy carbon electrode (Cu-MOF-GN/GCE). The modification procedure was carried out through casting metal-organic framework-graphene oxide composites (Cu-MOF-GO) on the bare glassy carbon electrode and followed by the transformation of Cu-MOF-GO to Cu-MOF-GN by an electrochemical reduction. The electrochemical behavior of HQ and CT at Cu-MOF-GN/GCE was investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Under the optimized conditions, the modified electrode had excellent electrocatalytic activity and high selectivity toward HQ and CT. The electrochemical sensor exhibited a linear response in the same range of 1.0 × 10⁻⁶ to 1.0 × 10⁻³M with the detection limits of 5.9 × 10⁻⁷M for HQ and 3.3 × 10⁻⁷M for CT (S/N = 3). Four samples of tap water spiked with different concentrations of HQ and CT were considered. The method has been applied to the analysis of these isomers in spiked tap water with recoveries from 99.0 ~ 102.9% and relative standard deviations (RSDs) for 5 successive measurements less than 5% were also acceptable. This method was successfully applied to detect target analytes in the real samples with satisfying results. The MOFs-based sensors in the field of electrochemical sensing held a great promise for routine sensing applications.

Graphical abstract

http://ift.tt/2F0Jqd4

Particle-based immobilized enzymatic reactors in microfluidic chips

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Adam Kecskemeti, Attila Gaspar
The research and applications of immobilized enzyme reactors (IMERs) have become more and more widespread due to the numerous advantages like reusability, easy handling, prolonged lifetime, easy separation from products and substrate specificity. The miniaturized form of these reactors (microchip IMERs) received outstanding attention due to their special features and advantages over the traditional, larger analytical systems. Large specific surface is essential for the efficient operation of the microreactors, thus these devices include one of the several types of porous solid supports, but in this work only the particle based microchip IMERs are reviewed. A very large variety of micro- or nanoparticles (beads) have been used in the microchip IMERs, however, incorporating these particles into microchips is still a challenge, because the common procedures used for the preparation of chromatographic columns are not well applicable at the microscopic level.Many detection systems were applied with microchip IMERs using on-chip or off-chip arrangement. The combination of microchip IMERs with mass spectrometry is particularly popular, because in these systems high-throughput analysis can be achieved by which the proteomic studies can be largely accelerated. In most chip IMER-MS systems, the chips are used for sample pretreatment including analyte (protein) digestion, preconcentration of analyte, removal of matrix materials. Additional applications of the IMERs - like the rapid protein digestion with proteolytic enzymes, the transformation of analytes to a more easily or more sensitively measurable form (detection signal amplification) and the design of microarrays/biosensors to analyze antigens based on specific interactions in immunoanalytical studies – are also reviewed.

Graphical abstract

http://ift.tt/2F6sNwz

A chemometric approach for characterization of serum transthyretin in familial amyloidotic polyneuropathy type I (FAP-I) by electrospray ionization-ion mobility mass spectrometry

Publication date: 1 May 2018
Source:Talanta, Volume 181
Author(s): Laura Pont, Victoria Sanz-Nebot, Marta Vilaseca, Joaquim Jaumot, Roma Tauler, Fernando Benavente
In this study, we describe a chemometric data analysis approach to assist in the interpretation of the complex datasets from the analysis of high-molecular mass oligomeric proteins by ion mobility mass spectrometry (IM-MS). The homotetrameric protein transthyretin (TTR) is involved in familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR(Met30)) that can be easily detected analyzing the monomeric forms of the mutant protein. However, the mechanism of protein misfolding and aggregation onset, which could be triggered by structural changes in the native tetrameric protein, remains under investigation. Serum TTR from healthy controls and FAP-I patients was purified under non-denaturing conditions by conventional immunoprecipitation in solution and analyzed by IM-MS. IM-MS allowed separation and characterization of several tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time. After an appropriate data pre-processing, multivariate curve resolution alternating least squares (MCR-ALS) was applied to the complex datasets. A group of seven independent components being characterized by their ion mobility profiles and mass spectra were resolved to explain the observed data variance in control and patient samples. Then, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were considered for exploration and classification. Only four out of the seven resolved components were enough for an accurate differentiation. Furthermore, the specific TTR ions identified in the mass spectra of these components and the resolved ion mobility profiles provided a straightforward insight into the most relevant oligomeric TTR proteoforms for the disease.

Graphical abstract

http://ift.tt/2F504bm

A polyethyleneimine-modified attapulgite as a novel solid support in matrix solid-phase dispersion for the extraction of cadmium traces in seafood products

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Tingting Wang, Yihui Chen, Junfeng Ma, Zhenfeng Jin, Mengsa Chai, Xunwen Xiao, Lihua Zhang, Yukui Zhang
In current study, a new polyethyleneimine (PEI)-modified attapulgite material was prepared serving as a solid support in matrix solid-phase dispersion for the extraction and determination (by atomic absorption spectrometry) of cadmium in seafood products. The major factors affecting PEI grafting were optimized using various PEI amounts and molecular weights. Parameters pivotal to MSPD extraction efficiency, like: pH, volume of eluting solvent, and the sorbent mass-to-sample ratio were investigated. Quantitative recoveries were achieved with 0.21g of fish sample, 0.13g of PEI-modified attapulgite dispersing agent, and 50% HNO3 eluting solution. The limit of detection and the limit of quantification were found to be 2.5 and 8.3μgkg⁻¹ for cadmium in surimi samples, respectively. The recoveries were in the range of 89.2–100.1%, with RSDs ranged from 3.0% to 7.9% (n = 5). When compared to the method stipulated by the Chinese National Standard GB 5009.15-2014, the newly developed MSPD provides comparable accuracy and even better repeatability for the analysis of the cadmium in real seafood samples.

Graphical abstract

http://ift.tt/2F4ZQRy

Upconversion particle@Fe3O4@molecularly imprinted polymer with controllable shell thickness as high-performance fluorescent probe for sensing quinolones

Publication date: 1 May 2018
Source:Talanta, Volume 181
Author(s): Yiwei Tang, Huan Liu, Jingwen Gao, Xiuying Liu, Xue Gao, Xiaonan Lu, Guozhen Fang, Junping Wang, Jianrong Li
Localized photo-polymerization was ingeniously applied to prepare a multifunctional molecularly imprinted polymer (MIP) fluorescent probe using the "layer-by-layer" assembly of MIP and Fe3O4 nanoparticles on NaYF4: Yb³⁺, Er³⁺ upconversion particles (MUCPs@MIP). Enrofloxacin was used as the template and chosen as the target molecular during the investigation of the adsorption property. This ternary probe has magnetic and broad-spectrum molecular recognition capability, fast response, and upconversion fluorescence. The results of the fluorescence quenching analysis showed good linear ranges of 1.03nmol/L to 0.28μmol/L for enrofloxacin, 1.69nmol/L to 0.22μmol/L for fleroxacin, 6.92nmol/L to 0.28μmol/L for levofloxacin, 7.54nmol/L to 0.30μmol/L for ciprofloxacin, and 3.90nmol/L to 0.25μmol/L for enoxacin. This probe was further used to determine five quinolones in fish tissues and the recoveries ranging from 90.33% to 108.43% were obtained with relative standard deviation below 5.53%. This work offers a new and general strategy to synthesize a MUCPs@MIP upconversion fluorescence probe with magnetic and selective molecular recognition capability for rapid and accurate sensing of multiple chemical residues in the environment and agri-food products.

Graphical abstract

http://ift.tt/2CYsVh6

Thrombodynamics, a new global coagulation test: Measurement of heparin efficiency

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Elena I. Sinauridze, Tatiana A. Vuimo, Ivan D. Tarandovskiy, Ruzanna A. Ovsepyan, Stepan S. Surov, Natalia G. Korotina, Ilya I. Serebriyskiy, Maxim M. Lutsenko, Alexander L. Sokolov, Fazoil I. Ataullakhanov
The actual coagulation status may be reliably measured using only highly sensitive global functional tests; however, they are not numerous and all of them have disadvantages. Thrombodynamics (TD), a novel global coagulation test, is sensitive to hypo- and hypercoagulable states. The main properties of this test were investigated, and its capabilities for hemostasis analysis were verified through pharmacodynamic monitoring of the most widely used anticoagulants, heparins. The anticoagulant effects in the plasma of donors (n = 20) and patients after hip replacement (n = 20) spiked with unfractionated heparin or enoxaparin were measured in vitro to eliminate the influence of pharmacokinetic factors. Sensitivity for heparins was compared for activated partial thromboplastin time, thrombin generation tests and TD. TD was shown to reliably characterize the pharmacodynamics of any heparin in the entire range of its prophylactic and therapeutic concentrations. Inter-individual variability for the anticoagulant action of heparins was also calculated using the TD data. This variability did not differ between the investigated groups and did not exceed 12% and 20% for the stationary clot growth rate in the presence of unfractionated heparin and enoxaparin, respectively. That finding was in accordance with the values determined earlier using the thrombin generation test. The study results showed that TD has advantages over the other global methods of coagulation analysis. These advantages are good standardization, high reproducibility, independence of the parameter values from patient age and gender, and a narrower parameter distribution in a normal population. These results indicate that TD is a promising universal assessment method that improves the quality of hemostasis analysis because it more reliably detects deviations from the parameters' reference values.

Graphical abstract

http://ift.tt/2F57b3U

Recent advances and developments on integrating nanotechnology with chemiluminescence assays

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Ashish Tiwari, S.J. Dhoble
Chemiluminescence (CL) techniques are extensively utilized for detection of analytes due to their high sensitivity, rapidity and selectivity. With the advent of nanotechnology and incorporation of the nanoparticles in the CL system has revolutionized the assays due to their unique optical and mechanical properties. Several CL-based reactions have been developed where these nanoparticle based CL sensors have evolved as excellent prospects for sensing in various analytical applications. This review article addresses the nanoparticles based CL detection system that are recently developed, the mechanisms has been summarized and the role of luminophors have been discussed. This article critically analyzes the optimal conditions for the CL detection along with quantitative assessment of the analytes. We have included the use of semiconductor nanoparticles, metal nanoparticles, graphene based nanostructures, mesoporous nanospheres, layered double hydroxides, clays for CL detection. The scope and application of these nanoscale material based CL system in various branches of science and technology including chemistry, biomedical applications, pharmaceutics, food, environmental and toxicological applications has been critically summarized.

Graphical abstract

http://ift.tt/2F7fZpW

Magnetic solid-phase extraction based on magnetic multiwalled carbon nanotubes for the simultaneous enantiomeric analysis of five β-blockers in the environmental samples by chiral liquid chromatography coupled with tandem mass spectrometry

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Zhaokun Wang, Xue Zhang, Shenmeng Jiang, Xingjie Guo
In this work, the magnetic multiwalled carbon nanotubes (Mag-MWCNTs) were prepared by self-assembly method and characterized by scanning electron microscopy, X-ray powder diffraction, energy dispersive X-ray and vibrating sample magnetometer. Then, these synthetic Mag-MWCNTs were used as sorbents to extract five β-blockers (atenolol, metoprolol, esmolol, pindolol and arotinolol) by magnetic solid-phase extraction. The target analytes adsorbed on Mag-MWCNTs were eluted and determined on a chiral α-acid glycoprotein column coupled with a triple quadrupole mass spectrometry. Eventually, the proposed method was applied to the analysis of the enantiomeric composition of the studied β-blockers in three environmental samples, including river water, influent wastewater and effluent wastewater. Method detection and quantification limits for all enantiomers were in the range of 0.50–1.45 and 1.63–3.75ng/L, respectively. Satisfactory recovery (82.9–95.6%), good intra-day precision (RSD 0.4–10.4%) and inter-day precision (RSD 2.9–7.4%) were also obtained. With numerous advantages such as simplicity of operation, rapidity and high enrichment factor, the newly developed method has potential to assess the enantioselectivity of chiral drugs in ecotoxicity and biodegradation processes, which is also a new expanded application of Mag-MWCNTs in the environmental analysis.

Graphical abstract

http://ift.tt/2F4aqZn

Mn2+-doped NaYF4:Yb,Er upconversion nanoparticles for detection of uric acid based on the Fenton reaction

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Yaoyao Zhou, Bo Ling, Hongqi Chen, Lun Wang
A novel fluorescence method for the determination of hydrogen peroxide (H2O2) and uric acid (UA) was developed. The procedure was based on the hydroxyl radicals (·OH), which effectively quenched the fluorescence of the Mn²⁺-doped NaYF4:Yb,Er upconversion nanoparticles (UCNPs). Based on the property of Mn²⁺-doped NaYF4:Yb,Er upconversion nanoparticles, the Fenton reaction and enzymatic reaction of uric acid, this method could be used for highly sensitive detection of H2O2 and uric acid. Under optimal conditions, we observed that the fluorescence quenching signal showed good linearity with the H2O2 concentration in the range of 3.00×10^-8 M ~ 6.00×10^-5 M, and the detection limit of this assay was 1.30×10^-8 M. Meanwhile, the linear concentration range for UA was 4.00×10^-9 M ~ 1.00×10^-5 M, and the lower limit of detection was 1.90×10^-9 M. Furthermore, the developed method was successfully used for the determination of UA levels in human serum with satisfactory results.

Graphical abstract

http://ift.tt/2F6q99Z

High Channel Count Microphone Array Accurately and Precisely Localizes Ultrasonic Signals from Freely-Moving Mice

Publication date: Available online 5 January 2018
Source:Journal of Neuroscience Methods
Author(s): Megan R. Warren, Daniel T. Sangiamo, Joshua P. Neunuebel
BackgroundAn integral component in the assessment of vocal behavior in groups of freely interacting animals is the ability to determine which animal is producing each vocal signal. This process is facilitated by using microphone arrays with multiple channels.New Method and Comparison with Existing MethodsHere, we made important refinements to a state-of-the-art microphone array based system used to localize vocal signals produced by freely interacting laboratory mice. Key changes to the system included increasing the number of microphones as well as refining the methodology for localizing and assigning vocal signals to individual mice.ResultsWe systematically demonstrate that the improvements in the methodology for localizing mouse vocal signals led to an increase in the number of signals detected as well as the number of signals accurately assigned to an animal.ConclusionsThese changes facilitated the acquisition of larger and more comprehensive data sets that better represent the vocal activity within an experiment. Furthermore, this system will allow more thorough analyses of the role that vocal signals play in social communication. We expect that such advances will broaden our understanding of social communication deficits in mouse models of neurological disorders.



http://ift.tt/2F5Y6aH

The transgenic mouse line Igsf9-eGFP allows targeted stimulation of inferior olive efferents

Publication date: 15 February 2018
Source:Journal of Neuroscience Methods, Volume 296
Author(s): Christina Pätz, Simone Brachtendorf, Jens Eilers
BackgroundThe inferior olive (IO) innervates the cerebellum forming synapses in the deep cerebellar nuclei (DCN) and the cerebellar cortex. Beside the well-known exception of synapses on Purkinje neurons, synapses between IO efferents and other neuronal targets have not been studied intensively, mostly due to the technical challenge of unequivocally identifying IO efferents in electrophysiological experiments.New methodWe describe the transgenic mouse line Igsf9-eGFP, which expresses GFP in IO neurons, as a suitable tool for studying IO efferents using live imaging, immunohistochemistry and electrophysiology.ResultsIn the Igsf9-eGFP line, GFP-positive neurons are found in all IO subnuclei. Their efferents show the expected trajectories innervating the DCN and, as climbing fibers (CFs), the cerebellar cortex. In the DCN the dentate nucleus shows the strongest innervation, and, within the cerebellar cortex, CFs show a rostral-to-caudal gradient. GFP-positive CFs undergo a normal postnatal maturation, and evoke normal synaptic responses in Purkinje neurons and DCN neurons.Comparison with existing methodsIO efferents have been labelled via anterograde labelling, viral transfection and in transgenic mouse lines. The latter approach does not require stereotactic injections. However, available mouse lines show only a sparse GFP expression, harbor GFP-positive axons of other cerebellar fibers, or have not been characterized in detail.ConclusionsThe Igsf9-eGFP line is characterized by a moderate density of GFP-positive IO efferents, which can be visually targeted for extracellular stimulation with micrometer precision. The mouse line will allow studying fiber-specific responses in all neurons targeted by the IO.



http://ift.tt/2Ed8U5Z

Vaccination with FasL-/TCL plus MHSP65 induces improved anti-lung cancer immunity in mice

Publication date: February 2018
Source:International Immunopharmacology, Volume 55
Author(s): Bohan Dong, Guangli Dai, Yuanyuan Ding, Beiru Wang, Siyuan Zhang
In a previous study, we constructed a MHSP65-TCL anti-lung cancer vaccine with Lewis lung carcinoma TCL plus MHSP65, and illustrated its anti-lung cancer effect through specific and nonspecific anti-tumor immunity. However, TCL contains some immunoinhibit components such as FasL. If this component can be eliminated from TCL, the anti-tumor immunity of MHSP65-TCL constructed with TCL should be improved. In the present study, we knocked down FasL from Lewis lung carcinoma cells and prepared MHSP65-(FasL-/TCL) with this cell line's TCL. After further investigation, MHSP65-(FasL-/TCL) exhibited a better ability to reduce splenocytes apoptosis, promote its activation and secretion of secretingTNF-β, IL-2 compared with MHSP65-(FasL+/TCL). Accordingly, specific and nonspecific antitumor immunity induced by MHSP65-(FasL-/TCL) is stronger than that of MHSP65-(FasL+/TCL). In vivo, MHSP65-(FasL-/TCL) immunization can prolong survival of Lewis lung carcinoma bearing mice. Thus, we report that the anti-lung cancer effect of MHSP65-TCL can be improved by removal of FasL from the TCL. It provides a new route to construct MHSP65-TCL and other antitumor vaccines based on TCL.



http://ift.tt/2m5OapR

Effects of guluronic acid (G2013) on SHIP1, SOCS1 induction and related molecules in TLR4 signaling pathway

Publication date: February 2018
Source:International Immunopharmacology, Volume 55
Author(s): Seyed Shahabeddin Mortazavi-Jahromi, Ali Farazmand, Nasrin Motamed, Shadi Sadat Navabi, Abbas Mirshafiey
ObjectiveThis research aimed to study the anti-inflammatory and immunomodulatory effects of guluronic acid (G2013) on gene expression of TLR4, MyD88, SHIP1, SOCS1, NF-κB, and assessment of the level of IL-1β as a pro-inflammatory cytokine in HEK-Blue hTLR4 cell line.MethodsThe cytotoxicity of G2013 was assessed by the MTT assay. The mRNA expression levels of the mentioned genes were measured by qRT-PCR. IL-1β concentration in culture media was determined using ELISA method.ResultsMTT assay demonstrated that G2013 (before the concentration of 125μg/ml) had no cytotoxic effect on HEK-Blue hTLR4 cells. Our results indicated that the low and high doses of this drug could significantly reduce the gene expression of TLR4 and MyD88, as compared to the control group (p<0.05). Moreover, it was found that the low dose of this drug could significantly increase the gene expression of SHIP1 and SOCS1, as compared to the control group (p<0.05). Furthermore, the study findings revealed that the level of NF-κB gene expression significantly reduced, in both doses of G2013 compared to the control group (p<0.05, p<0.01, respectively). Our data showed that the level of IL-1β in culture media decreased by both doses of this drug in comparison to control group (p<0.05).ConclusionThis study indicates that G2013 is able to induce SHIP1, SOCS1 and reduce TLR4, MyD88, NF-κB at the level of gene expression and decrease IL-1β as a pro-inflammatory cytokine which might be recommended for reduction of inflammatory reactions.



http://ift.tt/2qsEU3P

Zerumbone suppresses the activation of inflammatory mediators in LPS-stimulated U937 macrophages through MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways

Publication date: February 2018
Source:International Immunopharmacology, Volume 55
Author(s): Md. Areeful Haque, Ibrahim Jantan, Hemavathy Harikrishnan
Zerumbone (ZER), isolated mainly from the Zingiber zerumbet (Z. zerumbet) rhizomes was found to be effective against numerous inflammatory and immune disorders, however, the molecular and biochemical mechanisms underlying its anti-inflammatory and immunosuppressive properties have not been well studied. This study was carried out to examine the profound effects of ZER on inflammatory mediated MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways in LPS-stimulated U937 human macrophages. ZER significantly suppressed the up-regulation pro-inflammatory mediators, TNF-α, IL-1β, PGE2, and COX-2 protein in LPS-induced human macrophages. Moreover, ZER significantly downregulated the phosphorylation of NF-κB (p65), IκBα, and IKKα/β as well as restored the degradation of IκBα. ZER correspondingly showed remarkable attenuation of the expression of Akt, JNK, ERK, and p38 MAPKs phosphorylation in a concentration-dependent manner. ZER also diminished the expression of upstream signaling molecules TLR4 and MyD88, which are prerequisite for the NF-κB, MAPK and PI3K-Akt activation. Additionally, quantification of relative gene expression of TNF-α, IL-1β, and COX-2 indicated that, at a higher dose (50μM), ZER significantly downregulated the elevated mRNA transcription levels of the stated pro-inflammatory markers in LPS-stimulated U937 macrophages. The strong suppressive effects of ZER on the activation of inflammatory markers in the macrophages via MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways suggest that ZER can be a preventive and potent therapeutic candidate for the management of various inflammatory-mediated immune disorders.

Graphical abstract

http://ift.tt/2qwQN8Y

Cellulose binders for electric double-layer capacitor electrodes: The influence of cellulose quality on electrical properties

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Britta Andres, Christina Dahlström, Nicklas Blomquist, Magnus Norgren, Håkan Olin
Cellulose derivatives are widely used as binders and dispersing agents in different applications. Binders composed of cellulose are an environmentally friendly alternative to oil-based polymer binding agents. Previously, we reported the use of cellulose nanofibers (CNFs) as binders in electrodes for electric double-layer capacitors (EDLCs). In addition to good mechanical stability, we demonstrated that CNFs enhanced the electrical performance of the electrodes. However, cellulose fibers can cover a broad range of length scales, and the quality requirements from an electrode perspective have not been thoroughly investigated. To evaluate the influence of fiber quality on electrode properties, we tested seven samples with different fiber dimensions that are based on the same kraft pulp. To capture the length scale from fibers to nanofibrils, we evaluated the performance of the untreated kraft pulp, refined fibers, microfibrillated cellulose (MFC) and CNFs.Electrodes with kraft pulp or refined fibers showed the lowest electrical resistivity. The specific capacitances of all EDLCs were surprisingly similar, but slightly lower for the EDLC with CNFs. The same electrode sample with CNFs also showed a slightly higher equivalent series resistance (ESR), compared to those of the other EDLCs. Graphite dispersions with MFC showed the best dispersion stability.

Graphical abstract

http://ift.tt/2m3WqXr

Biphasic scaffolds of silk fibroin film affixed to silk fibroin/chitosan sponge based on surgical design for cartilage defect in osteoarthritis

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Khanitta Panjapheree, Suttatip Kamonmattayakul, Jirut Meesane
Osteoarthritis is inflammation that can occur at any joint, and is caused by cartilage degeneration. For severe cases, patients need surgery by substitution with performance tissue engineering scaffolds. Biphasic scaffolds of silk fibroin film affixed to a silk fibroin/chitosan sponge were constructed for osteoarthritis surgery. Silk fibroin film was fabricated before affixation to the sponge of silk fibroin/chitosan at different ratios of silk fibroin to chitosan: 100:0 (SF), 70:30 (SF70), 50:50 (SF50), 30:70 (SF30), and 0:100 (CS). The morphologies of the scaffolds were observed by scanning electron microscopy. Physical functionality as well as stability was evaluated from mechanical properties, and the percentage of swelling, and degradation. Biological functionality was evaluated using a rat mesenchymal stem cell (RMSCs) culture. Cell proliferation was analyzed and the histological structure was observed. SF30 showed suitable morphology, physical stability, and biological functionality to promote RMSC regulation into chondrocytes. This indicated that SF30 shows promise for cartilage regeneration in osteoarthritis surgery.

Graphical abstract

http://ift.tt/2m5GZhp

Numerical methodology to analyze the ice impact threat: Application to composite structures

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): J. Pernas-Sánchez, J.A. Artero-Guerrero, J. López-Puente, D. Varas
Impacts on composites produce interlaminar failure (delamination) which is difficult to detect in common maintenance tasks, and affects the structural integrity. Therefore it is critical, for safety, to improve prediction tools in order to perform tolerant damage designs. The numerical modeling of impacts of deformable objects (such as ice) on composite panels is still a challenge. Not only the modeling of the laminate should be appropriate to reproduce its behavior and failures, but also the modeling of the deformable projectile should be capable to induce the corresponding response and damages. In this work a two-step numerical methodology is proposed for the study of ice impact. First, the deformable impactor is analyzed, studying the impact process on a rigid target (a steel plate attached to a load cell). Once the deformable projectile behavior is fully captured, the ice impact on a deformable target (a carbon/epoxy laminate) is studied. The composite material model takes into account intralaminar and interlaminar failure in order to reproduce the laminate behavior. Different ice sphere diameters (30,40 and 50mm) and impact velocities (50−250m/s) are considered in this study. All the results from the numerical simulations have been compared with the experimental results.

Graphical abstract

http://ift.tt/2m2U0Zk

Microstructural evolution and compositional homogenization of a low Re-bearing Ni-based single crystal superalloy during through progression of heat treatment

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Xianglin Su, Qingyan Xu, Runnan Wang, Zilin Xu, Shizhong Liu, Baicheng Liu
Microstructural and chemical heterogeneities may exacerbate the high-temperature mechanical properties of single crystal turbine blades. The evolution of microstructure and compositional homogeneity of an as-cast low Re-containing multicomponent DD6 alloy during through progression of heat treatment was detailedly studied. Using optical microscope, field emission gun scanning electron microscope, electron probe microanalysis, differential scanning calorimetry, and complementary thermodynamic calculations, we investigated the time-dependent size and volume fraction variations of γ/γ′ eutectic during specific solution heat treatment steps, the evolution of γ′ precipitates, carbides, and compositional homogeneity, and the thermo-physical changes of as-cast DD6 alloy during through progression of heat treatment. Based on our experimental and theoretical results, the mechanism underlying the microstructure formation and chemical segregation of as-cast DD6 alloy was clarified. The mechanism of microstructural evolution and compositional homogenization, and the diffusion mechanism of elements that occurs between dendritic and interdendritic regions of as-cast DD6 alloy during through progression of heat treatment were elucidated. The correlations between microstructural evolution, compositional homogenization, and thermo-physical changes of as-cast DD6 alloy during through progression of heat treatment were established.

Graphical abstract

http://ift.tt/2m4A6x5

Electrical conductivity of electrospun nanofiber mats of polyamide 6/polyaniline coated with nitrogen-doped carbon nanotubes

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): João Paulo Ferreira Santos, Mohammad Arjmand, Guilherme Henrique França Melo, Kambiz Chizari, Rosario Elida Suman Bretas, Uttandaraman Sundararaj
Conductive nanostructures have emerged as the next generation of functional materials for electronic devices. In this work, electrospun nanofiber mats of polyamide 6/polyaniline (PA6/PAni), with high porosity and high surface area, coated with nitrogen-doped carbon nanotubes (N-CNTs) were developed. Employing the chemical vapor deposition technique, N-CNTs were synthesized at various temperatures, e.g., 650, 750, 850, and 950°C. PA6 and PA6/PAni nanofiber mats were produced employing the electrospinning technique. The mats were then dipped in an aqueous suspension containing dispersed and stabilized N-CNTs. The results revealed that the presence of PAni enhanced the adsorption of N-CNTs on the surface of nanofiber mats, thereby improving their electrical conductivity. The highest conductivity was obtained when the mats were coated with N-CNT650. However, the impact of PAni on the conductivity was higher when the mats were coated with N-CNTs synthesized at higher temperatures, i.e., 10⁻¹²S/cm for PA6/N-CNT950 and 10⁻⁵S/cm for PA6/PAni/N-CNT950, an increase of seven orders of magnitude. It was concluded that the physical features and nitrogen content of N-CNTs had a significant impact on the electrical behavior of the developed mats. Furthermore, it was realized that the synergistic effect between PAni and N-CNT can be employed to build nanostructures with improved conductivity.

Graphical abstract

http://ift.tt/2m3M9dR

Fatigue assessment of multilayer coatings using lock-in thermography

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Andreu Laborda, Andrew Robinson, Shuncai Wang, Yi Zhang, Philippa Reed
Plain bearings experience cyclic loading during operation, which may cause fatigue failure. In the bearings under study a steel backing has a leaded bronze interlayer, covered by a thin (20μm) multilayer coating, which consists of several electroplated layers composed of Sn, Ni and Cu. Commercial performance assessments simulate the conditions of engines in a 'Pass or Fail' test. A new methodology is proposed to assess the fundamental fatigue behaviour for such complex layered bearings. Accelerated fatigue tests on half-shell bearings have been conducted under 3-point bend, whilst the coated side of the bearings are recorded with an infrared camera. Cyclic tests with strain gauges placed on the coating have been performed to evaluate the strains developing during loading. By combining these tests we can rank different coatings. A compliance based failure criterion is also compared with a failure criterion based on early damage revealed by infrared thermography, showing that the latter is far less conservative. Thus, this methodology allows detection of small scale fatigue cracks in the coatings significantly earlier, facilitating assessment and identification of possible mechanisms to explain the differences in fatigue performance between coatings. This provides valuable information to develop new coatings for future bearing designs.

Graphical abstract

http://ift.tt/2m4Xx9e

Surgical and Endovascular Intervention for Dialysis Access Maturation Failure During and After Arteriovenous Fistula Surgery: Review of the Evidence

Publication date: Available online 5 January 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Jan H.M. Tordoir, Niek Zonnebeld, Magda M. van Loon, Maurizio Gallieni, Markus Hollenbeck
BackgroundMaturation failure is the major obstacle to establishing functional arteriovenous fistulae (AVF) for haemodialysis treatment. Various endovascular and surgical techniques have been advocated to enhance fistula maturation and to increase the number of functional AVFs. This narrative review considers the available evidence of interventional techniques for treatment of AVF non-maturation.ResultsIntra-operative vein dilation and anastomosis modification results in a clinical maturation rate of 74–92% and a 6 month cumulative AVF patency of 79–93%. Percutaneous transluminal angioplasty (PTA) with or without accessory vein obliteration is successful in 43–97% of patients. The long-term primary patency of PTA is rather low and multiple re-interventions are needed to achieve an acceptable cumulative fistula patency. The results of surgical revision exceed the results of endovascular intervention, with a mean primary one year patency of 73% (range 68–78%) compared with 49% (range 28–72%), respectively. The role of accessory vein obliteration remains unclear.ConclusionIntervention for autologous arteriovenous fistula non-maturation is worthwhile and results in an increased number of functional fistulae. The outcome of surgical revision is better than endovascular and might be preferable in certain patient populations.



http://ift.tt/2COl1tC

Commentary on “A Propensity Matched Comparison for Open and Endovascular Treatment of Post-carotid Endarterectomy Restenosis”

Publication date: Available online 5 January 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): A. Ross Naylor




http://ift.tt/2Az79xv

Spanish Translated Abstracts

Publication date: January 2018
Source:European Journal of Vascular and Endovascular Surgery, Volume 55, Issue 1





http://ift.tt/2COkQys

The Implications of Non-compliance to Endovascular Aneurysm Repair Surveillance: A Systematic Review and Meta-analysis

Publication date: Available online 5 January 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Matthew Joe Grima, Mourad Boufi, Martin Law, Dan Jackson, Kate Stenson, Benjamin Patterson, Ian Loftus, Matt Thompson, Alan Karthikesalingam, Peter Holt
Objective/backgroundIncreasingly, reports show that compliance rates with endovascular aneurysm repair (EVAR) surveillance are often suboptimal. The aim of this study was to determine the safety implications of non-compliance with surveillance.MethodsThe study was carried out according to the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search was undertaken by two independent authors using Embase, MEDLINE, Cochrane, and Web of Science databases from 1990 to July 2017. Only studies that analysed infrarenal EVAR and had a definition of non-compliance described as weeks or months without imaging surveillance were analysed. Meta-analysis was carried out using the random-effects model and restricted maximum likelihood estimation.ResultsThirteen articles (40,730 patients) were eligible for systematic review; of these, seven studies (14,311 patients) were appropriate for comparative meta-analyses of mortality rates. Three studies (8316 patients) were eligible for the comparative meta-analyses of re-intervention rates after EVAR and four studies (12,995 patients) eligible for meta-analysis for abdominal aortic aneurysm related mortality (ARM). The estimated average non-compliance rate was 42.0% (95% confidence interval [CI] 28–56%). Although there is some evidence that non-compliant patients have better survival rates, there was no statistically significant difference in all cause mortality rates (year 1: odds ratio [OR] 5.77, 95% CI 0.74–45.14; year 3: OR 2.28, 95% CI 0.92–5.66; year 5: OR 1.81, 95% CI 0.88–3.74) and ARM (OR 1.47, 95% CI 0.99–2.19) between compliant and non-compliant patients in the first 5 years after EVAR. The re-intervention rate was statistically significantly higher in compliant patients from 3 to 5 years after EVAR (year 1: OR 6.36, 95% CI 0.23–172.73; year 3: OR 3.94, 85% CI 1.46–10.69) year 5: OR 5.34, 95% CI 1.87–15.29).ConclusionThis systematic review and meta-analysis suggest that patients compliant with EVAR surveillance programmes may have an increased re-intervention rate but do not appear to have better survival rates than non-compliant patients.



http://ift.tt/2Ay0Lqs

Editorial Board

Publication date: January 2018
Source:European Journal of Vascular and Endovascular Surgery, Volume 55, Issue 1





http://ift.tt/2CMEFGq

Contents

Publication date: January 2018
Source:European Journal of Vascular and Endovascular Surgery, Volume 55, Issue 1





http://ift.tt/2AxZQpM

Selected Abstracts from the January Issue of the Journal of Vascular Surgery

Publication date: January 2018
Source:European Journal of Vascular and Endovascular Surgery, Volume 55, Issue 1





http://ift.tt/2CK0kz2

Forthcoming Events

Publication date: January 2018
Source:European Journal of Vascular and Endovascular Surgery, Volume 55, Issue 1





http://ift.tt/2AxK3aL

One year on: Test your knowledge from the previous year

Publication date: January 2018
Source:European Journal of Vascular and Endovascular Surgery, Volume 55, Issue 1





http://ift.tt/2COkrfq

Abstracts from Issue 37 of EJVES Short Reports

Publication date: January 2018
Source:European Journal of Vascular and Endovascular Surgery, Volume 55, Issue 1





http://ift.tt/2AxZ2Bg

Vascular function and cholecalciferol supplementation in CKD: A self-controlled case series

Publication date: Available online 5 January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Vivek Kumar, Ashok Kumar Yadav, Manphool Singhal, Vinod Kumar, Anupam Lal, Debasish Banerjee, Krishan Lal Gupta, Vivekanand Jha
Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) patients. Cardiovascular disease (CVD) is the commonest cause of mortality in CKD patients. In a randomized, double blind, placebo controlled trial, we have recently reported favorable effects of vitamin D supplementation on vascular & endothelial function and inflammatory biomarkers in vitamin D deficient patients with non-diabetic stage 3-4 CKD (J Am Soc Nephrol 28: 3100–3108, 2017). Subjects in the placebo group who had still not received vitamin D after completion of the trial received two oral doses 300000 IU of oral cholecalciferol at 8 weeks interval followed by flow mediated dilatation (FMD), pulse wave velocity (PWV), circulating endothelial and inflammatory markers (E-Selectin, vWF, hsCRP and IL-6), 1,25 (OH)2D, iPTH and iFGF-23 assessment at 16 weeks. 31 subjects completed this phase of the study. Last values recorded in the preceding clinical trial were taken as baseline values. Serum 25(OH)D and 1,25(OH)2D increased and FMD significantly improved after cholecalciferol supplementation [mean change in FMD%: 5.8% (95% CI: 4.0-7.5%, p<0.001]. Endothelium independent nitroglycerine mediated dilatation, PWV, iPTH, iFGF-23 and IL-6 also showed favorable changes. The data further cement the findings of beneficial effects of correction of vitamin D deficiency on vascular function.



http://ift.tt/2D0fugz

Comparison of treatment of basal cell carcinoma between surgery and intralesional photodynamic therapy: a cross-sectional study

Publication date: Available online 5 January 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): M.J. Suárez Valladares, J. Vega, M.A. Rodríguez Prieto
BackgroundSurgery is the treatment of choice in basal cell carcinoma (BCC), but new less invasive techniques are in development as photodynamic therapy. The main problem of this technique is the limited penetration. The use of an intralesional photosensitizer plus an irradiation with a 630 nm laser increased this penetration.ObjetivesTo compare the effectiveness in treatment of BCC between surgery and intralesional photodynamic therapy (I-PDT). To identify the clearance rate differences between intralesional or external irradiation in I-PTD group.MethodsA retrospective study of 102 patients with different histological types of BCC (mean depth of 2.44 mm) was performed. 51 patients were treated with surgery and 51 with I-PDT, injecting 5-aminolevulinic acid 1% in the tumor and later irradiated with a 630 nm laser (intralesionally or externally 25 and 26 patients respectivelly). Histological samples were obtained before and after treatment.Results41/51 patients in surgery group vs 42/51 patients in I-PDT group achieved a complete clearance after treatment (p 0.79). There were no differences in success rates between intralesional vs external irradiation in I-PDT group (p 0.46).Limitationssmall sample size and retrospective study.ConclusionI-PDT achieved high clearance rates in the treatment of BCC similar to surgery. There were no differences in success rates between intralesional vs external irradiation in I-PDT group. It might be an interesting option of treatment where surgery it is not possible.



http://ift.tt/2m6WKF9

5-aminolevulinic acid mediated photodynamic therapy inhibits survival activity and promotes apoptosis of A375 and A431 cells

Publication date: Available online 5 January 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Jingjing Cai, Qiuping Zheng, Huifang Huang, Buhong Li
ObjectivesThe purpose of this study was to investigate the effects of 5-aminolaevulinic acid mediated photodynamic therapy (ALA-PDT) on the survival activity and apoptosis of human melanoma cell line A375 and non-melanoma skin carcinoma cell line A431 cells. The mechanism for cellular apoptosis was explored.MethodsThe cell survival activity was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and the proportion of apoptotic cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression levels of Bcl-2, Bax, caspase-3, caspase-8 and caspase-9 protein were assessed by western blot. The subcellular localization of cytochrome c was comparatively investigated by immunohistochemistry between pre-ALA-PDT and post- ALA-PDT.ResultsALA-PDT significantly inhibited the survival activity of A375 cells and A431 cells in a dose- and time-dependent manner. The optimum inhibition efficiencies for A375 cells and A431 cells were obtained at 0.6 mM ALA at 4 h and 8 h after ALA-PDT, respectively. The phenomena of apoptosis were observed in ALA-PDT treated cells by TUNEL assay. The apoptotic rates of A375 cells and A431 cells were 90.0% and 61.5% at 6 h after ALA-PDT, respectively. Apoptosis induced by ALA-PDT involved in down-regulation of Bcl-2 protein, up-regulation of Bax protein and cleaved-PARP protein. It was observed that the expression of cleaved- caspase-3, caspase-8 and caspase-9 proteins in A375 cells and A431 cells gradually increased in 2 h and 4 h but decreased at 4–6 h and 6–8 h after ALA-PDT, respectively. In apoptosis cells immunohistochemical localization show that cytochrome C diffused from the mitochondria into the cytosol.ConclusionALA-PDT could significantly inhibit the survival activity of A375 and A431 cells. The apoptosis induced by ALA-PDT in A375 and A431 cells was related to the caspase-dependent death-receptor pathway and Cytochrome c-dependent mitochondrial pathway.



http://ift.tt/2qrlrQU

Moderate Treadmill Exercise Ameliorates Amyloid-β-Induced Learning and Memory Impairment, Possibly via Increasing AMPK Activity and Up-regulation of the PGC-1α/FNDC5/BDNF Pathway

Publication date: Available online 5 January 2018
Source:Peptides
Author(s): Mohammad Azimi, Reza Gharakhanlou, Nasser Naghdi, Davar Khodadadi, Soomaayeh Heysieattalab
Alzheimer's disease (AD) is a neurodegenerative disorder associated with loss of memory and cognitive abilities. Previous evidence suggested that exercise ameliorates learning and memory deficits by increasing brain derived neurotrophic factor (BDNF) and activating downstream pathways in AD animal models. However, upstream pathways related to increase BDNF induced by exercise in AD animal models are not well known. We investigated the effects of moderate treadmill exercise on Aβ-induced learning and memory impairment as well as the upstream pathway responsible for increasing hippocampal BDNF in an animal model of AD. Animals were divided into five groups: Intact, Sham, Aβ1-42, Sham-exercise (Sham-exe) and Aβ1-42-exercise (Aβ-exe). Aβ was microinjected into the CA1 area of the hippocampus and then animals in the exercise groups were subjected to moderate treadmill exercise (for 4 weeks with 5 sessions per week) 7 days after microinjection. In the present study the Morris water maze (MWM) test was used to assess spatial learning and memory. Hippocampal mRNA levels of BDNF, peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), fibronectin type III domain-containing 5 (FNDC5) as well as protein levels of AMPK-activated protein kinase (AMPK), PGC-1α, BDNF, phosphorylation of AMPK were measured. Our results showed that intra-hippocampal injection of Aβ1−42 impaired spatial learning and memory which was accompanied by reduced AMPK activity (p-AMPK/total-AMPK ratio) and suppression of the PGC-1α/FNDC5/BDNF pathway in the hippocampus of rats. In contrast, moderate treadmill exercise ameliorated the Aβ1−42-induced spatial learning and memory deficit, which was accompanied by restored AMPK activity and PGC-1α/FNDC5/BDNF levels. Our results suggest that the increased AMPK activity and up-regulation of the PGC-1α/FNDC5/BDNF pathway by exercise are likely involved in mediating the beneficial effects of exercise on Aβ-induced learning and memory impairment.



http://ift.tt/2m39OLu

Instructions to Authors

Publication date: January 2018
Source:The Kaohsiung Journal of Medical Sciences, Volume 34, Issue 1





http://ift.tt/2m2YqPA

Checklist

Publication date: January 2018
Source:The Kaohsiung Journal of Medical Sciences, Volume 34, Issue 1





http://ift.tt/2qvZNez

Authorship and conflict statements

Publication date: January 2018
Source:The Kaohsiung Journal of Medical Sciences, Volume 34, Issue 1





http://ift.tt/2m42GhN

Copyright transfer statement

Publication date: January 2018
Source:The Kaohsiung Journal of Medical Sciences, Volume 34, Issue 1





http://ift.tt/2quckzd

Permission request

Publication date: January 2018
Source:The Kaohsiung Journal of Medical Sciences, Volume 34, Issue 1





http://ift.tt/2m1v9Fi

Epithelial ovarian cancer mortality among Hispanic women: Sub-ethnic disparities and survival trend across time: An analysis of SEER 1992–2013

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Chen Chen, Talar W. Markossian, Abigail Silva, Yelena N. Tarasenko
BackgroundOver the past half century the proportion of Hispanics in the US population has been steadily increasing, and groups of Hispanic origin have diversified. Despite notable racial and ethnic disparities in ovarian cancer (OC) mortality, population-based studies on OC among Hispanic females are lacking.ObjectivesTo examine sub-ethnic disparities in OC mortality and survival trends using the Surveillance, Epidemiology, and End Results Program (SEER) 18 data on Hispanic women diagnosed with epithelial OC during 1992–2013.MethodsThe disparities in OC 5 year survival and mortality were examined using log-rank tests and Cox proportional hazards models, adjusted for sociodemographic and pathological characteristics, time of diagnosis, receipt of resection surgery and county socioeconomic status. Trends in 5-year survival rates were examined using joinpoint regression models.ResultsThe 5-year survival was lowest in Puerto Ricans (median survival: 33 months; survival rate: 31.07%) and was highest in the "Other" Hispanic subgroup (median survival: 59 months; survival rate: 49.14%) (log-rank test: P < 0.001). The OC-specific death hazards in Mexicans (HRadj: 0.82, 95%CI: 0.67–1.00, P = 0.048), South or Central Americans (HRadj: 0.77, 95%CI: 0.62–0.96, P = 0.005) and Other Hispanics (HRadj: 0.76, 95%CI: 0.63–0.92, P = 0.038) were significantly lower than for Puerto Ricans. Mortality rates of Cubans and Puerto Ricans were not significantly different. During 1992–2008, there were non-significant increasing trends in the 5-year all-cause and OC-specific survival rates: from 43.37% to 48.94% (APC = 0.41, P = 0.40) and from 48.72% to 53.46% (APC = 0.29, P = 0.50), respectively.ConclusionsOC mortality in Hispanic patients varied by sub-ethnicity. This heterogeneity should be considered in future cancer data collection, reports and research.



http://ift.tt/2m13DHd

Editorial Board

Publication date: January 2018
Source:Cancer Genetics, Volume 220





http://ift.tt/2F1vrDM

Dedifferentiated liposarcoma composed predominantly of rhabdoid/epithelioid cells: a frequently misdiagnosed highly aggressive variant

Publication date: Available online 5 January 2018
Source:Human Pathology
Author(s): Abbas Agaimy, Michael Michal, Ladislav Hadravsky, Michal Michal
Dedifferentiated liposarcoma is one of the most common sarcoma types in adults with a predilection for the retroperitoneum. We have recently encountered 6 cases of DDL composed predominantly of rounded, rhabdoid or epithelioid cells mimicking rhabdoid melanoma, epithelioid rhabdomyosarcoma or undifferentiated carcinoma. Patients were 5 males and one female aged 64 to 81 years (median, 68). Tumors originated in the retroperitoneum (n=5; 3 in the psoas muscle) and deep soft tissue of the thigh (n=1). All 3 patients with follow-up died of metastatic disease within 4 to 8 months. Preoperative biopsy diagnoses never suggested dedifferentiated liposarcoma as a possibility; instead carcinoma, rhabdomyosarcoma and lymphoma were on top of suggestions. Five resected tumors were composed predominantly (70-100%) of anaplastic rounded to oval rhabdoid cells with prominent central nucleoli and paranuclear rhabdoid inclusions. Bi- and multinucleation was a constant feature. The background stroma showed variable myxoid changes and minor mixed inflammatory cells. Two cases showed homologous dedifferentiation and another had sclerosing spindle cell nodule but a well differentiated lipomatous component was not seen in any. One biopsied case showed solely monotonous small round blue cells with scattered rhabdoid cells. Immunohistochemistry showed expression of MDM2 (6/6), CDK4 (5/6), pancytokeratin AE/1AE3 (4/6) and diffusely desmin + myogenin (2/6). All cases showed high-level co-amplification of MDM2/CDK4 by in-situ-hybridization. The SWI/SNF complex components (SMARCB1, SMARCA2, SMARCA4, ARID1A and PBRM1) were intact in all cases. This highly aggressive liposarcoma variant needs to be distinguished from a variety of neoplasms including undifferentiated carcinoma, melanoma, lymphoma, rhabdomyosarcoma and others.



http://ift.tt/2Ebl5jA

Decreased Expression of Megalin and Cubilin and Altered Mitochondrial Activity in Tenofovir Nephrotoxicity

Publication date: Available online 5 January 2018
Source:Human Pathology
Author(s): Alexandre Cez, Isabelle Brocheriou, François-Xavier Lescure, Clovis Adam, Pierre-Marie Girard, Gilles Pialoux, Søren K. Moestrup, Soraya Fellahi, Jean-Philippe Bastard, Pierre Ronco, Emmanuelle Plaisier
Tenofovir disoproxil fumarate (TDF) is a commonly used antiretroviral drug for HIV, rarely causing Fanconi syndrome and acute kidney injury. We retrospectively analyzed the clinico-pathological presentation of 20 cases of tenofovir-induced tubulopathy, and investigated the renal expression of the megalin and cubilin proteins, as well as the mitochondrial respiratory chain activity. Estimated glomerular filtration rate (eGFR) before TDF exposure was 92 ml/min/1,73m², decreasing to 27.5 ml/min/1,73m² at the time of biopsy, with 30% of patients requiring renal replacement therapy. Proximal tubular expression of megalin and cubilin was altered in 19 and 18 cases, respectively, whereas it was preserved in patients exposed to TDF without proximal tubular dysfunction and in HIV-negative patients with acute tubular necrosis. Loss of megalin/cubilin was correlated with low eGFR and high urine retinol binding protein at the time of biopsy, low eGFR at last follow-up, and was more severe in patients with multifactorial toxicity. Patients with additional nephrotoxic conditions promoting tenofovir accumulation showed a lower eGFR at presentation and at last follow-up, and more severe lesions of acute tubular necrosis, than those with isolated tenofovir toxicity. Altered mitochondrial COX activity in proximal tubules was observed and may be an early cellular alteration in tenofovir nephrotoxicity. In conclusion, altered megalin/cubilin expression represents a distinctive feature o in tenofovir-induced tubulopathy, and its severity is correlated with urine retinol binding protein loss and is associated with a poor renal prognosis. Concomitant exposure to other nephrotoxic conditions severely impacts the renal presentation and outcome.



http://ift.tt/2F2VM4D

Solitary fibrous tumor with neuroendocrine and squamous dedifferentiation: a potential diagnostic pitfall

Publication date: Available online 5 January 2018
Source:Human Pathology
Author(s): Chuanyong Lu, Deepu Alex, Ryma Benayed, Marc K. Rosenblum, Meera R. Hameed
Solitary fibrous tumor (SFT) is a ubiquitous mesenchymal neoplasm of deep soft tissue with variable and often unpredictable biological behavior. The lineage is presumed to be fibroblastic and histological features range from benign to overtly malignant with rare tumors showing "dedifferentiation" or transformation to undifferentiated pleomorphic sarcoma. Dedifferentiation in mesenchymal neoplasms is a phenomenon of histologic progression of a well-differentiated neoplasm to a high-grade sarcoma which can differentiate along divergent lines. It is extremely uncommon to encounter "transdifferentiation" to non-mesenchymal lineage and still maintaining the driver genetic event of the primary tumor. Herein we report two diagnostically challenging SFTs with transformation to neuroendocrine and squamous phenotypes. The index case is a pelvic malignant SFT which metastasized to the liver as a high grade neuroendocrine carcinoma. The second case is a recurrent brain tumor initially presenting as a typical SFT and evolving into a dedifferentiated SFT with foci of squamous differentiation. Positive immunohistochemical stains for CD34 and STAT6 and the detection of NAB2-STAT6 fusion supported the diagnosis of dedifferentiated SFT in both cases. In the first case, molecular study demonstrated that both the pelvic primary and liver metastasis harbored the same NAB2-STAT6 fusion. Dedifferentiation to a non-mesenchymal lineage/lineage infidelity can be a potential diagnostic pitfall in these tumors.



http://ift.tt/2EdCY17

Prognostic Role of Tumoral PDL1 Expression and Peritumoral FoxP3+ Lymphocytes in Vulvar Melanomas

Publication date: Available online 4 January 2018
Source:Human Pathology
Author(s): Agata Chłopik, M. Angelica Selim, Yan Peng, Cheng-Lin Wu, Gemma Tell-Marti, Kristen M. Paral, Sara C. Shalin, Stefan Kraft, Chao-Kai Hsu, Christopher R. Shea, Susana Puig, Maria-Teresa Fernandez-Figueras, Wojciech Biernat, Janusz Ryś, Andrzej Marszalek, Mai P. Hoang
Prognostic role of PDL1 expression, CD8+ and FoxP3+ lymphocytes in vulvar melanomas has not been studied. We correlated PDL1 expression, and CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 75 vulvar melanomas. Tumoral PDL1 expression (>5%) was seen in 23% of cases. By Fisher's Exact test, PDL1 expression and peritumoral FoxP3+ lymphocytes significantly correlated with less disease-specific death. By linear regression analysis, correlations between tumoral PDL1 expression with the density of tumoral CD8+ and peritumoral CD8+ lymphocytes; tumoral FoxP3+ with tumoral CD8+ lymphocytes; and peritumoral FoxP3+ with peritumoral CD8+ lymphocytes were observed. By univariate analyses, tumor thickness > 4mm predicted poorer progression-free survival, melanoma-specific survival and overall survival. PDL1 expression > 5%, peritumoral CD8+, peritumoral FoxP3+ and tumoral FoxP3+ lymphocytes correlated with better overall survival. By multivariate analyses, high peritumoral FoxP3+ lymphocytes independently predicted better melanoma-specific survival (p=0.023); and tumor thickness independently predicted poorer progression-free survival (p = 0.05) and overall survival (p = 0.039). In conclusion, our study shows that independent from tumor thickness an increased density of peritumoral FoxP3+ lymphocytes may positively impact survival in a subset of vulvar melanomas. Tumoral PDL1 expression correlated with tumoral as well as peritumoral CD8+ and FoxP3+ lymphocytes, supportive of an adaptive immune response. Although the frequency of PDL1 expression is low in vulvar melanoma, its expression may identify a subset of vulvar melanoma that might respond to immunotherapy.



http://ift.tt/2F40vmC

Genomic heterogeneity in primary colorectal carcinomas and their metastases: born bad or brought up a villain?

Publication date: Available online 4 January 2018
Source:Human Pathology
Author(s): Maja Hühns, Saskia Krohn, Hugo Murua Escobar, Friedrich Prall
Progression of solid cancers, colorectal carcinomas among them, from their primaries to metastatic lesions traditionally is thought to proceed by a step-wise acquisition of and selection for genomic aberrations. To test if patterns of genomic aberrations would be consistent with this model, we studied ten colorectal carcinoma primary-metastasis pairs, nine with one liver metastasis each, and one with two metastases. Next generation targeted sequencing (50 gene panel) with samples obtained from different regions of the primaries and their metastases demonstrated 1–11 gene mutations per lesion. But only in two tumors there were seen mutations in all samples from the metastasis and not any of the primaries (BRAF^D594N and SMARCB1^R377C mutation, respectively). However, allelotyping the multiregional samples with polymorphous microsatellite markers (17p13.1, D9S942, D9S1748, D5S346, D5S1385) and DNA methylation studies with a marker panel (MLH1, CDNK2A, NEUROG1, CRABP1, CACNA1G, IGF2, RUNX3, SOCS1) showed remarkably "insular" genomic aberrations in all cases for at least some of the analyses. The marked preponderance of mutations shared by the primaries and their metastases throughout the lesions over mutations private to metastases suggests that, at least in many cases, colorectal carcinomas might be endowed with a mutational load sufficient for fully-fledged metastases even at a very early stage ("born bad"). But the very focal allelic imbalances and methylations observed here, hypothetically, could play a role in clinically metastasizing disease, a process of years rather than months and very much a matter of tumor-host interactions when tumor cells adapt to the host microenvironment.



http://ift.tt/2Ebl3bs

Microvascular Mural Cell Organotypic Heterogeneity and Functional Plasticity

Publication date: Available online 5 January 2018
Source:Trends in Cell Biology
Author(s): Annegret Holm, Tina Heumann, Hellmut G. Augustin
Microvascular mural cells (MMCs), comprising pericytes and microvascular smooth muscle cells, are of increasing interest in multiple fields of research for their plasticity and their organotypic functional roles in microvascular homeostasis and disease. They have been described as a heterogeneous cell population constituting a continuum of cell phenotypes along the microvascular bed with vascular smooth muscle cells (VSMCs) at one end of the spectrum and pericytes at the other end. MMC organotypic subpopulations have been suggested to function in a tissue-context-dependent manner, thereby contributing to organ-specific functional roles. However, the phenotypic and organotypic heterogeneity as well as their origin and marker identification are hitherto poorly defined. Here we review recent work and emerging concepts regarding MMC phenotypic and organotypic heterogeneity and their functional plasticity in health and disease.



http://ift.tt/2F3SDl4

Adding HRV biofeedback to psychotherapy increases heart rate variability and improves the treatment of major depressive disorder

Publication date: Available online 5 January 2018
Source:International Journal of Psychophysiology
Author(s): Yoko Tsui Caldwell, Patrick R. Steffen
Heart rate variability (HRV) is a significant marker of health outcomes with decreased HRV predicting increased disease risk. HRV is decreased in major depressive disorder (MDD) but existing treatments for depression do not return heart rate variability to normal levels even with successful treatment of depression. Heart rate variability biofeedback (HRVB) increases heart rate variability but no studies to date have examined whether combining HRVB with psychotherapy improves outcome in MDD treatment. The present study used a randomized controlled design to compare the effects of HRVB combined with psychotherapy on MDD relative to a psychotherapy treatment as usual group and to a non-depressed control group. The HRVB+psychotherapy group showed a larger increase in HRV and a larger decrease in depressive symptoms relative to the other groups over a six-week period, whereas the psychotherapy group only did not improve HRV. Results support the supplementation of psychotherapy with HRVB in the treatment of MDD.



http://ift.tt/2CFltK7

Is Nanoclustering essential for all oncogenic KRas pathways? Can it explain why wild-type KRas can inhibit its oncogenic variant?

Publication date: Available online 5 January 2018
Source:Seminars in Cancer Biology
Author(s): Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Membrane-anchored oncogenic KRas can dimerize, form nanoclusters, and signal through the MAPK (Raf/MEK/ERK) and PI3Kα/Akt/mTOR. Both pathways are needed in KRAS-driven proliferation. Here we ask: Is oncogenic KRas nanoclustering (or dimerization) essential for all KRas signaling pathways? Raf kinase domain dimerization, thus MAPK activation, requires KRas nanoclusters. By contrast, the PI3Kα heterodimer acts as a monomeric unit; thus, does PI3Kα activation and PI3Kα/Akt/mTOR signaling require nanoclustering? Further, calmodulin binds only to oncogenic KRas4B. Here we ask: Does calmodulin downregulate KRas4B cancer development as suggested early on, or promote it? We also ask: Why is oncogenic KRas4B the most abundant isoform? Does wild-type Ras indeed inhibit its oncogenic variants as data appeared to suggest? And related to the last question, why is wild-type KRas a more potent inhibitor of its oncogenic form than wild-type NRas of its oncogenic form? Resolving these cardinal questions, and others, such as how exactly does RASSF5 (NORE1A) act as tumor suppressor, and why Ras isoforms tend to occur in distinct cancer types are crucial for effective pharmacology. In this review, we take a nanoclustering/dimerization-centric outlook and show that many questions can be explained by simply considering Ras nanoclustering.



http://ift.tt/2F5cfFd