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https://www.readbyqxmd.com/read/29777955/perspectives-and-limitations-for-nucleo-t-side-analogs-in-future-hbv-therapies
#1
REVIEW
Massimo Levrero, Miroslava Subic, Francois Villeret, Fabien Zoulim
The latest generation of nucleo(t)side analogs (NAs) provide robust virus suppression with high barrier to resistance. Long term NAs treatment is associated with a partial restoration in HBV-specific T-cell functions, regression of fibrosis, no disease progression and a reduction of HCC risk but rarely lead to cure and life-long treatments is often required. New insights into the hepatitis B viral life cycle and the host immune response have expanded the potential targets for drug therapies with interesting antiviral candidates and novel immunotherapeutic approaches in early stage development...
May 16, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29777855/polymer-lipid-hybrid-nanoparticles-as-enhanced-indomethacin-delivery-systems
#2
Annalisa Dalmoro, Sabrina Bochicchio, Shamil F Nasibullin, Paolo Bertoncin, Gaetano Lamberti, Anna Angela Barba, Rouslan I Moustafine
Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles...
May 16, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29777732/antinociceptive-effect-of-tadalafil-in-various-pain-models-involvement-of-opioid-receptors-and-nitric-oxide-cyclic-gmp-pathways
#3
Mohammad M Mehanna, Souraya Domiati, Hania Nakkash Chmaisse, Ahmed El Mallah
Nitric oxide has been proven to play an important role in nociception, accordingly, its promoters, phosphodiesterase inhibitors have been investigated as pain response modulators. Aiming to evaluate the central effect of tadalafil, a phosphodiesterase 5 inhibitor, and to determine its EC50, tail flick and hot plate tests were utilized. On the other hand, its nociceptive peripheral analgesic effect was assessed through acetic-acid induced writhing model. Formalin test was used to appraise both non-inflammatory and inflammatory pain responses...
May 16, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29777728/testosterone-induced-downregulation-of-migration-and-proliferation-in-human-umbilical-vein-endothelial-cells-by-androgen-receptor-dependent-and-independent-mechanisms
#4
Aulona Gaba, Mario Mairhofer, Zyhdi Zhegu, Nadja Leditznig, Ladislaus Szabo, Walter Tschugguel, Christian Schneeberger, Iveta Yotova
Recent research has emphasized the potential unfavorable effects of declining testosterone (T) levels in men and the putative beneficial effect of androgen therapy in select women. Some controversy surrounding the mechanism of action and the effects of T on endothelium remains. In this study, we evaluated the mechanism of T action on pooled primary Human Umbilical Vein Endothelial Cells (HUVEC) of mixed gender by focusing on two important processes, proliferation and migration. In our in vitro model system, we found that only the supra-physiological dose of T affected these two processes irrespective of the ratio of male to female cells in the pools...
May 16, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29777691/improving-electrical-properties-of-ipsc-cardiomyocytes-by-enhancing-cx43-expression
#5
Valentin Sottas, Carl-Mattheis Wahl, Mihnea C Trache, Michael Bartolf-Kopp, Sidney Cambridge, Markus Hecker, Nina D Ullrich
The therapeutic potential of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is limited by immature functional features including low impulse propagation and reduced cell excitability. Key players regulating electrical activity are voltage-gated Na+ channels (Nav 1.5) and gap junctions built from connexin-43 (Cx43). Here we tested the hypothesis that enhanced Cx43 expression increases intercellular coupling and influences excitability by modulating Nav 1.5. Using transgenic approaches, Cx43 and Nav 1...
May 16, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29777683/probing-the-binding-site-of-novel-selective-positive-allosteric-modulators-at-the-m-1-machr
#6
Elham Khajehali, Celine Valant, Manuela Jörg, Andrew B Tobin, P Jeffrey Conn, Craig W Lindsley, Patrick M Sexton, Peter J Scammells, Arthur Christopoulos
Subtype-selective allosteric modulation of the M1 muscarinic acetylcholine (ACh) receptor (M1 mAChR) is an attractive approach for the treatment of numerous disorders, including cognitive deficits. The discovery of benzyl quinolone carboxylic acid, BQCA, a selective M1 mAChR positive allosteric modulator (PAM), spurred the subsequent development of newer generation M1 PAMs representing diverse chemical scaffolds, different pharmacodynamic properties and, in some instances, improved pharmacokinetics. Key exemplar molecules from such efforts include PF-06767832 (N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-5-methyl-4-(4-(thiazol-4-yl)benzyl)pyridine-2-carboxamide), VU6004256 (4,6-difluoro-N-(1S,2S)-2-hydroxycyclohexyl-1-((6-(1-methyl-1H-pyrazol-4-yl)pyridine-3-yl)methyl)-1H-indole-3-carboxamide) and MIPS1780 (3-(2-hydroxycyclohexyl)-6-(2-((4-(1-methyl-1H-pyrazol-4-yl)-benzyl)oxy)phenyl)pyrimidin-4(3H)-one)...
May 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29777641/social-norms-and-adolescents-sexual-health-an-introduction-for-practitioners-working-in-low-and-mid-income-african-countries
#7
Beniamino Cislaghi, Holly Shakya
Donors, practitioners and scholars are increasingly interested in harnessing the potential of social norms theory to improve adolescents' sexual and reproductive health outcomes. However, social norms theory is multifaceted, and its application in field interventions is complex. An introduction to social norms that will be beneficial for those who intend to integrate a social norms perspective in their work to improve adolescents' sexual health in Africa is presented. First three main schools of thought on social norms, looking at the theoretical standpoint of each, are discussed...
March 2018: African Journal of Reproductive Health
https://www.readbyqxmd.com/read/29777637/thymol-inhibits-oral-squamous-cell-carcinoma-growth-via-mitochondria-mediated-apoptosis
#8
Jorge J De La Chapa, Prajjal Kanti Singha, Debbie R Lee, Cara B Gonzales
BACKGROUND: Thymol is a Transient Receptor Potential Ankyrin Subtype 1 channel, (TRPA1) agonist found in thyme and oregano. Thymol has antioxidant, anti-inflammatory, and antimicrobial properties; thus thymol is added to many commercially available products including Listerine mouthwash. Thymol is also cytotoxic to HL-60 (acute promyelotic leukemia) cells in vitro. Therefore, we evaluated the effects of thymol against oral squamous cell carcinoma (OSCC) and its anticancer mechanism-of-action...
May 19, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29777610/phenolic-rich-extracts-of-eurycoma-longifolia-and-cylicodiscus-gabunensis-inhibit-enzymes-responsible-for-the-development-of-erectile-dysfunction-and-are-antioxidants
#9
Ganiyu Oboh, Adeniyi A Adebayo, Ayokunle O Ademosun
BACKGROUND: Herbs have been used from ages to manage male sexual dysfunction. Hence, this study sought to investigate the effects of Eurycoma longifolia (EL) and Cylicodiscus gabunensis (CG) stem bark extracts on some enzymes implicated in erectile dysfunction in vitro. METHODS: The extracts were prepared, and their effects on phosphodiesterase-5 (PDE-5), arginase, and angiotensin-1-converting enzyme (ACE) as well as pro-oxidant-induced lipid peroxidation were assessed...
May 19, 2018: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29777554/development-and-feasibility-testing-of-an-avatar-based-education-application-for-patients-with-acute-coronary-syndrome
#10
Jintana Tongpeth, Hui Yun Du, Robyn A Clark
AIMS: To develop and evaluate an interactive, avatar-based education application, for improving patients' knowledge of, and response to, ACS symptoms. BACKGROUND: A patient's ability to recognise and respond to the symptoms of acute coronary syndrome (ACS) is imperative for seeking timely medical intervention. Innovative patient education interventions are needed to support patient education and patient self-care. METHODS: Participatory action research methods were used to engage consumers with cardiac and IT experts to develop an avatar-based education application...
May 18, 2018: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/29777411/spatial-environmental-risk-evaluation-of-potential-toxic-elements-in-stream-sediments
#11
I M H R Antunes, M T D Albuquerque, N Roque
Potential toxic elements (PTE), in stream sediments, were used as contamination indicators for the definition of high-/low-grade spatial clusters in the Monfortinho area (Central Portugal). A set of 271 stream sediment samples was used for spatial modelling and further definition of rings of enrichment-high and low rings. A three-step multivariate statistical and geostatistical approach was used: (1) principal components analysis for PTE's association evaluation and dimensionality reduction; (2) ordinary kriging as an unbiased interpolator for content inference and construction of a continuous representation of the considered attributes, at any arbitrary spatial location; (3) G clustering algorithm for the definition of high and low significance clusters...
May 18, 2018: Environmental Geochemistry and Health
https://www.readbyqxmd.com/read/29777193/on-spiking-behaviour-of-oyster-fungi-pleurotus-djamor
#12
Andrew Adamatzky
We recorded extra-cellular electrical potential of fruit bodies of oyster fungi Pleurotus djamor. We demonstrated that the fungi generate action potential like impulses of electrical potential. Trains of the spikes are observed. Two types of spiking activity are uncovered: high-frequency (period 2.6 min) and low-frequency (period 14 min); transitions between modes of spiking are illustrated. An electrical response of fruit bodies to short (5 sec) and long (60 sec) thermal stimulation with open flame is analysed in details...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29776400/associations-of-training-to-assist-a-suicidal-person-with-subsequent-quality-of-support-results-from-a-national-survey-of-the-australian-public
#13
Anthony F Jorm, Angela Nicholas, Jane Pirkis, Alyssia Rossetto, Nicola J Reavley
BACKGROUND: When a person is in severe distress, people in their social network can potentially take action to reduce the person's suicide risk. The present study used data from a community survey to examine whether people who had received training in how to assist a person at risk of suicide had higher quality intentions and actions to provide support. METHODS: A national telephone survey was carried out with 3002 Australian adults on attitudes and intentions toward helping someone in severe distress or at risk of suicide as well as actions taken...
May 18, 2018: BMC Psychiatry
https://www.readbyqxmd.com/read/29776331/genome-wide-detection-of-selection-signatures-in-chinese-indigenous-laiwu-pigs-revealed-candidate-genes-regulating-fat-deposition-in-muscle
#14
Minhui Chen, Jiying Wang, Yanping Wang, Ying Wu, Jinluan Fu, Jian-Feng Liu
BACKGROUND: Currently, genome-wide scans for positive selection signatures in commercial breed have been investigated. However, few studies have focused on selection footprints of indigenous breeds. Laiwu pig is an invaluable Chinese indigenous pig breed with extremely high proportion of intramuscular fat (IMF), and an excellent model to detect footprint as the result of natural and artificial selection for fat deposition in muscle. RESULT: In this study, based on GeneSeek Genomic profiler Porcine HD data, three complementary methods, FST , iHS (integrated haplotype homozygosity score) and CLR (composite likelihood ratio), were implemented to detect selection signatures in the whole genome of Laiwu pigs...
May 18, 2018: BMC Genetics
https://www.readbyqxmd.com/read/29776138/discretization-dependent-model-for-weakly-connected-excitable-media
#15
Pedro André Arroyo, Sergio Alonso, Rodrigo Weber Dos Santos
Pattern formation has been widely observed in extended chemical and biological processes. Although the biochemical systems are highly heterogeneous, homogenized continuum approaches formed by partial differential equations have been employed frequently. Such approaches are usually justified by the difference of scales between the heterogeneities and the characteristic spatial size of the patterns. Under different conditions, for example, under weak coupling, discrete models are more adequate. However, discrete models may be less manageable, for instance, in terms of numerical implementation and mesh generation, than the associated continuum models...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29776079/directed-motion-of-spheres-induced-by-unbiased-driving-forces-in-viscous-fluids-beyond-the-stokes-law-regime
#16
Jesús Casado-Pascual
The emergence of directed motion is investigated in a system consisting of a sphere immersed in a viscous fluid and subjected to time-periodic forces of zero average. The directed motion arises from the combined action of a nonlinear drag force and the applied driving forces, in the absence of any periodic substrate potential. Necessary conditions for the existence of such directed motion are obtained and an analytical expression for the average terminal velocity is derived within the adiabatic approximation...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775945/greenhouse-gas-emissions-reduction-in-different-economic-sectors-mitigation-measures-health-co-benefits-knowledge-gaps-and-policy-implications
#17
REVIEW
Jinghong Gao, Hongli Hou, Yunkai Zhai, Alistair Woodward, Sotiris Vardoulakis, Sari Kovats, Paul Wilkinson, Liping Li, Xiaoqin Song, Lei Xu, Bohan Meng, Xiaobo Liu, Jun Wang, Jie Zhao, Qiyong Liu
To date, greenhouse gas (GHG) emissions, mitigation strategies and the accompanying health co-benefits in different economic sectors have not been fully investigated. The purpose of this paper is to review comprehensively the evidence on GHG mitigation measures and the related health co-benefits, identify knowledge gaps, and provide recommendations to promote further development and implementation of climate change response policies. Evidence on GHG emissions, abatement measures and related health co-benefits has been observed at regional, national and global levels, involving both low- and high-income societies...
May 15, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29775839/veterinary-applications-of-pulsed-electromagnetic-field-therapy
#18
REVIEW
James S Gaynor, Sean Hagberg, Blake T Gurfein
Pulsed electromagnetic field (PEMF) therapy can non-invasively treat a variety of pathologies by delivering electric and magnetic fields to tissues via inductive coils. The electromagnetic fields generated by these devices have been found to affect a variety of biological processes and basic science understanding of the underlying mechanisms of action of PEMF treatment has accelerated in the last 10 years. Accumulating clinical evidence supports the use of PEMF therapy in both animals and humans for specific clinical indications including bone healing, wound healing, osteoarthritis and inflammation, and treatment of post-operative pain and edema...
May 7, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29775813/hyaluronate-lactoferrin-layer-by-layer-coated-lipid-nanocarriers-for-targeted-co-delivery-of-rapamycin-and-berberine-to-lung-carcinoma
#19
Dalia M Kabary, Maged W Helmy, Kadria A Elkhodairy, Jia-You Fang, Ahmed O Elzoghby
The self-tumor targeting polymers, lactoferrin (LF) and hyaluronic acid (HA) were utilized to develop layer-by-layer (LbL) lipid nanoparticles (NPs) for dual delivery of berberine (BER) and rapamycin (RAP) to lung cancer. To control its release from the NPs, BER was hydrophobically ion paired with SLS prior to incorporation into NPs. Spherical HA/LF-LbL-RAP-BER/SLS-NPs 250.5 nm in diameter, with a surface charge of -18.5 mV were successfully elaborated. The NPs exhibited sequential release pattern with faster release of BER followed by controlled release of RAP which enables sensitization of lung tumor cells to the anti-cancer action of RAP...
May 15, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29775783/ocimum-basilicum-mirnome-revisited-a-cross-kingdom-approach
#20
Maulikkumar Patel, Shanaya Patel, Naman Mangukia, Saumya Patel, Archana Mankad, Himanshu Pandya, Rakesh Rawal
O. basilicum is medicinally important herb having inevitable role in human health. However, the mechanism of action is largely unknown. Present study aims to understand the mechanism of regulation of key human target genes that could plausibly modulated by O. basilicum miRNAs in cross kingdom manner using computational and system biology approach. O. basilicum miRNA sequences were retrieved and their corresponding human target genes were identified using psRNA target and interaction analysis of hub nodes. Six O...
May 15, 2018: Genomics
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