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Shi-Long Jiang, Yi-di Guan, Xi-Sha Chen, Peng Ge, Xin-Luan Wang, Yuan-Zhi Lao, Song-Shu Xiao, Yi Zhang, Jin-Ming Yang, Xiao-Jun Xu, Dong-Sheng Cao, Yan Cheng
Autophagy, a form of cellular self-digestion by lysosome, is associated with various disease processes including cancers, and modulating autophagy has shown promise in the treatment of various malignancies. A number of natural products display strong antitumor activity, yet their mechanisms of action remain unclear. To gain a better understanding of how traditional Chinese medicine agents exert antitumor effects, we screened 480 natural compounds for their effects on autophagy using a high content screening assay detecting GFP-LC3 puncta in HeLa cells...
October 12, 2018: Acta Pharmacologica Sinica
Dimitri Stylemans, Sylvia Verbanck, Stefanie Vincken, Walter Vincken, Elke De Wachter, Eef Vanderhelst
BACKGROUND: While cystic fibrosis (CF) lung disease is generally considered to be an obstructive disorder, other pulmonary function patterns (PFP) may occur. Furthermore, little is known about possible associations between PFP and genotype or phenotypical characteristics. METHODS: Cross-sectional study including CF patients aged 16 years or more, identifying different PFP and exploring associations between PFP and genotype or phenotypical characteristics. RESULTS: Obstructive PFP was most prevalent in our population (n = 80), comprising obstructive lung disease (62...
October 12, 2018: Acta Clinica Belgica
K Veltman, C Harris, Y Ahmad, O Jolliet
Precise control of the glutathione/glutathione disulfide (GSH/GSSG) redox balance is vital for the developing embryo, but regulatory mechanisms are poorly understood. We developed a novel, mechanistic mass-balance model for GSH metabolism in the organogenesis stage (gestational day 10.0 to 11.13) rat conceptus predicting the dynamics of 8 unique metabolites in 3 conceptal compartments: the visceral yolk sac (VYS), the extra-embryonic fluid (EEF) and the embryo proper (EMB). Our results show that thiol concentrations in all compartments are well predicted by the model...
October 4, 2018: Reproductive Toxicology
Haci Ahmet Bircan, Nilgun Gurbuz, Apar Pataer, Ayse Caner, Nermin Kahraman, Emine Bayraktar, Recep Bayraktar, Mumin Alper Erdogan, Nashwa Kabil, Bulent Ozpolat
OBJECTIVES: Lung cancer is the leading cause of cancer related deaths in worldwide. Despite recent advances in treatment options, patient survival has not improved substantially due to lack of commonly expressed molecular targets and effective targeted therapeutics. Thus, better understanding of the biology of lung cancer and identification of novel therapeutic targets are urgently needed for development of highly effective molecularly targeted therapies. MATERIALS AND METHODS: Viability, proliferation and metastatic ability of lung cancer cells were evaluated using methylthiazoltetrazolium (MTT), colony formation and matrigel invasion assays, respectively...
October 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Daniela Diedrich, Katharina Stenzel, Eva Hesping, Yevgeniya Antonova-Koch, Tamirat Gebru, Sandra Duffy, Gillian Fisher, Andrea Schöler, Stephan Meister, Thomas Kurz, Vicky M Avery, Elizabeth A Winzeler, Jana Held, Katherine T Andrews, Finn K Hansen
Malaria drug discovery has shifted from a focus on targeting asexual blood stage parasites, to the development of drugs that can also target exo-erythrocytic forms and/or gametocytes in order to prevent malaria and/or parasite transmission. In this work, we aimed to develop parasite-selective histone deacetylase inhibitors (HDACi) with activity against the disease-causing asexual blood stages of Plasmodium malaria parasites as well as with causal prophylactic and/or transmission blocking properties. An optimized one-pot, multi-component protocol via a sequential Ugi four-component reaction and hydroxylaminolysis was used for the preparation of a panel of peptoid-based HDACi...
October 5, 2018: European Journal of Medicinal Chemistry
Yuan-Yuan Zhao, Ying Tian, Lin Liu, Jian-Hua Zhan, Xue Hou, Xi Chen, Ting Zhou, Yan Huang, Li Zhang
Aim: Our previous research showed that AKT inactivation via small molecule inhibitors did not induce significant apoptosis, but rather markedly increased autophagy in nasopharyngeal carcinoma (NPC). The purpose of the current study was to determine whether autophagy inhibition can enhance the anticancer efficacy of an AKT inhibitor (MK-2206). Materials and methods: NPC cell lines CNE-2 (Epstein-Barr virus negative) and C666-1 (Epstein-Barr virus positive) were used to conduct the research...
2018: Drug Design, Development and Therapy
Harish Jangra, Hendrik Zipse
We explored the influence of external electric fields (EEFs) on the stability of a glycine dipeptide model radical using high-level quantum chemical methods. Remotely located ions (Cl- /Na+ ) are used to implement EEF effects. The effects of these ions are reproduced using background point charges and oriented EEFs. Remote charges as far as 900 pm from the Cα radical center can be significantly stabilizing or destabilizing as a function of their relative orientation. The magnitude of these effects is also strongly dependent on the distance between the radical center and the charge location...
September 27, 2018: Journal of Physical Chemistry. B
Felipe Ten-Caten, Ricardo Z N Vêncio, Alan Péricles R Lorenzetti, Livia Soares Zaramela, Ana Carolina Santana, Tie Koide
Prokaryotic genomes show a high level of information compaction often with different molecules transcribed from the same locus. Although antisense RNAs have been relatively well studied, RNAs in the same strand, internal RNAs (intraRNAs), are still poorly understood. The question of how common is the translation of overlapping reading frames remains open. We address this question in the model archaeon Halobacterium salinarum. In the present work we used differential RNA-seq (dRNA-seq) in H. salinarum NRC-1 to locate intraRNA signals in subsets of internal transcription start sites (iTSS) and establish the open reading frames associated to them (intraORFs)...
2018: RNA Biology
Pradeep K Jatav, Ankita Sharma, Dinesh K Dahiya, Arif Khan, Atika Agarwal, S L Kothari, Sumita Kachhwaha
Finger millet [ Eleusine coracana (L.) Gaertn] is an excellent food and forage crop of arid and semiarid areas in Africa and Asia. It is well adapted to drought, heat, high salinity, poor soil fertility and low pH with an efficient C4 carbon fixation mechanism for high yield potential. To normalize the target gene expression data, the identification of suitable reference genes is essential. Ten candidate reference genes were selected and their expression stability was analyzed in various samples treated with different abiotic stress conditions...
September 2018: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
Amol S Phule, Kalyani M Barbadikar, M S Madhav, P Senguttuvel, M B B Prasad Babu, P Ananda Kumar
A set of reference genes expressing stably under aerobic and anaerobic conditions in rice is essential to execute omics studies relating to aerobic adaptations. Stability of expression of ten rice reference genes, viz. Actin, eEF-1a, eIF-5C, Exp1, Exp2, Memp, SKP1A, TF-SUI1, TPH , and UBQ5 was validated across six experimental sets in shoot and root tissues at seedling, tillering, and panicle initiation stages. Comprehensively, Memp (Membrane protein), TPH (Tumor protein homolog), and Exp1 (Expressed protein) were revealed as the most stable set with acceptable M and V value according to the gold standards of qRT-PCR using various algorithms/tools...
September 2018: 3 Biotech
Kelly A Foks, Crispijn L van den Brand, Hester F Lingsma, Joukje van der Naalt, Bram Jacobs, Eline de Jong, Hugo F den Boogert, Özcan Sir, Peter Patka, Suzanne Polinder, Menno I Gaakeer, Charlotte E Schutte, Kim E Jie, Huib F Visee, Myriam G M Hunink, Eef Reijners, Meriam Braaksma, Guus G Schoonman, Ewout W Steyerberg, Korné Jellema, Diederik W J Dippel
OBJECTIVE: To externally validate four commonly used rules in computed tomography (CT) for minor head injury. DESIGN: Prospective, multicentre cohort study. SETTING: Three university and six non-university hospitals in the Netherlands. PARTICIPANTS: Consecutive adult patients aged 16 years and over who presented with minor head injury at the emergency department with a Glasgow coma scale score of 13-15 between March 2015 and December 2016...
August 24, 2018: BMJ: British Medical Journal
Ruud Ubink, Eef Hc Dirksen, Myrthe Rouwette, Ebo Sijbren Bos, Ingrid Janssen, David F Egging, Eline M Loosveld, Tanja A van Achterberg, Kim Berentsen, Miranda M C van der Lee, Francis Bichat, Olivier Raguin, Monique A J van der Vleuten, Patrick G Groothuis, Wim H A Dokter
Carboxylesterase 1c (CES1c) is responsible for linker-drug instability and poor pharmacokinetics (PK) of several antibody-drug conjugates (ADCs) in mouse, but not in monkey or human. Preclinical development of these ADCs could be improved if the PK in mice would more closely resemble that of human and is not affected by an enzyme that is irrelevant for humans. SYD985, a HER2-targeting ADC based on trastuzumab and linker-drug vc-seco-DUBA is also sensitive to CES1c. In the present studies, we first focused on the interaction between CES1c and SYD985 by size- exclusion chromatography, Western blotting and LC-MS/MS analysis, using recombinant CES1c and plasma samples...
August 9, 2018: Molecular Cancer Therapeutics
Marcia C Inhorn, Daphna Birenbaum-Carmeli, Lynn M Westphal, Joseph Doyle, Norbert Gleicher, Dror Meirow, Martha Dirnfeld, Daniel Seidman, Arik Kahane, Pasquale Patrizio
PURPOSE: What are the specific pathways that lead women to freeze their eggs? In this binational study, women were asked directly about the life circumstances that led them on the path to elective egg freezing (EEF). METHODS: From June 2014 to August 2016, 150 women (114 in the USA, 36 in Israel) who had completed at least 1 cycle of EEF were interviewed by two medical anthropologists. Study participants were recruited through four American IVF clinics (two academic, two private) and three in Israel (one academic, two private)...
August 3, 2018: Journal of Assisted Reproduction and Genetics
Rute J Macedo-de-Araújo, Ana Amorim-de-Sousa, António Queirós, Eef van der Worp, José M González-Méijome
PURPOSE: To analyze the relationship between corneal sagittal height and asymmetry parameters derived from Placido-videokeratoscopy with the parameters of fitted scleral lenses (ScCLs). METHODS: Corneal topographies were measured with MedmontE300 in a total of 126 eyes with irregular and regular corneas before ScCL fitting were analyzed. Measurements of sagittal height (OC-SAG) at steep and flat corneal meridians were obtained for 10 mm and 12 mm chords. Estimated Height (EHChord) parameters were taken for a chord equal to the diameter of the lens that each subject was wearing at different semi-meridians...
July 25, 2018: Contact Lens & Anterior Eye: the Journal of the British Contact Lens Association
Elizabeth B de Sousa Fernandes Perna, Eef L Theunissen, Patrick C Dolder, Natasha L Mason, Nadia R P W Hutten, Stefan W Toennes, Kim P C Kuypers, Johannes G Ramaekers
Availability of novel psychoactive substances (NPS) exponentially increased over the last years. Risk evaluations of NPS are hampered by the lack of pharmacological studies in humans on health parameters. The aim of the present study was to evaluate safety and neurocognitive function of healthy volunteers ( N = 12) who received single doses of 100 and 150 mg 4-fluoroamphetamine (4-FA), a phenethylamine that has been associated with severe cardiovascular and cerebrovascular complications. The study was set-up as a placebo controlled, within subject, phase 1 trial as it was the first to administer 4-FA to humans under controlled conditions...
2018: Frontiers in Pharmacology
M C Inhorn, D Birenbaum-Carmeli, J Birger, L M Westphal, J Doyle, N Gleicher, D Meirow, M Dirnfeld, D Seidman, A Kahane, P Patrizio
BACKGROUND: What are the underlying socio-demographic factors that lead healthy women to preserve their fertility through elective egg freezing (EEF)? Many recent reviews suggest that women are intentionally postponing fertility through EEF to pursue careers and achieve reproductive autonomy. However, emerging empirical evidence suggests that women may be resorting to EEF for other reasons, primarily the lack of a partner with whom to pursue childbearing. The aim of this study is thus to understand what socio-demographic factors may underlie women's use of EEF...
July 23, 2018: Reproductive Biology and Endocrinology: RB&E
Guilherme Eustáquio Furtado, Adriana Caldo, Taís Rieping, Edith Filaire, Eef Hogervorst, Ana Maria Botelho Teixeira, José Pedro Ferreira
The aim of this meta-analysis was to analyse the magnitude of the effect-size of the cognitive status of populations over 60 years of age, when comparing nonfrail versus pre-frail and nonfrail versus frail subgroups. A systematic review of prospective studies published from 2000 to 2017 was completed in Medline, B-on, Ebsco, Ebsco Health, Scielo, ERIC, LILACS and Sport discus databases and observational, cohort and cross-sectional studies were selected. The Mini-Mental State Examination to screening cognitive status and the Fried phenotype for assess physical frailty state was used as clinical outcomes...
September 2018: Archives of Gerontology and Geriatrics
Peter H J Keizers, Celine Vanhee, Eef M W van den Elzen, Wim H de Jong, Bastiaan J Venhuis, Hennie M Hodemaekers, Paul Schwillens, Daan G W Lensen
Facial treatments with dermal fillers for medical or esthetic purposes occasionally give rise to adverse effects, ranging from temporary effects such as reddening of the skin, to long term effects such as hardening of tissue. There appears to be a relationship between the lifetime of the filler product and the risk for adverse effects. The lifetime of hyaluronic acid-based fillers is dependent on the presence and amount of crosslinking agents such as 1,4-butanediol diglycidyl ether (BDDE). It would therefore make sense to establish methodology to analyze the crosslinking grade of HA-based filler products on a routine basis...
September 10, 2018: Journal of Pharmaceutical and Biomedical Analysis
Sason Shaik, Rajeev Ramanan, David Danovich, Debasish Mandal
This is a tutorial on use of external-electric-fields (EEFs) as effectors of chemical change. The tutorial instructs readers how to conceptualize and design electric-field effects on bonds, structures, and reactions. Most effects can be comprehended as the field-induced stabilization of ionic structures. Thus, orienting the field along the "bond axis" will facilitate bond breaking. Similarly, orienting the field along the "reaction axis", the direction in which "electron pairs transform" from reactants- to products-like, will catalyse the reaction...
July 17, 2018: Chemical Society Reviews
Y Cheng, X Ren, Y Yuan, Y Shan, L Li, X Chen, L Zhang, Y Takahashi, J W Yang, B Han, J Liao, Y Li, H Harvey, A Ryazanov, G P Robertson, G Wan, D Liu, A F Chen, Y Tao, J-M Yang
In this article, the authors recently noticed that the tubulin blots in Figs. 2a and 6a were inadvertently misplaced during the preparation of these figures due to their similarity. The amended versions of the figures are now shown below. The conclusions of this paper are not affected. The authors sincerely apologize for these errors.
August 2018: Oncogene
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