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Retinoic acid receptors

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https://www.readbyqxmd.com/read/29350913/environmentally-triggerable-retinoic-acid-inducible-gene-i-agonists-using-synthetic-polymer-overhangs
#1
Christian R Palmer, Max E Jacobson, Olga Fedorova, Anna M Pyle, John T Wilson
Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor (PRR) that potently activates antiviral innate immunity upon recognition of 5' triphosphorylated double-stranded RNA (pppRNA). Accordingly, RNA ligands of the RIG-I pathway have recently emerged as promising antiviral agents, vaccine adjuvants, and cancer immunotherapeutics. However, RIG-I is expressed constitutively in virtually all cell types, and therefore administration of RIG-I agonists causes risk for systemic inflammation and possible dose-limiting toxicities...
January 19, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29350486/inflammatory-response-and-treatment-tolerance-of-long-term-infusion-of-the-anti-gd2-antibody-ch14-18-cho-in-combination-with-interleukin-2-in-patients-with-high-risk-neuroblastoma
#2
Kiraz Ceylan, Luciana J Jahns, Bjoern N Lode, Karoline Ehlert, Silke Kietz, Sascha Troschke-Meurer, Nikolai Siebert, Holger N Lode
BACKGROUND: The monoclonal anti-GD2 antibody ch14.18/CHO in combination with IL-2 is active and effective in high-risk neuroblastoma (NB) patients. Here, we investigated the inflammatory response and treatment tolerance of long-term infusion (LTI) of ch14.18/CHO (10 × 10 mg/m2 ; 24 hr) in combination with subcutaneous (s.c.) IL-2 in a single center program. METHODS: Fifty-three NB patients received up to six cycles of 100 mg/m2 ch14.18/CHO (d8-18, where d represents day(s)) as LTI combined with 6 × 106 IU/m2 s...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29348488/interferon-alpha-enhances-the-antitumour-activity-of-egfr-targeted-therapies-by-upregulating-rig-i-in-head-and-neck-squamous-cell-carcinoma
#3
Hailong Ma, Shufang Jin, Wenyi Yang, Ge Zhou, Mei Zhao, Sijie Fang, Zhiyuan Zhang, Jingzhou Hu
BACKGROUND: The epidermal growth factor receptor (EGFR)-targeted therapies have been tested in the clinic as treatments for head and neck squamous cell carcinoma (HNSCC). Owing to intrinsic or acquired resistance, EGFR-targeted therapies often lead to a low response rate and treatment failure. Interferon-alpha (IFNα) is a chemosensitising agent and multi-functional cytokine with a tumour inhibitory effect. However, the synergic effect of IFNα and EGFR-targeted therapies (erlotinib and nimotuzumab) and their mechanisms in HNSCC remain unclear...
January 18, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29345621/the-circulating-t-helper-subsets-and-regulatory-t-cells-in-patients-with-common-variable-immunodeficiency-with-no-known-monogenic-disease
#4
G Azizi, A Mirshafiey, H Abolhassani, R Yazdani, F J Ansariha, M Shaghaghi, S S Mortazavi-Jahromi, F Noorbakhsh, N Rezaei, A Aghamohammadi
BACKGROUND: Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID), characterized by heterogeneous clinical manifestations and defects in B- and T- cells. In the present study, we investigated the T helper (Th) cell subsets and regulatory T (Treg) cells, and their related cytokines and transcription factors in the CVID patients with no definite genetic diagnosis. METHODS: The study population comprised 13 CVID patients and 13 healthy controls (HC)...
January 18, 2018: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/29344234/an-oncogenic-function-of-retinoic-acid-receptor-%C3%AE-in-the-development-of-laryngeal-squamous-cell-carcinoma
#5
Cheng-Fu Cai, Cun-Shan Liu, Han-Jing Shang-Guan, Cai-Hong Yang, Xian-Yang Luo, Dong-Yan Shen, Shu-Yu Yang
The aberrant expression of retinoic acid receptor-α (RARα) has been reported in various types of cancer. However, its association with the prognosis and development of laryngeal squamous cell carcinoma (LSCC) has not yet been determined. Therefore, the present study aimed to examine the expression and function of RARα in patients with LSCC. The expression of RARα in LSCC tissues was investigated using immunostaining. An MTT assay and flow cytometry analysis were also performed to investigate the function of RARα in the proliferation and cell cycle of LSCC cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344139/nls-rar%C3%AE-is-a-novel-transcriptional-factor
#6
Kai-Ling Jiang, Liang Zhong, Xiao-Qun Yang, Peng-Peng Ma, Hui Wang, Xin-Yu Zhu, Bei-Zhong Liu
Acute promyelocytic leukemia (APL) is characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid receptor-α (RAR-α) fusion protein. PML-RARα can be cleaved by neutrophil elastase (NE) in several positions in cells in the promyelocytic stage, nuclear location signal (NLS)-negative PML and NLS-RARα may be the products of PML-RARα by NE. The function of NLS-RARα may be affected by the addition of NLS, which would alter its localization in cells, as the role of NLS is to identify proteins for transport to the nucleus...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343779/characterization-of-signaling-pathways-regulating-the-expression-of-pro-inflammatory-long-form-thymic-stromal-lymphopoietin-upon-human-metapneumovirus-infection
#7
Youxian Li, Cecilie Lund, Ida Nervik, Simon Loevenich, Henrik Døllner, Marit W Anthonsen, Ingvild B Johnsen
Thymic stromal lymphopoietin (TSLP) is associated with several allergic diseases including asthma. Two isoforms of TSLP exist in humans, a long form (lfTSLP) and a short form (sfTSLP), displaying distinct immunological functions. Recently, TSLP was found to be upregulated in human airway cells upon human metapneumovirus (hMPV) infection, yet it remains unclear if the two isoforms are regulated differently during hMPV infection. Importantly, the molecular mechanisms underlying hMPV-mediated TSLP induction remain undescribed...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29342416/identification-of-novel-quinazolinedione-derivatives-as-ror%C3%AE-t-inverse-agonist
#8
Yoshiyuki Fukase, Ayumu Sato, Yoshihide Tomata, Atsuko Ochida, Mitsunori Kono, Kazuko Yonemori, Keiko Koga, Toshitake Okui, Masashi Yamasaki, Yasushi Fujitani, Hideyuki Nakagawa, Ryoukichi Koyama, Masaharu Nakayama, Robert Skene, Bi-Ching Sang, Isaac Hoffman, Junya Shirai, Satoshi Yamamoto
Novel small molecules were synthesized and evaluated as retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists for the treatment of inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high-throughput screening of our compound library. The structure-activity relationship (SAR) study of compound 1 showed that the introduction of a chlorine group at the 3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane-1,5-diamide linker is favorable for the activity...
December 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29339732/glyburide-and-retinoic-acid-synergize-to-promote-wound-healing-by-anti-inflammation-and-rip140-degradation
#9
Yi-Wei Lin, Pu-Ste Liu, Kasey Ah Pook, Li-Na Wei
Chronic inflammation underlies the development of metabolic diseases and individuals with metabolic disease often also suffer from delayed wound healing due to prolonged inflammation. Resolving inflammation provides a therapeutic strategy in treating metabolic diseases. We previously showed that during an anti-inflammatory response when macrophages were alternatively (M2) polarized, retinoic acid (RA) dramatically activated arginase 1 gene (Arg1), a gene crucial for wound healing. Here we report that a widely used sulfonylurea drug for type 2 diabetes mellitus (T2DM), glyburide, enhances the anti-inflammatory response and synergizes with RA to promote wound healing...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339104/region-specific-innate-antiviral-responses-of-the-human-epididymis
#10
James A Browne, Shih Hsing Leir, Scott Eggener, Ann Harris
Viral infections of the epididymis are associated with epididymitis, which damages the epithelium and impairs fertility. We showed previously that innate immune response genes were differentially expressed in the corpus and cauda region of the human epididymis in comparison to the caput. Here we investigate the antiviral defense response mechanisms of human epididymis epithelial (HEE) cells. Toll-like receptor (TLR) 3 and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are enriched in HEE cells from the corpus and cauda region...
January 12, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29330906/generating-retinoic-acid-gradients-by-local-degradation-during-craniofacial-development-one-cell-s-cue-is-another-cell-s-poison
#11
REVIEW
Aditi Dubey, Rebecca E Rose, Drew R Jones, Jean-Pierre Saint-Jeannet
Retinoic acid (RA) is a vital morphogen for early patterning and organogenesis in the developing embryo. RA is a diffusible, lipophilic molecule that signals via nuclear RA receptor heterodimeric units that regulate gene expression by interacting with RA response elements in promoters of a significant number of genes. For precise RA signaling, a robust gradient of the morphogen is required. The developing embryo contains regions that produce RA, and specific intracellular concentrations of RA are created through local degradation mediated by Cyp26 enzymes...
January 13, 2018: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/29327456/discovery-and-characterization-of-cd12681-a-potent-ror%C3%AE-inverse-agonist-preclinical-candidate-for-the-topical-treatment-of-psoriasis
#12
Gilles Ouvry, Nicolas Atrux-Tallau, Franck Bihl, Aline Bondu, Claire Bouix-Peter, Isabelle Carlavan, Olivier Christin, Marie-Josée Cuadrado, Claire Defoin-Platel, Sophie Deret, Denis Duvert, Christophe Feret, Mathieu Forissier, Jean-François Fournier, David Froude, Fériel Hacini-Rachinel, Craig Steven Harris, Catherine Hervouet, Hélène Huguet, Guillaume Lafitte, Anne-Pascale Luzy, Branislav Musicki, Danielle Orfila, Benjamin Ozello, Coralie Pascau, Jonathan Pascau, Véronique Parnet, Guillaume Peluchon, Romain Pierre, David Piwnica, Catherine Raffin, Patricia Rossio, Delphine Spiesse, Nathalie Taquet, Etienne Thoreau, Rodolphe Vatinel, Emmanuel Vial, Laurent François Hennequin
With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor RORγ has become a very sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated with the discovery of CD12681 (compound 14; N-(2,4-dimethylphenyl)-N-isobutyl-2-oxo-1-((tetrahydro-2H-pyran-4-yl)methyl)-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide), a potent inverse agonist with in vivo activity in an IL-23 induced skin inflammation model in mouse...
January 12, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29327110/the-role-of-interleukin-2-all-trans-retinoic-acid-and-natural-killer-cells-surveillance-mechanisms-in-anti-gd2-antibody-therapy-in-neuroblastoma
#13
Rosa Nguyen, Jim Houston, Wing K Chan, David Finkelstein, Michael A Dyer
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy...
January 11, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29326073/retinoic-acid-promotes-stem-cell-differentiation-and-embryonic-development-by-transcriptionally-activating-cftr
#14
Xiaofeng Li, Kin Lam Fok, Jinghui Guo, Yan Wang, Zhenqing Liu, Ziyi Chen, Chengdong Wang, Ye Chun Ruan, Sidney Siubun Yu, Hui Zhao, Ji Wu, Xiaohua Jiang, Hsiao Chang Chan
Retinoic acid (RA) plays a pivotal role in many cellular processes; however, the signaling mechanisms mediating the effect of RA are not fully understood. Here, we show that RA transcriptionally upregulates cystic fibrosis transmembrane conductance regulator (Cftr) by promoting the direct binding of its receptor RARα to Cftr promoter in mouse spermatogonia and embryonic stem (ES) cells. The RA/CFTR pathway is involved in the differentiation of spermatogonia and organogenesis during the embryo development of Xenopus laevis...
January 8, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29323028/surgical-reconstruction-of-spinal-cord-circuit-provides-functional-return-in-humans
#15
REVIEW
Thomas Carlstedt, Nicholas James, Mårten Risling
This mini review describes the current surgical strategy for restoring function after traumatic spinal nerve root avulsion in brachial or lumbosacral plexus injury in man. As this lesion is a spinal cord or central nervous injury functional return depends on spinal cord nerve cell growth within the central nervous system. Basic science, clinical research and human application has demonstrated good and useful motor function after ventral root avulsion followed by spinal cord reimplantation. Recently, sensory return could be demonstrated following spinal cord surgery bypassing the injured primary sensory neuron...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29321952/fasciculation-and-elongation-zeta-1-protein-fez1-interacts-with-the-retinoic-acid-receptor-and-participates-in-transcriptional-regulation-of-the-hoxb4-gene
#16
Mariana Bertini Teixeira, Ana Carolina M Figueira, Ariane S Furlan, Bruno Aquino, Marcos R Alborghetti, Adriana F Paes Leme, Li-Na Wei, Jörg Kobarg
Fasciculation and elongation zeta-1 (FEZ1) protein is involved in axon outgrowth and is highly expressed in the brain. It has multiple interaction partners, with functions varying from the regulation of neuronal development and intracellular transport mechanisms to transcription regulation. One of its interactors is retinoic acid receptor (RAR), which is activated by retinoic acid and controls many target genes and physiological process. Based on previous evidence suggesting a possible nuclear role for FEZ1, we wanted to deepen our understanding of this function by addressing the FEZ1-RAR interaction...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29310426/il-1-receptor-antagonist-reduced-chemical-induced-keratinocyte-apoptosis-through-antagonism-to-il-1%C3%AE-il-1%C3%AE
#17
Hyejin Lee, Kyung Ah Cheong, Ji-Young Kim, Nan-Hyung Kim, Minsoo Noh, Ai-Young Lee
Extracellular interleukin 1 alpha (IL-1α) released from keratinocytes is one of the endpoints for in vitro assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-1α is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals...
January 9, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29305858/identification-of-a-candidate-enhancer-for-dmrt3-involved-in-spastic-cerebral-palsy-pathogenesis
#18
Naoto Kubota, Toshifumi Yokoyama, Nobuhiko Hoshi, Mikita Suyama
Cerebral palsy (CP) is a major neuronal disease and the most common movement disorder in children. Although environmental factors leading to CP have been greatly investigated, the genetic mechanism underlying CP is not well understood. Here we focused on two clinical reports that characterized a deletion involving the KANK1 gene locus in the 9p24.3 region. One report shows spastic CP and the other shows no spastic CP phenotype. Based on the epigenetic status and evolutionary conservation, we first found a functional genomic element at the noncoding region that was deleted only in patients with spastic CP...
January 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29299171/melatonin-up-regulates-the-expression-of-the-gata-4-transcription-factor-and-increases-testosterone-secretion-from-leydig-cells-through-ror%C3%AE-signaling-in-an-in-vitro-goat-spermatogonial-stem-cell-differentiation-culture-system
#19
Shou-Long Deng, Yan Zhang, Kun Yu, Xiu-Xia Wang, Su-Ren Chen, De-Ping Han, C Yan Cheng, Zheng-Xing Lian, Yi-Xun Liu
Because androgen function is regulated by its receptors, androgen-androgen receptor signaling is crucial for regulating spermatogenesis. Androgen is mainly testosterone secreted by testis. Based on the results of early studies in goats, the administration of melatonin over an extended period of time increases steroid production, but the underlying mechanism remains unclear. Here, we report the expression of the melatonin membrane receptors MT1 and MT2 and the retinoic acid receptor-related orphan receptor-alpha (RORα) in the goat testis...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298833/production-of-il-17-by-mait-cells-is-increased-in-multiple-sclerosis-and-is-associated-with-il-7-receptor-expression
#20
Anne Willing, Jan Jäger, Stefanie Reinhardt, Nina Kursawe, Manuel A Friese
Multiple sclerosis (MS) is a T cell-driven inflammatory disease of the CNS. Research on T cell subsets involved in MS pathogenesis has mainly focused on classical CD4+ T cells, especially Th17 cells, as they produce the proinflammatory, MS-associated cytokine IL-17. However, the abundant unconventional mucosal-associated invariant T (MAIT) cells are also able to produce IL-17. MAIT cells are characterized by high CD161 expression and a semi-invariant Vα7.2 TCR, with which they recognize bacterial and yeast Ags derived from the riboflavin (vitamin B2) metabolism...
January 3, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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