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https://www.readbyqxmd.com/read/28444139/multi-label-classifier-based-on-histogram-of-gradients-for-predicting-the-anatomical-therapeutic-chemical-class-classes-of-a-given-compound
#1
Loris Nanni, Sheryl Brahnam
Motivation: Given an unknown compound, is it possible to predict its ATC (Anatomical Therapeutic Chemical) class/classes? This is a challenging yet important problem since such a prediction could be used to deduce not only a compound's possible active ingredients but also its therapeutic, pharmacological, and chemical properties, thereby substantially expediting the pace of drug development. The problem is challenging because some drugs and compounds belong to two or more ATC classes, making machine learning extremely difficult...
April 24, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28442062/retinoic-acid-triggers-c-kit-gene-expression-in-spermatogonial-stem-cells-through-an-enhanceosome-constituted-between-transcription-factor-binding-sites-for-retinoic-acid-response-element-rare-spleen-focus-forming-virus-proviral-integration-oncogene-spfi1-pu
#2
Swanand Koli, Ayan Mukherjee, Kudumula Venkata Rami Reddy
Restricted availability of retinoic acid (RA) in the testicular milieu regulates transcriptional activity of c-kit (KIT, CD117), which aids in the determination of spermatogonial stem-cell differentiation. The effect of RA on c-kit has been reported previously, but its mode of genomic action remains unresolved. We studied the molecular machinery guiding RA responsiveness to the c-kit gene using spermatogonial stem-cell line C18-4 and primary spermatogonial cells. A novel retinoic acid response element (RARE) positioned at -989 nucleotides upstream of the transcription start site (TSS) was identified, providing a binding site for a dimeric RA receptor (i...
March 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28440511/simultaneously-increased-expression-of-glucocorticoid%C3%A2-induced-tumor-necrosis-factor-receptor-and-its-ligand-contributes-to-increased-interleukin%C3%A2-5-13%C3%A2-producing-group-2-innate-lymphocytes-in-murine-asthma
#3
Mengying Zhang, Jie Wan, Yunyun Xu, Danyi Zhang, Jingjing Peng, Chen Qi, Qi Guo, Sheng Xia, Zhaoliang Su, Shengjun Wang, Huaxi Xu
Glucocorticoid‑induced tumor necrosis factor receptor (GITR) is expressed at high levels on CD4+CD25+ regulatory T cells (Tregs). Following activation by its ligand (GITRL), GITR influences the activity of effector T cells and Tregs and participates in the development of numerous autoimmune and inflammatory diseases, including asthma. However, the GITR/GITRL expression level in lung tissue and its influence on group 2 innate lymphocytes (ILC2s) in asthma remains unclear. The present study detected the number of ILC2s and the expression levels of GITR and GITRL in the lung tissues of asthmatic mice by flow cytometry analysis, immunofluorescence staining and reverse transcription quantitative polymerase chain reaction...
April 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439009/estrogen-receptor-%C3%AE-a-regulator-of-androgen-receptor-signaling-in-the-mouse-ventral-prostate
#4
Wan-Fu Wu, Laure Maneix, Jose Insunza, Ivan Nalvarte, Per Antonson, Juha Kere, Nancy Yiu-Lin Yu, Virpi Tohonen, Shintaro Katayama, Elisabet Einarsdottir, Kaarel Krjutskov, Yu-Bing Dai, Bo Huang, Wen Su, Margaret Warner, Jan-Åke Gustafsson
As estrogen receptor β(-/-) (ERβ(-/-)) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young (2-mo-old) and aging (18-mo-old) ERβ(-/-) mice and their WT littermates. We also treated young and old WT mice with an ERβ-selective agonist and evaluated protein expression. The most significant findings were that ERβ down-regulates androgen receptor (AR) signaling and up-regulates the tumor suppressor phosphatase and tensin homolog (PTEN)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438785/nuclear-receptor-research-in-zebrafish
#5
Marcel J M Schaaf
Nuclear receptors (NRs) form a superfamily of transcription factors that can be activated by ligands and are involved in a wide range of physiological processes. NRs are well conserved between vertebrate species. The zebrafish, an increasingly popular animal model system, contains a total of 73 NR genes, and orthologues of almost all human NRs are present. In this review article, an overview is presented of NR research in which the zebrafish has been used as a model. Research is described on the three most studied zebrafish NRs: the Estrogen Receptors (ERs), Retinoic Acid Receptors (RARs) and Peroxisome Proliferator-Activated Receptors (PPARs)...
April 24, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28438539/recurrent-acute-rhinosinusitis-prevention-by-azithromycin-in-children-with-nonallergic-rhinitis
#6
Jittima Veskitkul, Patcharaporn Wongkaewpothong, Tanita Thaweethamchareon, Kitirat Ungkanont, Nualanong Visitsunthorn, Punchama Pacharn, Pakit Vichyanond, Orathai Jirapongsananuruk
BACKGROUND: Recurrent acute rhinosinusitis (RARS) is characterized by multiple episodes of acute rhinosinusitis between which symptoms and signs resolve completely. The role of antibiotic prophylaxis to prevent RARS in children with nonallergic rhinitis (NAR) has not been investigated. OBJECTIVE: To evaluate the effect of azithromycin to prevent RARS in children with NAR. METHODS: A randomized, double-blind, placebo-controlled study was conducted in NAR children (5-15 years) with RARS...
April 21, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28432217/rar%C3%AE-2-is-required-for-vertebrate-somitogenesis
#7
Amanda Janesick, Weiyi Tang, Tuyen T L Nguyen, Bruce Blumberg
During vertebrate somitogenesis, retinoic acid is known to establish the position of the determination wavefront, controlling where new somites are permitted to form along the anteroposterior body axis. Less is understood about how RAR regulates somite patterning, rostral-caudal boundary setting, specialization of myotome subdivisions, or the specific RAR subtype that is required for somite patterning. Characterizing the function of RARβ has been challenging due to the absence of embryonic phenotypes in murine loss-of-function studies...
April 21, 2017: Development
https://www.readbyqxmd.com/read/28430123/functional-analysis-of-the-rs774872314-rs116171003-rs200231898-and-rs201107751-polymorphisms-in-the-human-ror%C3%AE-t-gene-promoter-region
#8
Marcin Ratajewski, Marcin Słomka, Kaja Karaś, Marta Sobalska-Kwapis, Małgorzata Korycka-Machała, Anna Sałkowska, Jarosław Dziadek, Dominik Strapagiel, Jarosław Dastych
RAR-related orphan receptor gamma RORγT, a tissue-specific isoform of the RORC gene, plays a critical role in the development of naive CD4+ cells into fully differentiated Th17 lymphocytes. Th17 lymphocytes are part of the host defense against numerous pathogens and are also involved in the pathogenesis of inflammatory diseases, including autoimmune disorders. In this study, we functionally examined four naturally occurring polymorphisms located within one of the previously identified GC-boxes in the promoter region of the gene...
April 21, 2017: Genes
https://www.readbyqxmd.com/read/28427488/nr2e1-downregulation-is-involved-in-excess-retinoic-acid-induced-developmental-abnormality-in-the-mouse-brain
#9
Juan Yu, Qian Guo, Jian Bing Mu, Ting Zhang, Ren Ke Li, Jun Xie
OBJECTIVE: This study aimed to investigate the expression pattern and function of Nuclear receptor subfamily 2 group E member 1 (Nr2e1) in retinoic acid (RA)-induced brain abnormality. METHODS: The mouse model of brain abnormality was established by administering 28 mg/kg RA, and neural stem cells (NSCs) were isolated from the mouse embryo and cultured in vitro. Nr2e1 expression was detected by whole mount in situ hybridization, RT-PCR, and Western blotting. Nr2e1 function was determined by transducing Nr2e1 shRNA into NSCs, and the effect on the sonic hedgehog (Shh) signaling pathway was assessed in the cells...
March 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28426724/cloning-retinoid-and-peroxisome-proliferator-activated-nuclear-receptors-of-the-pacific-oyster-and-in-silico-binding-to-environmental-chemicals
#10
Susanne Vogeler, Tamara S Galloway, Michail Isupov, Tim P Bean
Disruption of nuclear receptors, a transcription factor superfamily regulating gene expression in animals, is one proposed mechanism through which pollution causes effects in aquatic invertebrates. Environmental pollutants have the ability to interfere with the receptor's functions through direct binding and inducing incorrect signals. Limited knowledge of invertebrate endocrinology and molecular regulatory mechanisms, however, impede the understanding of endocrine disruptive effects in many aquatic invertebrate species...
2017: PloS One
https://www.readbyqxmd.com/read/28420144/retinoids-regulate-adipogenesis-involving-the-tgf%C3%AE-smad-and-wnt-%C3%AE-catenin-pathways-in-human-bone-marrow-mesenchymal-stem-cells
#11
Jun Cao, Yuhong Ma, Weiqi Yao, Xiaoye Zhang, Dongcheng Wu
Retinoids may regulate cell differentiation as ligands of retinoic acid receptors (RARs) and/or retinoid X receptors (RXRs). We showed that RAR agonists promoted adipogenesis by upregulating the expression of CCAAT/enhancer-binding protein β (C/EBPβ) in the early stages, but blocked adipogenesis at a later stage in human bone marrow mesenchymal stem cells (hBMSCs). RXR agonists promoted adipogenesis at all time points in hBMSCs. The effect of RAR agonists was mediated mainly by the RARβ subtype. RAR agonists, in contrast to RXR agonists, significantly promoted the expression of RARβ...
April 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28418498/suppression-by-an-rar-%C3%AE-agonist-of-collagen-degradation-mediated-by-corneal-fibroblasts
#12
Kazuhiro Kimura, Hongyan Zhou, Tomoko Orita, Masaaki Kobayashi, Teruo Nishida, Koh-Hei Sonoda
Purpose: To examine the role of retinoic acid receptor (RAR) isoforms in interleukin-1β (IL-1β)-induced collagen degradation by corneal fibroblasts. Methods: Primary rabbit corneal fibroblasts embedded in a three-dimensional collagen gel were incubated with or without all-trans retinoic acid (ATRA), the RAR-α agonist Am580, the RAR-β agonist AC55649, or the RAR-γ agonist R667. Collagen degradation was determined by measurement of hydroxyproline produced in acid hydrolysates of culture supernatants...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28411882/in-vitro-generation-of-interleukin-10-secreting-b-regulatory-cells-from-donor-adipose-tissue-derived-mesenchymal-stem-cells-and-recipient-peripheral-blood-mononuclear-cells-for-potential-cell-therapy
#13
Kunal S Gupte, Aruna V Vanikar, Hargovind L Trivedi, Chetan N Patel, Jignesh V Patel
BACKGROUND: Interleukin-10 secreting B-cells are a major subset of B-regulatory cells (B-regs), commonly recognized as CD19(+)/38(hi)/24(hi)/IL10(+). They carry out immunomodulation by release of specific cytokines and/or cell-to-cell contact. We have generated B-regs in-vitro from donor adipose tissue derived mesenchymal stem cells (AD-MSC) and renal allograft recipient (RAR) peripheral blood mononuclear cells (PBMC) for potential cell therapy. MATERIAL AND METHODS: Mononuclear cells separated by density gradient centrifugation from 50 ml anti-coagulated blood of 15-RAR and respective donors were analysed for baseline B-regs using appropriate antibodies...
February 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28394332/mafb-prevents-excess-inflammation-after-ischemic-stroke-by-accelerating-clearance-of-damage-signals-through-msr1
#14
Takashi Shichita, Minako Ito, Rimpei Morita, Kyoko Komai, Yoshiko Noguchi, Hiroaki Ooboshi, Ryusuke Koshida, Satoru Takahashi, Tatsuhiko Kodama, Akihiko Yoshimura
Damage-associated molecular patterns (DAMPs) trigger sterile inflammation after tissue injury, but the mechanisms underlying the resolution of inflammation remain unclear. In this study, we demonstrate that common DAMPs, such as high-mobility-group box 1 (HMGB1), peroxiredoxins (PRXs), and S100A8 and S100A9, were internalized through the class A scavenger receptors MSR1 and MARCO in vitro. In ischemic murine brain, DAMP internalization was largely mediated by MSR1. An elevation of MSR1 levels in infiltrating myeloid cells observed 3 d after experimental stroke was dependent on the transcription factor Mafb...
April 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28392320/contrasting-effects-of-atp-and-adenosine-on-capsaicin-challenge-in-asthmatic-patients
#15
Ozen K Basoglu, Amir Pelleg, Sergei A Kharitonov, Peter J Barnes
BACKGROUND: Adenosine 5'-triphosphate (ATP) stimulates pulmonary vagal slow conducting C-fibres and fast conducting Aδ-fibres with rapidly adapting receptors (RARs). Pulmonary C-fibres but not RARs are also sensitive to capsaicin, a potent tussigenic agent in humans. Thus, the aim of this study was to determine the effects of ATP and its metabolite adenosine (given as adenosine 5'-monophosphate, AMP) on capsaicin challenge in asthmatic patients. METHODS: Cough (quantified as visual analogue scale, VAS), dyspnoea (quantified as Borg score), and FEV1 were quantified following bronchoprovocation using capsaicin, adenosine and ATP in healthy non-smokers (age 40±4y, 6 males), smokers (45±4y, 5 males) and asthmatic patients (37±3y, 5 males); n = 10 in each group...
April 6, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28381549/a-dominant-mutation-in-nuclear-receptor-interacting-protein-1-causes-urinary-tract-malformations-via-dysregulation-of-retinoic-acid-signaling
#16
Asaf Vivante, Nina Mann, Hagith Yonath, Anna-Carina Weiss, Maike Getwan, Michael M Kaminski, Tobias Bohnenpoll, Catherine Teyssier, Jing Chen, Shirlee Shril, Amelie T van der Ven, Hadas Ityel, Johanna Magdalena Schmidt, Eugen Widmeier, Stuart B Bauer, Simone Sanna-Cherchi, Ali G Gharavi, Weining Lu, Daniella Magen, Rachel Shukrun, Richard P Lifton, Velibor Tasic, Horia C Stanescu, Vincent Cavaillès, Robert Kleta, Yair Anikster, Benjamin Dekel, Andreas Kispert, Soeren S Lienkamp, Friedhelm Hildebrandt
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of CKD in the first three decades of life. However, for most patients with CAKUT, the causative mutation remains unknown. We identified a kindred with an autosomal dominant form of CAKUT. By whole-exome sequencing, we identified a heterozygous truncating mutation (c.279delG, p.Trp93fs*) of the nuclear receptor interacting protein 1 gene (NRIP1) in all seven affected members. NRIP1 encodes a nuclear receptor transcriptional cofactor that directly interacts with the retinoic acid receptors (RARs) to modulate retinoic acid transcriptional activity...
April 5, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28375930/retinoic-acid-receptor-%C3%AE-a-potential-therapeutic-target-in-retinoic-acid-treatment-of-endometrial-cancer
#17
Keita Tsuji, Hiroki Utsunomiya, Yasuhiro Miki, Mayu Hanihara, Misaki Fue, Kiyoshi Takagi, Mitsuo Nishimoto, Fumihiko Suzuki, Nobuo Yaegashi, Takashi Suzuki, Kiyoshi Ito
OBJECTIVE: Several studies have reported that retinoic acid (RA) might be used to treat malignancies. The effects of RA are mediated by the RA receptor (RAR), and RARα/RARβ especially acts as a tumor suppressor. However, little is known about its role in human endometrial cancer. MATERIALS AND METHODS: In this study, we examined the effects of all-trans RA (ATRA) on progression of human endometrial cancer cell line, RL95-2 and Hec1A. We then examined the expression of RARα and RARβ in 50 endometrial cancer tissues by using immunohistochemistry...
May 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28370539/rar%C3%AE-rxr-synergism-potentiates-retinoid-responsiveness-in-cutaneous-t-cell-lymphoma-cell-lines
#18
Lei Wang, Sebastian S DeMarco, Mary Stuart Peaks, Abigail L Maiorana-Boutilier, JianMing Chen, Miranda J Crouch, Brian M Shewchuk, Saame Raza Shaikh, Charles M Phillips, Lance C Bridges
Retinoids, natural and synthetic derivatives of vitamin A, induce cellular changes by activating nuclear retinoic acid receptors (RAR) and retinoid X receptors (RXR). Although the ability of retinoids to govern gene expression is exploited clinically for cancer therapeutics, the full benefit of retinoid-based strategies is unrealized due to detrimental side effects. Delineating the receptors that prompt cellular outcomes is critical to advancing retinoid-based approaches. Here we identify the receptors that evoke multiple responses in cutaneous T cell lymphoma (CTCL)...
March 31, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28369371/pattern-fusion-analysis-by-adaptive-alignment-of-multiple-heterogeneous-omics-data
#19
Qianqian Shi, Chuanchao Zhang, Minrui Peng, Xiangtian Yu, Tao Zeng, Juan Liu, Luonan Chen
Motivation: Integrating different omics profiles is a challenging task, which provides a comprehensive way to understand complex diseases in a multi-view manner. One key for such an integration is to extract intrinsic patterns in concordance with data structures, so as to discover consistent information across various data types even with noise pollution. Thus, we proposed a novel framework called "pattern fusion analysis" (PFA), which performs automated information alignment and bias correction, to fuse local sample-patterns (e...
March 28, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28361683/comparative-network-stratification-analysis-for-identifying-functional-interpretable-network-biomarkers
#20
Chuanchao Zhang, Juan Liu, Qianqian Shi, Tao Zeng, Luonan Chen
BACKGROUND: A major challenge of bioinformatics in the era of precision medicine is to identify the molecular biomarkers for complex diseases. It is a general expectation that these biomarkers or signatures have not only strong discrimination ability, but also readable interpretations in a biological sense. Generally, the conventional expression-based or network-based methods mainly capture differential genes or differential networks as biomarkers, however, such biomarkers only focus on phenotypic discrimination and usually have less biological or functional interpretation...
March 14, 2017: BMC Bioinformatics
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