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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/28088735/long-non-coding-rna-ccat1-promotes-human-retinoblastoma-so-rb50-and-y79-cells-through-negative-regulation-of-mir-218-5p
#2
Hongxu Zhang, Jianguang Zhong, Zhenyu Bian, Xiang Fang, You Peng, Yongping Hu
OBJECTIVE: To investigate the regulatory role and potential mechanism of long non-coding RNAs (lncRNA) in human retinoblastoma (RB). METHODS: The lncRNA profile in RB tissues were analyzed by microarray and quantitative reverse transcription PCR (qRT-PCR). One of the identified lncRNAs (LncRNA CCAT1) was selected for further experiments. SO-RB50 and Y79 cells were transfected with negative control, siRNA targeting lncRNA CCAT1 (si-CCAT1) and si-CCAT1+miR218-5p inhibitor, respectively...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088716/unveiling-the-transformation-and-bioavailability-of-dissolved-organic-matter-in-contrasting-hydrothermal-vents-using-fluorescence-eem-parafac
#3
Liyang Yang, Wan-E Zhuang, Chen-Tung Arthur Chen, Bing-Jye Wang, Fu-Wen Kuo
The submarine hydrothermal systems are extreme environments where active cycling of dissolved organic matter (DOM) may occur. However, little is known about the optical properties and bioavailability of hydrothermal DOM, which could provide valuable insights into its transformation processes and biogeochemical reactivity. The quantity, quality, and bioavailability of DOM were investigated for four very different hydrothermal vents east of Taiwan, using dissolved organic carbon (DOC), absorption spectroscopy, and fluorescence excitation-emission matrices-parallel factor analysis (EEM-PARAFAC)...
January 3, 2017: Water Research
https://www.readbyqxmd.com/read/28088658/exposure-to-chronic-early-life-stress-lastingly-alters-the-adipose-tissue-the-leptin-system-and-changes-the-vulnerability-to-western-style-diet-later-in-life-in-mice
#4
K Y Yam, E F G Naninck, M R Abbink, S E la Fleur, L Schipper, J C van den Beukel, A Grefhorst, A Oosting, E M van der Beek, P J Lucassen, A Korosi
Early-life stress (ES) increases the vulnerability to develop psychopathologies and cognitive decline in adulthood. Interestingly, this is often comorbid with metabolic disorders, such as obesity. However, it is unclear whether ES leads to lasting metabolic changes and to what extent this is associated with the ES-induced cognitive impairments. Here, we used an established chronic ES mouse model (from postnatal day (P) 2 to P9) to investigate the short- and long-term effects of ES exposure on parameters of the adipose tissue and the leptin system (i...
December 23, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28088596/indirect-evidence-of-reporting-biases-was-found-in-a-survey-of-medical-research-studies
#5
Loai N Albarqouni, José A López-López, Julian Pt Higgins
OBJECTIVE: To explore indirect evidence of reporting biases by examining the distribution of P-values reported in published medical articles, and to compare P-values distributions across different contexts. METHODS: We selected a random sample (N=1500) of articles published in PubMed in March 2014. We extracted information on study type, design, medical discipline and P-values for the first reported outcome and primary outcome (if specified) from each article. We plotted the P-values transformed to the z-score scale and used caliper tests to investigate threshold effects...
January 11, 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/28088542/interaction-of-earthworms-microbe-facilitating-biofilm-dewaterability-performance-during-wasted-activated-sludge-reduction-and-stabilization
#6
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/28088539/the-dna-damage-response-of-c-elegans-affected-by-gravity-sensing-and-radiosensitivity-during-the-shenzhou-8-spaceflight
#7
Ying Gao, Dan Xu, Lei Zhao, Yeqing Sun
Space radiation and microgravity are recognized as primary and inevitable risk factors for humans traveling in space, but the reports regarding their synergistic effects remain inconclusive and vary across studies due to differences in the environmental conditions and intrinsic biological sensitivity. Thus, we studied the synergistic effects on transcriptional changes in the global genome and DNA damage response (DDR) by using dys-1 mutant and ced-1 mutant of C. elegans, which respectively presented microgravity-insensitivity and radiosensitivity when exposure to spaceflight condition (SF) and space radiation (SR)...
January 7, 2017: Mutation Research
https://www.readbyqxmd.com/read/28088487/adenosine-receptors-and-caffeine-in-retinopathy-of-prematurity
#8
REVIEW
Jiang-Fan Chen, Shuya Zhang, Rong Zhou, Zhenlang Lin, Xiaohong Cai, Jing Lin, Yuqin Huo, Xiaoling Liu
Retinopathy of prematurity (ROP) is a major cause of childhood blindness in the world and is caused by oxygen-induced damage to the developing retinal vasculature, resulting in hyperoxia-induced vaso-obliteration and subsequent delayed retinal vascularization and hypoxia-induced pathological neovascularization driven by vascular endothelial growth factor (VEGF) signaling pathway in retina. Current anti-VEGF therapy has shown some effective in a clinical trial, but is associated with the unintended effects on delayed eye growth and retinal vasculature development of preterm infants...
January 11, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28088354/uncovering-oxysterol-binding-protein-osbp-as-a-target-of-the-anti-enteroviral-compound-ttp-8307
#9
Lucian Albulescu, Joëlle Bigay, Bishyajit Biswas, Marion Weber-Boyvat, Cristina M Dorobantu, Leen Delang, Hilde M van der Schaar, Young-Sik Jung, Johan Neyts, Vesa M Olkkonen, Frank J M van Kuppeveld, Jeroen R P M Strating
The genus Enterovirus (e.g. poliovirus, coxsackievirus, rhinovirus) of the Picornaviridae family of positive-strand RNA viruses includes many important pathogens linked to a range of acute and chronic diseases for which no approved antiviral therapy is available. Targeting a step in the life cycle that is highly conserved provides an attractive strategy for developing broad-range inhibitors of enterovirus infection. A step that is currently explored as a target for the development of antivirals is the formation of replication organelles, which support replication of the viral genome...
January 11, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28088325/molecular-dynamics-simulations-of-ternary-lipid-bilayers-containing-plant-sterol-and-glucosylceramide
#10
Shiva Emami, Sodeif Azadmard-Damirchi, Seyed Hadi Peighambardoust, Javad Hesari, Hadi Valizadeh, Roland Faller
An atomic-level molecular dynamics simulation was carried out to study the effects of a plant sterol (sitosterol) and glucosylceramide (GlcCer) on a 1,2-dilinoleoylposphocholine (DLiPC) membrane. Initially, a membrane containing 50mol % sitosterol was compared with that containing the same ratio of cholesterol. These simulations showed differential condensing and ordering effects of sitosterol and cholesterol, with cholesterol being slightly more efficient than sitosterol in packing the membrane more tightly to a liquid ordered phase...
January 11, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28088177/a-novel-quantitative-pcr-detects-babesia-infection-in-patients-not-identified-by-currently-available-non-nucleic-acid-amplification-tests
#11
Lavoisier Akoolo, Samantha Schlachter, Rasel Khan, Laura Alter, Albert D Rojtman, Kristine Gedroic, Purnima Bhanot, Nikhat Parveen
BACKGROUND: Ticks transmit Babesia microti, the causative agents of babesiosis in North America and Europe. Babesiosis is now endemic in Northeastern USA and affects people of all ages. Babesia species infect erythrocytes and can be transmitted through blood transfusion. Whole blood and blood products, which are not tested for Babesia, can cause transfusion-transmitted babesiosis (TTB) resulting in severe consequences in the immuno-compromised patients. The purpose of this study was epidemiological evaluation of babesiosis in a tick-infested state...
January 14, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28088165/genomic-characterization-of-ensifer-aridi-a-proposed-new-species-of-nitrogen-fixing-rhizobium-recovered-from-asian-african-and-american-deserts
#12
Antoine Le Quéré, Nisha Tak, Hukam Singh Gehlot, Celine Lavire, Thibault Meyer, David Chapulliot, Sonam Rathi, Ilham Sakrouhi, Guadalupe Rocha, Marine Rohmer, Dany Severac, Abdelkarim Filali-Maltouf, Jose-Antonio Munive
BACKGROUND: Nitrogen fixing bacteria isolated from hot arid areas in Asia, Africa and America but from diverse leguminous plants have been recently identified as belonging to a possible new species of Ensifer (Sinorhizobium). In this study, 6 strains belonging to this new clade were compared with Ensifer species at the genome-wide level. Their capacities to utilize various carbon sources and to establish a symbiotic interaction with several leguminous plants were examined. RESULTS: Draft genomes of selected strains isolated from Morocco (Merzouga desert), Mexico (Baja California) as well as from India (Thar desert) were produced...
January 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28088085/new-pyridazinone-4-carboxamides-as-new-cannabinoid-receptor-type-2-inverse-agonists-synthesis-pharmacological-data-and-molecular-docking
#13
Giulio Ragusa, María Gómez-Cañas, Paula Morales, Carmen Rodríguez-Cueto, María R Pazos, Battistina Asproni, Elena Cichero, Paola Fossa, Gerard A Pinna, Nadine Jagerovic, Javier Fernández-Ruiz, Gabriele Murineddu
In the last few years, cannabinoid type-2 receptor (CB2R) selective ligands have shown a great potential as novel therapeutic drugs in several diseases. With the aim of discovering new selective cannabinoid ligands, a series of pyridazinone-4-carboxamides was designed and synthesized, and the new derivatives tested for their affinity toward the hCB1R and hCB2R. The 6-(4-chloro-3-methylphenyl)-2-(4-fluorobenzyl)-N-(cis-4-methylcyclohexyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (9) displayed high CB2-affinity (KiCB2 = 2...
January 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28087933/ecology-of-fungal-plant-pathogens
#14
Aad J Termorshuizen
Fungal plant pathogens are ubiquitous and highly diverse. Key to their success is high host density, which notably is the case in agroecosystems. Several hypotheses related to the effects of plant pathogens on plant diversity (the Janzen-Connell hypothesis, the dilution effect hypothesis) and the phenomenon of higher biomass in plant mixtures (i.e., overyielding) can all be explained by the quantitative interplay between host and pathogen density. In many agroecosystems, fungal plant pathogens cause great losses, since in monocultures diseased plants cannot be replaced by healthy plants...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087897/fgfr1-analyses-in-four-patients-with-hypogonadotropic-hypogonadism-with-split-hand-foot-malformation-implications-for-the-promoter-region
#15
Kohnosuke Ohtaka, Yasuko Fujisawa, Fumio Takada, Yukihiro Hasegawa, Tatsuya Miyoshi, Tomonobu Hasegawa, Hideaki Miyoshi, Hiraku Kameda, Misuzu Kurokawa Seo, Maki Fukami, Tsutomu Ogata
Heterozygous loss-of-function mutations of FGFR1 cause various disorders including hypogonadotropic hypogonadism with split-hand/foot malformation (HH-SHFM). We examined FGFR1 in four Japanese patients with HH-SHFM (cases 1-4) and the mother of case 4 with HH only. Cases 1 and 2 had heterozygous loss-of-function mutations with no dominant negative effect [c.289G>A, p.(G97S); and c.2231G>C, p.(R744T)], and case 3 had a splice donor site mutation [c.1663+1G>T]. Notably, case 4 had a maternally inherited 8,312 bp microdeletion that involved non-coding exon 1U and impaired FGFR1 expression...
January 13, 2017: Human Mutation
https://www.readbyqxmd.com/read/28087642/stxbp4-drives-tumor-growth-and-is-associated-with-poor-prognosis-through-pdgf-receptor-signaling-in-lung-squamous-cell-carcinoma
#16
Yukihiro Otaka, Susumu Rokudai, Kyoichi Kaira, Michiru Fujieda, Ikuko Horikoshi, Reika Kawabata, Shinji Yoshiyama, Takehiko Yokobori, Yoichi Ohtaki, Kimihiro Shimizu, Tetsunari Oyama, Jun'ichi Tamura, Carol Prives, Masahiko Nishiyama
PURPOSE: Expression of the ΔN isoform of p63 (ΔNp63) is a diagnostic marker highly specific for lung squamous cell carcinoma (SCC). We previously found that Syntaxin Binding Protein 4 (STXBP4) regulates ΔNp63 ubiquitination, suggesting that STXBP4 may also be a SCC biomarker. To address this issue, we investigated the role of STXBP4 expression in SCC biology and the impact of STXBP4 expression on SCC prognosis. EXPERIMENTAL DESIGN: We carried out a clinicopathological analysis of STXBP4 expression in 87 lung SCC patients...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28087599/long-non-coding-rna-linc00092-acts-in-cancer-associated-fibroblasts-to-drive-glycolysis-and-progression-of-ovarian-cancer
#17
Linjie Zhao, Gaili Ji, Xiaobing Le, Chenlu Wang, Lian Xu, Min Feng, Yaguang Zhang, Huiliang Yang, Yu Xuan, Yanfei Yang, Lingzi Lei, Qilian Yang, Wayne Bond Lau, Bonnie Lau, Yi Chen, Xiangbing Deng, Shaohua Yao, Tao Yi, Xia Zhao, Yuquan Wei, Shengtao Zhou
The majority of patients with epithelial ovarian cancer are diagnosed at a late stage when peritoneal metastases exist, however, there is little knowledge of the metastatic process in this disease setting. In this study, we report the identification of the long non-coding RNA LINC00092 as a nodal driver of metastatic progression mediated by cancer-associated fibroblasts (CAF). Pro-metastatic properties of CAF in vitro and in vivo were found to associate with elevated expression of the chemokine CXCL14. In clinical specimens, elevated levels of CXCL14 in CAF also correlated with poor prognosis...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28087511/invited-commentary-ambient-environment-and-the-risk-of-preterm-birth
#18
Sandie Ha, Pauline Mendola
Preterm birth is a common adverse birth outcome known to be associated with increased infant mortality, and it often results in a higher burden of offspring morbidity in both the short and long terms. The potential for environmental factors, particularly air pollution and meteorological parameters, to increase preterm birth risk has received significant attention worldwide, but the findings are generally inconsistent, with variations in study designs and methods across populations and geographic locations. In the current issue of the Journal, Giorgis-Allemand et al...
January 13, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28087387/orbital-fibroblasts-of-graves-orbitopathy-stimulated-with-proinflammatory-cytokines-promote-b-cell-survival-by-secreting-baff
#19
Fen Tang, Xiaoqing Chen, Yuxiang Mao, Shangtao Wan, Siming Ai, Huasheng Yang, Guangming Liu, Yusha Zou, Miaoli Lin, Liang Dan
The success of rituximab for the treatment of active Graves' orbitopathy (GO) suggests that B cells play a critical role in intraorbital inflammation. B cell activating factor (BAFF) and its homolog a proliferation-inducing ligand (APRIL) are critical for B cell survival. However, the contribution of BAFF/APRIL to GO remains unclear. We sought to determine the role of BAFF/APRIL in the orbits of GO, and found that BAFF was markedly upregulated, while APRIL was not. Additionally, cultured GO orbital fibroblasts (GO-OFs)(2) expressing BAFF were induced to produce a large amount of BAFF...
January 10, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28087272/synthesis-and-evaluation-of-5-1h-indol-3-yl-n-aryl-1-3-4-oxadiazol-2-amines-as-bcl-2-inhibitory-anticancer-agents
#20
Rania Hamdy, Noha I Ziedan, Samia Ali, Cinzia Bordoni, Mohamed El-Sadek, Elsaid Lashin, Andrea Brancale, Arwyn T Jones, Andrew D Westwell
A series of 5-(1H-indol-3-yl)-N-aryl-1,3,4-oxadiazol-2-amines 8a-j has been designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2-inhibitory anticancer agents based on our previous lead compound 8a. Synthesis of the target compounds was readily accomplished through a cyclisation reaction between indole-3-carboxylic acid hydrazide (5) and substituted isothiocyanates 6a-j, followed by oxidative cyclodesulfurization of the corresponding thiosemicarbazide 7a-j using 1,3-dibromo-5,5-dimethylhydantoin...
December 27, 2016: Bioorganic & Medicinal Chemistry Letters
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