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https://www.readbyqxmd.com/read/28528528/ustekinumab-a-review-in-moderate-to-severe-crohn-s-disease
#1
Yvette N Lamb, Sean T Duggan
Ustekinumab (Stelara(®)) has been recently approved in the EU and the USA as intravenous induction and subcutaneous maintenance therapy for adult patients with moderately to severely active Crohn's disease who have failed or were intolerant to treatment with immunomodulators, corticosteroids or at least one tumour necrosis factor (TNF) antagonist. Ustekinumab, a monoclonal antibody to the shared p40 subunit of the proinflammatory interleukin (IL)-12 and IL-23 cytokines, has a unique mechanism of action distinct from that of TNF antagonists...
May 20, 2017: Drugs
https://www.readbyqxmd.com/read/28528399/bacterial-microbiome-and-nematode-occurrence-in-different-potato-agricultural-soils
#2
Juan D Castillo, Jorge M Vivanco, Daniel K Manter
Pratylenchus neglectus and Meloidogyne chitwoodi are the main plant-parasitic nematodes in potato crops of the San Luis Valley, Colorado. Bacterial microbiome (16S rRNA copies per gram of soil) and nematode communities (nematodes per 200 g of soil) from five different potato farms were analyzed to determine negative and positive correlations between any bacterial genus and P. neglectus and M. chitwoodi. Farms showed differences in bacterial communities, percentage of bacterivorous and fungivorous nematodes, and numbers of P...
May 20, 2017: Microbial Ecology
https://www.readbyqxmd.com/read/28528302/nanomolar-anti-sickling-compounds-identified-by-ligand-based-pharmacophore-approach
#3
Odailson Santos Paz, Milena de Jesus Pinheiro, Renan Fernandes do Espirito Santo, Cristiane Flora Villarreal, Marcelo Santos Castilho
Adenosine receptors are considered as potential targets for drug development against several diseases. The discovery of subtype 2B adenosine receptors role in erythrocyte sickling process proved its importance to neglected diseases such as sickle cell anemia, which affects approximately 29.000 people around the world, but whose treatment is restricted to just one FDA approved drug (hydroxyurea). In order to widen the therapeutic arsenal available to treat sickle cell anemia patients, it is imperative to identify new lead compounds that modify the sickling course and not just its symptoms...
May 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28528288/cancer-atrial-fibrillation-and-stroke
#4
REVIEW
Tess Fitzpatrick, Marc Carrier, Grégoire Le Gal
Cancer patients appear to be at increased risk for atrial fibrillation. Although surgery and chemotherapy exacerbate this risk, this association is observed even in the absence of any cancer-specific treatment. The underlying mechanism of this is likely multifactorial, but systemic inflammation and autonomic dysregulation are hypothesized to play critical roles. Cancer and atrial fibrillation are both independent risk factors for ischemic stroke; however, it is not clear whether this translates to an increased risk of stroke in patients with both comorbidities...
May 9, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28528135/presymptomatically-applied-ampa-receptor-antagonist-prevents-calcium-increase-in-vulnerable-type-of-motor-axon-terminals-of-mice-modeling-amyotrophic-lateral-sclerosis
#5
Roland Patai, Melinda Paizs, Massimo Tortarolo, Caterina Bendotti, Izabella Obál, József I Engelhardt, László Siklós
Increased intracellular calcium (Ca), which might be the consequence of an excess influx through Ca-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, plays a crucial role in degeneration of motor neurons. Previously we demonstrated that the presymptomatic application of AMPA receptor antagonist, talampanel, could reduce Ca elevation in spinal motor neurons of mice carrying the G93A mutation of superoxide dismutase 1 (SOD1), modeling amyotrophic lateral sclerosis (ALS). It remained to be examined whether the remote, functionally semi-autonomous motor axon terminals could be rescued from the Ca overload, or if the terminals, where the degeneration possibly starts, already experience intractable changes at early time points...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28527920/emerging-bronchoscopic-treatments-for-chronic-obstructive-pulmonary-disease
#6
REVIEW
Wouter H van Geffen, Huib A M Kerstjens, Dirk-Jan Slebos
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by pathophysiological factors including airflow limitation, hyperinflation and reduced gas exchange. Treatment consists of lifestyle changes, lung rehabilitation and pharmacological therapies such as long acting beta-2-agonists (LABA) and long acting muscarinic antagonists (LAMA). More recently bronchoscopic treatments are emerging for COPD. Among them endobronchial valves(EBV) and endobronchial coils (EBC), next to endobronchial stents, sclerosing agents, targeted lung denervation and liquid nitrogen metered cryospray...
May 17, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28527896/molecular-characterization-and-expression-analyses-of-the-solea-senegalensis-interferon-stimulated-gene-15-isg15-following-nnv-infections
#7
Daniel Álvarez-Torres, Ana María Podadera, M Carmen Alonso, Isabel Bandín, Julia Béjar, Esther García-Rosado
Interferons are essential in fish resistance to viral infections. They induce interferon-stimulated genes, such as isg15. In this study, the Senegalese sole isg15 gene (ssisg15) has been characterized. As other isg15, ssisg15 contains a 402-bp intron sited in the 5'-UTR, and the full length cDNA is 1492-bp, including a 480-bp ORF. The expression analyses revealed basal levels of isg15 transcripts, and a clear induction after poly I:C injection, that reached maximum values in brain, head kidney and gills. The ssisg15 induction patterns were similar in RGNNV- and SJNNV-inoculated fish, whereas the reassortant (RG/SJ) isolate, which has higher replication fitness, triggered delayed but higher transcript levels...
May 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28527850/complement-activation-by-pulp-capping-materials-plays-a-significant-role-in-both-inflammatory-and-pulp-stem-cells-recruitment
#8
Thomas Giraud, Pierre Rufas, Fanny Chmilewsky, Charlotte Rombouts, Jacques Dejou, Charlotte Jeanneau, Imad About
INTRODUCTION: The role of complement, especially through the C5a fragment, is well-known for the initiation of inflammation. Its involvement in regeneration has been shown more recently by the recruitment of mesenchymal stem cells. C5a can be produced locally by the pulp fibroblasts in response to injury or infection. This work aims to investigate the effect of different pulp capping biomaterials on complement activation and its possible influence on inflammatory and pulp stem cell recruitment...
May 17, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28527783/identification-of-novel-selective-p2y6-receptor-antagonists-by-high-throughput-screening-assay
#9
Masaaki Ito, Shin-Ichiro Egashira, Kazuki Yoshida, Tomoko Mineno, Kazuo Kumagai, Hirotatsu Kojima, Takayoshi Okabe, Tetsuo Nagano, Michio Ui, Isao Matsuoka
AIMS: The P2Y6 nucleotide receptor is widely involved in inflammatory responses, and is a promising molecular target for the treatment of inflammatory diseases. Although several P2Y6 receptor antagonists have been developed and evaluated thus far, none has successfully been developed into a therapeutic drug. In this study, we explored new promising compounds that inhibit the human P2Y6 receptor. MAIN METHODS: High-throughput screening (HTS) was used to study the effects of various compounds on human P2Y6 receptors expressed in 1321N1 human astrocytoma cells by monitoring intracellular Ca(2+) concentration ([Ca(2+)]i) levels using an FDSS7000 real-time fluorescence detector...
May 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28527692/regional-differences-in-dopamine-receptor-blockade-affect-timing-impulsivity-that-are-altered-by-d-amphetamine-on-differential-reinforcement-of-low-rate-responding-drl-behavior-in-rats
#10
Ruey-Kuang Cheng, Ruey-Ming Liao
The ability to control when to start an action and when to stop is crucial in human and animal behavior. A failure to suppress premature behavior or carry out an action in a timely manner is commonly seen in several neuropsychological disorders. Despite the phenomenon, the exact neural mechanisms underlying this timing impulsivity remain to be elucidated. Systemic injection of d-amphetamine (AMP) has been shown to disrupt rat's performance in the differential reinforcement of low-rate (DRL) task that requires both optimal timing and proper impulsive control as measured by peak time and non-reinforced responses, respectively...
May 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28527590/phosphate-scouting-by-root-tips
#11
REVIEW
Steffen Abel
Chemistry assigns phosphate (Pi) dominant roles in metabolism; however, it also renders the macronutrient a genuinely limiting factor of plant productivity. Pi bioavailability is restricted by low Pi mobility in soil and antagonized by metallic toxicities, which force roots to actively seek and selectively acquire the vital element. During the past few years, a first conceptual outline has emerged of the sensory mechanisms at root tips, which monitor external Pi and transmit the edaphic cue to inform root development...
May 17, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28527581/nuclear-receptors-in-skeletal-homeostasis
#12
Hao Zuo, Yihong Wan
Nuclear receptors are a family of transcription factors that can be activated by lipophilic ligands. They are fundamental regulators of development, reproduction, and energy metabolism. In bone, nuclear receptors enable bone cells, including osteoblasts, osteoclasts, and osteocytes, to sense their dynamic microenvironment and maintain normal bone development and remodeling. Our views of the molecular mechanisms in this process have advanced greatly in the past decade. Drugs targeting nuclear receptors are widely used in the clinic for treating patients with bone disorders such as osteoporosis by modulating bone formation and resorption rates...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28527428/physicochemical-and-biological-interactions-between-cerium-oxide-nanoparticles-and-a-1-8-naphthalimide-derivative
#13
Gerardo Pulido-Reyes, Esperanza Martín, J L Gu Coronado, Francisco Leganes, Roberto Rosal, Francisca Fernández-Piñas
Cerium (Ce) oxide nanoparticles (CNPs) have attracted attention due to their high bioactivity and unique redox-chemistry. The oxygen vacancies at the surface of the nanoparticle explain the autocatalytic properties of CNPs in which the Ce(3+) atoms occupy the center of the oxygen vacancies surrounded by Ce(4+) atoms. Until now, CNPs have been associated with organic molecules at the synthesis stage to extend their applications or improve their stability. However, there is a lack of information regarding the post-synthesis interaction of CNPs and organic molecules that could enhance or induce new properties...
May 10, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28527051/new-treatments-for-headache
#14
Kasra Maasumi, Stewart J Tepper, Alan M Rapoport
Headache disorders are common worldwide and often disabling. Until recently, treatments were borrowed from other branches of neurology and medicine. Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) ligand and receptor, small molecule CGRP receptor antagonist gepants, serotonin1F agonists, new devices to deliver currently available drugs, and neuromodulation devices have recently been in the forefront of headache treatments that are rather specific for various headache disorders. These novel therapies are changing the field of headache medicine...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28526929/analytical-management-of-patients-undergoing-oral-anticoagulant-therapy-could-have-a-strong-impact-on-clinical-outcomes-a-follow-up-study
#15
Vincenzo De Iuliis, Sebastiano Ursi, Gianfranco Vitullo, Irma Griffo, Antonio Marino, Marika Caruso, Francesco Cipollone, Sabrina Capodifoglio, Veronica Breda, Elena Toniato, Alfonso Pennelli, Pio Conti, Stefano Martinotti
INTRODUCTION: Oral anticoagulant therapy, such as vitamin K antagonists (VKAs), is prominent for the prevention of cerebral ischemic stroke or systemic embolism and all-cause mortality in patients with atrial fibrillation, venous thromboembolism, and mechanical or biological valve. VKA treatment requires monitoring of the international normalized ratio (INR) in order to maintain it in a therapeutic range, avoiding side effects, the main and most significant of which is bleeding. The aim of the present study was to evaluate the event rates of several clinical composite outcomes, such as bleeding, thromboembolic events, and all-cause death...
May 19, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28526784/trpv4-mediates-the-calcium-influx-required-for-flightless-non-muscle-myosin-interaction-and-collagen-remodeling
#16
P D Arora, M Di Gregorio, P He, C A McCulloch
Collagen remodeling by phagocytosis requires cell extension formation, which in turn involves interaction of the actin binding protein Flightless I (FliI) with non-muscle myosin IIA (NMMIIA) at cell-matrix adhesion sites. As Ca(2+) plays a central role in controlling actomyosin-dependent functions, we examined how Ca(2+) controls the generation of cell extensions and collagen remodeling. Ratio fluorimetry demonstrated localized Ca(2+) influx at extensions of fibroblasts. Western Blotting and qPCR showed high expression levels of the Ca(2+)-permeable, Transient Receptor Potential Vanilloid-4 (TRPV4) channel, which co-immunoprecipitated with β1 integrin and localized to adhesions...
May 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28526687/ffa2-activation-combined-with-ulcerogenic-cox-inhibition-induces-duodenal-mucosal-injury-via-the-5-ht-pathway-in-rats
#17
Yasutada Akiba, Koji Maruta, Kazuyuki Narimatsu, Hyder Said, Izumi Kaji, Ayaka Kuri, Ken-Ichi Iwamoto, Atsukazu Kuwahara, Jonathan D Kaunitz
Serotonin (5-HT), predominantly synthesized and released by enterochromaffin cells, is implicated in gastrointestinal symptoms such as emesis, abdominal pain and diarrhea. Since luminal short-chain fatty acids (SCFAs) release 5-HT from enterochromaffin cells, which express the SCFA receptor FFA2 in rat duodenum, we examined the effects of the selective FFA2 agonist phenylacetamide-1 (PA1) on duodenal 5-HT release with consequent bicarbonate secretion (DBS) and on indomethacin (IND)-induced enteropathy. Intestinal injury was induced by IND (10 mg/kg, sc) with or without PA1...
May 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28526610/11-12-epoxyeicosatrienoic-acid-11-12-eet-reduces-excitability-and-excitatory-transmission-in-the-hippocampus
#18
Nandkishor K Mule, Anette C Orjuela Leon, John R Falck, Michael Arand, Anne Marowsky
Recent studies suggest a role for the arachidonic acid-derived epoxyeicosatrienoic acids (EETs) in attenuating epileptic seizures. However, their effect on neurotransmission has never been investigated in detail. Here, we studied how 11,12- and 14,15 EET affect excitability and excitatory neurotransmission in mouse hippocampus. 11,12 EET (2 μM), but not 14,15 EET (2 μM), induced the opening of a hyperpolarizing K(+) conductance in CA1 pyramidal cells. This action could be blocked by BaCl2, the G protein blocker GDPβ-S and the GIRK1/4 blocker tertiapin Q and the channel was thus identified as a GIRK channel...
May 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28526404/airborne-polycyclic-aromatic-hydrocarbons-trigger-human-skin-cells-aging-through-aryl-hydrocarbon-receptor
#19
Yuan Qiao, Qiang Li, Hong-Yang Du, Qiao-Wei Wang, Ye Huang, Wei Liu
Accumulating evidence suggests that polycyclic aromatic hydrocarbons (PAH) which adsorbed on the surface of ambient air particulate matters (PM), are the major toxic compound to cause cardiovascular and respiratory diseases, even cancer. However, its detrimental effects on human skin cell remain unclear. Here, we demonstrated that SRM1649b, a reference urban dust material of PAH, triggers human skin cells aging through cell cycle arrest, cell growth inhibition and apoptosis. Principally, SRM1649b facilitated Aryl hydrocarbon receptor (AhR) translocated into nucleus, subsequently activated ERK/MAPK signaling pathway, and upregulated aging-related genes expression...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526263/n-stearoyl-l-tyrosine-inhibits-the-cell-senescence-and-apoptosis-induced-by-h2o2-in-hek293-tau-cells-via-the-cb2-receptor
#20
Yue Hu, Kai-Yi Zhou, Ze-Jian Wang, Yang Lu, Ming Yin
Although considerable energy and money have been spent trying to inhibit Aβ production and its related metabolic enzyme activities, there are still no drug treatments available to cure even slow for Alzheimer's disease. Therefore, tau protein has been focused recently as the new target for the treatment of Alzheimer's disease. The transfected human embryonic kidney 293 (HEK 293) cells with or without Tau 411 plasmid were used to evaluate the effect of tau protein on cell viability. H2O2 was added to simulate microenvironment of oxidative stress (OS) during aging...
May 16, 2017: Chemico-biological Interactions
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