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https://www.readbyqxmd.com/read/28088788/dual-syk-jak-inhibition-overcomes-ibrutinib-resistance-in-chronic-lymphocytic-leukemia-cerdulatinib-but-not-ibrutinib-induces-apoptosis-of-tumor-cells-protected-by-the-microenvironment
#1
Ailin Guo, Pin Lu, Greg Coffey, Pamela Conley, Anjali Pandey, Y Lynn Wang
Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL. However, the drug, to a large extent, does not cause cell death directly and does not eradicate CLL malignant clones. Inability to eradicate CLL has fostered resistance generation. Once patients become resistant, they do poorly with a median survival of 3-4 months. Novel therapeutic strategies are needed to prevent resistance, improve treatment outcome and ultimately cure the disease. Herein, we explore dual targeting of the BCR and JAK-STAT pathways with a novel single agent, cerdulatinib, which selectively inhibits both SYK (a BCR component) and JAK kinases...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088766/staphylococcus-aureus-cc395-harbours-a-novel-composite-staphylococcal-cassette-chromosome-mec-element
#2
Jesper Larsen, Paal S Andersen, Volker Winstel, Andreas Peschel
BACKGROUND: CoNS species are likely reservoirs of the staphylococcal cassette chromosome mec (SCCmec) in Staphylococcus aureus S aureus CC395 is unique as it is capable of exchanging DNA with CoNS via bacteriophages, which are also known to mediate transfer of SCCmec OBJECTIVES: To analyse the structure and putative origin of the SCCmec element in S aureus CC395. METHODS: The only MRSA CC395 strain described in the literature, JS395, was subjected to WGS, and its SCCmec element was compared with those found in CoNS species and other S...
January 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28088717/removal-of-antibiotic-resistance-genes-from-wastewater-treatment-plant-effluent-by-coagulation
#3
Na Li, Guo-Ping Sheng, Yong-Ze Lu, Raymond J Zeng, Han-Qing Yu
Antibiotic resistance genes (ARGs), as emerging environmental contaminants, have become a threat to human health. Recent studies have demonstrated that the effluent from wastewater treatment plants is a significant point source of ARGs released into the environment. In this study, we investigated the effectiveness of coagulation technology in the removal of ARGs from treated wastewater. Specifically, we measured the removal of five ARGs (two sulfonamide resistance genes, sulI and sulII, and three tetracycline resistance genes, tetO, tetW and tetQ) and the class 1 integron intI1 gene via the application of two coagulants: FeCl3 and polyferric chloride (PFC)...
January 4, 2017: Water Research
https://www.readbyqxmd.com/read/28088693/reinforcement-of-a-pmma-resin-for-interim-fixed-prostheses-with-silica-nanoparticles
#4
Marianthi Topouzi, Eleana Kontonasaki, Dimitrios Bikiaris, Lambrini Papadopoulou, Konstantinos M Paraskevopoulos, Petros Koidis
PURPOSE: Fractures in long span provisional/interim restorations are a common complication. Adequate fracture toughness is necessary to resist occlusal forces and crack propagation, so these restorations should be constructed with materials of improved mechanical properties. The aim of this study was to investigate the possible reinforcement of neat silica nanoparticles and trietoxyvinylsilane-modified silica nanoparticles in a PMMA resin for fixed interim restorations. MATERIALS AND METHODS: Composite PMMA-Silica nanoparticles powders were mixed with PMMA liquid and compact bar shaped specimens were fabricated according to the British standard BS EN ISO 127337:2005...
January 9, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28088638/the-dlno-dlco-ratio-physiological-significance-and-clinical-implications
#5
J M B Hughes, A T Dinh-Xuan
DLNO/DLCO directly measures the ratio of the diffusing capacities of the lung for nitric oxide (NO) and carbon monoxide (CO). In terms of the Roughton and Forster, 1957; equation, 1/DL=1/Dm+1/θVc, where Dm is the membrane (Dm) and θVc is the red cell component of the overall diffusing conductance (DL), DLNO mostly reflects the Dm component and DLCO the θVc red cell component. The DLNO/DLCO ratio is positively related to the DmCO/Vc ratio and the CO red cell resistance (1/θCOVc) as a percentage of the total resistance (1/DLCO), independent of the absolute values of DLNO or DLCO...
January 11, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28088627/the-telomere-binding-protein-trf2-is-required-for-metronomic-therapeutic-effects-of-gemcitabine-and-capecitabine
#6
Wei-Ping Lee, Keng-Hsin Lan, Chung-Pin Li, Yee Chao, Ming-Chih Hou, Han-Chieh Lin, Shou-Dong Lee
Gemcitabine and capecitabine are two effective anticancer agents against solid tumors. The pharmacological mechanisms have been known as incorporation into DNA and thereby inhibition of DNA synthesis. When used as metronomic chemotherapy, they may inhibit angiogenesis and induce immunity. In our previous study, we showed that low-dose gemcitabine caused telomere shortening by stabilizing TRF2 that was required for XPF-dependent telomere loss. In this report, we established a SKOV3.ip1 ascites cell model. Tumor-bearing mice were treated with low-dose gemcitabine (GEM) or capecitabine (CAP)...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088622/reactive-oxygen-species-and-cancer-paradox-to-promote-or-to-suppress
#7
REVIEW
Sehamuddin Galadari, Anees Rahman, Siraj Pallichankandy, Faisal Thayyullathil
Reactive oxygen species (ROS), a group of highly reactive ions and molecules, are increasingly being appreciated as powerful signaling molecules involved in the regulation of a variety of biological processes. Indeed, their role is continuously being delineated in a variety of pathophysiological conditions. For instance, cancer cells are shown to have increased ROS levels in comparison to their normal counterparts. This is partly due to an enhanced metabolism and mitochondrial dysfunction in cancer cells. The escalated ROS generation in cancer cells contributes to the biochemical and molecular changes necessary for the tumor initiation, promotion and progression, as well as, tumor resistance to chemotherapy...
January 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28088621/4-hydroxynonenal-causes-impairment-of-human-subcutaneous-adipogenesis-and-induction-of-adipocyte-insulin-resistance
#8
Mohamed Elrayess, Shamma Al-Muraikhy, Wael Kafienah, Afnan Al-Menhali, Fatima Al-Khalaifi, Moataz Bashah, Kamelija Zarkovic, Neven Zarkovic, Georg Waeg, Mohammed Alsayrafi, Morana Jaganjac
OBJECTIVE: Increased adipose production of 4-hydroxynonenal (4-HNE), a bioreactive aldehyde, directly correlates with obesity and insulin resistance. The aim of this study was to elucidate the impact of 4-HNE in mediating adipocyte differentiation and function in two metabolically distinct obese groups; the insulin sensitive (IS) and the insulin resistant (IR). METHODS: Subcutaneous (SC) adipose tissues were obtained from eighteen clinically well characterized obese premenopausal women undergoing weight reduction surgery...
January 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28088614/ccaat-enhancer-binding-protein-%C3%AE-promotes-pathogenesis-of-eae
#9
Michelle R Simpson-Abelson, Gerard Hernandez-Mir, Erin E Childs, J Agustin Cruz, Amanda C Poholek, Ansuman Chattopadhyay, Sarah L Gaffen, Mandy J McGeachy
The CCAAT/Enhancer Binding Protein β (C/EBPβ) transcription factor is activated by multiple inflammatory stimuli, including IL-17 and LPS, and C/EBPβ itself regulates numerous genes involved in inflammation. However, the role of C/EBPβ in driving autoimmunity is not well understood. Here, we demonstrate that Cebpb(-/-) mice are resistant to EAE. Cebpb(-/-) mice exhibited reduced lymphocyte and APC infiltration into CNS following EAE induction. Furthermore, MOG-induced Th17 cytokine production was impaired in draining LN, indicating defects in Th17 cell priming...
January 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28088613/adipocyte-and-epidermal-fatty-acid-binding-protein-serum-concentrations-in-patients-with-lipodystrophy
#10
Konstanze Miehle, Thomas Ebert, Susan Kralisch, Annett Hoffmann, Jürgen Kratzsch, Haiko Schlögl, Michael Stumvoll, Mathias Fasshauer
OBJECTIVE: Lipodystrophy (LD) syndromes are associated with diabetes mellitus, hypertriglyceridemia, and coronary artery disease. One pathogenetic factor of LD is dysregulation of several adipokines. However, the insulin resistance- and dyslipidemia-promoting adipokines adipocyte (AFABP) and epidermal (EFABP) fatty acid-binding protein have not been investigated in non-HIV-associated LD so far. MATERIAL AND METHODS: We performed a cross-sectional analysis of AFABP and EFABP serum concentrations in 37 LD patients and 37 age-, gender-, and body mass index-matched healthy controls...
January 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28088587/late-onset-neonatal-sepsis-in-arab-states-in-the-gulf-region-two-year-prospective-study
#11
Majeda S Hammoud, Abdullah Al-Taiar, Sameer Y Al-Abdi, Hussain Bozaid, Anwar Khan, Laila M AlMuhairi, Moghis Ur Rehman
OBJECTIVES: This study aimed to investigate the incidence of Late-Onset Sepsis (LOS) in neonatal intensive care units (NICUs) in Arab states in the gulf region and describe the main causative organisms and their antibiotic resistance. METHODS: Observational prospective cohort study was conducted over two-year period in five NICUs in Kuwait, Saudi Arabia and United Arab Emirates. LOS was defined as the growth of a single potentially pathogenic organism from blood or cerebrospinal fluid in infants >3days of age with clinical and laboratory findings consistent with infection...
January 11, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28088563/a-novel-fabrication-of-a-high-performance-sio2-graphene-oxide-go-nanohybrids-characterization-of-thermal-properties-of-epoxy-nanocomposites-filled-with-sio2-go-nanohybrids
#12
S Z Haeri, B Ramezanzadeh, M Asghari
In this study it has been aimed to enhance the thermal resistance of epoxy coating through incorporation of SiO2-GO nanohybrids. SiO2-GO nanohybrids were synthesized through one-step sol-gel route using a mixture of Tetraethylorthosilane (TEOS) and 3-Aminopropyl triethoxysilane (APTES) silanes. The SiO2-GO nanohybrids were prepared at various hydrolysis times of 24, 48 and 72h. Then 0.2wt.% of GO and SiO2-GO nanohybrids were separately incorporated into the epoxy coating. Results revealed that amino functionalized SiO2 nanoparticles with particle size around 20-30nm successfully synthesized on the basal plane of GO...
January 5, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28088558/the-effects-of-upper-body-exercise-across-different-levels-of-blood-flow-restriction-on-arterial-occlusion-pressure-and-perceptual-responses
#13
Kevin T Mattocks, Matthew B Jessee, Brittany R Counts, Samuel L Buckner, J Grant Mouser, Scott J Dankel, Gilberto C Laurentino, Jeremy P Loenneke
Recent studies have investigated relative pressures that are applied during blood flow restriction exercise ranging from 40%-90% of resting arterial occlusion pressure; however, no studies have investigated relative pressures below 40% arterial occlusion pressure. The purpose of this study was to characterize the cardiovascular and perceptual responses to different levels of pressures. Twenty-six resistance trained participants performed four sets of unilateral elbow flexion exercise using 30% of their 1RM in combination with blood flow restriction inflated to one of six relative applied pressures (0%, 10%, 20%, 30%, 50%, 90% arterial occlusion pressure)...
January 11, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28088556/regulation-of-docetaxel-sensitivity-in-prostate-cancer-cells-by-hsa-mir-125a-3p-via-modulation-of-mta1-signaling
#14
Jian-Zhou Liu, Feng-Yan Yin, Chang-You Yan, Hui Wang, Xiao-Hui Luo
OBJECTIVE: To identify the potential down-stream targets of hsa-miR-125a-3p, a mature form of miR-125a, during the pathogenesis of chemoresistance in prostate cancer (PCa). METHODS: Expression levels of hsa-miR-125a-3p was assessed in chemoresistant PCa tissues and experimentally-established chemoresistant cells using quantitative RT-PCR (qRT-PCR). The effect of hsa-miR-125a-3p knockdown or hsa-miR-125a-3p overexpression on the Dox-induced cell death was evaluated using apoptosis ELISA in chemosensitive PC-3 cells or in chemoresistant PC-3 cells (PC-3R)...
January 11, 2017: Urology
https://www.readbyqxmd.com/read/28088542/interaction-of-earthworms-microbe-facilitating-biofilm-dewaterability-performance-during-wasted-activated-sludge-reduction-and-stabilization
#15
Yadan Zheng, Meiyan Xing, Luziyu Cai, Tao Xiao, Yufan Lu, Jinzhou Jiang
Sludge dewaterability was chemically and morphologically explored during sewage sludge treatment by vermifiltration. The results, with a conventional biofilter (BF, no earthworms) as a control, demonstrated that the capillary suction time(CST) and specific resistance of filtration(SRF) of vermifilter (VF, with earthworms) treated sludge were 64.9±1.7s and (23.1±1.3)×10(12)m/kg,16.8% and 36.0% lower than that of the BF, respectively. Additionally, the VF could efficiently decompose loosely bound extracellular polymeric substances (LB-EPS), releasing more water trapped inside biofilm...
January 11, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28088530/distribution-of-antibiotic-resistance-in-the-effluents-of-ten-municipal-wastewater-treatment-plants-in-china-and-the-effect-of-treatment-processes
#16
Weiwei Ben, Jian Wang, Rukun Cao, Min Yang, Yu Zhang, Zhimin Qiang
Municipal wastewater treatment plant (WWTP) effluents represent an important contamination source of antibiotic resistance, threatening the ecological safety of receiving environments. In this study, the release of antibiotic resistance to sulfonamides and tetracyclines in the effluents of ten WWTPs in China was investigated. Results indicate that the concentrations of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) ranged from 1.1 × 10(1) to 8.9 × 10(3) CFU mL(-1) and 3.6 × 10(1) (tetW) to 5...
January 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/28088515/the-membrane-tethered-nac-transcription-factor-atntl7-contributes-to-er-stress-resistance-in-arabidopsis
#17
Yong Hun Chi, Sarah Mae Boyles Melencion, Cresilda Vergara Alinapon, Min Ji Kim, Eun Seon Lee, Seol Ki Paeng, Joung Hun Park, Ganesh M Nawkar, Young Jun Jung, Ho Byeong Chae, Chang Ho Kang, Sang Yeol Lee
We screened for endoplasmic reticulum (ER) stress-resistant mutants among 25 mutants of the Arabidopsis NTL (NAC with Transmembrane motif 1-Like) family. We identified a novel mutant, SALK_044777, showing strong resistance to ER stress. RT-PCR and genomic DNA sequence analyses identified the mutant as atntl7, which harbors a T-DNA insertion in the fourth exon of AtNTL7. Two other atntl7-mutant alleles, in which T-DNA was inserted in the second exon and third intron of AtNTL7, respectively, showed ER-stress sensitive phenotypes, suggesting that SALK_044777 is a gain-of-function mutant...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#18
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088481/saxs-structural-studies-of-dps-from-deinococcus-radiodurans-highlights-the-conformation-of-the-mobile-n-terminal-extensions
#19
Sandra P Santos, Maxime G Cuypers, Adam Round, Stephanie Finet, Theyencheri Narayanan, Edward P Mitchell, Célia V Romão
The radiation resistant bacterium Deinococcus radiodurans contains two DNA binding proteins from starved cells (Dps): Dps1 (DR2263) and Dps2 (DRB0092). These are suggested to play a role in DNA interaction, manganese and iron storage. The proteins assemble as a conserved dodecameric structure with structurally uncharacterized N-terminal extensions. In the case of DrDps1 these extensions have been proposed to be involved in DNA interactions, while in DrDps2 their function has yet to be established. The reported data reveals the relative position of the N-terminal extensions to the dodecameric sphere in solution for both Dps...
January 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28088472/cholesterol-and-ergosterol-affect-the-activity-of-staphylococcus-aureus-antibiotic-efflux-pumps
#20
S R Tintino, C D M Oliveira-Tintino, F F Campina, M S Costa, R P Cruz, R L S Pereira, J C Andrade, E O Sousa, J P Siqueira-Junior, H D M Coutinho, T C Leal-Balbino, V Q Balbino
The aim of this study is to evaluate the effect of ergosterol on steroids and cholesterol efflux pumps in multidrug resistant strains of S. aureus. Were used RN4220 harboring plasmid pUL5054, which carries the gene encoding the MsrA macrolide efflux protein; and IS-58, which possesses the TetK tetracycline efflux protein; 1199B resists hydrophilic fluoroquinolones via a NorA-mediated mechanism and wild strain 1199B. The Minimal Inhibitory Concentration (MIC) was determined and the evaluation of possible inhibition of efflux pumps by reduction of MIC...
January 11, 2017: Microbial Pathogenesis
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