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https://www.readbyqxmd.com/read/28916831/the-melanocortin-signaling-camp-axis-accelerates-repair-and-reduces-mutagenesis-of-platinum-induced-dna-damage
#1
Stuart G Jarrett, Katharine M Carter, Brent J Shelton, John A D'Orazio
Using primary melanocytes and HEK293 cells, we found that cAMP signaling accelerates repair of bi- and mono-functional platinum-induced DNA damage. Elevating cAMP signaling either by the agonistic MC1R ligand melanocyte stimulating hormone (MSH) or by pharmacologic cAMP induction by forskolin enhanced clearance of intrastrand cisplatin-adducts in melanocytes or MC1R-transfected HEK293 cells. MC1R antagonists human beta-defensin 3 and agouti signaling protein blocked MSH- but not forskolin-mediated enhancement of platinum-induced DNA damage...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915603/estrogen-promotes-tumor-metastasis-via-estrogen-receptor-beta-mediated-regulation-of-matrix-metalloproteinase-2-in-non-small-cell-lung-cancer
#2
Sheng Fan, Yongde Liao, Changyu Liu, Quanfu Huang, Huifang Liang, Bo Ai, Shegnling Fu, Sheng Zhou
In non-small cell lung cancer (NSCLC), estrogen significantly promotes NSCLC cell growth via estrogen receptor beta (ERβ). However, the effects by which ERβ contributes to metastasis in NSCLC have not been previously reported. This study aims at defining whether the stimulation of ERβ promotes NSCLC metastasis in vitro and in vivo. Here, Our results showed that estrogen and ERβ agonist enhanced aggressiveness of two lung cancer cell lines (A549 and H1793) and promoted murine lung metastasis formation. ER-inhibitor Fulvestrant treatment or ERβ-knockdown significantly suppressed the migration, invasion and nodule formation of NSCLC cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28906080/persistence-and-adherence-with-mirabegron-vs-antimuscarinics-in-overactive-bladder-retrospective-analysis-of-a-uk-general-practice-prescription-database
#3
Adrian S Wagg, Steve Foley, John Peters, Jameel Nazir, Leanne Kool-Houweling, Ludmila Scrine
INTRODUCTION AND OBJECTIVES: Persistence with antimuscarinic (AM) drugs prescribed for overactive bladder (OAB) is poor. This study aimed to compare persistence and adherence with the beta-3-adrenoceptor agonist mirabegron (MIR) vs AMs over 12 months. PATIENTS AND METHODS: This retrospective cohort analysis included patients aged ≥18 years who were prescribed MIR, or any AM. A 12-month look-back was used to assess inclusion eligibility. The primary end-point was persistence, defined as time to first discontinuation of index drug, during 1 year follow-up...
September 14, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28905149/interactions-between-the-canonical-wnt-beta-catenin-pathway-and-ppar-gamma-on-neuroinflammation-demyelination-and-remyelination-in-multiple-sclerosis
#4
REVIEW
Alexandre Vallée, Jean-Noël Vallée, Rémy Guillevin, Yves Lecarpentier
Multiple sclerosis (MS) is marked by neuroinflammation and demyelination with loss of oligodendrocytes in the central nervous system. The immune response is regulated by WNT/beta-catenin pathway in MS. Activated NF-kappaB, a major effector of neuroinflammation, and upregulated canonical WNT/beta-catenin pathway positively regulate each other. Demyelinating events present an upregulation of WNT/beta-catenin pathway, whereas proper myelinating phases show a downregulation of WNT/beta-catenin pathway essential for the promotion of oligodendrocytes precursors cells proliferation and differentiation...
September 13, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28893517/differential-effects-of-levodopa-and-apomorphine-on-neuronal-population-oscillations-in-the-cortico-basal-ganglia-loop-circuit-in-vivo-in-experimental-parkinsonism
#5
Johanna Kühn, Jens K Haumesser, Maximilian H Beck, Jennifer Altschüler, Andrea A Kühn, Vadim N Nikulin, Christoph van Riesen
The current pharmacotherapy of Parkinson's disease (PD) is primarily based on two classes of drugs: dopamine precursors, namely levodopa, and dopamine receptor agonists, such as apomorphine. Although both types of agents exert their beneficial clinical effects on motor and non-motor symptoms in PD via dopamine receptors, clinical efficiency and side effects differ substantially between levodopa and apomorphine. Levodopa can provide a greater symptomatic relief than dopamine receptor agonists. However, because long-term levodopa use is associated with early debilitating motor fluctuations, dopamine receptor agonists are often recommended in younger patients...
September 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28892561/beta-2-receptor-agonist-exposure-in-the-uterus-associated-with-subsequent-risk-of-childhood-asthma
#6
Kohei Ogawa, Satomi Tanaka, Limin Yang, Naoko Arata, Haruhiko Sago, Kiwako Yamamoto-Hanada, Masami Narita, Yukihiro Ohya
BACKGROUND: Although the beta-2 receptor agonist (B2RA) is occasionally prescribed in the prenatal period for women with preterm labor, few studies have referred to the long-term effects of intrauterine exposure to B2RA on fetus. We examined the association between intrauterine exposure to B2RA and asthma in the offspring. METHODS: We obtained data from a hospital-based birth cohort study conducted in Tokyo, Japan. The outcomes of interest were three indicators, consisting of current wheeze, current asthma and ever asthma at 5 years of age, based on the International Study of Asthma and Allergies in Childhood questionnaire...
September 11, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/28891349/next-generation-beta-adrenoreceptor-agonists-for-the-treatment-of-asthma
#7
Ernesto Crisafulli, Annalisa Frizzelli, Alberto Fantin, Alessandra Manco, Angelo Mangia, Giovanna Pisi, Valentina Fainardi, Veronica Alfieri, Marina Aiello, Giuseppina Bertorelli, Alfredo Chetta
A fixed-dose inhalation of a long-acting β-agonist (LABA) and inhaled corticosteroids (ICS) is commonly recommended for moderate to severe asthmatic patients not adequately controlled by an ICS only. In order to improve the patients' adherence and the control of disease there is a noteworthy interest for the next generation inhaled β adrenoreceptor agonists maintaining an over 24 hours bronchodilatation and used once-daily (ultra-LABAs). This review focuses on the currently available evidences on the clinical role of any single ultra-LABAs in the treatment of asthmatic patients...
October 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28889900/a-62-year-old-woman-with-wheezing-respiratory-failure-and-an-abnormal-ct%C3%A2-scan
#8
Peter Hountras, Hector Cajigas
A previously healthy 62-year-old woman was transferred to the ICU from the medical ward with acute bronchospastic respiratory failure requiring intubation and mechanical ventilation. Four weeks before, the patient was vacationing in Arizona and acquired a mildly productive cough as well as mild dyspnea. She presented to an urgent care facility and was diagnosed with community-acquired pneumonia. She received a 5-day course of azithromycin, with partial improvement of her symptoms. The patient returned home 1 week prior to admission, reporting worsening dyspnea, chest pressure, cough, and fever...
September 2017: Chest
https://www.readbyqxmd.com/read/28887333/rapid-estrogen-receptor-alpha-signaling-mediated-by-erk-activation-regulates-vascular-tone-in-male-and-ovary-intact-female-mice
#9
Seong Chul Kim, Austin C Boese, Matthew H Moore, Rea M Cleland, Lin Chang, Patrice Delafontaine, Ke-Jie Yin, Jean-Pyo Lee, Milton H Hamblin
Estrogen has been shown to affect vascular reactivity. Here, we assessed estrogen receptor-alpha (ERα) dependency of estrogenic effects on vasorelaxation via a rapid nongenomic pathway in both male and ovary-intact female mice. We compared the effect of a primary estrogen, 17 beta-estradiol (E2) or 4,4',4"-(4-propyl-[1H]pyrazole-1,3,5-triyl)tris-phenol (PPT) (selective ERα agonist). We found that E2 and PPT induced greater aortic relaxation in females than males, indicating ERα mediation, which is further validated by employing ERα antagonism...
September 8, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28881155/seasonal-patterns-of-asthma-medication-fills-among-diverse-populations-of-the-united-states
#10
Kedir N Turi, Tebeb Gebretsadik, Rees L Lee, Tina V Hartert, Amber M Evans, Cosby Stone, Nicholas M Sicignano, Ann C Wu, Carlos Iribarren, Melissa G Butler, Edward Mitchel, James Morrow, Emma K Larkin, Pingsheng Wu
OBJECTIVE: Nonadherence to controller and overuse of reliever asthma medications are associated with exacerbations. We aimed to determine patterns of seasonal asthma medication use and to identify time period(s) during which interventions to improve medication adherence could reduce asthma morbidity. METHODS: We conducted a retrospective cohort study of asthmatics 4-50 years of age and enrolled in three diverse health insurance plans. Seasonal patterns of medications were reported by monthly prescription fill rates per 1000 individuals with asthma from 1998 to 2013, and stratified by healthcare plan, sex, and age...
September 7, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28881139/fracture-targeted-delivery-of-%C3%AE-catenin-agonists-via-peptide-functionalized-nanoparticles-augments-fracture-healing
#11
Yuchen Wang, Maureen R Newman, Marian Ackun-Farmmer, Michael P Baranello, Tzong-Jen Sheu, J Edward Puzas, Danielle S W Benoit
Despite several decades of progress, bone specific drug delivery is still a major challenge. Current bone-acting drugs require high-dose systemic administration which decreases therapeutic efficacy and increases off-target tissue effects. Here, a bone-targeted nanoparticle (NP) delivery system for a β-catenin agonist, 3-amino-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-N-(pyridin-3-yl)pyrazine-2-carboxamide, a glycogen synthase kinase 3 beta (GSK-3β) inhibitor, was developed to enhance fracture healing...
September 7, 2017: ACS Nano
https://www.readbyqxmd.com/read/28877011/tezepelumab-in-adults-with-uncontrolled-asthma
#12
Jonathan Corren, Jane R Parnes, Liangwei Wang, May Mo, Stephanie L Roseti, Janet M Griffiths, René van der Merwe
BACKGROUND: In some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids...
September 7, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28875459/once-daily-triple-therapy-in-patients-with-advanced-copd-healthcare-resource-utilization-data-and-associated-costs-from-the-fulfil-trial
#13
Afisi S Ismaila, Ruby Birk, Dhvani Shah, Shiyuan Zhang, Noushin Brealey, Nancy A Risebrough, Maggie Tabberer, Chang-Qing Zhu, David A Lipson
INTRODUCTION: Chronic obstructive pulmonary disease is associated with a high healthcare resource and cost burden. Healthcare resource utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study. Patients received either once-daily, single inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy (budesonide/formoterol) 400 µg/12 µg...
September 5, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28874749/structural-and-pharmacological-basis-for-the-induction-of-mitochondrial-biogenesis-by-formoterol-but-not-clenbuterol
#14
Robert B Cameron, Craig C Beeson, Rick G Schnellmann
Mitochondrial dysfunction is associated with numerous acute and chronic degenerative diseases. The beta-2 adrenergic receptor (β2AR) agonist formoterol induces mitochondrial biogenesis (MB), but other β2AR agonists, such as clenbuterol, do not. We sought to identify the MB signaling pathway of formoterol and the differences in signaling between these two ligands that result in the differential induction of MB. While formoterol and clenbuterol increased cAMP, only formoterol increased the phosphorylation of Akt and its downstream target eNOS...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28873389/treatment-of-diabetes-and-obesity-by-rationally-designed-peptide-agonists-functioning-at-multiple-metabolic-receptors
#15
Noushafarin Khajavi, Heike Biebermann, Matthias Tschöp, Richard DiMarchi
Obesity and its comorbidities such as type 2 diabetes constitute major worldwide health threats, and the identification of an effective medical intervention has emerged as a global priority. The limited effectiveness of historical, anti-obesity treatments is commonly attributed to the complexity of the disease and the redundancy of metabolic regulatory mechanisms that sustain body weight. At the forefront of obesity research is the development of combinational drug therapies that simultaneously target multiple regulatory pathways, which promote dysfunctional metabolism...
2017: Endocrine Development
https://www.readbyqxmd.com/read/28873383/incretins-and-their-endocrine-and-metabolic-functions
#16
Jochen Seufert
Incretins are hormones secreted into the blood stream from the gut mucosa in response to nutrient intake. They have been characterized based on their capacity to lower blood glucose levels. The more potent reduction of blood glucose coupled to a more intensive stimulation of insulin secretion, in response to oral glucose uptake, as compared to intravenous glucose infusion has further been termed the "incretin effect." As a prototype incretin hormone, the biology of glucagon-like peptide 1 (GLP-1) has been intensively studied...
2017: Endocrine Development
https://www.readbyqxmd.com/read/28870238/bet-bromodomain-inhibitors-and-agonists-of-the-beta-2-adrenergic-receptor-identified-in-screens-for-compounds-that-inhibit-dux4-expression-in-fshd-muscle-cells
#17
Amy E Campbell, Jonathan Oliva, Matthew P Yates, Jun Wen Zhong, Sean C Shadle, Lauren Snider, Nikita Singh, Shannon Tai, Yosuke Hiramuki, Rabi Tawil, Silvère M van der Maarel, Stephen J Tapscott, Francis M Sverdrup
BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is a progressive muscle disease caused by mutations that lead to epigenetic derepression and inappropriate transcription of the double homeobox 4 (DUX4) gene in skeletal muscle. Drugs that enhance the repression of DUX4 and prevent its expression in skeletal muscle cells therefore represent candidate therapies for FSHD. METHODS: We screened an aggregated chemical library enriched for compounds with epigenetic activities and the Pharmakon 1600 library composed of compounds that have reached clinical testing to identify molecules that decrease DUX4 expression as monitored by the levels of DUX4 target genes in FSHD patient-derived skeletal muscle cell cultures...
September 4, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28868931/emerging-inhaled-long-acting-beta-2-adrenoceptor-agonists-for-the-treatment-of-copd
#18
Thomas J Monaco, Nicola A Hanania
Chronic obstructive pulmonary disease (COPD), characterized by persistent and partially reversible airflow obstruction, is a leading cause of morbidity and mortality worldwide. Long-acting inhaled bronchodilators form the backbone for the maintenance therapy for this disease. The ultra-long-acting β2-agonists (ultra-LABAs) represent novel pharmacologic agents with interesting potential benefits as stand-alone therapy or in combination with other therapies for the treatment of COPD. Areas covered: In this review, we will focus newly developed ultra-LABAs, describing currently available evidence of their clinical effect and safety, their comparison relative to older long-acting β2-agonists, and their potential niche in the maintenance treatment of COPD...
September 3, 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28864864/the-anticancer-estrogen-receptor-antagonist-tamoxifen-impairs-consolidation-of-inhibitory-avoidance-memory-through-estrogen-receptor-alpha
#19
Martina Lichtenfels, Arethuza da Silva Dornelles, Fernanda Dos Santos Petry, Martina Blank, Caroline Brunetto de Farias, Rafael Roesler, Gilberto Schwartsmann
Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats...
September 2, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28864529/thyroid-hormone-receptor-beta-and-ncoa4-regulate-terminal-erythrocyte-differentiation
#20
Xiaofei Gao, Hsiang-Ying Lee, Wenbo Li, Randall Jeffrey Platt, M Inmaculada Barrasa, Qi Ma, Russell R Elmes, Michael G Rosenfeld, Harvey F Lodish
An effect of thyroid hormone (TH) on erythropoiesis has been known for more than a century but the molecular mechanism(s) by which TH affects red cell formation is still elusive. Here we demonstrate an essential role of TH during terminal human erythroid cell differentiation; specific depletion of TH from the culture medium completely blocked terminal erythroid differentiation and enucleation. Treatment with TRβ agonists stimulated premature erythroblast differentiation in vivo and alleviated anemic symptoms in a chronic anemia mouse model by regulating erythroid gene expression...
September 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
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