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Sarah Fernandes Teixeira, Ricardo Alexandre de Azevedo, Arthur Carvalho Silva, Rodolpho Campos Braga, Salomão Dória Jorge, José Alexandre Marzagão Barbuto, Carolina Horta Andrade, Adilson Kleber Ferreira
Even with all improvements in both diagnostic and therapeutic techniques, lung cancer remains as the most lethal and prevalent cancer in the world. Therefore, new therapeutic drugs and new strategies of drug combination are necessary to provide treatments that are more efficient. Currently, standard therapy regimen for lung cancer includes platinum drugs, such as cisplatin, oxaliplatin, and carboplatin. Besides of the better toxicity profile of oxaliplatin when compared with cisplatin, peripheral neuropathy remains as a limitation of oxaliplatin dose...
October 18, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ann M Buysse, Maurice C H Yap, Ricky Hunter, Jonathan Babcock, Xinpei Huang, Marshall H Parker
BACKGROUND: Optimization studies on compounds initially designed to be herbicides led to the discovery of a series of [6-(3-pyridyl)pyridazin-3-yl]amides exhibiting aphicidal properties. Systematic modifications of the amide moiety as well as the pyridine and pyridazine rings were carried out to determine if these changes could improve insecticidal potency. RESULTS: Structure-activity relationship (SAR) studies showed that changes to the pyridine and pyridazine rings generally resulted in a significant loss of insecticidal potency against green peach aphids (Myzus persicae (Sulzer) and cotton aphids (Aphis gossypii (Glover)...
October 21, 2016: Pest Management Science
C S Bruells, G Marx
Diaphragm function is crucial for patient outcome in the ICU setting and during the treatment period. The occurrence of an insufficiency of the respiratory pump, which is predominantly formed by the diaphragm, may result in intubation after failure of noninvasive ventilation. Especially patients suffering from chronic obstructive pulmonary disease are in danger of hypercapnic respiratory failure. Changes in biomechanical properties and fiber texture of the diaphragm are further cofactors directly leading to a need for intubation and mechanical ventilation...
October 20, 2016: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Nidhi Singh, Priyanka Shah, Hemlata Dwivedi, Shikha Mishra, Renu Tripathi, Amogh A Sahasrabuddhe, Mohammad Imran Siddiqi
N-Myristoyltransferase (NMT) catalyzes the transfer of myristate to the amino-terminal glycine of a subset of proteins, a co-translational modification involved in trafficking substrate proteins to membrane locations, stabilization and protein-protein interactions. It is a studied and validated pre-clinical drug target for fungal and parasitic infections. In the present study, a machine learning approach, docking studies and CoMFA analysis have been integrated with the objective of translation of knowledge into a pipelined workflow towards the identification of putative hits through the screening of large compound libraries...
October 21, 2016: Molecular BioSystems
Yuhang Zhou, Shaji Abraham, Stephanie Renna, Leonard C Edelstein, Carol A Dangelmaier, Alexander Y Tsygankov, Satya P Kunapuli, Paul F Bray, Steven E McKenzie
OBJECTIVE: The objective of this study is to investigate the role of T-cell ubiquitin ligand-2 (TULA-2) in the platelet Fc receptor for IgG IIA (FcγRIIA) pathway and in the pathogenesis of heparin-induced thrombocytopenia (HIT). APPROACH AND RESULTS: HIT is a life-threatening thrombotic disease in which IgG antibodies against the heparin-platelet factor 4 complex activate platelets via FcγRIIA. We reported previously differential expression of TULA-2 in human population was linked to FcγRIIA responsiveness...
October 20, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Verena Stahn, Inga Nagel, Susan Fischer-Huchzermeyer, Florian Oyen, Reinhard Schneppenheim, Stefan Gesk, Axel Bohring, Levan Chikobava, Peter Young, Burkhard Gess, Mathias Werner, Volker Senner, Anja Harder
Neurofibromas and schwannomas are benign Schwann cell-derived peripheral nerve sheath tumors arising sporadically and within neurofibromatoses. Multiple tumors are a hallmark of neurofibromatosis type 1 (NF1) and type 2 (NF2) and schwannomatosis. Neurofibromas in NF1 and schwannomas in NF2 or schwannomatosis are defined by distinctive molecular hits. Among these, multiple hybrid neurofibromas/schwannomas may also appear, not yet being defined by a molecular background. We therefore performed molecular analysis of 22 hybrid neurofibromas/schwannomas using array comparative genomic hybridization, immunohistochemistry, quantitative RT-PCR, and functional analyses of cultured Schwann cells...
October 17, 2016: American Journal of Pathology
Yan Wang, Jian-Shu Hu, Huang-Quan Lin, Tsz-Ming Ip, David Chi-Cheong Wan
BACKGROUND: Traditionally, molecular docking is primarily employed to screen pure compounds; the top-ranking chemicals are subsequently selected for experimental validation. Unlike synthetic chemicals, most natural products are commercially unavailable. The isolation and purification of each natural product is extremely time-consuming, which has restricted the screening of lead compounds from natural products. PURPOSE: We developed a protocol, Herbalog, to facilitate the identification of bioactive phytochemicals through molecular docking...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Kishore Polireddy, Ruochen Dong, Peter R McDonald, Tao Wang, Brendan Luke, Ping Chen, Melinda Broward, Anuradha Roy, Qi Chen
BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition...
2016: PloS One
Shelby A Montague, Bruce S Baker
An animal's ability to learn and to form memories is essential for its survival. The fruit fly has proven to be a valuable model system for studies of learning and memory. One learned behavior in fruit flies is courtship conditioning. In Drosophila courtship conditioning, male flies learn not to court females during training with an unreceptive female. He retains a memory of this training and for several hours decreases courtship when subsequently paired with any female. Courtship conditioning is a unique learning paradigm; it uses a positive-valence stimulus, a female fly, to teach a male to decrease an innate behavior, courtship of the female...
2016: PloS One
Paulo Esteves Pinto Faria, Abrahão Cavalcante Gomes de Souza Carvalho, Bárbara Masalskas, Letícia Chihara, Eduardo Sant'Ana, Osvaldo Magro Filho
One of the most impressive soft tissue injuries is the facial degloving, normally associated with industrial machines and traffic accidents. This injury is characterized by the separation of the skin and cartilage from the bones, compromising the soft tissues correlated in the trauma area, nerves, and blood vessels. A 28-year-old patient, male, was referred to Araçatuba's Santa Casa Hospital, after a motorcycle accident, hitting his face on the sidewalk. The patient was conscious, oriented, denying fainting and unconsciousness during the accident, and complaining of pain in the nasal region of the face...
October 2016: Journal of Craniofacial Surgery
Seok-Youl Choi, Jong Woong Park, Dong Hwee Kim
Ultrasonographic study is useful for decision making of treatment for focal neuropathy with unusual electrodiagnostic findings. We present a patient with severe acute radial neuropathy with sensory sparing around the distal arm secondary to twisting of the radial nerve following blunt trauma. A 24-year-old man with a 2-week history of left wrist drop and severe pain around the left elbow presented after hitting the left distal arm on the doorknob. The left wrist and finger extensions were grade 0, but elbow extension could not be tested because of severe pain during this action...
November 2016: American Journal of Physical Medicine & Rehabilitation
Ingo Muegge, Prasenjit Mukherjee
A statistical analysis of 203 high-throughput screens was conducted studying the propensity of small molecules in the Boehringer Ingelheim screening deck to show biological activity after having tested inactive previously in a growing number of screening assays. Dark chemical matter (DCM) compounds, which have been tested and found inactive in 50 or more assays, exhibit hit rates that are comparable to those of compounds tested in much fewer assays. Only compounds tested inactive in 125 or more assays start showing a hit rate deterioration of up to 40% compared to compounds tested in less than 25 assays...
October 20, 2016: Journal of Medicinal Chemistry
Traci Watson
No abstract text is available yet for this article.
October 13, 2016: Nature
Chiara Tani, Leopoldo Trieste, Valentina Lorenzoni, Sara Cannizzo, Giuseppe Turchetti, Marta Mosca
Recent advances in health information technologies (HIT) in systemic lupus erythematosus have included electronic databases and registries, computerised clinical charts for patient monitoring, computerised diagnostic tools, computerised prediction rules and, more recently, disease-specific applications for mobile devices for physicians, health care professionals, and patients. Traditionally, HIT development has been oriented primarily to physicians and public administrators. However, more recent development of patient-centered Apps could improve communication and empower patients in the daily management of their disease...
September 2016: Clinical and Experimental Rheumatology
Y Liu, L Huang, H Ye, X Lv
Interferon regulatory factor-7 (IRF-7) is involved in pulmonary infection and pneumonia. Here, a synthetic strategy that combined quantitative structure-activity relationship (QSAR)-based virtual screening and in vitro binding assay was described to identify new and potent mediator ligands of IRF-7 from natural products. In the procedure, a QSAR scoring function was developed and validated using Gaussian process (GP) regression and a structure-based set of protein-ligand affinity data. By integrating hotspot pocket prediction, pharmacokinetics profile analysis and molecular docking calculations, the scoring function was successfully applied to virtual screening against a large library of structurally diverse, drug-like natural products...
October 20, 2016: SAR and QSAR in Environmental Research
Hsing-Hua Tsai, Chin-Pu Lin, Yi-Hui Lin, Chih-Chin Hsu, Jong-Shyan Wang
PURPOSE: Exercise training improves endothelium-dependent vasodilation, whereas hypoxic stress causes vascular endothelial dysfunction. Monocyte-derived endothelial progenitor cells (Mon-EPCs) contribute to vascular repair process by differentiating into endothelial cells. This study investigates how high-intensity interval (HIT) and moderate-intensity continuous (MCT) exercise training affect circulating Mon-EPC levels and EPC functionality under hypoxic condition. METHODS: Sixty healthy sedentary males were randomized to engage in either HIT (3-min intervals at 40 and 80 % VO2max for five repetitions, n = 20) or MCT (sustained 60 % VO2max, n = 20) for 30 min/day, 5 days/week for 6 weeks, or to a control group (CTL) that did not received exercise intervention (n = 20)...
October 19, 2016: European Journal of Applied Physiology
Robyn T Rebbeck, Maram M Essawy, Florentin R Nitu, Benjamin D Grant, Gregory D Gillispie, David D Thomas, Donald M Bers, Razvan L Cornea
Using time-resolved fluorescence resonance energy transfer (FRET), we have developed and validated the first high-throughput screening (HTS) method to discover compounds that modulate an intracellular Ca(2+) channel, the ryanodine receptor (RyR), for therapeutic applications. Intracellular Ca(2+) regulation is critical for striated muscle function, and RyR is a central player. At resting [Ca(2+)], an increased propensity of channel opening due to RyR dysregulation is associated with severe cardiac and skeletal myopathies, diabetes, and neurological disorders...
October 19, 2016: Journal of Biomolecular Screening
Zosia Kmietowicz
No abstract text is available yet for this article.
October 19, 2016: BMJ: British Medical Journal
Nehal Eldeeb, Samia Halileh, Khalid A Alyafei, Rula Ghandour, Soha Dargham, Rita Giacaman, Madeeha Kamal, Sawsan Imseeh, Mona Korayem, Shiraz Nasr, Ziyad Mahfoud, Niveen Abu-Rmeileh, Mohamed H Mahmoud, Hassan Tawfik, Margaret A Lynch, Marcellina Mian
To compare the nature and determinants of child discipline in Qatar and Palestine among young adults through retrospective survey to develop legislation, policies and interventions for effective prevention of child maltreatment, and educational materials to promote positive discipline among parents and caregivers. Cross-sectional random household surveys were conducted in each country (Qataris N=697, Palestinians N=2064) using ISPCAN Child Abuse Screening Tool-Retrospective (ICAST-R) for young adults (18-24 years), to investigate child discipline methods into the maltreatment range...
October 16, 2016: Child Abuse & Neglect
Tao He, Didier Surdez, Juha K Rantala, Saija Haapa-Paananen, Jozef Ban, Maximilian Kauer, Eleni Tomazou, Vidal Fey, Javier Alonso, Heinrich Kovar, Olivier Delattre, Kristiina Iljin
A translocation leading to the formation of an oncogenic EWS-ETS fusion protein defines Ewing sarcoma. The most frequent gene fusion, present in 85 percent of Ewing sarcomas, is EWS-FLI1. Here, a high-throughput RNA interference screen was performed to identify genes whose function is critical for EWS-FLI1 driven cell viability. In total, 6781 genes were targeted by siRNA molecules and the screen was performed both in presence and absence of doxycycline-inducible expression of the EWS-FLI1 shRNA in A673/TR/shEF Ewing sarcoma cells...
October 16, 2016: Gene
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