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https://www.readbyqxmd.com/read/28646789/data-mining-for-detecting-signals-of-adverse-drug-reactions-of-fluoxetine-using-the-korea-adverse-event-reporting-system-kaers-database
#1
Seonji Kim, Kyounghoon Park, Mi-Sook Kim, Bo Ram Yang, Hyun Jin Choi, Byung-Joo Park
Selective serotonin reuptake inhibitors (SSRIs) have become one of the most broadly used medications in psychiatry. Fluoxetine is the first representative antidepressant SSRI drug approved by the Food and Drug Administration (FDA) in 1987. Safety information on fluoxetine use alone was less reported than its combined use with other drugs. There were no published papers on adverse drug reactions (ADRs) of fluoxetine analyzing spontaneous adverse events reports. We detected signals of the adverse drug reactions of fluoxetine by data mining using the Korea Adverse Events Reporting System (KAERS) database...
June 13, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28646017/ror%C3%AE-modulates-semaphorin-3e-transcription-and-neurovascular-interaction-in-pathological-retinal-angiogenesis
#2
Ye Sun, Chi-Hsiu Liu, Zhongxiao Wang, Steven S Meng, Samuel B Burnim, John Paul SanGiovanni, Theodore M Kamenecka, Laura A Solt, Jing Chen
Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28641219/comparison-of-brand-versus-generic-antiepileptic-drug-adverse-event-reporting-rates-in-the-u-s-food-and-drug-administration-adverse-event-reporting-system-faers
#3
Md Motiur Rahman, Yasser Alatawi, Ning Cheng, Jingjing Qian, Annya V Plotkina, Peggy L Peissig, Richard L Berg, David Page, Richard A Hansen
OBJECTIVE: Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. METHODS: Events reported to the U...
June 13, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28637769/potential-contribution-of-tandem-circadian-enhancers-to-nonlinear-oscillations-in-clock-gene-expression
#4
Isao T Tokuda, Akihiko Okamoto, Ritsuko Matsumura, Toru Takumi, Makoto Akashi
Limit cycle oscillations require the presence of nonlinear processes. Although mathematical studies have long suggested that multiple nonlinear processes are required for autonomous circadian oscillation in clock gene expression, the underlying mechanism remains controversial. Here, we experimentally show that cell-autonomous circadian transcription of a mammalian clock gene requires a functionally interdependent tandem E-box motif; the lack of either of the two E-boxes results in arrhythmic transcription. Although previous studies have indicated the role of the tandem motifs in increasing circadian amplitude, enhancing amplitude does not explain the mechanism for limit cycle oscillations in transcription...
June 21, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28635401/inhibition-of-long-non-coding-rna-ror-reverses-resistance-to-tamoxifen-by-inducing-autophagy-in-breast-cancer
#5
Yuehua Li, Baohong Jiang, Hongbo Zhu, Xiaofei Qu, Liqin Zhao, Yeru Tan, Yiling Jiang, Mingchu Liao, Xiaoping Wu
This study explored the mechanism underlying long non-coding RNA ROR regulating autophagy on Tamoxifen resistance in breast cancer. Cancer tissues and adjacent normal tissues were collected from 74 breast cancer patients. Human breast cancer BT474 cells were assigned into blank, phosphate buffered saline, Tamoxifen, negative control + Tamoxifen, siROR + Tamoxifen, 3-methyladenine + Tamoxifen, and siROR + 3-methyladenine + TA groups. The expression of long non-coding RNA ROR and expressions of multi-drug resistance-associated P-glycoprotein and glutathione S-transferase-π messenger RNA were detected using quantitative real-time polymerase chain reaction...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28625476/feedback-loops-interlocked-at-competitive-binding-sites-amplify-and-facilitate-genetic-oscillations
#6
Koichiro Uriu, Hajime Tei
Positive and negative feedback loops are often present in regulatory networks for genetic oscillations. Relative time scales and integration of these feedback loops are key to robust oscillations in expression levels. Using examples from the circadian clock and synthetic genetic oscillators, we study positive and negative feedback loops interlocked at competitive binding sites. In the mammalian circadian clock, a key clock gene Bmal1 is regulated by the activator ROR and the repressor REV-ERB. Conversely, Bmal1 activates both of them, forming interlocked feedback loops...
June 15, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28612433/musculin-inhibits-human-t-helper-17-cell-response-to-interleukin-2-by-controlling-stat5b-activity
#7
Veronica Santarlasci, Alessio Mazzoni, Manuela Capone, Maria Caterina Rossi, Laura Maggi, Gianni Montaini, Beatrice Rossettini, Rolando Cimaz, Matteo Ramazzotti, Giusi Barra, Raffaele De Palma, Enrico Maggi, Francesco Liotta, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
We recently demonstrated that human T helper (Th) 17 cells, unlike Th1 cells, do not proliferate in response to T-cell receptor stimulation, mainly because of their reduced capacity to produce and respond to IL-2. In this study we show that their lower responsiveness to IL-2 is due to the selective expression of Musculin (MSC), a member of the basic helix-loop-helix transcription factors. We show that MSC expression in human Th17 cells is retinoic acid orphan receptor (ROR)γt-dependent, and allows the up-regulation of PPP2R2B, a regulatory member of the protein phosphatase 2A (PP2A) enzyme...
June 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28607111/a-distinct-inhibitory-function-for-mir-18a-in-th17-cell-differentiation
#8
Misty M Montoya, Julia Maul, Priti B Singh, Heather H Pua, Frank Dahlström, Nanyan Wu, Xiaozhu Huang, K Mark Ansel, Dirk Baumjohann
Th17 cell responses orchestrate immunity against extracellular pathogens but also underlie autoimmune disease pathogenesis. In this study, we uncovered a distinct and critical role for miR-18a in limiting Th17 cell differentiation. miR-18a was the most dynamically upregulated microRNA of the miR-17-92 cluster in activated T cells. miR-18a deficiency enhanced CCR6(+) RAR-related orphan receptor (ROR)γt(+) Th17 cell differentiation in vitro and increased the number of tissue Th17 cells expressing CCR6, RORγt, and IL-17A in airway inflammation models in vivo...
June 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28606480/sphingosine-kinase-2-in-autoimmune-inflammatory-disease-and-the-development-of-sphingosine-kinase-2-inhibitors
#9
REVIEW
Nigel J Pyne, David R Adams, Susan Pyne
The purpose of this Opinion is to present a case for targeting sphingosine kinase 2 (SK2) in autoimmune/inflammatory disease. Data obtained using Sphk2(-/-) mice suggest that SK2 is an anti-inflammatory enzyme, although this might be misleading because of a compensatory increase in the expression of a second isoform, sphingosine kinase 1 (SK1), which functions as a proinflammatory enzyme. SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling and, potentially, retinoid-related orphan receptor gamma t (ROR-γt) stability linked with T helper (Th) 17 cell polarisation...
June 9, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28603878/the-reactivity-of-nhc-alane-adducts-towards-n-heterocyclic-carbenes-and-cyclic-alkyl-amino-carbenes-ring-expansion-ring-opening-and-al-h-bond-activation
#10
Udo Radius, Heidi Schneider, Andreas Hock, Rüdiger Bertermann
The synthesis of the mono NHC alane adducts of the type (NHC)·AlH3 (NHC = Me2Im 1, Me2ImMe 2, iPr2Im 3 and 3-d3, iPr2ImMe 4, Dipp2Im 10) and (NHC)·AliBu2H (NHC = iPr2Im 11, Dipp2Im 12) as well as their reactivity towards different types of carbenes is presented. While the mono NHC adducts remain stable at elevated temperatures, ring expansion reaction occurs when (iPr2Im)·AlH3 3 is reacted with a second equivalent of the carbene iPr2Im to give (iPr2Im)·AlH(RER-iPr2ImH2) 6. In 6, {(iPr2Im}AlH} is inserted into the NHC ring...
June 12, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28588761/apixaban-concomitant-medicines-and-spontaneous-reports-of-haemorrhagic-events
#11
Gillian E Caughey, Lisa M Kalisch Ellett, John D Barratt, Sepehr Shakib
INTRODUCTION: Little is known about the potential safety issues associated with apixaban in clinical practice and their reporting in spontaneous adverse event (SAE) databases. OBJECTIVE: To describe SAE reports associated with the oral anticoagulant apixaban from Australia, Canada and USA and to examine associated concomitant medicine use. METHODS: SAE report databases from Australia, Canada and the USA were examined for all reports of adverse events associated with apixaban and concomitant medicines from 1 January 2012 to 30 September 2014...
May 2017: Therapeutic Advances in Drug Safety
https://www.readbyqxmd.com/read/28586319/rev-erb-and-ror-therapeutic-targets-for-treating-myopathies
#12
REVIEW
Ryan D Welch, Colin A Flaveny
Muscle is primarily known for its mechanical roles in locomotion, maintenance of posture, and regulation of cardiac and respiratory function. There are numerous medical conditions that adversely affect muscle, myopathies that disrupt muscle development, regeneration and protein turnover to detrimental effect. Skeletal muscle is also a vital secretory organ that regulates thermogenesis, inflammatory signaling and directs context specific global metabolic changes in energy substrate preference on a daily basis...
June 6, 2017: Physical Biology
https://www.readbyqxmd.com/read/28586019/protective-effects-of-astragaloside-iv-against-ovalbumin-induced-allergic-rhinitis-are-mediated-by-t-box-protein-expressed-in-t-cells-gata-3-and-forkhead-box-protein-3-retinoic-acid-related-orphan-nuclear-receptor-%C3%AE-t
#13
Keqiong Li, Yi Chen, Rong Jiang, Dilong Chen, Hong Wang, Wei Xiong, Danyang Li, Zehong Liu, Xiaopeng Li, Jing Li, Ke Yuan
3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosyl-cycloastragenol, or Astragaloside IV (AST), is one of the major active ingredients isolated from Astragalus membranaceous with distinct pharmacological effects, and possesses anti-inflammatory, immunoregulatory and antifibrotic properties. However, the effects of AST on allergic rhinitis remain to be elucidated. The present study aimed to examine the effects of AST on immunoglobulin (Ig) E‑mediated allergic reactions in vivo, by using a mouse model of allergic rhinitis established via repetitive sensitization and intranasal challenge with ovalbumin (OVA)...
June 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28580169/endogenous-mirna-sponge-lincrna-ror-promotes-proliferation-invasion-and-stem-cell-like-phenotype-of-pancreatic-cancer-cells
#14
Zhiqiang Fu, Guolin Li, Zhihua Li, Yingxue Wang, Yue Zhao, Shangyou Zheng, Huilin Ye, Yuming Luo, Xiaohui Zhao, Lusheng Wei, Yimin Liu, Qing Lin, Quanbo Zhou, Rufu Chen
The long intergenic non-coding RNA, regulator of reprogramming (linc-ROR) is an oncogene and plays a key role in the embryonic stem cell maintenance and is involved in cancer progression. The objective of this study was to analyze linc-ROR expression in pancreatic ductal adenocarcinoma (PDAC) and determine the regulation effects of linc-ROR on proliferation and invasion of cancer cells, as well as properties of cancer stem-like cells (CSLCs). In this study, we found that linc-ROR was up-regulated in PDAC tissues and related to poor prognosis...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28579428/biochanin-a-enhances-ror%C3%AE-activity-through-stat3-mediated-recruitment-of-ncoa1
#15
Miki Takahashi, Ryuta Muromoto, Hiroyuki Kojima, Shinji Takeuchi, Yuichi Kitai, Jun-Ichi Kashiwakura, Tadashi Matsuda
Interleukin (IL)-17-producing T cells play important roles in autoimmunity, chronic inflammation and host protection against extracellular bacteria and fungi. The retinoic acid receptor-related orphan receptors (ROR) α and γ are key regulators of the IL-17-producing phenotype. We previously showed that the isoflavone biochanin A enhanced ROR-mediated transcriptional activity. Here, we investigated the possible mechanisms underlying this ROR activation. Biochanin A-treated murine thymoma EL4 and primary splenocytes demonstrated enhanced induction of IL-17...
June 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28578255/development-and-validation-of-an-ultra-performance-liquid-chromatography-tandem-mass-spectrometry-method-for-quantification-of-sr1001-an-inverse-agonist-of-retinoid-related-orphan-receptors-and-its-application-to-pharmacokinetic-studies-in-streptozotocin-induced
#16
Cuipei Lin, Hanqing Wang, Hua Sun, Chengju Xiao, Yunxia Xue, Jun Liu, Ting Fu, Yifei Wang, Dong Dong, Zhijie Li
Retinoic acid receptor-related orphan receptors (RORs) play critical roles in the onset and progression of type I diabetes, an autoimmune disease characterized by the destruction of pancreatic β-cells. SR1001, an ROR inverse agonist, has been proven to be an effective diabetes treatment in the non-obese diabetic (NOD) mouse model. However, optimization of this treatment is challenging because knowledge of SR1001 pharmacokinetic (PK) behaviors in type I diabetic animals is limited. The aim of our study was to develop and validate a specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to measure the concentrations of SR1001 in plasma and biological samples...
May 24, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28571538/high-throughput-screening-assay-to-identify-modulators-of-il-17-expression
#17
Mohamed Boudjelal, Ana Maria Ruiz-Avendano, Gonzalo Colmenarejo, Sergio A Senar-Sancho, Ashley Barnes, Stephen A Harrison
Herein we demonstrate the successful development of a new RORt-enhanced IL-17F promoter-luciferase reporter assay and its use in a parallel high throughput screening approach, alongside a RORt TR-FRET assay, to rapidly identify new small molecule RORt/IL-17 inhibitors and evaluate their mode of action. We sought to identify cell-permeable small-molecule inhibitors of RORt for rapid progression into hit-to-lead chemistry. As such, we developed the IL-17F promoter luciferase reporter assay in a stable human T-cell (Jurkat) line expressing the RORt receptor and miniaturised it to a final volume of 8 μL in 1536 well plates for HTS use in screening a library of > 350k compounds...
June 1, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28566626/analysis-of-adverse-drug-reaction-risk-in-elderly-patients-using-the-japanese-adverse-drug-event-report-jader-database
#18
Yugo Chisaki, Shoki Aoji, Yoshitaka Yano
In general, the risk of adverse drug reactions (ADRs) is higher in elderly patients than in younger patients. In this study, we performed a comprehensive assessment of the risks of possible drug-ADR combinations in elderly patients using the Japanese Adverse Drug Event Report (JADER) database of the Pharmaceutical and Medical Devices Agency (PMDA, Japan) using the reporting odds ratio (ROR) as an index. Data recorded from April 2004 to September 2015 in the JADER database were downloaded from the PMDA website...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28560450/upregulation-of-socs3-in-lung-cd4-t-cells-in-a-mouse-model-of-chronic-pa-lung-infection-and-suppression-of-th17%C3%A2-mediated-neutrophil-recruitment-in-exogenous-socs3-transfer-in-vitro
#19
Feng-Ming Ding, Ruo-Min Liao, Yu-Qing Chen, Guo-Gang Xie, Peng-Yu Zhang, Ping Shao, Min Zhang
Neutrophilic airway inflammation in chronic lung infections caused by Pseudomonas aeruginosa (PA) is associated with T helper (Th)17 responses. Suppressor of cytokine signaling 3 (SOCS3) is the major negative modulator of Th17 function through the suppression of signal transducer and activator of transcription (STAT)3 activation. The aim of the present study was to investigate the expression of SOCS3 in lung CD4+ T cells in a mouse model of chronic PA lung infection and the effect of exogenous SOCS3 on Th17‑mediated neutrophil recruitment in vitro...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28557790/long-non-coding-rna-profile-in-mantle-cell-lymphoma-identifies-a-functional-lncrna-ror1-as1-associated-with-ezh2-prc2-complex
#20
Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed...
May 17, 2017: Oncotarget
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