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https://www.readbyqxmd.com/read/29151074/interferon-lambda-2-promotes-mammary-tumor-metastasis-via-angiogenesis-extension-and-stimulation-of-cancer-cell-migration
#1
R Pingwara, K Witt-Jurkowska, K Ulewicz, J Mucha, K Tonecka, Z Pilch, B Taciak, K Zabielska-Koczywas, M Mori, S Berardozzi, B Botta, T P Rygiel, M Krol
Myeloid-derived suppressor cells (MDSCs) support tumor development by stimulation of angiogenesis and immune response inhibition. In our previous study, we showed that interferon lambda 2 (IFN-λ2), secreted by MDSCs, enhances production of pro-angiogenic factors by cancer cells via phosphorylation of STAT3 and therefore promotes blood vessels formation. In the present study IFN-λ2 level was evaluated by ELISA in serum of tumor-bearing mice, whereas its expression in MDSCs isolated from the lungs with metastatic tumors and normal lungs was assessed by qPCR...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29151056/between-professional-values-social-regulations-and-patient-preferences-medical-doctors-perceptions-of-ethical-dilemmas
#2
Berit Bringedal, Karin Isaksson Rø, Morten Magelssen, Reidun Førde, Olaf Gjerløv Aasland
BACKGROUND: We present and discuss the results of a Norwegian survey of medical doctors' views on potential ethical dilemmas in professional practice. METHODS: The study was conducted in 2015 as a postal questionnaire to a representative sample of 1612 doctors, among which 1261 responded (78%). We provided a list of 41 potential ethical dilemmas and asked whether each was considered a dilemma, and whether the doctor would perform the task, if in a position to do so...
November 18, 2017: Journal of Medical Ethics
https://www.readbyqxmd.com/read/29150942/a-novel-epididymal-quiescence-factor-inhibits-sperm-motility-by-modulating-nos-activity-and-intracellular-no-cgmp-pathway
#3
Prasanta Ghosh, Sandipan Mukherjee, Arpita Bhoumik, Sandhya Rekha Dungdung
Mature and potentially motile spermatozoa stored in cauda epididymis in an inactive state for approximately 30 days; however during ejaculation they regain motility. To understand the actual molecular mechanism of the sperm quiescence during caudal stay, a proteinaceous quiescence factor (QF) has been purified from caprine epididymal plasma to apparent homogeneity. In the present study complete purification, detailed characterization as well as mechanistic pathway of QF has been described. QF was purified to 215 fold with 45% activity recovery...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150918/central-role-of-transforming-ggrowth-factor-type-beta-1-in-skeletal-muscle-dysfunctions-an-update-on-therapeutic-strategies
#4
Johanna Abrigo, Felipe Simon, Daniel Cabrera, Gonzalo Cordova, Capucine Trollet, Claudio Cabello Verrugio
Among the soluble factors that regulate skeletal muscle function, Transforming Growth Factor type Beta 1 (TGF-b1) is one of the most studied. This factor inhibits myogenesis and regeneration by regulating the activity and function of satellite cells (SCs). Indeed, TGF-b has a central role in muscle pathologies in which there is development of fibrosis and/or atrophy of skeletal muscle. Thus, in this review we present the critical and recent antecedents regarding the mechanisms and cellular targets involved in the effects of TGF-b1 in the muscle, in pathological processes such as the inhibition of regeneration, fibrosis and atrophy...
November 16, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29150838/gi-530159-a-novel-selective-mechano-sensitive-k2p-channel-opener-reduces-rat-dorsal-root-ganglion-drg-neuron-excitability
#5
Alexandre J C Loucif, Pierre-Philippe Saintot, Jia Liu, Brett M Antonio, Shannon G Zellmer, Katrina Yoger, Emma L Veale, Anna Wilbrey, Kiyoyuki Omoto, Lishuang Cao, Alex Gutteridge, Neil A Castle, Edward B Stevens, Alistair Mathie
BACKGROUND AND PURPOSE: TREK two pore domain potassium channels play a critical role in regulating the excitability of somatosensory nociceptive neurons and are important mediators of pain perception. An understanding of the roles of TREK channels in pain perception and, indeed, in other pathophysiological conditions, has been severely hampered by the lack of potent and/or selective activators and inhibitors. In this study we describe a new, selective opener of TREK channels, GI-530159 (4,4'-(Hexafluoroisopropylidene)bis(p-phenyleneoxy)dianiline)...
November 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29150734/the-sirtuin-1-2-inhibitor-tenovin-1-induces-a-nonlinear-apoptosis-inducing-factor-dependent-cell-death-in-a-p53-null-ewing-s-sarcoma-cell-line
#6
Christian Marx, Lisa Marx-Blümel, Nora Lindig, René Thierbach, Doerte Hoelzer, Sabine Becker, Susan Wittig, Roland Lehmann, Hortense Slevogt, Thorsten Heinzel, Zhao-Qi Wang, James F Beck, Jürgen Sonnemann
The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing's sarcoma cells to tenovin-1. We examined its effects in two Ewing's sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting...
November 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29150680/potential-landscape-of-high-dimensional-nonlinear-stochastic-dynamics-with-large-noise
#7
Ying Tang, Ruoshi Yuan, Gaowei Wang, Xiaomei Zhu, Ping Ao
Quantifying stochastic processes is essential to understand many natural phenomena, particularly in biology, including the cell-fate decision in developmental processes as well as the genesis and progression of cancers. While various attempts have been made to construct potential landscape in high dimensional systems and to estimate transition rates, they are practically limited to the cases where either noise is small or detailed balance condition holds. A general and practical approach to investigate real-world nonequilibrium systems, which are typically high-dimensional and subject to large multiplicative noise and the breakdown of detailed balance, remains elusive...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150666/dogs-reaction-to-inequity-is-affected-by-inhibitory-control
#8
Désirée Brucks, Friederike Range, Sarah Marshall-Pescini
Inequity aversion is thought to act as a mechanism to ensure cooperation and has been studied in many different species, consistently revealing inter-individual variation. Inhibitory control has been proposed to act as one factor responsible for this variation since individuals need to inhibit performing the required action and/or refuse rewards in order to exhibit inequity aversion. Here, we investigated if dogs' sensitivity to inequity is affected by their capacity for inhibitory control, assessed in a test battery and questionnaire...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150536/availability-sales-and-affordability-of-tobacco-cessation-medicines-in-kerala-india
#9
Smitha Sarma, Sivadasanpillai Harikrishnan, Abigail S Baldridge, Raji Devarajan, Aashna Mehta, Sakhtivel Selvaraj, Mohammed K Ali, Padinhare P Mohanan, Dorairaj Prabhakaran, Mark D Huffman
BACKGROUND: India is the world's second largest consumer of tobacco, but tobacco cessation remains uncommon due, at least in part, to underutilization of cessation pharmacotherapy. We evaluated the availability, sales, and affordability of nicotine replacement therapy, bupropion, and varenicline in the South Indian state of Kerala to understand potential reasons for underutilization. METHODS AND RESULTS: From November 2016 to April 2017, we collected data on availability, inventory, and pricing of cessation medication through a cross-sectional survey of 199 public, semiprivate (Karunya), and private pharmacies across 5 districts in Kerala using World Health Organization/Health Action International methodology...
November 2017: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/29150333/design-synthesis-and-evaluation-of-novel-dihydrostilbene-derivatives-as-potential-anti-melanogenic-skin-protecting-agents
#10
Yu Zhu, Wen-Hui Pan, Chuen Fai Ku, Hong-Jie Zhang, Siu Wai Tsang
The stems of Dendrobium orchids (Orchidaceae), also known as Shi Hu, have been used for medicinal purposes for centuries in oriental countries. In fact, the health benefits of Shi Hu have been evidenced by its modern pharmacological actions on conquering oxidative stress in pathological conditions. From the extracts of two commonly used Dendrobium species, we obtained discernible amounts of stilbenoids, explicitly trans-resveratrol (1) and dihydro-resveratrol (2), which are prototypical antioxidants. When applied to cultured melanocytes, these stilbenoids, dihydro-resveratrol (2) in particular, significantly reduced melanin formation via inhibiting tyrosinase activity and expression of tyrosinase-related proteins...
October 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29150079/mechanism-hypotheses-for-the-electrophysiological-manifestations-of-two-cases-of-endplate-acetylcholinesterase-deficiency-related-congenital-myasthenic-syndrome
#11
Qingyun Ding, Dongchao Shen, Yi Dai, Youfang Hu, Yuzhou Guan, Mingsheng Liu, Liying Cui
OBJECTIVE: To summarize the electrophysiological characteristics of two cases of endplate acetylcholinesterase deficiency (EAD) related congenital myasthenic syndrome (CMS) caused by COLQ mutation and to discuss the possible mechanism of these electrophysiological phenomena. METHODS: Electrophysiological examinations were conducted including nerve conduction studies, routine electromyography (EMG), repetitive nerve stimulation (RNS) and single fiber EMG (SFEMG)...
November 14, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29149821/statins-therapy-for-connective-tissue-diseases-new-therapeutic-opportunities
#12
Przemyslaw J Kotyla, Eugene J Kucharz
Background and Objective Statins, 3-hydroxyl-3-methyl-glutharyl Coenzyme A reductase inhibitors showed their therapeutic potential in the treatment of atherosclerosis-related diseases. Recently, the properties of statins, separate from their lipid lowering activity have attracted much attention. These properties that cover a wide area of physiopathological activities including cell maturation, immune response regulation, tissue fibrosis, endothelial activity and are called pleiotropic activity. Many in vitro studies demonstrated significant, statins-dependent regulation of immune system reactivity, reduction of pro-inflammatory and pro-fibrotic cytokines as well as suppression of endothelial activity and damage...
November 15, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29149812/architectures-and-mechanical-properties-of-drugs-and-complexes-of-surface-active-compounds-at-air-water-and-oil-water-interfaces
#13
Dipak K Sarker
BACKGROUND: Drugs can represents a multitude of compounds from proteins and peptides, such as growth hormones and insulin and on to simple organic molecules such as flurbiprofen, ibuprofen and lidocaine. Given the chemical nature of these compounds two features are always present. A portion or portions of the molecule that has little affinity for apolar surfaces and media and the opposite a series of part or one large part that has considerable affinity for hydrophilic, polar or charged media and surfaces...
November 17, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29149660/a-systems-level-approach-for-investigating-organophosphorus-pesticide-toxicity
#14
Jingbo Zhu, Jing Wang, Yan Ding, Baoyue Liu, Wei Xiao
The full understanding of the single and joint toxicity of a variety of organophosphorus (OP) pesticides is still unavailable, because of the extreme complex mechanism of action. This study established a systems-level approach based on systems toxicology to investigate OP pesticide toxicity by incorporating ADME/T properties, protein prediction, and network and pathway analysis. The results showed that most OP pesticides are highly toxic according to the ADME/T parameters, and can interact with significant receptor proteins to cooperatively lead to various diseases by the established OP pesticide -protein and protein-disease networks...
November 14, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29149530/proteases-and-protease-inhibitors-in-infectious-diseases
#15
REVIEW
Ayodeji A Agbowuro, Wilhelmina M Huston, Allan B Gamble, Joel D A Tyndall
There are numerous proteases of pathogenic organisms that are currently targeted for therapeutic intervention along with many that are seen as potential drug targets. This review discusses the chemical and biological makeup of some key druggable proteases expressed by the five major classes of disease causing agents, namely bacteria, viruses, fungi, eukaryotes, and prions. While a few of these enzymes including HIV protease and HCV NS3-4A protease have been targeted to a clinically useful level, a number are yet to yield any clinical outcomes in terms of antimicrobial therapy...
November 17, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29149346/novel-pathways-of-endocrine-disruption-through-pesticides-interference-with-human-mineralocorticoid-receptors
#16
Jianyun Zhang, Xin Huang, Hongling Liu, Weiping Liu, Jing Liu
Mineralocorticoid receptor (MR) is one member of the steroid receptor family. In addition to its important role in Na+/K+ homeostasis, MR is reported as a tumor-suppressor in carcinogenesis. So far, little was known about the ability of pesticides to interfere with MR. In this study, a total of 43 pesticides and/or metabolites were investigated for their potential effects on human MR. None of the tested pesticides exhibited MR agonistic potency, while 16 compounds showed antagonistic activities. Further investigations indicated that these 16 chemicals individually antagonized aldosterone-induced alkaline phosphatase expression in vascular smooth muscle cells and aldosterone-inhibited hepatocellular carcinoma cell proliferation at higher concentrations, and the mixture of these 16 pesticides at environmentally relevant concentrations significantly disrupted MR activity...
November 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29149262/a-food-environments-feedback-system-foodback-for-empowering-citizens-and-change-agents-to-create-healthier-community-food-places
#17
Stefanie Vandevijvere, Rachel Williams, Essa Tawfiq, Boyd Swinburn
This study developed a systems-based approach (called FoodBack) to empower citizens and change agents to create healthier community food places. Formative evaluations were held with citizens and change agents in six diverse New Zealand communities, supplemented by semi-structured interviews with 85 change agents in Auckland and Hamilton in 2015-2016. The emerging system was additionally reviewed by public health experts from diverse organizations. A food environments feedback system was constructed to crowdsource key indicators of the healthiness of diverse community food places (i...
November 14, 2017: Health Promotion International
https://www.readbyqxmd.com/read/29149235/isolated-complexes-of-the-amino-acid-arginine-with-polyether-and-polyamine-macrocycles-the-role-of-proton-transfer
#18
Juan Ramón Avilés-Moreno, Giel Berden, Jos Oomens, Bruno Martínez-Haya
The distinct basicity of the guanidinium side-group of arginine (Arg) sustains specific interactions involved in essential biochemical processes. The sensing of arginine is therefore key in modern biotechnology and bioanalysis. In this context, the development of molecular receptors based on crown ether building blocks has demonstrated great potential. We investigate the complexes formed by arginine with two benchmark macrocycles, 12-crown-4 (1,4,7,10-tetraoxacyclododecane) and its N-substituted analog cyclen (1,4,7,10-tetraazacyclododecane)...
November 17, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29148520/an-in-vitro-prototype-of-a-porcine-biomimetic-testis-like-cell-culture-system-a-novel-tool-for-the-study-of-reassembled-sertoli-and-leydig-cells
#19
Iva Arato, Giovanni Luca, Francesca Mancuso, Catia Bellucci, Cinzia Lilli, Mario Calvitti, Barbara C Hansen, Domenico Milardi, Giuseppe Grande, Riccardo Calafiore
At present, there is no reliable in vitro assembled prepubertal testis-like biomimetic organ culture system designed to assess the functional effects of human gonadotropins on Sertoli and Leydig cells. Spermatogenesis is regulated by endocrine, paracrine, and juxtacrine factors (testicular cross-talk), mainly orchestrated by gonadotropins such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) that play a pivotal role by stimulating Leydig and Sertoli cells, respectively. The aim of our study was to set up an in vitro prepubertal porcine bioengineered construct as a new model for experimental studies on reassembled Sertoli and Leydig cells...
November 10, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29148067/should-theophylline-be-added-to-the-j-wave-syndrome-therapeutic-armamentarium
#20
EDITORIAL
Charles Antzelevitch, Sami Viskin
The substrate for both early repolarization syndrome (ERS) and Brugada syndrome (BrS), the so-called J wave syndromes, has been shown to develop as a consequence of genetic variants causing a loss of function of inward currents such sodium (INa ) and calcium (ICa ) channel currents or a gain of function in outward currents such as the transient outward current (Ito ). These changes in ion channel function result in an outward shift of the balance of currents active during the early phases of the epicardial action potential in the right ventricular outflow tract (RVOT) of the heart in the case BrS and in the inferior left ventricle in the case of ERS...
November 16, 2017: Pacing and Clinical Electrophysiology: PACE
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