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https://www.readbyqxmd.com/read/29050333/characterization-of-cadd522-a-small-molecule-that-inhibits-runx2-dna-binding-and-exhibits-antitumor-activity
#1
Myoung Sook Kim, Ramkishore Gernapudi, Eun Yong Choi, Rena G Lapidus, Antonino Passaniti
The RUNX2 transcription factor promotes breast cancer growth and metastasis through interactions with a variety of cofactors that activate or repress target genes. Using a direct drug discovery approach we identified CADD522 as a small molecule that inhibits the DNA binding of the runt box domain protein, RUNX2. The current study defines the effect of CADD522 on breast cancer growth and metastasis, and addresses the mechanisms by which it exerts its anti-tumor activity. CADD522 treatment resulted in significant growth inhibition, clonogenic survival, tumorsphere formation, and invasion of breast cancer cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050293/proapoptotic-function-of-deubiquitinase-dusp31-in-drosophila
#2
Sergey A Sinenko
Drosophila have been used to identify new components in apoptosis regulation. The Drosophila protein Dark forms an octameric apoptosome complex that induces the initiator caspase Dronc to trigger the caspase cell death pathway and, therefore, plays an important role in controlling apoptosis. Caspases and Dark are constantly expressed in cells, but their activity is blocked by DIAP1 E3 ligase-mediated ubiquitination and subsequent inactivation or proteasomal degradation. One of the regulatory mechanisms that stabilize proapoptotic factors is the removal of ubiquitin chains by deubiquitinases...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050261/alpha-linolenic-acid-stabilizes-hif-1-%C3%AE-and-downregulates-fasn-to-promote-mitochondrial-apoptosis-for-mammary-gland-chemoprevention
#3
Subhadeep Roy, Atul Kumar Rawat, Shreesh Raj Sammi, Uma Devi, Manjari Singh, Swetlana Gautam, Rajnish Kumar Yadav, Jitendra Kumar Rawat, Lakhveer Singh, Mohd Nazam Ansari, Abdulaziz S Saeedan, Rakesh Pandey, Dinesh Kumar, Gaurav Kaithwas
Alpha linolenic acid is an essential polyunsaturated fatty acid and is reported to have the anti-cancer potential with no defined hypothesis or mechanism/s. Henceforth present study was in-quested to validate the effect of alpha linolenic acid on mitochondrial apoptosis, hypoxic microenvironment and de novo fatty acid synthesis using in-vitro and in-vivo studies. The IC50 value of alpha linolenic acid was recorded to be 17.55μM against ER+MCF-7 cells. Treatment with alpha linolenic acid was evident for the presence of early and late apoptotic signals along with mitochondrial depolarization, when studied through acridine orange/ethidium bromide and JC-1 staining...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050245/von-hippel-lindau-regulates-interleukin-32%C3%AE-stability-in-ovarian-cancer-cells
#4
Hyo Jeong Yong, Jeong Su Park, Ae Lee Jeong, Sora Han, Sunyi Lee, Hye In Ka, Buyanravjkh Sumiyasuren, Hyun Jeong Joo, Su Jeong So, Ji Young Park, Do-Young Yoon, Jong-Seok Lim, Myeong-Seok Lee, Hee Gu Lee, Young Yang
Hypoxia-induced interleukin-32β (IL-32β) shifts the metabolic program to the enhanced glycolytic pathway. In the present study, the underlying mechanism by which hypoxia-induced IL-32β stability is regulated was investigated in ovarian cancer cells. IL-32β expression increased under hypoxic conditions in ovarian cancer cells as it did in breast cancer cells. The amount of IL-32β was regulated by post-translational control rather than by transcriptional activation. Under normoxic conditions, IL-32β was continuously eliminated through ubiquitin-dependent degradation by the von-Hippel Lindau (VHL) E3 ligase complex...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050241/combination-treatment-with-rucaparib-rubraca-and-mdm2-inhibitors-nutlin-3-and-rg7388-has-synergistic-and-dose-reduction-potential-in-ovarian-cancer
#5
Maryam Zanjirband, Nicola Curtin, Richard J Edmondson, John Lunec
Ovarian cancer is the seventh most common cancer worldwide for females and the most lethal of all gynecological malignancies. The treatment of ovarian cancer remains a challenge in spite of advances in debulking surgery and changes in both chemotherapy schedules and routes of administration. Cancer treatment has recently been improving with the introduction of targeted therapies to achieve greater specificity and less cytotoxicity. Both PARP inhibitors and MDM2-p53 binding antagonists are targeted therapeutic agents entered into clinical trials...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050010/calcium-sensing-receptor-stimulation-in-cultured-glomerular-podocytes-induces-trpc6-dependent-calcium-entry-and-rhoa-activation
#6
Lei Zhang, Tianrong Ji, Qin Wang, Kexin Meng, Rui Zhang, He Yang, Chang Liao, Linlin Ma, Jundong Jiao
BACKGROUND/AIMS: Recent studies provided compelling evidence that stimulation of the calcium sensing receptor (CaSR) exerts direct renoprotective action at the glomerular podocyte level. This protective action may be attributed to the RhoA-dependent stabilization of the actin cytoskeleton. However, the underlying mechanisms remain unclear. METHODS: In the present study, an immortalized human podocyte cell line was used. Fluo-3 fluorescence was utilized to determine intracellular Ca2+ concentration ([Ca2+]i), and western blotting was used to measure canonical transient receptor potential 6 (TRPC6) protein expression and RhoA activity...
October 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29049992/iridoids-with-genipin-stem-nucleus-inhibit-lipopolysaccharide-induced-inflammation-and-oxidative-stress-by-blocking-the-nf-%C3%AE%C2%BAb-pathway-in-polycystic-ovary-syndrome
#7
Tao Zuo, Minghui Zhu, Wenming Xu, Zhixia Wang, Hang Song
BACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, and it is usually characterized by chronic inflammation, oxidative stress, and altered microRNA expression. The aim of this study is to investigate how the effects of iridoids with genipin stem nucleus inhibit PCOS complications. The interactions between iridoids were investigated, as well. METHODS: The chronic inflammation cell model was induced using lipopolysaccharide (LPS) in the RAW 264...
October 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29049897/nonenzymatic-flexible-field-effect-transistor-based-glucose-sensor-fabricated-using-nio-quantum-dots-modified-zno-nanorods
#8
Da-Un-Jin Jung, Rafiq Ahmad, Yoon-Bong Hahn
Herein, we fabricated nonenzymatic flexible field-effect transistor (f-FET) based glucose sensor using nickel oxide quantum dots (NiO QDs) modified zinc oxide nanorods (ZnO NRs). The ZnO NRs surfaces were coated with NiO QDs using radio frequency (RF) magnetron sputtering to enhance the electrocatalytic feature and the surface area of ZnO NRs. Under physiological conditions (pH 7.4), the nonenzymatic f-FET glucose sensor shows two linear ranges of 0.001-10mM and 10-50mM with the high sensitivity of 13.14μAcm(-2)mM(-1) and 7...
October 12, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29049887/all-atom-molecular-dynamics-based-analysis-of-membrane-stabilizing-copolymer-interactions-with-lipid-bilayers-probed-under-constant-surface-tensions
#9
Evelyne M Houang, Frank S Bates, Yuk Yin Sham, Joseph M Metzger
An all-atom phospholipid bilayer and triblock copolymer model was developed for Molecular Dynamics (MD) studies. These were performed to investigate the mechanism of interaction between membrane stabilizing triblock copolymer P188 and 1-palmitoyl-2-oleoyl-sn- glycero-3-phosphatidylcholine (POPC) lipid bilayers under applied lateral surface tension (γ) to model membrane mechanical stress. Results showed that P188 insertion is driven by the hydrophobic polypropylene oxide (PPO) core and dependent on bilayer area per lipid...
October 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29049884/a-highly-efficient-and-robust-cation-ordered-perovskite-oxides-as-a-bi-functional-catalyst-for-rechargeable-zinc-air-batteries
#10
Yunfei Bu, Ohhun Gwon, Gyutae Nam, Haeseong Jang, Seona Kim, Qin Zhong, Jaephil Cho, Guntae Kim
Of the various catalysts that have been developed to date for high performance and low cost, perovskite oxides have attracted the attention due to their inherent catalytic activity as well as structural and structural flexibility. Especially, high amount of Pr substitution of the cation ordered perovskite oxide originated from the state-of-the-art Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF) electrode could be a good electrode or catalyst because of its high oxygen kinetics, electrical conductivity, oxygen capacity and structural stability...
October 19, 2017: ACS Nano
https://www.readbyqxmd.com/read/29049791/the-stability-and-influence-of-barriers-to-medication-adherence-on-seizure-outcomes-and-adherence-in-children-with-epilepsy-over-2-years
#11
Rachelle R Ramsey, Nanhua Zhang, Avani C Modi
To determine the stability and influence of adherence barriers on medication adherence and seizure control in pediatric epilepsy. Caregivers of 118 children aged 2-12 years old with epilepsy completed the Pediatric Epilepsy Medication Self-Management Questionnaire at nine time points over 2 years post diagnosis. Electronically monitored antiepileptic drug adherence and seizure outcome data were collected. Hierarchical linear modeling results for overall barriers remained stable over 2 years. Specific item-level barriers were also generally stable over time, with the exception of running out of medication becoming more of a barrier over time...
June 22, 2017: Journal of Pediatric Psychology
https://www.readbyqxmd.com/read/29049500/evidence-based-guidelines-to-eliminate-repetitive-laboratory-testing
#12
Kevin P Eaton, Kathryn Levy, Christine Soong, Amit K Pahwa, Christopher Petrilli, Justin B Ziemba, Hyung J Cho, Rodrigo Alban, Jaime F Blanck, Andrew S Parsons
Routine daily laboratory testing of hospitalized patients reflects a wasteful clinical practice that threatens the value of health care. Choosing Wisely initiatives from numerous professional societies have identified repetitive laboratory testing in the face of clinical stability as low value care. Although laboratory expenditure often represents less than 5% of most hospital budgets, the impact is far-reaching given that laboratory tests influence nearly 60% to 70% of all medical decisions. Excessive phlebotomy can lead to hospital-acquired anemia, increased costs, and unnecessary downstream testing and procedures...
October 16, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/29049423/dynamic-water-patterns-change-the-stability-of-the-collapsed-filter-conformation-of-the-kcsa-k-channel
#13
Di Wu
The selectivity filter of the KcsA K+ channel has two typical conformations-the conductive and the collapsed conformations, respectively. The transition from the conductive to the collapsed filter conformation can represent the process of inactivation that depends on many environmental factors. Water molecules permeating behind the filter can influence the collapsed filter stability. Here we perform the molecular dynamics simulations to study the stability of the collapsed filter of the KcsA K+ channel under the different water patterns...
2017: PloS One
https://www.readbyqxmd.com/read/29049414/wavelet-imaging-on-multiple-scales-wims-reveals-focal-adhesion-distributions-dynamics-and-coupling-between-actomyosin-bundle-stability
#14
Tim Toplak, Benoit Palmieri, Alba Juanes-García, Miguel Vicente-Manzanares, Martin Grant, Paul W Wiseman
We introduce and use Wavelet Imaging on Multiple Scales (WIMS) as an improvement to fluorescence correlation spectroscopy to measure physical processes and features that occur across multiple length scales. In this study, wavelet transforms of cell images are used to characterize molecular dynamics at the cellular and subcellular levels (i.e. focal adhesions). We show the usefulness of the technique by applying WIMS to an image time series of a migrating osteosarcoma cell expressing fluorescently labelled adhesion proteins, which allows us to characterize different components of the cell ranging from optical resolution scale through to focal adhesion and whole cell size scales...
2017: PloS One
https://www.readbyqxmd.com/read/29049408/long-term-trends-of-phosphorus-concentrations-in-an-artificial-lake-socio-economic-and-climate-drivers
#15
Yuliya Vystavna, Josef Hejzlar, Jiří Kopáček
European freshwater ecosystems have undergone significant human-induced and environmentally-driven variations in nutrient export from catchments throughout the past five decades, mainly in connection with changes in land-use, agricultural practice, waste water production and treatment, and climatic conditions. We analysed the relations among concentration of total phosphorus (TP) in the Slapy Reservoir (a middle reservoir of the Vltava River Cascade, Czechia), and socio-economic and climatic factors from 1963 to 2015...
2017: PloS One
https://www.readbyqxmd.com/read/29049314/evaluation-of-characteristic-of-human-turbinate-derived-mesenchymal-stem-cells-cultured-in-the-serum-free-media
#16
Se Hwan Hwang, WeonSun Lee, Sang Hi Park, Hee Jin Lee, Sun Hwa Park, Dong Chang Lee, Mi Hyun Lim, Sang A Back, Byeong Gon Yun, Jung Ho Jeun, Jung Yeon Lim, Jun Myung Kang, Sung Won Kim
We evaluated the effect of serum-free and xeno-cultivation (SFXFM) on the characterization, proliferation, and differentiation properties of human nasal stem cells (airway tissue; hTMSCs). hTMSCs were isolated from 10 patients, after which patient samples were separated into two groups, an SFXFM group and a control group. The control group was treated with bovine serum-containing medium. FACS analysis revealed that SFXFM-cultured hTMSCs maintained a characteristic mesenchymal stem cell phenotype. hTMSC proliferation was not influenced by SFXFM...
2017: PloS One
https://www.readbyqxmd.com/read/29049300/increased-cell-survival-and-cytogenetic-integrity-by-spatial-dose-redistribution-at-a-compact-synchrotron-x-ray-source
#17
Karin Burger, Katarina Ilicic, Martin Dierolf, Benedikt Günther, Dietrich W M Walsh, Ernst Schmid, Elena Eggl, Klaus Achterhold, Bernhard Gleich, Stephanie E Combs, Michael Molls, Thomas E Schmid, Franz Pfeiffer, Jan J Wilkens
X-ray microbeam radiotherapy can potentially widen the therapeutic window due to a geometrical redistribution of the dose. However, high requirements on photon flux, beam collimation, and system stability restrict its application mainly to large-scale, cost-intensive synchrotron facilities. With a unique laser-based Compact Light Source using inverse Compton scattering, we investigated the translation of this promising radiotherapy technique to a machine of future clinical relevance. We performed in vitro colony-forming assays and chromosome aberration tests in normal tissue cells after microbeam irradiation compared to homogeneous irradiation at the same mean dose using 25 keV X-rays...
2017: PloS One
https://www.readbyqxmd.com/read/29049297/functional-connectivity-structure-of-cortical-calcium-dynamics-in-anesthetized-and-awake-mice
#18
Patrick W Wright, Lindsey M Brier, Adam Q Bauer, Grant A Baxter, Andrew W Kraft, Matthew D Reisman, Annie R Bice, Abraham Z Snyder, Jin-Moo Lee, Joseph P Culver
The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI and optical intrinsic signal imaging), which are an indirect and relatively slow report of neural activity, and underlying synaptic electrical and metabolic activity through neurovascular coupling is a topic of ongoing research and debate. As application of resting state functional connectivity measures is extended further into topics such as brain development, aging and disease, the importance of understanding the fundamental physiological basis for functional connectivity will grow...
2017: PloS One
https://www.readbyqxmd.com/read/29049294/impact-of-dynamic-changes-of-elevated-bilirubin-on-survival-in-patients-on-veno-arterial-extracorporeal-life-support-for-acute-circulatory-failure
#19
Miriam Freundt, Dirk Lunz, Alois Philipp, Bernd Panholzer, Matthias Lubnow, Christine Friedrich, Leopold Rupprecht, Stephan Hirt, Assad Haneya
AIMS: Veno-arterial extracorporeal life support (ECLS) is an established method to stabilize acute circulatory failure. Parameters and data on when to ideally wean circulatory support are limited. Bilirubin is a marker of end-organ damage. Therefore, the purpose of this large study was to evaluate the impact of dynamic changes of elevated bilirubin levels on survival in patients on ECLS. METHODS AND RESULTS: We reviewed 502 consecutive cases of ECLS from 2007 to 2015...
2017: PloS One
https://www.readbyqxmd.com/read/29049224/primary-stability-in-total-hip-replacement-a-biomechanical-investigation
#20
Paul Schmitz, Boyko Gueorguiev, Ivan Zderic, Christian Pfeifer, Michael Nerlich, Stephan Grechenig
BACKGROUND: In total hip replacement (THR), it is essential to achieve a primary stability to guarantee good long-term results. A novel locking screw hip (LSH)-stem, anchored to the medial cortex of the proximal femur by 5 monocortical locking screws, was developed to overcome the shortcomings of uncemented press-fit and cemented straight stems while simultaneously achieving primary stability. The aim of this study was to investigate the biomechanical competence of the LSH-stem in comparison to an uncemented press-fit stem...
October 2017: Medicine (Baltimore)
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