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https://www.readbyqxmd.com/read/28092804/enhancement-of-nk-cell-mediated-lysis-of-non-small-lung-cancer-cells-by-npkc-activator-ingenol-3-20-dibenzoate
#1
Chenyuan Gong, Chao Yao, Zihang Xu, Zhongya Ni, Xiaowen Zhu, Lixin Wang, Xuewei Yan, Wuxiong Zhou, Shiguo Zhu
The IFN-γ production is crucial for NK cell-mediated lysis of cancer cells. Thus increasing the IFN-γ production by NK cells may be an ideal strategy to improve their tumoricidal effect. Since the focus on new drug development has shifted towards natural products, limited information is out there about natural products that enhance the IFN-γ production by NK cells. In this study, through a high-throughput screening, we have identified a natural product ingenol 3,20 dibenzoate (IDB), an activator of tumor suppressor protein kinase C (PKC) isozymes, could increase the IFN-γ production and degranulation by NK cells, especially when NK cells were stimulated by non-small lung cancer (NSCLC) cells...
January 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28092460/a-three-dimensional-lymphatic-endothelial-cell-tube-formation-assay-to-identify-novel-kinases-involved-in-lymphatic-vessel-remodeling
#2
T Jessica Gambino, Steven P Williams, Carol Caesar, Daniel Resnick, Cameron J Nowell, Rae H Farnsworth, Marc G Achen, Steven A Stacker, Tara Karnezis
The lymphatic system is a series of vessels that transport cells and excess fluid from tissues to the blood vascular system. Normally quiescent, the lymphatics can grow or remodel in response to developmental, immunological, or cells pathological stimuli. Lymphatic vessels comprise lymphatic endothelial cells (LECs) that can respond to external growth factors by undergoing proliferation, migration, adhesion, and tube and lumen formation into new vessel structures, a process known as lymphangiogenesis. To understand the key gene and signaling pathways necessary for lymphangiogenesis and lymphatic vessel remodeling, we have developed a three-dimensional LEC tube formation assay to explore the role of kinase signaling in these processes...
January 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28092392/the-in-silico-identification-of-human-bile-salt-export-pump-abcb11-inhibitors-associated-with-cholestatic-drug-induced-liver-injury
#3
Lili Xi, Jia Yao, Yuhui Wei, Xin'an Wu, Xiaojun Yao, Huanxiang Liu, Shuyan Li
Drug-induced liver injury (DILI) is one of the major causes of drug attrition and failure. Currently, there is increasing evidence that direct inhibition of the human bile salt export pump (BSEP/ABCB11) by drugs and/or metabolites is one of the most important mechanisms of cholestatic DILI. In the present study, we employ two in silico methods, random forest (RF) and the pharmacophore method, to recognize potential BSEP inhibitors that could cause cholestatic DILI, with the aim of mitigating the risk of cholestatic DILI to some extent...
January 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28092382/a-vascularized-and-perfused-organ-on-a-chip-platform-for-large-scale-drug-screening-applications
#4
Duc T T Phan, Xiaolin Wang, Brianna M Craver, Agua Sobrino, Da Zhao, Jerry C Chen, Lilian Y N Lee, Steven C George, Abraham P Lee, Christopher C W Hughes
There is a growing awareness that complex 3-dimensional (3D) organs are not well represented by monolayers of a single cell type - the standard format for many drug screens. To address this deficiency, and with the goal of improving screens so that drugs with good efficacy and low toxicity can be identified, microphysiological systems (MPS) are being developed that better capture the complexity of in vivo physiology. We have previously described an organ-on-a-chip platform that incorporates perfused microvessels, such that survival of the surrounding tissue is entirely dependent on delivery of nutrients through the vessels...
January 16, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28092111/design-and-synthesis-of-5-substituted-benzo-d-1-3-dioxole-derivatives-as-potent-anticonvulsant-agents
#5
Shiyang Dong, Tiantian Wang, Chundi Hu, Xiaodong Chen, Yi Jin, Zengtao Wang
A series of 5-substituted benzo[d][1,3]dioxole derivatives was designed, synthesized, and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Neurotoxicity was determined by rotarod test. In the preliminary screening, six compounds, 3a, 3c, 3d, and 4d-f, showed promising anticonvulsant activities in the MES model, and compounds 4c and 4d exhibited full protection against seizures at doses of 300 mg/kg in the scPTZ model. Among the synthesized compounds, 3c as the most active compound showed high protection against the MES-induced seizures with an ED50 value of 9...
January 16, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28092049/rosette-assay-highly-customizable-dot-blot-for-sh2-domain-screening
#6
Khong Y Ng, Kazuya Machida
With a growing number of high-throughput studies, structural analyses, and availability of protein-protein interaction databases, it is now possible to apply web-based prediction tools to SH2 domain-interactions. However, in silico prediction is not always reliable and requires experimental validation. Rosette assay is a dot blot-based reverse-phase assay developed for the assessment of binding between SH2 domains and their ligands. It is conveniently customizable, allowing for low- to high-throughput analysis of interactions between various numbers of SH2 domains and their ligands, e...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28091672/a-rapid-way-to-discover-nonstandard-macrocyclic-peptide-modulators-of-drug-targets
#7
Toby Passioura, Hiroaki Suga
Studies of the fundamental nature of RNA catalysis and the potential mechanism of a shift from the "RNA world" to proteinaceous life lead us to identify a set of ribozymes (flexizymes) capable of promiscuous tRNA acylation. Whilst theoretically and mechanistically interesting in their own right, flexizymes have turned out to have immense practical value for the simple synthesis of tRNAs acylated with unusual amino acids, which in turn can be used for the ribosomal synthesis of peptides containing non-canonical residues...
January 16, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28090641/in-vivo-quantitative-assessment-of-the-therapeutic-response-in-a-mouse-model-of-collagen-induced-arthritis-using-18-f-fluorodeoxyglucose-positron-emission-tomography
#8
Anupam Mitra, Smriti Kundu-Raychaudhuri, Christine Abria, Angelica Rona, Abhijit J Chaudhari, Siba P Raychaudhuri
BACKGROUND: Mouse collagen induced arthritis (CIA) is the most commonly used animal model to investigate underlying pathogenesis of autoimmune arthritis and to demonstrate therapeutic efficacy of novel drugs in autoimmune arthritis. The conventional read out of CIA are clinical score and histopathology, which have several limitations including (i) subjected to observer bias; (ii) longitudinal therapeutic efficacy of a new drug cannot be determined. Thus a robust, non-invasive, in vivo drug screening tool is currently an unmet need...
January 16, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28090514/pancreatic-cancer-from-bench-to-bedside
#9
REVIEW
Yaokai Ma, Qing Wu, Xin Li, Xiaoqiang Gu, Jiahua Xu, Jinzu Yang
Pancreatic cancer is recognized as the king of carcinoma, and the gap between basic research and clinical practice is difficult to improve the treatment effect. Translational medicine builds an important bridge between pancreatic cancer basic research and clinical practice from the pathogenesis, early diagnosis of pancreatic carcinoma, drug screening, treatment strategies and metastasis prediction. This article will carry on the concrete elaboration to the above several aspects.
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28090431/a-role-for-3d-printing-in-kidney-on-a-chip-platforms
#10
Ryan D Sochol, Navin R Gupta, Joseph V Bonventre
The advancement of "kidney-on-a-chip" platforms - submillimeter-scale fluidic systems designed to recapitulate renal functions in vitro - directly impacts a wide range of biomedical fields, including drug screening, cell and tissue engineering, toxicity testing, and disease modelling. To fabricate kidney-on-a-chip technologies, researchers have primarily adapted traditional micromachining techniques that are rooted in the integrated circuit industry; hence the term, "chip." A significant challenge, however, is that such methods are inherently monolithic, which limits one's ability to accurately recreate the geometric and architectural complexity of the kidney in vivo...
March 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28090167/novel-screening-test-sparks-new-ideas-about-old-drugs
#11
(no author information available yet)
No abstract text is available yet for this article.
January 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/28090109/substance-use-attitudes-behaviors-education-and-prevention-in-colleges-of-pharmacy-in-the-united-states
#12
REVIEW
Samah F Al-Shatnawi, Matthew Perri, Henry N Young, Merrill Norton
This review describes and summarizes student pharmacists' substance use behavior in the United States. Current literature indicates that there are problems with alcohol and other drug use among student pharmacists. Although researchers have found variations in the type and rate of reported substance use, significant proportions of student pharmacists were identified as being at high risk for substance use disorders (SUDs). Findings from this review suggest that pharmacy schools should encourage and stimulate more research in order to implement effective screening and early intervention programs in an effort to address this important student health issue...
November 25, 2016: American Journal of Pharmaceutical Education
https://www.readbyqxmd.com/read/28090089/transfer-of-minimally-manipulated-cmv-specific-t-cells-from-stem-cell-or-third-party-donors-to-treat-cmv-infection-after-allohsct
#13
M Neuenhahn, J Albrecht, M Odendahl, F Schlott, G Dössinger, M Schiemann, S Lakshmipathi, K Martin, D Bunjes, S Harsdorf, E M Weissinger, H Menzel, M Verbeek, L Uharek, N Kröger, E Wagner, G Kobbe, T Schroeder, M Schmitt, G Held, W Herr, L Germeroth, H Bonig, T Tonn, H Einsele, D H Busch, G U Grigoleit
Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drug-refractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo MHC-Streptamer-isolated CMV epitope-specific donor T cells...
January 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28089889/myc-drives-progression-of-small-cell-lung-cancer-to-a-variant-neuroendocrine-subtype-with-vulnerability-to-aurora-kinase-inhibition
#14
Gurkan Mollaoglu, Matthew R Guthrie, Stefanie Böhm, Johannes Brägelmann, Ismail Can, Paul M Ballieu, Annika Marx, Julie George, Christine Heinen, Milind D Chalishazar, Haixia Cheng, Abbie S Ireland, Kendall E Denning, Anandaroop Mukhopadhyay, Jeffery M Vahrenkamp, Kristofer C Berrett, Timothy L Mosbruger, Jun Wang, Jessica L Kohan, Mohamed E Salama, Benjamin L Witt, Martin Peifer, Roman K Thomas, Jason Gertz, Jane E Johnson, Adi F Gazdar, Robert J Wechsler-Reya, Martin L Sos, Trudy G Oliver
Loss of the tumor suppressors RB1 and TP53 and MYC amplification are frequent oncogenic events in small cell lung cancer (SCLC). We show that Myc expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors, that are initially sensitive to chemotherapy followed by relapse, similar to human SCLC. Importantly, MYC drives a neuroendocrine-low "variant" subset of SCLC with high NEUROD1 expression corresponding to transcriptional profiles of human SCLC. Targeted drug screening reveals that SCLC with high MYC expression is vulnerable to Aurora kinase inhibition, which, combined with chemotherapy, strongly suppresses tumor progression and increases survival...
December 31, 2016: Cancer Cell
https://www.readbyqxmd.com/read/28089738/evaluation-of-the-diuretic-activity-of-the-aqueous-and-80-methanol-extracts-of-the-root-of-euclea-divinorum-hiern-ebenaceae-in-sprague-dawley-rats
#15
Beharu Woldemedhin, Teshome Nedi, Workineh Shibeshi, Mekonnen Sisay Shiferaw
BACKGROUND: Diuretics are drugs that increase the formation of urine and are important for the treatment of various diseases including hypertension and edema. The root decoction of Euclea divinorum has been used as a diuretic agent in the traditional medicine. Therefore, this study was aimed to evaluate the diuretic activity of the crude extracts of the roots of Euclea divinorum in Sprague Dawley rats. METHODS: The aqueous extract (AE) and 80% methanol extract (80ME) of the plant were prepared using decoction and maceration, respectively...
January 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28089347/virtual-screening-and-experimental-validation-identify-novel-modulators-of-nuclear-receptor-rxr%C3%AE-from-drugbank-database
#16
Dan Xu, Lijun Cai, Shangjie Guo, Lei Xie, Meimei Yin, Ziwen Chen, Hu Zhou, Ying Su, Zhiping Zeng, Xiaokun Zhang
Retinoid X receptor alpha (RXRα), an important ligand-dependent transcription factor, plays a critical role in the development of various cancers and metabolic and neurodegenerative diseases. Therefore, RXRα represents one of the most important targets in modern drug discovery. In this study, Drugbank 2.0 with 1280 old drugs were virtually screened by Glide according to the crystal structure of ligand-binding domain (LBP) of RXRα. 15 compounds selected were tested for their binding and transcriptional activity toward RXRα by Biacore and reporter gene assay, respectively...
December 26, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28088086/design-and-synthesis-of-new-raf-kinase-inhibiting-antiproliferative-quinoline-derivatives-part-2-diarylurea-derivatives
#17
Mohammed I El-Gamal, Mohammad Ashrafuddin Khan, Hamadeh Tarazi, Mohammed S Abdel-Maksoud, Mahmoud M Gamal El-Din, Kyung Ho Yoo, Chang-Hyun Oh
This article describes the design, synthesis, and biological screening of a new series of diarylurea derivatives possessing quinoline nucleus. Nine target compounds were selected by the National Cancer Institute (NCI, Bethesda, Maryland, USA) for in vitro antiproliferative screening against a panel of 58 cancer cell lines of nine cancer types. Following one-dose initial screening, compounds 1d-g and 2b were selected for 5-dose screening in order to calculate their IC50 and total growth inhibition (TGI) values against the cell lines...
January 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28088050/pharmacists-knowledge-of-issues-in-pharmacotherapy-of-epilepsy-using-antiepileptic-drugs-a-cross-sectional-study-in-palestinian-pharmacy-practice
#18
Ramzi Shawahna, Ahlam Atrash, Aman Jebril, Areen Khalaf, Eman Shaheen, Hala Tahboosh
OBJECTIVE: Antiepileptic drugs (AEDs) are mainstay in controlling epileptic seizures. As experts in medications, pharmacists should be able to ensure accuracy of dosing regimens, explain adverse effects, and screen for and alert people with epilepsy (PWE) and their physicians to possible drug-drug interactions (DDIs). The aim of this study was to evaluate pharmacists' knowledge of issues in pharmacotherapy of epilepsy using AEDs. METHODS: This was a cross-sectional observational study conducted in the Palestinian pharmacy practice...
January 11, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28087837/off-target-effects-of-neuroleptics-and-antidepressants-on-saccharomyces-cerevisiae
#19
M Caldara, S Graziano, M Gullì, S Cadonici, Nelson Marmiroli
Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation, these drugs display many side effects. Toxicogenomic studies aim to limit this problem by trying to identify cellular targets and off-targets of medical compounds. The baker yeast Saccharomyces cerevisiae has been shown to be a key player in this approach, as it represents an incredible toolbox for the dissection of complex biological processes...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087488/cathepsin-k-targeted-sub-micron-particles-for-regenerative-repair-of-vascular-elastic-matrix
#20
Brenton Jennewine, Jonathan Fox, Anand Ramamurthi
: Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to breakdown of structural matrix components, such as elastic fibers by chronically overexpressed matrix metalloproteinases (MMPs), primarily, MMPs-2 and -9. Auto-regenerative repair of disrupted elastic fibers by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents restoration of elastin homeostasis, necessary to enable AAA growth arrest or regression to a healthy state...
January 10, 2017: Acta Biomaterialia
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