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https://www.readbyqxmd.com/read/29054529/development-of-amide-based-fluorescent-probes-for-selective-measurement-of-carboxylesterase-1-activity-in-tissue-extracts
#1
Sean D Kodani, Morgane Barthélemy, Shizuo G Kamita, Bruce Hammock, Christophe Morisseau
Carboxylesterases are well known for their role in the metabolism of xenobiotics. However, recent studies have also implicated carboxylesterases in regulating a number of physiological processes including metabolic homeostasis and macrophage development, underlying the need to quantify them individually. Unfortunately, current methods for selectively measuring the catalytic activity of individual carboxylesterases are not sufficiently sensitive to support many biological studies. In order to develop a more sensitive and selective method to measure the activity of human carboxylesterase 1 (hCE1), we generated and tested novel substrates with a fluorescent aminopyridine leaving group...
October 17, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29054476/extracellular-vesicles-as-emerging-targets-in-cancer-recent-development-from-bench-to-bedside
#2
REVIEW
Kerui Wu, Fei Xing, Shih-Ying Wu, Kounosuke Watabe
Extracellular vesicles (EVs) have emerged as important players of cancer initiation and progression through cell-cell communication. They have been recognized as critical mediators of extracellular communications, which promote transformation, growth invasion, and drug-resistance of cancer cells. Interestingly, the secretion and uptake of EVs are regulated in a more controlled manner than previously anticipated. EVs are classified into three groups, (i) exosomes, (ii) microvesicles (MVs), and (iii) apoptotic bodies (ABs), based on their sizes and origins, and novel technologies to isolate and distinguish these EVs are evolving...
October 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29054369/exosome-is-a-mechanism-of-intercellular-drug-transfer-application-of-quantitative-pharmacology
#3
Jin Wang, Bertrand Z Yeung, Minjian Cui, Cody J Peer, Ze Lu, William D Figg, M Guillaume Wientjes, Sukyung Woo, Jessie L-S Au
PURPOSE: Exosomes are small membrane vesicles (30-100nm in diameter) secreted by cells into extracellular space. The present study evaluated the effect of chemotherapeutic agents on exosome production and/or release, and quantified the contribution of exosomes to intercellular drug transfer and pharmacodynamics. METHODS: Human cancer cells (breast MCF7, breast-to-lung metastatic LM2, ovarian A2780 and OVCAR4) were treated with paclitaxel (PTX, 2-1000nM) or doxorubicin (DOX, 20-1000nM) for 24-48h...
October 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29054297/hemolytic-uremic-syndrome-due-to-shiga-toxin-producing-escherichia-coli-infection
#4
REVIEW
M Bruyand, P Mariani-Kurkdjian, M Gouali, H de Valk, L A King, S Le Hello, S Bonacorsi, C Loirat
The leading cause of hemolytic uremic syndrome (HUS) in children is Shiga toxin-producing Escherichia coli (STEC) infection, which has a major outbreak potential. Since the early 2010s, STEC epidemiology is characterized by a decline of the historically predominant O157 serogroup and the emergence of non-O157 STEC, especially O26 and O80 in France. STEC contamination occurs through the ingestion of contaminated food or water, person-to-person transmission, or contact with ruminants or their contaminated environment...
October 17, 2017: Médecine et Maladies Infectieuses
https://www.readbyqxmd.com/read/29053679/measuring-the-effect-of-chemicals-on-the-growth-and-reproduction-of-caenorhabditis-elegans
#5
So Young Lee, Kyungsu Kang
Toxicological evaluation is crucial for understanding the effects of chemicals on living organisms in basic and applied biological science fields. A non-mammalian soil round worm, Caenorhabditis elegans, is a valuable model organism for toxicology studies due to its convenience and lack of animal ethics issues compared with mammalian animal systems. In this protocol, a detailed procedure of toxicological evaluation of chemicals in C. elegans is described. A clinical anticancer drug, etoposide, which targets human topoisomerase II and inhibits DNA replication of human cancer cells, was selected as a model testing chemical...
October 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053672/sample-extraction-and-simultaneous-chromatographic-quantitation-of-doxorubicin-and-mitomycin-c-following-drug-combination-delivery-in-nanoparticles-to-tumor-bearing-mice
#6
Rui Xue Zhang, Tian Zhang, King Chen, Ji Cheng, Paris Lai, Andrew M Rauth, K Sandy Pang, Xiao Yu Wu
Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit. Nanoparticle-based drug combination has been shown to mitigate the problems encountered by free drug combination therapy. Our previous studies have shown that the combination of two anticancer drugs, doxorubicin (DOX) and mitomycin C (MMC), produced a synergistic effect against both murine and human breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer multidrug resistance and demonstrated enhanced efficacy in breast tumor models...
October 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053625/traditional-uses-origins-chemistry-and-pharmacology-of-bombyx-batryticatus-a-review
#7
REVIEW
Meibian Hu, Zhijie Yu, Jiaolong Wang, Wenxiang Fan, Yujie Liu, Jianghua Li, He Xiao, Yongchuan Li, Wei Peng, Chunjie Wu
Bombyx batryticatus (B. batryticatus), a well-known traditional animal Chinese medicine, has been commonly used in China for thousands of years. The present paper reviewed advances in traditional uses, origin, chemical constituents, pharmacology and toxicity studies of B. batryticatus. The aim of the paper is to provide more comprehensive references for modern B. batryticatus study and application. In Traditional Chinese Medicine (TCM) culture, drugs containing B. batryticatus have been used to treat convulsions, headaches, skin prurigo, scrofula, tonsillitis and fever...
October 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29053277/utilizing-inverse-emulsion-polymerization-to-generate-responsive-nanogels-for-cytosolic-protein-delivery
#8
Kishore Raghupathi, Scott J Eron, Francesca Anson, Jeanne A Hardy, S Thayumanavan
Therapeutic biologics have various advantages over synthetic drugs in terms of selectivity, their catalytic nature and thus, therapeutic efficacy. These properties offer the potential for more effective treatments that may also overcome the undesirable side effects observed due to off-target toxicities of small-molecule drugs. Unfortunately, systemic administration of biologics is challenging due to cellular penetration, renal clearance and enzymatic degradation difficulties. A delivery vehicle that can overcome these challenges and deliver biologics to specific cellular populations has the potential for significant therapeutic impact...
October 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29053081/pcl-and-pcl-based-materials-in-biomedical-applications
#9
Elbay Malikmammadov, Tugba Endogan Tanir, Aysel Kiziltay, Vasif Hasirci, Nesrin Hasirci
Biodegradable polymers have met withan increasing demand in medical usage over the last decades. One of such polymers is poly(ε-caprolactone) (PCL), whichis a polyester that has been widely used in tissue engineering field for its availability, relatively inexpensive price and suitability for modification. Its chemical and biological properties, physicochemical state, degradability and mechanical strengthcan be adjusted, and therefore,it can be usedunderharsh mechanical, physical and chemical conditions without significant loss of its properties...
October 20, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/29053080/aerosolizing-lipid-dispersions-enables-antibiotic-transport-across-mimics-of-the-lung-airway-surface-even-in-the-presence-of-pre-existing-lipid-monolayers
#10
Steven V Iasella, Amy Z Stetten, Timothy E Corcoran, Stephen Garoff, Todd M Przybycien, Robert D Tilton
BACKGROUND: Secondary lung infections are the primary cause of morbidity associated with cystic fibrosis lung disease. Aerosolized antibiotic inhalation is potentially advantageous but has limited effectiveness due to altered airway aerodynamics and deposition patterns that limit drug access to infected regions. One potential strategy to better reach infected areas is to formulate aerosols with surfactants that induce surface tension gradients and drive postdeposition drug dispersal via Marangoni transport along the airway surface liquid (ASL)...
October 20, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/29052925/structural-insights-into-natural-compounds-as-inhibitors-of-fasciola-gigantica-thioredoxin-glutathione-reductase
#11
Rohit Shukla, Harish Shukla, Parismita Kalita, Timir Tripathi
Fascioliasis is caused by the helminth parasites of genus Fasciola. Thioredoxin glutathione reductase (TGR) is an important enzyme in parasitic helminths and plays an indispensable role in its redox biology. In the present study, we conducted a structure-based virtual screening of natural compounds against the Fasciola gigantica TGR (FgTGR). The compounds were docked against FgTGR in four sequential docking modes. The screened ligands were further assessed for Lipinski and ADMET prediction so as to evaluate drug proficiency and likeness property...
October 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29052818/out-of-pocket-cost-is-a-barrier-to-therapeutic-drug-monitoring-in-inflammatory-bowel-disease
#12
James P Campbell, Erin Burton, Shelly Wymer, Michael Shaw, Byron P Vaughn
BACKGROUND: Therapeutic drug monitoring (TDM) is increasingly performed to optimize biologic therapy in inflammatory bowel disease (IBD). However, patients and physicians may be reluctant to perform TDM due to concerns related to potential out-of-pocket costs. AIMS: The aim of this study was to evaluate patient understanding and attitudes toward TDM in different clinical scenarios with and without potential out-of-pocket costs. METHODS: Adult IBD patients at a tertiary gastroenterology clinic were anonymously surveyed from March to September 2016 to assess their understanding of and willingness to undergo TDM in a variety of clinical scenarios, both with and without a potential out-of-pocket cost...
October 20, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29052539/engineering-diagnostic-and-therapeutic-gut-bacteria
#13
Brian P Landry, Jeffrey J Tabor
Genetically engineered bacteria have the potential to diagnose and treat a wide range of diseases linked to the gastrointestinal tract, or gut. Such engineered microbes will be less expensive and invasive than current diagnostics and more effective and safe than current therapeutics. Recent advances in synthetic biology have dramatically improved the reliability with which bacteria can be engineered with the sensors, genetic circuits, and output (actuator) genes necessary for diagnostic and therapeutic functions...
October 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/29052423/streamlined-total-synthesis-of-trioxacarcins-and-its-application-to-the-design-synthesis-and-biological-evaluation-of-analogues-thereof-discovery-of-simpler-designed-and-potent-trioxacarcin-analogues
#14
K C Nicolaou, Pengxi Chen, Shugao Zhu, Quan Cai, Rohan D Erande, Ruofan Li, Hongbao Sun, Kiran Kumar Pulukuri, Stephan Rigol, Monette Aujay, Joseph Sandoval, Julia Gavrilyuk
A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthraquinones and chloro anthraquinones from simple ketone precursors and phenylselenyl chloride is also described...
October 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29052416/n-heterocycle-forming-amino-carboperfluoroalkylations-of-aminoalkenes-by-using-perfluoro-acid-anhydrides-mechanistic-studies-and-applications-directed-toward-perfluoroalkylated-compound-libraries
#15
Shintaro Kawamura, Kento Dosei, Elena Valverde, Kiminori Ushida, Mikiko Sodeoka
This work describes a practical and efficient method for synthesizing a diverse array of perfluoroalkylated amines, including N-heterocycles, to afford perfluoroalkylated chemical libraries as potential sources of drug candidates, agrochemicals, and probe molecules for chemical-biology research. Perfluoro acid anhydrides, which are commonly used in organic synthesis, were employed as a perfluoroalkyl source for intramolecular amino- and carbo-perfluoroalkylations of aminoalkenes, affording perfluoroalkylated N-heterocycles, including: aziridines, pyrrolidines, benzothiazinane dioxides, indolines, and hydroisoquinolinones...
October 20, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29052384/-research-progress-of-serum-pharmacochemistry-of-traditional-chinese-medicine
#16
REVIEW
Fei-Xiang Ma, Pei-Feng Xue, Yuan-Yuan Wang, Yi-Nuo Wang, Shu-Yuan Xue
Serum pharmacochemistry of traditional Chinese medicine(TCM) is an effective method to rapidly screen the effective substances and reveal the compatibility law of compound by identification and analysis of constituents migrating to blood after oral administration. In the last two decades, it has been universally accepted and widely applied in the field. With the cross-fusion with other disciplines, such as serum pharmacology, pharmacokinetics, metabolomics, network pharmacology and systems biology, serum pharmacochemistry shows comprehensive superiority in explaining drug changes in vivo and in vitro, interactions between drugs, interactions between drug and body, which coincides with the complexity of TCM compatibility, multi-components, multi-targets and multi-mechanisms...
April 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29052221/advance-in-physiologically-based-pharmacokinetic-modelling-from-the-organ-level-to-sub-organ-level-based-on-experimental-data
#17
Zhoumeng Lin
Understanding the pharmacokinetics and target organ dosimetry properties of small molecular drugs and large molecular biologics is essential in the design of proper therapeutic regimens for disease treatments. This article is protected by copyright. All rights reserved.
October 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29052220/efficacy-from-strange-sources
#18
Lawrence Lesko
Reverse translation (RT) refers to perceptions and observations of clinical outcomes, both beneficial and harmful, that can lead to a hypothesis intended to identify a new use of a drug that is different than the original use. I provide a panoramic view of successes in RT from the historic discovery of penicillin to the contemporary development of CAR T therapies. I delineate the core principles of RT that shift discovery from serendipity to a systematic strategy based on target identification based on causal biology, pharmacodynamic biomarkers that recapitulates disease pathophysiology, confirmation of target engagement by clinical proof of concept studies, and optimal selection of dose and interval...
October 20, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29052131/merkel-cell-polyomavirus-a-new-dna-virus-associated-with-human-cancer
#19
Margo MacDonald, Jianxin You
Merkel cell polyomavirus (MCPyV or MCV) is a novel human polyomavirus that has been discovered in Merkel cell carcinoma (MCC), a highly aggressive skin cancer. MCPyV infection is widespread in the general population. MCPyV-associated MCC is one of the most aggressive skin cancers, killing more patients than other well-known cancers such as cutaneous T-cell lymphoma and chronic myelogenous leukemia (CML). Currently, however, there is no effective drug for curing this cancer. The incidence of MCC has tripled over the past two decades...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29052093/emerging-small-molecule-approaches-to-enhance-the-antimyeloma-benefit-of-proteasome-inhibitors
#20
James J Driscoll, Magen Brailey
Multiple myeloma (MM) is a clonal plasma cell malignancy which, despite recent treatment advances, remains incurable in the vast majority of the over 118,000 patients in the USA afflicted with this disease. Treatment of MM has dramatically improved in the past decade with the introduction of new drugs into therapeutic strategies in both the frontline and relapse settings that has led to a significant improvement in the median overall survival (OS). These drugs have been incorporated into clinical guidelines and transformed the treatment approach to MM...
October 19, 2017: Cancer Metastasis Reviews
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