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https://www.readbyqxmd.com/read/29793215/in-silico-insight-into-voltage-gated-sodium-channel-1-7-inhibition-for-anti-pain-drug-discovery
#1
Mingxing Wang, Wei Li, Ying Wang, Yongbo Song, Jian Wang, Maosheng Cheng
Studies on human genetics have implicated the voltage-gated sodium channel Nav1.7 as an appealing target for the treatment of pain. In this study, we put forward a ligand-based pharmacophore for the first time, which was generated by a set of multiple chemical scaffolds including sulfonamide and non-sulfonamide derivatives and consisted of four chemical features: an aromatic ring, a hydrophobic group and two hydrogen acceptors. The active cavity was divided into three regions according to the properties of the amino acids surrounded and was used for the docking of 16 known active inhibitors...
May 18, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29793167/improvement-of-neuronal-differentiation-by-carbon-monoxide-role-of-pentose-phosphate-pathway
#2
Ana S Almeida, Nuno L Soares, Catarina O Sequeira, Sofia A Pereira, Ursula Sonnewald, Helena L A Vieira
Over the last decades, the silent-killer carbon monoxide (CO) has been shown to also be an endogenous cytoprotective molecule able to inhibit cell death and modulate mitochondrial metabolism. Neuronal metabolism is mostly oxidative and neurons also use glucose for maintaining their anti-oxidant status by generation of reduced glutathione (GSH) via the pentose-phosphate pathway (PPP). It is established that neuronal differentiation depends on reactive oxygen species (ROS) generation and signalling, however there is a lack of information about modulation of the PPP during adult neurogenesis...
May 15, 2018: Redox Biology
https://www.readbyqxmd.com/read/29793094/effects-of-chronic-antipsychotic-drug-exposure-on-the-expression-of-translocator-protein-and-inflammatory-markers-in-rat-adipose-tissue
#3
Anita Calevro, Marie-Caroline Cotel, Sridhar Natesan, Michel Modo, Anthony C Vernon, Valeria Mondelli
The precise effect of antipsychotic drugs on either central or peripheral inflammation remains unclear. An important issue in this debate is to what extent the known peripheral metabolic effects of antipsychotics, including increased adiposity, may contribute to increased inflammation. Adipose tissue is known to contribute to the development of systemic inflammation, which can eventually lead to insulin resistance and metabolic dysregulation. As a first step to address this question, we evaluated whether chronic exposure to clinically comparable doses of haloperidol or olanzapine resulted in the immune activation of rat adipose tissue...
May 16, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29793051/promising-antileishmanial-activity-of-novel-imidazole-antifungal-drug-luliconazole-against-leishmania-major-in-vitro-and-in-silico-studies
#4
Azar Shokri, Mahdi Abastabar, Masoud Keighobadi, Saeed Emami, Mahdi Fakhar, Saeed Hosseini Teshnizi, Koichi Makimura, Ali Rezaei-Matehkolaei, Hassan Mirzaei
OBJECTIVES: Pentavalent antimonials have been used for the treatment of leishmaniasis for more than 70 years; however their toxicity limits their benefits. Unfortunately, the efficacy of the first line drugs has been decreased and resistance seems to be noticeable. Luliconazole is a new azole with unique effects on fungi which has not been tested on Leishmania parasites yet. METHODS: In the present study, we evaluated cytotoxicity and anti-leishmanial activities of Luliconazole on promastigotes and intracellular amastigotes of Leishmania major (L...
May 21, 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29792920/inner-ear-drug-delivery-recent-advances-challenges-and-perspective
#5
Jinsong Hao, S Kevin Li
Effective and safe treatment of auditory and vestibular diseases has become increasingly dependent on inner ear drug delivery systems. This review highlights recent advances in inner ear drug delivery research and technologies. The focus is on strategies to overcome delivery barriers and to improve drug residence and targeting, with special attention to in vivo animal and human studies. The research in gene and stem cell delivery to the inner ear is briefly reviewed. Newly developed research tools to address experimental challenges and safety issues are discussed...
May 21, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29792888/oral-vitamin-a-coupled-valsartan-nanomedicine-high-hepatic-stellate-cell-receptors-accessibility-and-prolonged-enterohepatic-residence
#6
Nesrine S El-Mezayen, Wessam F El-Hadidy, Wessam M El-Refaie, Thanaa I Shalaby, Mahmoud M Khattab, Aiman S El-Khatib
So far, liver fibrosis still has no clinically-approved treatment. The loss of stored vitamin-A (VA ) in hepatic stellate cells (HSCs), the main regulators to hepatic fibrosis, can be applied as a mechanism for their targeting. Valsartan is a good candidate for this approach; it is a marketed oral-therapy with inverse- and partial-agonistic activity to the over-expressed angiotensin-II type1 receptor (AT1R) and depleted nuclear peroxisome proliferator-activated receptor-gamma (PPAR-γ), respectively, in activated HSCs...
May 21, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29792857/tgf-%C3%AE-plays-a-vital-role-in-triple-negative-breast-cancer-tnbc-drug-resistance-through-regulating-stemness-emt-and-apoptosis
#7
Xiaodan Xu, Lu Zhang, Xiaogang He, Ping Zhang, Caihong Sun, Xiaojun Xu, Yaojuan Lu, Feifei Li
Triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer in which the cell surface lacks usual targets for drug to exhibit its effects. Epirubicin (Epi) is widely used for TNBC, but a substantial number of patients develop Epi resistance that is usually associated with poor prognosis. Transforming growth factor (TGF-β) is a multifunctional cytokine. In recent study, it appears that TGF-β influences the cancer stem cell population, thus, the drug resistance of cancer may also be affected...
May 21, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29792808/eradication-of-established-tumors-by-chemically-self-assembled-nanoring-csan-targeted-t-cells
#8
Jacob Petersburg, Jingjing Shen, Clifford M Csizmar, Katherine A Murphy, Justin Spanier, Kari Gabrielse, Thomas S Griffith, Brian Fife, Carston R Wagner
Our laboratory has developed chemically self-assembled nanorings (CSANs) as prosthetic antigen receptors (PARs) for the non-genetic modification of T-cell surfaces. PARs have been successfully employed in vitro to activate T cells for the selective killing of leukemia cells. However, PAR efficacy has yet to be evaluated in vivo or against solid tumors. Therefore, we developed bispecific PARs that selectively target the human CD3 receptor and human Epithelial Cell Adhesion Molecule (EpCAM), which is overexpressed on multiple carcinomas and cancer stem cells...
May 24, 2018: ACS Nano
https://www.readbyqxmd.com/read/29792731/apr3-modulates-oxidative-stress-and-mitochondrial-function-in-arpe-19-cells
#9
Yuan Li, Xuan Zou, Jing Gao, Ke Cao, Zhihui Feng, Jiankang Liu
Impairment of retinal pigment epithelial (RPE) cells is considered a key contributor to the development of age-related macular degeneration. Apoptosis-related protein 3 (APR3) was recently discovered after treatment with all- trans retinoic acid, a pivotal molecule in RPE cells. However, the function of APR3 remains poorly understood. In the present study, we found that APR3 could interact with nuclear factor (erythroid-derived 2)-like 2, which is a regulator of phase II enzymes, and that knockdown of APR3 promoted nuclear factor (erythroid-derived 2)-like 2 nuclear translocation and activated expression of phase II enzymes, which was accompanied by improved redox status and mitochondrial activity...
May 24, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29792726/i-like-them%C3%A2-will-they-like-me-evidence-for-the-role-of-the-ventrolateral-prefrontal-cortex-during-mismatched-social-appraisals-in-anxious-youth
#10
Ashley R Smith, Eric E Nelson, Brent I Rappaport, Daniel S Pine, Ellen Leibenluft, Johanna M Jarcho
OBJECTIVE: Socially anxious adolescents report distress during social decision-making, wherein their favorable view of peers directly conflicts with their expectation to be viewed negatively by peers; a phenomenon we refer to as "mismatch bias." The present study utilizes a novel paradigm with dynamic social stimuli to explore the correlates of mismatch biases in anxious and healthy youth. METHOD: The behavioral and neural correlates of mismatch biases were assessed in healthy (N = 17) and anxious (N = 14) youth during functional MRI...
May 24, 2018: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/29792714/docking-screens-for-dual-inhibitors-of-disparate-drug-targets-for-parkinson-s-disease
#11
Mariama Jaiteh, Alexey Zeifman, Marcus Saarinen, Per Svenningsson, José M Brea, Maria Isabel Loza, Jens Carlsson
Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrelated proteins relevant for Parkinson's disease. A library with 5.4 million molecules was docked to crystal structures of the A2A adenosine receptor (A2AAR) and monoamine oxidase B (MAO-B)...
May 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29792533/efficacy-of-the-resilience-and-adjustment-intervention-after-traumatic-brain-injury-a-randomized-controlled-trial
#12
Jeffrey S Kreutzer, Jennifer H Marwitz, Adam P Sima, Ana Mills, Nancy H Hsu, Herman R Lukow
OBJECTIVE: Examine a psychoeducational and skill-building intervention's effectiveness for individuals after traumatic brain injury (TBI), using a two-arm, parallel, randomized, controlled trial with wait-listed control. METHODS: The Resilience and Adjustment Intervention (RAI) targets adjustment challenges and emphasizes education, skill-building and psychological support. Overall, 160 outpatients were randomly assigned to a treatment or wait-list control (WLC) group...
May 24, 2018: Brain Injury: [BI]
https://www.readbyqxmd.com/read/29792404/culotte-stenting-for-coronary-bifurcation-lesions-with-2nd-and-3rd-generation-everolimus-eluting-stents-the-celtic-bifurcation-study
#13
Simon J Walsh, Colm G Hanratty, Stuart Watkins, Keith G Oldroyd, Niall T Mulvihill, Mark Hensey, Alex Chase, Dave Smith, Nick Cruden, James C Spratt, Darren Mylotte, Tom Johnson, Jonathan Hill, Hafiz M Hussein, Kris Bogaerts, Marie-Claude Morice, David P Foley
AIMS: The aim of this study was to provide contemporary outcome data for patients with de novo coronary disease and Medina 1,1,1 lesions who were treated with a culotte two-stent technique, and to compare the performance of two modern-generation drug-eluting stent (DES) platforms, the 3-connector XIENCE and the 2-connector SYNERGY. METHODS AND RESULTS: Patients with Medina 1,1,1 bifurcation lesions who had disease that was amenable to culotte stenting were randomised 1:1 to treatment with XIENCE or SYNERGY DES...
May 24, 2018: EuroIntervention
https://www.readbyqxmd.com/read/29792395/how-are-patients-with-heart-failure-treated-in-primary-care
#14
Hélène Vaillant-Roussel, Bruno Pereira, Sylvaine Gibot-Boeuf, Romain Eschalier, Claude Dubray, Rémy Boussageon, Philippe Vorilhon
OBJECTIVE: The aim of this study was to assess the adherence of general practitioners (GPs) to guidelines in patients with heart failure with reduced ejection fraction (HFrEF) and to describe GPs' prescribing behavior regarding patients with heart failure with preserved ejection fraction (HFpEF). MATERIALS AND METHODS: Cross-sectional study as part of the ETIC trial. Five classes of drugs were described: angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs); β-blockers (BBs); mineralocorticoid receptor antagonists (MRAs); diuretics (thiazide or loop diuretics); and digoxin...
May 24, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29792380/alirocumab-as-add-on-therapy-to-statins-current-evidence-and-clinical-potential
#15
Johann Auer, Robert Berent
Atherosclerotic cardiovascular diseases (ASCVDs) are associated with a substantial mortality, physical morbidity, and mental disability. Elevated plasma low-density lipoprotein cholesterol (LDL-C) levels play a major role in the pathophysiology of ASCVDs. Statins have been shown to reduce ASCVD risk and associated events and are recommended as first-line therapy for treatment of hypercholesterolemia by current international guidelines. The key issue is to attain guideline-recommended LDL-C levels (below 70 mg/dl) for patients at very high cardiovascular risk...
May 1, 2018: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/29792310/bet-inhibition-overcomes-receptor-tyrosine-kinase-mediated-cetuximab-resistance-in-hnscc
#16
Brandon Leonard, Toni M Brand, Rachel A O'Keefe, Eliot Lee, Yan Zang, Jacquelyn D Kemmer, Hua Li, Jennifer R Grandis, Neil E Bhola
Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK) including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29792307/putative-vaccine-candidates-and-drug-targets-identified-by-reverse-vaccinology-and-subtractive-genomics-approaches-to-control-haemophilus-ducreyi-the-causative-agent-of-chancroid
#17
Alissa de Sarom, Arun Kumar Jaiswal, Sandeep Tiwari, Letícia de Castro Oliveira, Debmalya Barh, Vasco Azevedo, Carlo Jose Oliveira, Siomar de Castro Soares
Chancroid is a sexually transmitted infection (STI) caused by the Gram-negative bacterium Haemophilus ducreyi The control of chancroid is difficult and the only current available treatment is antibiotic therapy; however, antibiotic resistance has been reported in endemic areas. Owing to recent outbreaks of STIs worldwide, it is important to keep searching for new treatment strategies and preventive measures. Here, we applied reverse vaccinology and subtractive genomic approaches for the in silico prediction of potential vaccine and drug targets against 28 strains of H...
May 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29792241/efficacy-of-digital-cbt-for-insomnia-to-reduce-depression-across-demographic-groups-a-randomized-trial
#18
Philip Cheng, Annemarie I Luik, Cynthia Fellman-Couture, Edward Peterson, Christine L M Joseph, Gabriel Tallent, Kieulinh Michelle Tran, Brian K Ahmedani, Timothy Roehrs, Thomas Roth, Christopher L Drake
BACKGROUND: Insomnia and depression are highly comorbid and mutually exacerbate clinical trajectories and outcomes. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces both insomnia and depression severity, and can be delivered digitally. This could substantially increase the accessibility to CBT-I, which could reduce the health disparities related to insomnia; however, the efficacy of digital CBT-I (dCBT-I) across a range of demographic groups has not yet been adequately examined...
May 24, 2018: Psychological Medicine
https://www.readbyqxmd.com/read/29792227/integrated-time-course-omics-analysis-distinguishes-immediate-therapeutic-response-from-acquired-resistance
#19
Genevieve Stein-O'Brien, Luciane T Kagohara, Sijia Li, Manjusha Thakar, Ruchira Ranaweera, Hiroyuki Ozawa, Haixia Cheng, Michael Considine, Sandra Schmitz, Alexander V Favorov, Ludmila V Danilova, Joseph A Califano, Evgeny Izumchenko, Daria A Gaykalova, Christine H Chung, Elana J Fertig
BACKGROUND: Targeted therapies specifically act by blocking the activity of proteins that are encoded by genes critical for tumorigenesis. However, most cancers acquire resistance and long-term disease remission is rarely observed. Understanding the time course of molecular changes responsible for the development of acquired resistance could enable optimization of patients' treatment options. Clinically, acquired therapeutic resistance can only be studied at a single time point in resistant tumors...
May 23, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29792198/radioligand-therapy-of-metastatic-castration-resistant-prostate-cancer-current-approaches
#20
REVIEW
Zool Hilmi Awang, Markus Essler, Hojjat Ahmadzadehfar
Prostate Cancer is the forth most common type of cancer. Prostate-specific membrane antigen (PSMA) is anchored in the cell membrane of prostate epithelial cells. PSMA is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer. Therefore it is an appropriate target for diagnostic and therapy of prostate cancer and its metastases. This article discusses several articles on radionuclide treatments in prostate cancer and the results on PSMA therapy with either beta or alpha emitters as a salvage therapy...
May 23, 2018: Radiation Oncology
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