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Novel Steroid

M Sacchetti, I Abicca, A Bruscolini, C Cavaliere, M Nebbioso, A Lambiase
Allergic conjunctivitis (AC) includes a wide spectrum of clinical entities characterized by different incidence, age of onset, natural course, clinical outcome and response to treatment. Taken together, they represent one of the most frequent ocular surface diseases affecting more than 30% of the young-adult population and show an increasing incidence over the years. Moreover, comorbidities with other systemic atopic conditions such as asthma, atopic dermatitis and rhinitis require a multidisciplinary approach...
January 2018: Journal of Biological Regulators and Homeostatic Agents
Lin Hai Kurahara, Keizo Hiraishi, Yaopeng Hu, Kaori Koga, Miki Onitsuka, Mayumi Doi, Kunihiko Aoyagi, Hidetoshi Takedatsu, Daibo Kojima, Yoshitaka Fujihara, Yuwen Jian, Ryuji Inoue
Background & Aims: The transient receptor potential ankyrin 1 (TRPA1) channel is highly expressed in the intestinal lamina propria, but its contribution to gut physiology/pathophysiology is unclear. Here, we evaluated the function of myofibroblast TRPA1 channels in intestinal remodeling. Methods: An intestinal myofibroblast cell line (InMyoFibs) was stimulated by transforming growth factor-β1 to induce in vitro fibrosis. Trpa1 knockout mice were generated using the Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Danmei Zhou, Kehan Ren, Jigang Wang, Hong Ren, Wenlin Yang, Wenjuan Wang, Qiong Li, Xiuping Liu, Feng Tang
Erythropoietin-producing hepatocellular A6 (EphA6) is a member of the Eph receptor tyrosine kinase family, which has been implicated in tumorigenesis. However, little is known about the expression and function of EphA6 in breast cancer. The aim of the present study was to investigate the expression of EphA6 and the possible association between EphA6 and clinicopathological characteristics in breast cancer. In the present study, EphA6 mRNA expression was measured in 26 paired breast cancer tissues and adjacent non-cancerous tissues by reverse transcription-quantitative polymerase chain reaction...
April 2018: Oncology Letters
Fred Chasalow, Lori Pierce-Cohen
We describe a novel steroid, which we have named "Ionotropin." Its unique features are: [1] it has 23 carbon atoms and [2] it is a phosphocholine ester. There are no other known mammalian steroids with either structural feature. Ionotropin cross reacts with digoxin-specific antibodies and may be the long-sought, endogenous, mammalian digoxin-like material (DLM). Using LC-MS, we identified three other phosphocholine steroids in serum. Two of these steroids also cross-react with digoxin specific antibodies...
March 14, 2018: Steroids
Adriana Maggi, Sara Della Torre
BACKGROUND: Epidemiological and clinical studies have largely demonstrated major differences in the prevalence of metabolic disorders in males and females, but the biological cause of these dissimilarities remain to be elucidated. Mammals are characterized by a major change in reproductive strategies and it is conceivable that these changes subjected females to a significant evolutionary pressure that perfected the coupling between energy metabolism and reproduction. SCOPE OF REVIEW: This review will address the plausibility that female liver functions diverged significantly from males given the role of liver in the control of metabolism...
February 27, 2018: Molecular Metabolism
Eva Roos, Lowiek M Hubers, Robert J S Coelen, Marieke E Doorenspleet, Niek de Vries, Joanne Verheij, Ulrich Beuers, Thomas M van Gulik
BACKGROUND: Distinguishing perihilar cholangiocarcinoma (PHC) from benign forms of sclerosing cholangitis affecting the hilar bile ducts is challenging, since histological confirmation of PHC is difficult to obtain and accurate non-invasive diagnostic tests are not available. IgG4-associated cholangitis (IAC), an imitator of PHC, may present with clinical and radiographical signs of PHC. IAC can be accurately diagnosed with a novel qPCR test. The aim of this study was to investigate the incidence and long-term activity of IAC in patients resected for PHC in a single tertiary center over a period of 30 years...
March 16, 2018: American Journal of Gastroenterology
Myrna R Nahas, Robert J Soiffer, Haesook T Kim, Edwin Alyea, Jon Arnason, Robin Joyce, Joseph H Antin, Vincent Ho, Dina Stroopinsky, Shuli Li, James D Levine, Malgorzata McMasters, Salvia Jain, Ayad Hamdan, Dimitrios Tzachanis, Mary Paty Bryant, Emma Logan, Josie Bazemore, Jeremy Stewart, Amy Joyce, Susan Stephenson, Abigail Washington, Leandra Cole, Athalia Pyzer, Rebecca Karp Leaf, David Avigan, Jacalyn Rosenblatt
Steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains a major cause of morbidity and mortality following allogeneic transplantation. Innovative immunotherapeutic strategies are urgently needed for the treatment of SR-cGVHD. We conducted a phase I clinical trial to evaluate the safety, efficacy, and immune effects of abatacept, a novel immunomodulatory drug that acts as an inhibitor of T cell activation via co-stimulatory blockade, in the treatment of SR-cGVHD. The study followed a 3+3 design with two escalating abatacept doses: 3 mg/kg and 10 mg/kg, with an expansion cohort treated at 10 mg/kg...
March 16, 2018: Blood
Jonatan Barrera-Chimal, Gabriel R Estrela, Sebastian M Lechner, Sébastien Giraud, Soumaya El Moghrabi, Shiem Kaaki, Peter Kolkhof, Thierry Hauet, Frédéric Jaisser
Acute kidney injury induced by ischemia/reperfusion is an independent risk factor for chronic kidney disease. Macrophage recruitment plays an essential role during the injury and repair phases after an ischemic episode in the kidney. Here we show that the novel non-steroidal mineralocorticoid receptor antagonist finerenone or selective myeloid mineralocorticoid receptor ablation protects against subsequent chronic dysfunction and fibrosis induced by an episode of bilateral kidney ischemia/reperfusion in mice...
March 13, 2018: Kidney International
Guillermo de Anda-Jáuregui, Kai Guo, Brett A McGregor, Junguk Hur
The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs)...
2018: Frontiers in Physiology
Hyun-Jung Moon, Hak-Bong Kim, Su-Hoon Lee, So-Eun Jeun, Chi-Dug Kang, Sun-Hee Kim
NSAIDs (non-steroidal anti-inflammatory drugs) have potential use as anticancer agents, either alone or in combination with other cancer therapies. We found that NSAIDs including celecoxib (CCB) and ibuprofen (IBU) significantly potentiated the cytotoxicity of Hsp90 inhibitors in human multidrug-resistant (MDR) cells expressing high levels of mutant p53 (mutp53) protein and P-glycoprotein (P-gp), and reversed Hsp90 inhibitor resistance caused by activation of heat shock factor 1 (HSF1) and by up-regulation of heat shock proteins (Hsps) and P-gp...
February 16, 2018: Oncotarget
Éverton L Vogt, Jorge F A Model, Anapaula S Vinagre
Organotins (OTs) are considered some of the most toxic chemicals introduced into aquatic environments by anthropogenic activities. They are widely used for agricultural and industrial purposes and as antifouling additives on boat hull's paints. Even though the use of OTs was banned in 2008, elevated levels of OTs can still be detected in aquatic environments. OTs' deleterious effects upon wildlife and experimental animals are well documented and include endocrine disruption, immunotoxicity, neurotoxicity, genotoxicity, and metabolic dysfunction...
2018: Frontiers in Endocrinology
Bin Yang, Jingxia Huang, Xuefeng Zhou, Xiuping Lin, Juan Liu, Shengrong Liao, Junfeng Wang, Feng-An Liu, Huaming Tao, Yonghong Liu
Malaria caused by Plasmodium parasites is amongst many prevalent public health concerns in several tropical regions of the world. Nowadays, the parasite resistance patterns to most currently used drugs in therapy and insecticides have created an urgent need for new chemical entities exhibiting new modes of action and management strategies. Fungus have been proven to be excellent sources of biologically active compounds, which have been screened for antiplasmodial activity as potential sources of new antimalarial drugs...
March 12, 2018: Current Medicinal Chemistry
Jia Wu, Zilin Xu, Yixuan Pan, Yi Shi, Xiujie Bao, Jun Li, Yu Tong, Han Tang, Shuyan Ma, Xuedong Wang, Jianxin Lyu
Herein, a novel magnetic effervescence tablet-assisted microextraction coupled to in situ metathesis reaction of ionic liquid (IS-META-ILDM) is presented for the determination of four endogenous steroids in human urine, pregnant women's blood, and fetal umbilical cord blood. The magnetic effervescent tablets, which were composed of Fe3 O4 nanoparticles, sodium carbonate (alkaline source), and tartaric acid (acidic source), were used to disperse the extractant and for convenient magnetic separation. After the effervescent reaction, in situ reaction between NH4 PF6 and [C6 MIM]BF4 was adopted to change hydrophilic ionic liquid to hydrophobic liquid, which could be separated from the aqueous phase...
March 12, 2018: Analytical and Bioanalytical Chemistry
Kinnosuke Yahiro, Sayaka Nagasawa, Kimitoshi Ichimura, Hiroki Takeuchi, Kohei Ogura, Hiroyasu Tsutsuki, Takeshi Shimizu, Sunao Iyoda, Makoto Ohnishi, Hirotaro Iwase, Joel Moss, Masatoshi Noda
Shiga toxigenic Escherichia coli (STEC) are responsible for a worldwide foodborne disease, which is characterized by severe bloody diarrhea and hemolytic uremic syndrome (HUS). Subtilase cytotoxin (SubAB) is a novel AB5 toxin, which is produced by Locus for Enterocyte Effacement (LEE)-negative STEC. Cleavage of the BiP protein by SubAB induces endoplasmic reticulum (ER) stress, followed by induction of cytotoxicity in vitro or lethal severe hemorrhagic inflammation in mice. Here we found that steroids and diacylglycerol (DAG) analogues (e...
December 2018: Cell Death Discovery
Adriana Carino, Michele Biagioli, Silvia Marchianò, Paolo Scarpelli, Angela Zampella, Vittorio Limongelli, Stefano Fiorucci
Liver fibrosis, a major health concern worldwide, results from abnormal collagen deposition by activated hepatic stellate cells (HSCs) in a injured liver. The farnesoid-x-receptor (FXR) is a bile acid sensor that counteracts HSCs transdifferentiation. While targeting FXR holds promise, 6-ethyl-CDCA known as obeticholic acid, the first in class of FXR ligands, causes side effects, partially because the lack of selectivity toward GPBAR1, a putative itching receptor. Here, we describe the 3-deoxy-6-ethyl derivative of CDCA, BAR704, as a highly selective steroidal FXR agonist...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Kate M Richmond, Katharine G Warburton, Simon J Finney, Sachin Shah, Benjamin A J Reddi
INTRODUCTION: Comprehensive clinical examination can be compromised in patients on veno-venous extracorporeal membrane oxygenation (VV-ECMO). Adjunctive diagnostic imaging strategies range from bedside imaging only to routine computed tomography (CT). The risk-benefit of either approach remains to be evaluated. Patients retrieved to the Royal Brompton Hospital (RBH) on VV-ECMO routinely undergo admission CT imaging of head, chest, abdomen and pelvis. This study aimed to identify how frequently changes in therapy or adverse events could be attributed to routine CT scanning...
March 1, 2018: Perfusion
Xueping Hu, Bin Yin, Kaat Cappelle, Luc Swevers, Guy Smagghe, Xinling Yang, Li Zhang
Insect growth is regulated by the steroid hormone 20-hydroxyecdysone (20E), which works via the ecdysone receptor (EcR). To identify biologically active and novel ecdysone agonists/antagonists, ligand/structure-based virtual screening combined with pharmacophore modeling and molecular docking was performed to identify novel nonsteroidal lead compounds. Nine molecules were screened and selected for an in vitro cell-based reporter bioassay. The results showed that VS-006 and VS-009 exhibited antagonistic activity in S2 cells, whereas only VS-006 exhibited antagonistic activity in Bm5 cells...
March 2, 2018: Journal of Molecular Graphics & Modelling
Eleni Theocharidou, Michael A Heneghan
Autoimmune hepatitis occurs in genetically susceptible individuals as a result of loss of immunological tolerance to hepatic autoantigens that can be precipitated by environmental triggers. The clinical manifestation is usually insidious but can be also acute with liver failure. The diagnosis is made on the basis of antibody positivity, elevated immunoglobulin G levels and interface hepatitis on liver histology. Induction of remission is achieved with high-dose steroids in the majority of cases, and maintenance of remission with azathioprine...
March 2, 2018: British Journal of Hospital Medicine
Maykel Hernández-Mesa, Bruno Le Bizec, Fabrice Monteau, Ana M García-Campaña, Gaud Dervilly-Pinel
Ion mobility spectrometry enhances the performance characteristics of liquid chromatography-mass spectrometry workflows intended to steroid profiling by providing a new separation dimension and a novel characterization parameter, the so-called collision cross section (CCS). This work proposes the first CCS database for 300 steroids (i.e. endogenous, including phase I and phase II metabolites, and exogenous synthetic compounds), which involves 1080 ions and covers the CCS of 127 androgens, 84 estrogens, 50 corticosteroids and 39 progestagens...
March 12, 2018: Analytical Chemistry
Danielle H Dube
"Drug Discovery" is a 13-week lecture and laboratory-based course that was developed to introduce non-science majors to foundational chemistry and biochemistry concepts as they relate to the unifying theme of drug discovery. The first part of this course strives to build students' understanding of molecules, their properties, the differences that enable them to be separated from one another, and their abilities to bind to biological receptors and elicit physiological effects. After building students' molecular worldview, the course then focuses on four classes of drugs: antimicrobials, drugs that affect the mind, steroid-based drugs, and anti-cancer drugs...
March 12, 2018: Biochemistry and Molecular Biology Education
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