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Yanping Chen, Yingjun Chi, Qingchang Meng, Xiaolin Wang, Deyue Yu
In plants, various proteins are regulated by the ubiquitin-mediated system in response to different environmental stresses, such as drought, cold and heat. The Skp1-Cullin-F-box (SCF) complex, one of the multisubunit E3 ligases, has been shown to be involved in abiotic response pathways. In this study, Glycine max SKP1-like 1 (GmSK1), which had the typical characteristics of an SKP1 protein, with an alpha/beta structure, targeted to the cytoplasm and nucleus, was isolated from soybean [Glycine max (L.)]. GmSK1 was constitutively expressed in all the tested tissues, especially in the roots...
March 7, 2018: Plant Physiology and Biochemistry: PPB
Pavel Šauer, Alžběta Stará, Oksana Golovko, Olga Valentová, Adam Bořík, Roman Grabic, Hana Kocour Kroupová
Vast numbers of xenobiotics are known still to be present in treated municipal wastewater treatment plant (WWTP) effluents. Some of these possess endocrine-disrupting potency and pose risks for exposed aquatic animals. We searched for 17 potential environmental contaminants having affinity to the progesterone receptor. Relative potency values of these progesterone receptor-active chemicals were obtained. On the basis of relative potencies and measured environmental concentrations, the contribution of progestins to measured progestagenic activities was evaluated...
March 2, 2018: Water Research
Anushka C Galasiti Kankanamalage, Yunjeong Kim, Vishnu C Damalanka, Athri D Rathnayake, Anthony R Fehr, Nurjahan Mehzabeen, Kevin P Battaile, Scott Lovell, Gerald H Lushington, Stanley Perlman, Kyeong-Ok Chang, William C Groutas
There are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties...
March 6, 2018: European Journal of Medicinal Chemistry
Amanda N Seddon, Joshua Chaim, Oguz Akin, Esther Drill, Angela G Michael, Nelly Adel, Martin S Tallman
BACKGROUND: The current standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) is an anthracycline plus cytarabine. Both anthracyclines and cytarabine have been associated with the development of typhlitis, a serious adverse event characterized by inflammation of the bowel wall in patients with profound neutropenia, diagnosed by abdominal CT imaging and clinical symptoms. Given the paucity of available data, the aim of our study was to determine the incidence of typhlitis among AML patients receiving induction chemotherapy with idarubicin 12 mg/m2 (IDA), daunorubicin 60 mg/m2 (DNA60), or daunorubicin 90 mg/m2 (DNA90)...
March 8, 2018: Leukemia Research
Sung-Eun Lee, Ji Yoon Lee, A-Reum Han, Hee-Sun Hwang, Woo-Sung Min, Hee-Je Kim
Although vascular endothelial growth factor-C (VEGF-C) is known to be expressed in acute myeloid leukemia (AML) blasts, the relevance of VEGF-C in the clinical setting remains to be fully explored. We examined the effect of VEGF-C on achievement of complete remission (CR) in adult de novo AML and immune cell population profiles according to VEGF-C mRNA expression. In comparison of VEGF-C expression between the no-CR and CR groups, the CR group showed a trend toward higher levels of plasma VEGF-C (P = .088), whereas mRNA expression of VEGF-C was downregulated (P = ...
March 12, 2018: Translational Oncology
Vesa M Olkkonen, Juha Sinisalo, Matti Jauhiainen
Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk...
March 8, 2018: Atherosclerosis
Juliana C C Dallagnol, Elham Khajehali, Emma T van der Westhuizen, Manuela Jörg, Celine Valant, Alan G Goncalves, Ben Capuano, Arthur Christopoulos, Peter J Scammells
Targeting allosteric sites at M1 muscarinic acetylcholine receptors is a promising strategy for the treatment of Alzheimer's disease. Positive allosteric modulators may not only potentiate binding and/or signaling of the endogenous agonist acetylcholine (ACh), but may also possess direct agonist activity (thus referred to as PAM-agonists). Recent studies suggest that PAM-agonists with robust intrinsic efficacy are more likely to produce adverse effects in vivo. Herein we present the synthesis and pharmacological evaluation of a series of pyrrole-3-carboxamides with a diverse range of allosteric profiles...
March 15, 2018: Journal of Medicinal Chemistry
Tanya Moutray, Jennifer R Evans, Noemi Lois, David J Armstrong, Tunde Peto, Augusto Azuara-Blanco
BACKGROUND: Diabetic retinopathy (DR) is a chronic progressive disease of the retinal microvasculature associated with prolonged hyperglycaemia. Proliferative DR (PDR) is a sight-threatening complication of DR and is characterised by the development of abnormal new vessels in the retina, optic nerve head or anterior segment of the eye. Argon laser photocoagulation has been the gold standard for the treatment of PDR for many years, using regimens evaluated by the Early Treatment of Diabetic Retinopathy Study (ETDRS)...
March 15, 2018: Cochrane Database of Systematic Reviews
Vincent Plagnol, Samuel Woodhouse, Karen Howarth, Stefanie Lensing, Matt Smith, Michael Epstein, Mikidache Madi, Sarah Smalley, Catherine Leroy, Jonathan Hinton, Frank de Kievit, Esther Musgrave-Brown, Colin Herd, Katherine Baker-Neblett, Will Brennan, Peter Dimitrov, Nathan Campbell, Clive Morris, Nitzan Rosenfeld, James Clark, Davina Gale, Jamie Platt, John Calaway, Greg Jones, Tim Forshew
Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA...
2018: PloS One
Azael Che-Mendoza, Anuar Medina-Barreiro, Edgar Koyoc-Cardeña, Valentín Uc-Puc, Yamili Contreras-Perera, Josué Herrera-Bojórquez, Felipe Dzul-Manzanilla, Fabian Correa-Morales, Hilary Ranson, Audrey Lenhart, Philip J McCall, Axel Kroeger, Gonzalo Vazquez-Prokopec, Pablo Manrique-Saide
BACKGROUND: There is a need for effective methods to control Aedes aegypti and prevent the transmission of dengue, chikungunya, yellow fever and Zika viruses. Insecticide treated screening (ITS) is a promising approach, particularly as it targets adult mosquitoes to reduce human-mosquito contact. METHODOLOGY/PRINCIPAL FINDINGS: A cluster-randomised controlled trial evaluated the entomological efficacy of ITS based intervention, which consisted of the installation of pyrethroid-impregnated long-lasting insecticide-treated netting material fixed as framed screens on external doors and windows...
March 15, 2018: PLoS Neglected Tropical Diseases
Jianwen Long, Qiqige Menggen, Qimige Wuren, Quan Shi, Xianming Pi
BACKGROUND Malignant melanoma is a class of malignant tumors derived from melanocytes. lncRNAs have been considered as pro-/anti-tumor factors in progression of cancers. The function of lncRNA TUG1 on growth of melanoma was investigated in this study. MATERIAL AND METHODS The TUG1 and miR-129-5p expression were examined via qRT-PCR. The protein expression was investigated by Western blotting assay. Luciferase reporter assay was used to assess if lncRNA TUG1 can bind to miR-129-5p and if miR-129-5p can target AEG1 mRNA...
March 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Vanessa Lin Lin Lee, Brandon Kar Meng Choo, Yin-Sir Chung, Uday P Kundap, Yatinesh Kumari, Mohd Farooq Shaikh
Metabolic epilepsy is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals. Commonly used antiepileptic drugs are typically ineffective against metabolic epilepsy as they do not address its root cause. Presently, there is no review available which summarizes all the treatment options for metabolic epilepsy. Thus, we systematically reviewed literature which reported on the treatment, therapy and management of metabolic epilepsy from four databases, namely PubMed, Springer, Scopus and ScienceDirect...
March 15, 2018: International Journal of Molecular Sciences
Fabio Sonvico, Adryana Clementino, Francesca Buttini, Gaia Colombo, Silvia Pescina, Silvia Stanisçuaski Guterres, Adriana Raffin Pohlmann, Sara Nicoli
In the field of nasal drug delivery, nose-to-brain delivery is among the most fascinating applications, directly targeting the central nervous system, bypassing the blood brain barrier. Its benefits include dose lowering and direct brain distribution of potent drugs, ultimately reducing systemic side effects. Recently, nasal administration of insulin showed promising results in clinical trials for the treatment of Alzheimer's disease. Nanomedicines could further contribute to making nose-to-brain delivery a reality...
March 15, 2018: Pharmaceutics
Leslee Sprague, Joel M Lee, Brian J Hutzen, Pin-Yi Wang, Chun-Yu Chen, Joe Conner, Lynne Braidwood, Kevin A Cassady, Timothy P Cripe
High Mobility Group Box 1 (HMGB1) is a multifunctional protein that plays various roles in the processes of inflammation, cancer, and other diseases. Many reports document abundant HMGB1 release following infection with oncolytic viruses (OVs). Further, other groups including previous reports from our laboratory highlight the synergistic effects of OVs with chemotherapy drugs. Here, we show that virus-free supernatants have varying cytotoxic potential, and HMGB1 is actively secreted by two established fibroblast cell lines (NIH 3T3 and 3T6-Swiss albino) following HSV1716 infection in vitro...
March 15, 2018: Viruses
Matthew G K Benesch, Iain T K MacIntyre, Todd P W McMullen, David N Brindley
A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironment which promotes cancer growth, immune evasion, metastasis, and treatment resistance...
March 15, 2018: Cancers
Daniel L Riddle, Mark P Jensen, Dennis Ang, James Slover, Robert Perera, Levent Dumenci
BACKGROUND: Pain-coping strategies and appraisals are responses to the pain experience. They can influence patient-reported and physical performance outcome measures in a variety of disorders, but the associations between a comprehensive profile of pain-coping responses and preoperative pain/function and physical performance measures in patients scheduled for knee arthroplasty have not been examined. Patients with moderate to high pain catastrophizing (a pain appraisal approach associated with an exaggerated focus on the threat value of pain) may represent an excellent study population in which to address this knowledge gap...
April 2018: Clinical Orthopaedics and related Research
Francisco S Barreto, Adriano J M Chaves Filho, Márcia C C R de Araújo, Manoel O de Moraes, Maria E A de Moraes, Michael Maes, David F de Lucena, Danielle S Macedo
Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells...
April 2018: Behavioural Pharmacology
Ramón Medel Jiménez, Juan C Sánchez España, José Visa Nassarre, Eva Ayala Barroso, Alfredo Pueyo Ferrer, Alejandra Tapia Bahamondes, Luz M Vasquez
PURPOSE: To describe our experience and outcomes managing complete third cranial nerve palsy. METHODS: This was a retrospective analysis of the clinical records of 7 consecutive patients treated at our centre for unilateral third nerve palsy over the period 2010-2016. We describe our surgical approach using a frontalis muscle flap to correct the eyelid ptosis associated with medial fixation of the rectus muscle tendon to the orbit to correct the horizontal deviation...
March 15, 2018: Orbit
Jing Wu, Wei-Wei Tao, Dan-Yang Chong, Shan-Shan Lai, Chuang Wang, Qi Liu, Tong-Yu Zhang, Bin Xue, Chao-Jun Li
Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Nubia A Mayorga, Charles Jardin, Jafar Bakhshaie, Lorra Garey, Andres G Viana, Jodi Berger Cardoso, Michael Zvolensky
Although recent work has highlighted the relation of acculturative stress with depression and anxiety symptoms specifically among Latino/a university students, the potential mechanisms underlying these associations remain relatively unknown. The present study aims to examine difficulties in emotion regulation as an explanatory factor in the relation of acculturative stress with symptoms of depression, suicidality, social anxiety, and anxious arousal. A sample of 448 Latino/a college students (Mage = 20.67 years, SD = 1...
March 2018: Journal of Counseling Psychology
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