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https://www.readbyqxmd.com/read/28346103/discovery-of-novel-gq-biased-lpa1-negative-allosteric-modulators
#1
Yuji Shimizu, Masaharu Nakayama
Lysophosphatidic acid (LPA) activates the G-protein-coupled receptor LPA1, which regulates various cellular processes, including cell proliferation and migration. Although LPA1 transduces cellular responses via Gq, Gi, and G12/13, associations between these signaling molecules and cellular phenotypes remain poorly characterized due to the lack of signal-specific pharmacological tools. Here, we characterized novel signal-biased modulators using multiple assays, including label-free impedance assays. LPA caused dramatic changes in cellular impedance in LPA1-expressing recombinant cells, which were susceptible to G-protein and protein kinase inhibitors...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346095/identification-by-high-throughput-screening-of-pseudomonas-acyl-coenzyme-a-synthetase-inhibitors
#2
Lorenzo Turcano, Daniela Visaggio, Emanuela Frangipani, Antonino Missineo, Matteo Andreini, Sergio Altamura, Paolo Visca, Alberto Bresciani
Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease patients. These infections are recalcitrant to common antibacterial therapies due to inherent antibiotic resistance. To meet the need of new anti- Pseudomonas drugs, a sensitive, homogenous, and robust assay was developed with the aim of identifying inhibitors of acyl-coenzyme A synthetases (ACSs) from Pseudomonas. Given the importance of fatty acids for in vivo nutrition of Pseudomonas, such inhibitors might have the potential to reduce the bacterial fitness during infection...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346093/a-label-free-continuous-fluorescence-based-assay-for-monitoring-ornithine-decarboxylase-activity-with-a-synthetic-putrescine-receptor
#3
Mohamed Nilam, Philip Gribbon, Jeanette Reinshagen, Kathrin Cordts, Edzard Schwedhelm, Werner M Nau, Andreas Hennig
Polyamines play an important role in cell growth, differentiation, and cancer development, and the biosynthetic pathway of polyamines is established as a drug target for the treatment of parasitic diseases, neoplasia, and cancer chemoprevention. The key enzyme in polyamine biosynthesis is ornithine decarboxylase (ODC). We report herein an analytical method for the continuous fluorescence monitoring of ODC activity based on the supramolecular receptor cucurbit[6]uril (CB6) and the fluorescent dye trans-4-[4-(dimethylamino)styryl]-1-methylpyridinium iodide (DSMI)...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345862/quantification-of-lipid-metabolism-in-living-cells-through-the-dynamics-of-lipid-droplets-measured-by-stimulated-raman-scattering-imaging
#4
Chi Zhang, Junjie Li, Lu Lan, Ji-Xin Cheng
Dysregulation of lipid metabolism is associated with many diseases including cancer. Lipid droplet (LD), a ubiquitous organelle in mammalian cells, serves as a hub for lipid metabolism. Conventional assays on the measurement of lipid metabolism rely on the quantification of the lipid composition or amount. Such methods cannot distinguish LDs having different bio-functionalities in living cells, and thus could be inaccurate in measuring the instantaneous lipogenesis of the living cells. We applied label-free stimulated Raman scattering microscopy to quantify the LDs' spatial-temporal dynamics, which showed direct links to cellular lipid metabolisms and can separate LDs involving in different metabolic events...
March 27, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28345821/antioxidant-and-antiproliferative-activities-of-an-ethylacetate-fraction-of-picria-fel-terrae-lour-herbs
#5
Denny Satria, Jansen Silalahi, Ginda Haro, Syafruddin Ilyas, Poppy Anjelisa Z Hsb
Background: Excessive production of oxygen free radicals and imbalance in the mechanisms responsible for antioxidant protection may result in the onset of many diseases including breast cancer. Objective: To evaluate antiproliferative and antioxidant activity of an ethylacetate fraction (EAF) of Picria fel-terrae Lour. Herbs in the T47D cell line. Methods: Phenolic and total flavonoid contents in EAF were determined. EAF was tested for cytotoxicity and effects on the cell cycle and apoptosis, as well as antioxidant activity...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28344470/prolonged-exposure-of-colon-cancer-cells-to-5-fluorouracil-nanoparticles-improves-its-anticancer-activity
#6
Essam Tawfik, Maqusood Ahamed, Abdulaziz Almalik, Mohammad Alfaqeeh, Aws Alshamsan
In this study, we aimed to improve the anticancer effect of 5-FU on human colon cancer cell lines by incorporating in poly(d,l lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The 5-FU-PLGA NPs were prepared by nanoprecipitation technique. Prepared NPs were moderately dispersed with an average diameter of 133 ± 25.19 nm. Scanning Electron Microscope (SEM) images revealed spherical structures with subtle surface irregularity. Free 5-FU dose-response curves were constructed (12.5-2000 μM) using MTT assay on HCT 116 and HT-29 cell lines for 1, 3, and 5 days...
February 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28343945/as-human-lung-microvascular-endothelia-achieve-confluence-src-family-kinases-are-activated-and-tyrosine-phosphorylated-p120-catenin-physically-couples-neu1-sialidase-to-cd31
#7
Sang W Hyun, Anguo Liu, Zhenguo Liu, Erik P Lillehoj, Joseph A Madri, Albert B Reynolds, Simeon E Goldblum
In postconfluent human pulmonary microvascular endothelial cell (HPMEC)s, NEU1 sialidase associates with and desialylates the src family kinase (SFK) substrate, CD31, and disrupts angiogenesis. We asked whether the NEU1-CD31 interaction might be SFK-driven. We found that normalized phospho-SFK (PY416) signal is increased in postconfluent HPMECs compared to subconfluent cells and prior SFK inhibition with PP2 or SU6656 completely blocked NEU1 association with and desialylation of CD31. Prior silencing of each of the four SFKs expressed in HPMECs, as well as CD31, dramatically reduced confluence-induced SFK activation...
March 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28343384/n6-n6-and-o4-modifications-to-neomycin-affect-ribosomal-selectivity-without-compromising-antibacterial-activity
#8
Girish C Sati, Dimitri Scherbakov, Sven N Hobbie, Andrea Vasella, Erik C Böttger, David Crich
The synthesis of a series of neomycin derivatives carrying the 2-hydroxyethyl substituent on N6' and/or N6''' both alone and in combination with a 4'-O-ethyl group is described. By means of cell-free translation assays with wild-type bacterial ribosomes and their hybrids with eukaryotic decoding A sites, we investigate how individual substituents and their combinations affect activity and selectivity at the target level. In principle, and as shown by cell-free translation assays, modifications of the N6' and N6''' positions allow to enhance target selectivity without compromising antibacterial activity...
March 27, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28342898/temperature-induces-significant-changes-in-both-glycolytic-reserve-and-mitochondrial-spare-respiratory-capacity-in-colorectal-cancer-cell-lines
#9
Mihail I Mitov, Jennifer W Harris, Michael C Alstott, Yekaterina Y Zaytseva, B Mark Evers, D Allan Butterfield
Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, in a microplate, label-free detection approach. This study investigate how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology...
March 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28342773/generation-of-enhanced-definitive-endoderm-from-human-embryonic-stem-cells-under-an-albumin-insulin-free-and-chemically-defined-condition
#10
Su Qu, Liang Yan, Bo Fang, Shoudong Ye, Ping Li, Shengyang Ge, Jian Wu, Di Qu, Houyan Song
AIM: To enhance survival and generation of definitive endoderm cells from human embryonic stem cells in a simple and reproducible system. MAIN METHODS: Definitive endoderm (DE) differentiation from human embryonic stem cells (hESCs) was induced under a chemical-defined condition withdrawn insulin supplement and serum albumin. We dissected influence of "alternative growth factors", WNT3A, BMP4 and bFGF in activin A-driven differentiation by detection of DE-associated genes expression and cell viability...
March 22, 2017: Life Sciences
https://www.readbyqxmd.com/read/28342316/comparison-of-cytomegalovirus-cmv-specific-neutralization-capacity-of-hyperimmunoglobulin-hig-versus-standard-intravenous-immunoglobulin-ivig-preparations-impact-of-cmv-igg-normalization
#11
Matthias Stefan Schampera, Katrin Schweinzer, Harald Abele, Karl Oliver Kagan, Reinhild Klein, Ingo Rettig, Gerhard Jahn, Klaus Hamprecht
BACKGROUND: Based on a non-randomized study of Nigro et al. (2005) the intravenous administration of hyperimmunoglobulins (HIGs) is applied frequently to women with primary CMV-infection as "off-label use" in Germany. OBJECTIVES: In order to describe their CMV-specific neutralization-capacity in vitro, we analyzed the HIG preparations Cytotect(®), and Cytogam(®) as well as the standard intravenous immunoglobulins (IVIG) Octagam(®), Gamunex(®), Kiovig(®). STUDY DESIGN: We performed short-term cell-free CMV neutralization assays (CFNT) and long-term cell-adapted neutralization-plaque-reduction assays (PRANT)...
March 16, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28342135/pacap-protects-against-ethanol-and-nicotine-toxicity-in-sh-sy5y-cells-implications-for-drinking-smoking-co-morbidity
#12
Sridharan Manavalan, Bruk Getachew, Kebreten F Manaye, Syed J Khundmiri, Antonei B Csoka, Raechel McKinley, Andrea Tamas, Dora Reglodi, Yousef Tizabi
The detrimental effects of heavy drinking and smoking are multiplied when the two are combined. Treatment modalities for each and especially for the combination are very limited. Although in low concentration, alcohol and nicotine, each may have beneficial effects including neuroprotection, their combination, instead of providing additive protection, may actually lead to toxicity in cell cultures. Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous 38 amino-acid peptide with demonstrated protection against neuronal injury, trauma as well as various endogenous and exogenous toxic agents...
March 24, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28341974/free-radical-and-superoxide-reactivity-detection-in-semen-quality-assessment-past-present-and-future
#13
REVIEW
Jaime Gosalvez, Eva Tvrda, Ashok Agarwal
Oxidative stress is a well-established cause of male infertility, with reactive oxygen species (ROS) impairing sperm production, motility, membrane, and DNA integrity. Currently, most clinics do not test infertile patients for the imbalance between ROS generation and the ability of the antioxidants to scavenge them, although there is a clear need for andrology laboratories to be able to identify and/or quantify seminal oxidative stress. As such there is a clinical urgency for an inexpensive and easy-to-perform assay able to identify oxidative stress in semen...
March 25, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28341052/factors-associated-with-intramammary-infection-in-dairy-cows-caused-by-coagulase-negative-staphylococci-staphylococcus-aureus-streptococcus-uberis-streptococcus-dysgalactiae-corynebacterium-bovis-or-escherichia-coli
#14
S Taponen, E Liski, A-M Heikkilä, S Pyörälä
The aim of this study was to determine risk factors for bovine intramammary infection (IMI) associated with the most common bacterial species in Finland. Large databases of the Finnish milk-recording system and results of microbiological analyses of mastitic milk samples from Valio Ltd. (Helsinki, Finland) were analyzed. The study group comprised 29,969 cows with IMI from 4,173 dairy herds. A cow with a quarter milk sample in which DNA of target species was detected in the PathoProof Mastitis PCR Assay (Thermo Fisher Scientific, Waltham, MA) was determined to have IMI...
January 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28340773/label-free-molecular-beacons-based-cascade-amplification-dna-machine-for-sensitive-detection-of-telomerase-activity
#15
Kan Li, Lei Wang, Xiaowen Xu, Wei Jiang
Sensitive detection of telomerase activity is critical to cancer diagnosis, screening of anticancer drugs and evaluation of cancer therapy. Herein, a label-free molecular beacons-based DNA machine was developed for sensitive detection of telomerase activity. The DNA machine consisted of T7 exonuclease (T7 Exo), label-free recognition molecular beacon (RMB) and signal molecular beacon (SMB) with projecting 5'-terminuses, which can protect RMB and SMB from being digested by T7 Exo. Firstly, telomerase elongated telomerase substrate (TS) primer, generating a telomerase elongation production (TEP) with tandem repeats (TTAGGG)n...
May 15, 2017: Talanta
https://www.readbyqxmd.com/read/28340497/p450-inhibitor-ketoconazole-increased-the-intratumor-drug-levels-and-antitumor-activity-of-fenretinide-in-human-neuroblastoma-xenograft-models
#16
Lluis Lopez-Barcons, Barry J Maurer, Min H Kang, C Patrick Reynolds
We previously reported that concurrent ketoconazole, an oral anti-fungal agent and P450 enzyme inhibitor, increased plasma levels of the cytotoxic retinoid, fenretinide (4-HPR) in mice. We have now determined the effects of concurrent ketoconazole on 4-HPR cytotoxic dose-response in four neuroblastoma (NB) cell lines in vitro and on 4-HPR activity against two cell line-derived, subcutaneous NB xenografts (CDX) and three patient-derived NB xenografts (PDX). Cytotoxicity in vitro was assessed by DIMSCAN assay...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28339066/microrna%C3%A2-499-rs3746444-a-g-polymorphism-functions-as-a-biomarker-to-predict-recurrence-following-endoscopic-submucosal-dissection-in-primary-early-gastric-cancer
#17
Huiyong Shi, Xiangshan Yang, Yanan Zhen, Shoujun Huo, Ruixue Xiao, Zhongfa Xu
The aim of the present study was to investigate the molecular mechanism, including the potential regulatory and signaling pathways, of platelet‑derived growth factor receptor β (PDGFRB), which underlies the recurrence of early gastric cancer (EGC) following endoscopic submucosal dissection (ESD). Online microRNA (miRNA) target prediction tools were used, which identified PDGFRB as the candidate target gene of miR‑499a in gastric cancer cells, and PFGRBR was then confirmed as the direct gene using a luciferase reporter assay system...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338391/modifications-in-human-oral-fibroblast-ultrastructure-collagen-production-and-lysosomal-compartment-in-response-to-e-cigarette-fluids
#18
Silvia Sancilio, Marialucia Gallorini, Amelia Cataldi, Laura Sancillo, Rosa Alba Rana, Viviana di Giacomo
Background Many smokers have recently turned to electronic cigarettes (e-cigarettes) because they have been marketed as a cheaper and safer smokeless alternative to traditional cigarettes, and a possible smoking cessation tool. Even though the safety of these electronic devices is still not fully known, there is evidence of their cytotoxicity on cells which belong to the oral cavity. In a previous paper the increase of reactive oxygen production and Bax expression, followed by the occurrence of apoptosis, were demonstrated in human gingival fibroblasts...
March 24, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28338288/a-comparison-inhibitory-effects-of-cisplatin-and-mnps-peg-cisplatin-on-the-adhesion-capacity-of-bone-metastatic-breast-cancer
#19
Mohammad Javad Mokhtari, Fatemeh Koohpeima, Hadi Mohammadi
To date, high mortality in women due to malignancy breast cancer related to the metastasis to the bone is a significant challenge. Since, magnetic nanoparticles (MNPs) conjugated with the biocompatible polymers was employed for the delivery of some hydrophobic anti-cancer agents, so the main aim of the current research was to assess whether cisplatin-loaded MNPs enhanced the anti-cancer effect of free cisplatin in breast cancer cells.MNPs decorated with PEG were synthesized by an improved co-precipitation technique, and then cisplatin was loaded onto the MNPs via a simple mixing method...
March 24, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28337711/circulating-tumor-dna-for-mutation-detection-and-identification-of-mechanisms-of-resistance-in-non-small-cell-lung-cancer
#20
REVIEW
Kay T Yeung, Soham More, Brian Woodward, Victor Velculescu, Hatim Husain
Targeted therapies have changed the treatment landscape of non-small cell lung cancer over the past decade. Analyses of cell free circulating tumor DNA (ctDNA) provide a non-invasive and robust approach for cancer diagnosis and prognosis, real-time monitoring of treatment response, and the identification of appropriate therapeutic targets based on the detection of tumor genetic aberrations. Recent improvements in the sensitivity, specificity, and feasibility of ctDNA detection assays allow the possibility for implementation into clinical practice...
March 24, 2017: Molecular Diagnosis & Therapy
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