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https://www.readbyqxmd.com/read/29933103/human-oatp1b1-slco1b1-transports-sulfated-bile-acids-and-bile-salts-with-particular-efficiency
#1
Beáta Tóth, Márton Jani, Erzsébet Beéry, Teresa Heslop, Mark Bayliss, Neil R Kitteringham, B Kevin Park, Richard J Weaver, Peter Krajcsi
Human OATP1B1 is highly expressed at the basolateral membrane of the hepatocyte. It plays an important role in the sodium-independent transport of bile acids and bile salts and contributes to the systemic clearance of many drugs. In this study, the interaction of at least one representative of all major chemical classes of bile acids and bile salts, which include the bile acid chenodeoxycholate (CDC), monovalent (amidated) bile salts glycochenodeoxycholate (GCDC), taurochenodeoxycholate (TCDC) and taurocholate (TC), a sulfated bile acid 3-sulfo-chenodeoxycholate (3S-CDC) and a divalent (amidated and sulfated) bile salt 3-sulfo-glycolithocholate (3S-GLC) were tested with OATP1B1 overexpressed in HEK293 cells...
June 19, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29933101/annealing-novel-nucleobase-lipids-with-oligonucleotides-or-plasmid-dna-based-on-h-bonding-or-%C3%AF-%C3%AF-interaction-assemblies-and-transfections
#2
Yuan Ma, Yuejie Zhu, Chao Wang, Delin Pan, Shuang Liu, Mengyi Yang, Zhangping Xiao, Xiantao Yang, Wenting Zhao, Xinyang Zhou, Yiding Li, Yufei Pan, Jing Sun, Shuhe Wang, Zhu Guan, Lihe Zhang, Zhenjun Yang
Lipid derivatives of nucleoside analogs have been highlighted for their potential for effective gene delivery. A novel class of nucleobase-lipids are rationally designed and readily synthesized, comprising thymine/cytosine, an ester/amide linker and an oleyl lipid. The diversity of four nucleobase-lipids termed DXBAs (DOTA, DNTA, DOCA and DNCA) is investigated. Besides, DNCA is demonstrated to be an effective neutral transfection material for nucleic acid delivery, which enbles to bind to oligonucleotides via H-bonding and π-π stacking with reduced toxicity in vitro and in vivo...
June 14, 2018: Biomaterials
https://www.readbyqxmd.com/read/29933060/systematic-modifications-of-amino-acid-based-organogelators-for-the-investigation-of-structure-property-correlations-in-drug-delivery-system
#3
Beibei Hu, Wei Sun, Haiting Li, Helin Sui, Sanming Li
Thermogels, used as multi-functional drug-loading materials, have properties that mainly rely on their gelator structure. Although a large variety of organogel systems are used as drug delivery carriers, relatively few have been investigated in terms of their structure-property correlations based on amino acid derivative gelators. Here, a series of amino acid based gelators were synthesized to explore the role of the gelator structure on functional properties, with the aim of establishing a connection between the molecular parameters and gel properties...
June 19, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29933016/potential-therapeutic-applications-of-the-genus-annona-local-and-traditional-uses-and-pharmacology
#4
REVIEW
A M Quílez, M A Fernández-Arche, M D García-Giménez, R De la Puerta
ETHNO-PHARMACOLOGICAL RELEVANCE: Annona species (Annonaceae) have long been used as traditional herbal medicines by native peoples in tropical areas. In different countries they are used against a large variety of illnesses, such as parasitic and infectious diseases, cancer, diabetes, peptic ulcers, and mental disorders. AIM OF THE STUDY: This review aims to achieve a comprehensive understanding of the research conducted so far on the local and traditional uses, pharmacological activities, mechanism of actions of active compounds, toxicity, and possible interactions with other drugs of the Annona species...
June 19, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29932943/synthetic-lethal-networks-for-precision-oncology-promises-and-pitfalls
#5
REVIEW
John Paul Shen, Trey Ideker
Synthetic lethal interactions, in which the simultaneous loss-of-function of two genes produces a lethal phenotype, are being explored as a means to therapeutically exploit cancer-specific vulnerabilities and expand the scope of precision oncology. Currently, three FDA approved drugs work by targeting the synthetic lethal interaction between BRCA1/2 and PARP. This review examines additional efforts to discover networks of synthetic lethal interactions and discusses both challenges and opportunities regarding the translation of new synthetic lethal interactions into the clinic...
June 19, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29932942/ccr5-revisited-how-mechanisms-of-hiv-entry-govern-aids-pathogenesis
#6
REVIEW
Anne Brelot, Lisa A Chakrabarti
The chemokine receptor CCR5 has been the focus of intensive studies since its role as a coreceptor for HIV entry was discovered in 1996. These studies lead to the development of small molecular drugs targeting CCR5, with maraviroc becoming in 2007 the first clinically approved chemokine receptor inhibitor. More recently, the apparent HIV cure in a patient transplanted with hematopoietic stem cells devoid of functional CCR5 rekindled the interest for inactivating CCR5 through gene therapy and pharmacological approaches...
June 19, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29932793/the-intranasal-gels-of-box-behnken-experimental-design-for-preparation-and-optimization-of-selegiline-hydrochloride
#7
Sara Salatin, M Alami-Milani, R Daneshgar, M Jelvehgari
Selegiline hydrochloride (SL) is chosen as an adjunct for the control of clinical signs of Parkinsonian patients. The aim of the present work is to develop and optimize thermosensitive gels using Pluronic (F-127) for enhancing transport of SL into the brain through the nasal route. SL gels were prepared using a cold method and the Box-Behnken experimental design methodology. Drug (SL), gelling agent (F-127) and emulsifier (Propylene glycol, PG) were selected as independent variables while the gelation temperature, gel strength, pH, gel content, and gel erosion were considered as dependent variables...
June 22, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29932660/interactions-of-artefenomel-oz-439-with-milk-during-digestion-insights-into-digestion-driven-solubilization-and-polymorphic-transformations
#8
Malinda Salim, Jamal Khan, Gisela Ramirez, Andrew J Clulow, Adrian Hawley, Hanu Ramachandruni, Ben J Boyd
Milk has been used as a vehicle for the delivery of antimalarial drugs during clinical trials to test for a food effect and artefenomel (OZ439) showed enhanced oral bioavailability with milk. However, the nature of the interaction between milk and OZ439 in the gastrointestinal tract remains poorly understood. To understand the role of milk digestion on the solubilization of OZ439 and polymorphism, we conducted real-time monitoring of crystalline drug in suspension during in vitro intestinal lipolysis of milk containing OZ439 using synchrotron X-ray scattering...
June 22, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29932649/genetically-engineered-mucoadhesive-spider-silk
#9
Georgia Petrou, Ronnie Jansson, Mark Högqvist, Johan Erlandsson, Lars Wågberg, My Hedhammar, Thomas Crouzier
Mucoadhesion is defined as the adhesion of a material to the mucus gel covering the mucous membranes. The mechanisms controlling mucoadhesion include nonspecific electrostatic interactions and specific interactions between the materials and the mucins, the heavily glycosylated proteins that form the mucus gel. Mucoadhesive materials can be used to develop mucosal wound dressings, and noninvasive transmucosal drug delivery systems. Spider silk, which is strong, biocompatible, biodegradable, nontoxic and lightweight would serve as an excellent base for the development of such materials...
June 22, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29932455/mobile-phone-based-interventions-for-improving-adherence-to-medication-prescribed-for-the-primary-prevention-of-cardiovascular-disease-in-adults
#10
REVIEW
Melissa J Palmer, Sharmani Barnard, Pablo Perel, Caroline Free
BACKGROUND: Cardiovascular disease (CVD) is a major cause of disability and mortality globally. Premature fatal and non-fatal CVD is considered to be largely preventable through the control of risk factors via lifestyle modifications and preventive medication. Lipid-lowering and antihypertensive drug therapies for primary prevention are cost-effective in reducing CVD morbidity and mortality among high-risk people and are recommended by international guidelines. However, adherence to medication prescribed for the prevention of CVD can be poor...
June 22, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29932320/self-regulated-carboxyphenylboronic-acid-modified-mesoporous-silica-nanoparticles-with-touch-switch-releasing-property-for-insulin-delivery
#11
Lin Hou, Yazhen Zheng, Yongchao Wang, Yurong Hu, Jinjin Shi, Qi Liu, Huijuan Zhang, Zhenzhong Zhang
Glucose-responsive insulin delivery systems, which can maintain a stable level of blood glucose, have been proposed as a promising method to treat diabetes. Such systems can reduce potential toxicity and enhance patient compliance compared to traditional therapies. Accordingly, we designed a mesoporous silica nanoparticle (MSN)-based glucose-sensitive and self-regulated drug release system to achieve the goal of long circulation and "touch switch" in vivo. In this system, carboxyphenylboronic acid (CPBA) was first modified on the surface of MSN using amidation reaction...
June 22, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29932300/potential-issues-with-complementary-medicines-commonly-used-in-the-cancer-population-a-retrospective-review-of-a-tertiary-cancer-center-s-experience
#12
Sally L Brooks, Gail Rowan, Michael Michael
AIM: Complementary medicine (CAM) use in the cancer population is higher than the general population: some studies estimate up to 70%. Our Medicines Information Centre, in a tertiary cancer institution, receives many enquiries regarding use and safety of CAM with conventional cancer therapies (chemotherapy, radiotherapy and surgery). This project aims to review the CAM most commonly enquired about with an emphasis on potential interactions with conventional cancer therapies. METHODS: An audit and review of CAM enquiries from patients or medical professionals at our center, over a 2-year period (July 2011-June 2013), was conducted...
June 22, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29932108/proximal-pathway-enrichment-analysis-for-targeting-comorbid-diseases-via-network-endopharmacology
#13
Joaquim Aguirre-Plans, Janet Piñero, Jörg Menche, Ferran Sanz, Laura I Furlong, Harald H H W Schmidt, Baldo Oliva, Emre Guney
The past decades have witnessed a paradigm shift from the traditional drug discovery shaped around the idea of “one target, one disease” to polypharmacology (multiple targets, one disease). Given the lack of clear-cut boundaries across disease (endo)phenotypes and genetic heterogeneity across patients, a natural extension to the current polypharmacology paradigm is to target common biological pathways involved in diseases via endopharmacology (multiple targets, multiple diseases). In this study, we present proximal pathway enrichment analysis (PxEA) for pinpointing drugs that target common disease pathways towards network endopharmacology...
June 22, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29931471/comparisons-of-analysis-methods-for-assessment-of-pharmacodynamic-interactions-including-design-recommendations
#14
Chunli Chen, Sebastian G Wicha, Rikard Nordgren, Ulrika S H Simonsson
Quantitative evaluation of potential pharmacodynamic (PD) interactions is important in tuberculosis drug development in order to optimize Phase 2b drug selection and ultimately to define clinical combination regimens. In this work, we used simulations to (1) evaluate different analysis methods for detecting PD interactions between two hypothetical anti-tubercular drugs in in vitro time-kill experiments, and (2) provide design recommendations for evaluation of PD interactions. The model used for all simulations was the Multistate Tuberculosis Pharmacometric (MTP) model linked to the General Pharmacodynamic Interaction (GPDI) model...
June 21, 2018: AAPS Journal
https://www.readbyqxmd.com/read/29931468/young-drug-users-a-vulnerable-population-and-an-underutilized-resource-in-hiv-hcv-prevention
#15
REVIEW
Pedro Mateu-Gelabert, H Guarino, K Quinn, P Meylakhs, S Campos, A Meylakhs, D Berbesi, D Toro-Tobón, E Goodbody, D C Ompad, S R Friedman
PURPOSE OF REVIEW: The social networks of people who inject drugs (PWID) have long been studied to understand disease transmission dynamics and social influences on risky practices. We illustrate how PWID can be active agents promoting HIV, HCV, and overdose prevention. RECENT FINDINGS: We assessed drug users' connections and interactions with others at risk for HIV/HCV in three cities: New York City (NYC), USA (n = 539); Pereira, Colombia (n = 50); and St...
June 22, 2018: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/29931259/escherichia-coli-itat-is-a-type-ii-toxin-that-inhibits-translation-by-acetylating-isoleucyl-trnaile
#16
Brendan Wilcox, Ilya Osterman, Marina Serebryakova, Dmitry Lukyanov, Ekaterina Komarova, Bridget Gollan, Natalia Morozova, Yuri I Wolf, Kira S Makarova, Sophie Helaine, Petr Sergiev, Svetlana Dubiley, Sergei Borukhov, Konstantin Severinov
Prokaryotic toxin-antitoxin (TA) modules are highly abundant and are involved in stress response and drug tolerance. The most common type II TA modules consist of two interacting proteins. The type II toxins are diverse enzymes targeting various essential intracellular targets. The antitoxin binds to cognate toxin and inhibits its function. Recently, TA modules whose toxins are GNAT-family acetyltransferases were described. For two such systems, the target of acetylation was shown to be aminoacyl-tRNA: the TacT toxin targets aminoacylated elongator tRNAs, while AtaT targets the amino acid moiety of initiating tRNAMet...
June 21, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29931010/in-vitro-ftir-microspectroscopy-analysis-of-primary-oral-squamous-carcinoma-cells-treated-with-cisplatin-and-5-fluorouracil-a-new-spectroscopic-approach-for-studying-the-drug-cell-interaction
#17
Elisabetta Giorgini, Simona Sabbatini, Romina Rocchetti, Valentina Notarstefano, Corrado Rubini, Carla Conti, Giulia Orilisi, Elisa Mitri, Diana E Bedolla, Lisa Vaccari
In the present study, human primary oral squamous carcinoma cells treated with cisplatin and 5-fluorouracil were analyzed, for the first time, by in vitro FTIR Microspectroscopy (FTIRM), to improve the knowledge on the biochemical pathways activated by these two chemotherapy drugs. To date, most of the studies regarding FTIRM cellular analysis have been executed on fixed cells from immortalized cell lines. FTIRM analysis performed on primary tumor cells under controlled hydrated conditions provides more reliable information on the biochemical processes occurring in in vivo tumor cells...
June 22, 2018: Analyst
https://www.readbyqxmd.com/read/29931001/computational-simulations-determining-disulfonic-stilbene-derivative-bioavailability-within-human-serum-albumin
#18
Titouan Jaunet-Lahary, Daniel P Vercauteren, Fabrice Fleury, Adèle D Laurent
Disulfonic stilbene (DS) derivatives are a member of the large family of compounds widely employed in medicine and biology as modulators for membrane transporters or inhibitors of a protein involved in DNA repair. They constitute interesting compounds that have not yet been investigated within the bioavailability framework. No crystallographic structures exist involving such compounds embedded in the most common drug carrier, human serum albumin (HSA). The present work studies, for the first time, the physico-chemical features driving the inclusion of three DS derivatives (amino, nitro and acetamido, named DADS, DNDS and DATDS, respectively) within the four common HSA binding sites using combined molecular docking and molecular dynamics simulations...
June 22, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29930947/heparin-oligosaccharides-have-antiarrhythmic-effect-by-accelerating-the-sodium-calcium-exchanger
#19
Carlos M G de Godoy, Ênio R Vasques, Afonso Caricati-Neto, José G P Tavares, Beatriz J Alves, Juliana Duarte, Regiane Miranda-Ferreira, Marcelo A Lima, Helena B Nader, Ivarne L Dos Santos Tersariol
Background: Blockage of the Na+ /Ca2+ exchanger (NCX) is used to determine the role of NCX in arrhythmogenesis. Trisulfated heparin disaccharide (TD) and Low Molecular Weight Heparins (LMWHs) can directly interact with the NCX and accelerate its activity. Objective: In this work, we investigated the antiarrhythmic effect of heparin oligosaccharides related to the NCX activity. Methods: The effects of heparin oligosaccharides were tested on the NCX current (patch clamping) and intracellular calcium transient in rat cardiomyocytes...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29930804/potential-candidate-treatment-agents-for-targeting-of-cholangiocarcinoma-identified-by-gene-expression-profile-analysis
#20
Suthipong Chujan, Tawit Suriyo, Teerapat Ungtrakul, Yotsawat Pomyen, Jutamaad Satayavivad
Cholangiocarcinoma (CCA) remains to be a major health problem in several Asian countries including Thailand. The molecular mechanism of CCA is poorly understood. Early diagnosis is difficult, and at present, no effective therapeutic drug is available. The present study aimed to identify the molecular mechanism of CCA by gene expression profile analysis and to search for current approved drugs which may interact with the upregulated genes in CCA. Gene Expression Omnibus (GEO) was used to analyze the gene expression profiles of CCA patients and normal subjects...
July 2018: Biomedical Reports
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