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https://www.readbyqxmd.com/read/28350451/ros-switchable-polymeric-nanoplatform-with-stimuli-responsive-release-for-active-targeted-drug-delivery-to-breast-cancer
#1
Yu Zhang, Qin Guo, Sai An, Yifei Lu, Jianfeng Li, Xi He, Lisha Liu, Yujie Zhang, Tao Sun, Chen Jiang
Tumor microenvironment plays a vital role in the process of tumor development, proliferation, invasion, and metastasis. It is well acknowledged that reduction in pH, reactive oxygen species (ROS), and increased level of glucose transporter 1 (GLUT1) have become featured intracellular and extracellular biochemical markers of cancer owing to oncogenic transformation and abnormal metabolism. To establish a distinctive drug delivery system directed against the tumor microenvironment features, we develop a newly engineered polymeric nanoplatform for efficient doxorubicin (DOX) delivery with reduced systemic toxicity and high antitumor efficiency...
March 28, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28350442/engineered-polymer-transferrin-conjugates-as-self-assembling-targeted-drug-delivery-systems
#2
Hiteshri Makwana, Francesca Mastrotto, Johannes Pall Magnusson, Darrell Sleep, Joanna Hay, Karl J Nicholls, Stephanie Allen, Cameron Alexander
Polymer-protein conjugates can be engineered to self-assemble into discrete and well-defined drug delivery systems which combine the advantages of receptor targeting and controlled drug release. We designed specific conjugates of the iron-binding and transport protein, transferrin (Tf), to combine the advantages of this serum-stable protein as a targeting agent for cancer cells with self-assembling polymers to act as carriers of cytotoxic drugs. Tf variants were expressed with cysteine residues at sites spanning different regions of the protein surface and the polymer conjugates grown from these variants were compared with polymer conjugates grown from non-selectively derivatised sites on native Tf...
March 28, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28346376/blend-hydrogel-microspheres-of-carboxymethyl-chitosan-and-gelatin-for-the-controlled-release-of-5-fluorouracil
#3
Vanarchi Rajini Kanth, Praveen B Kajjari, Priya M Madalageri, Sakey Ravindra, Lata S Manjeshwar, Tejraj M Aminabhavi
Carboxymethyl chitosan (CMCS) was synthesized and blended with gelatin (GE) to prepare hydrogel microspheres by w/o emulsion cross-linking in the presence of glutaraldehyde (GA), which acted as a cross-linker. 5-Fluorouracil (5-FU) was encapsulated to investigate its controlled release (CR) characteristics in acidic (pH 1.2) and alkaline (pH 7.4) buffer media. The microspheres which formed were spherical in nature, with smooth surfaces, as judged by the scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) confirmed the carboxymethylation of CS and the chemical stability of 5-FU in the formulations...
March 27, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28346059/deferasirox-pharmacogenetic-influence-on-pharmacokinetic-efficacy-and-toxicity-in-a-cohort-of-pediatric-patients
#4
Sarah Allegra, Silvia De Francia, Jessica Cusato, Arianna Arduino, Davide Massano, Filomena Longo, Antonio Piga, Antonio D'Avolio
AIM: We aimed to evaluate the influence of genetic polymorphisms involved in deferasirox metabolism and transport on its pharmacokinetics and treatment toxicity, in a cohort of β-thalassaemic children. PATIENTS & METHODS: Drug plasma concentrations were measured by a HPLC-UV method. Allelic discrimination for UGT1A1, UGT1A3, CYP1A1, CYP1A2, CYP2D6, MRP2 and BCRP1 polymorphisms was performed by real-time PCR. RESULTS: CYP1A1 rs2606345AA influenced Ctrough (p = 0...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28346018/antiretroviral-treatment-in-hiv-infected-children-who-require-a-rifamycin-containing-regimen-for-tuberculosis
#5
Helena Rabie, Eric H Decloedt, Anthony J Garcia-Prats, Mark F Cotton, Lisa Frigati, Marc Lallemant, Anneke Hesseling, H Simon Schaaf
In high prevalence settings, tuberculosis and HIV dual infection and co-treatment is frequent. Rifamycins, especially rifampicin, in combination with isoniazid, ethambutol and pyrazinamide are key components of short-course antituberculosis therapy. Areas covered: We reviewed available data, for which articles were identified by a Pubmed search, on rifamycin-antiretroviral interactions in HIV-infected children. Rifamycins have potent inducing effects on phase I and II drug metabolising enzymes and transporters...
March 27, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28345587/derivation-of-functional-human-astrocytes-from-cerebral-organoids
#6
Rômulo Sperduto Dezonne, Rafaela Costa Sartore, Juliana Minardi Nascimento, Verônica M Saia-Cereda, Luciana Ferreira Romão, Soniza Vieira Alves-Leon, Jorge Marcondes de Souza, Daniel Martins-de-Souza, Stevens Kastrup Rehen, Flávia Carvalho Alcantara Gomes
Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344977/chromatographic-studies-of-protein-based-chiral-separations
#7
Cong Bi, Xiwei Zheng, Shiden Azaria, Sandya Beeram, Zhao Li, David S Hage
The development of separation methods for the analysis and resolution of chiral drugs and solutes has been an area of ongoing interest in pharmaceutical research. The use of proteins as chiral binding agents in high-performance liquid chromatography (HPLC) has been an approach that has received particular attention in such work. This report provides an overview of proteins that have been used as binding agents to create chiral stationary phases (CSPs) and in the use of chromatographic methods to study these materials and protein-based chiral separations...
September 2016: Separations
https://www.readbyqxmd.com/read/28344832/in-silico-functional-elucidation-of-uncharacterized-proteins-of-chlamydia-abortus-strain-llg
#8
Gagandeep Singh, Dixit Sharma, Vikram Singh, Jyoti Rani, Francessco Marotta, Manoj Kumar, Gorakh Mal, Birbal Singh
AIM: This study reports structural modeling, molecular dynamics profiling of hypothetical proteins in Chlamydia abortus genome database. METHODOLOGY: The hypothetical protein sequences were extracted from C. abortus LLG Genome Database for functional elucidation using in silico methods. RESULTS: Fifty-one proteins with their roles in defense, binding and transporting other biomolecules were unraveled. Forty-five proteins were found to be nonhomologous to proteins present in hosts infected by C...
March 2017: Future Science OA
https://www.readbyqxmd.com/read/28344781/patient-specific-three-dimensional-explant-spheroids-derived-from-human-nasal-airway-epithelium-a-simple-methodological-approach-for-ex-vivo-studies-of-primary-ciliary-dyskinesia
#9
June Kehlet Marthin, Elizabeth Munkebjerg Stevens, Lars Allan Larsen, Søren Tvorup Christensen, Kim Gjerum Nielsen
BACKGROUND: Three-dimensional explant spheroid formation is an ex vivo technique previously used in studies of airway epithelial ion and water transport. Explanted cells and sheets of nasal epithelium form fully differentiated spheroids enclosing a partly fluid-filled lumen with the ciliated apical surface facing the outside and accessible for analysis of ciliary function. METHODS: We performed a two-group comparison study of ciliary beat pattern and ciliary beat frequency in spheroids derived from nasal airway epithelium in patients with primary ciliary dyskinesia (PCD) and in healthy controls...
2017: Cilia
https://www.readbyqxmd.com/read/28344492/cyp2c9-cypc19-and-cyp2d6-gene-profiles-and-gene-susceptibility-to-drug-response-and-toxicity-in-turkish-population
#10
Merve Arici, Gül Özhan
Pharmacogenetics is a vast field covering drug discovery research, the genetic basis of pharmacokinetics and dynamics, genetic testing and clinical management in diseases. Pharmacogenetic approach usually focuses on variations of drug transporters, drug targets, drug metabolizing enzymes and other biomarker genes. Cytochrome P450 (CYP) enzymes, an essential source of variability in drug-response, play role in not only phase I-dependent metabolism of xenobiotics but also metabolism of endogenous compounds such as steroids, vitamins and fatty acids...
March 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28344173/exploring-the-structure-permeation-relationship-of-topical-tricyclic-antidepressants-used-for-skin-analgesia
#11
Kuo-Sheng Liu, Tse-Hung Huang, Ibrahim A Aljuffali, En-Li Chen, Jhi-Joung Wang, Jia-You Fang
The purpose of this study was to evaluate the skin permeation of tricyclic antidepressants (TCAs) with propamine moiety to select candidates for the development of topical analgesics to treat cutaneous pain. We sought to establish the structure-permeation relationship (SPR) of topical TCAs. The lipophilicity, melting point, and aqueous solubility were determined to develop the physicochemical characterization. The TCA permeation into pig and nude mouse skins was estimated using Franz diffusion cell. TCAs and lidocaine were comparatively examined for cutaneous analgesia by pinprick assay...
March 23, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28344011/the-epidemiology-pathogenesis-transmission-diagnosis-and-management-of-multidrug-resistant-extensively-drug-resistant-and-incurable-tuberculosis
#12
REVIEW
Keertan Dheda, Tawanda Gumbo, Gary Maartens, Kelly E Dooley, Ruth McNerney, Megan Murray, Jennifer Furin, Edward A Nardell, Leslie London, Erica Lessem, Grant Theron, Paul van Helden, Stefan Niemann, Matthias Merker, David Dowdy, Annelies Van Rie, Gilman K H Siu, Jotam G Pasipanodya, Camilla Rodrigues, Taane G Clark, Frik A Sirgel, Aliasgar Esmail, Hsien-Ho Lin, Sachin R Atre, H Simon Schaaf, Kwok Chiu Chang, Christoph Lange, Payam Nahid, Zarir F Udwadia, C Robert Horsburgh, Gavin J Churchyard, Dick Menzies, Anneke C Hesseling, Eric Nuermberger, Helen McIlleron, Kevin P Fennelly, Eric Goemaere, Ernesto Jaramillo, Marcus Low, Carolina Morán Jara, Nesri Padayatchi, Robin M Warren
Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis)...
March 15, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28344002/establishment-of-a-human-blood-brain-barrier-co-culture-model-mimicking-the-neurovascular-unit-using-induced-pluri-and-multipotent-stem-cells
#13
Antje Appelt-Menzel, Alevtina Cubukova, Katharina Günther, Frank Edenhofer, Jörg Piontek, Gerd Krause, Tanja Stüber, Heike Walles, Winfried Neuhaus, Marco Metzger
In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm(2) and distinct upregulation of typical BBB genes...
March 22, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28343802/-the-effect-of-methylphenidate-on-appetite-and-weight
#14
R Bou Khalil, N Fares, Y Saliba, J Tamraz, S Richa
OBJECTIVES: To better delineate in the medical literature the effect of methylphenidate on weight and appetite. METHODS: A search on PubMed was carried out for articles published with no restrictions on language or year of publication using the terms: "methylphenidate"; "weight"; "appetite". RESULTS: Methylphenidate increases dopamine and noradrenaline in synapses because of its blockage of the transporters of these monoamines in the frontal cortex and insular lobe...
March 23, 2017: L'Encéphale
https://www.readbyqxmd.com/read/28343125/structural-modeling-of-human-organic-cation-transporters
#15
Tikam Chand Dakal, Rajender Kumar, Dindial Ramotar
Human organic cation transporters (hOCTs) belong to solute carriers (SLC) 22 family of membrane proteins that play a central role in transportation of chemotherapeutic drugs for several clinical and pathological conditions, including cancer and diabetes. These transporters mediate drug transport; however, the precise mechanism of drug-binding and transport by them is not fully uncovered yet, partly due to unavailability of any crystal structure record. In this work, we performed a multi-phasic approach to compute the 3D structural models of seven human organic cation transporters (hOCTs) starting from primary protein sequence...
March 18, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28342338/antidepressants-and-risk-of-cataract-development-a-population-based-nested-case-control-study
#16
Po-Han Chou, Che-Sheng Chu, Yi-Huei Chen, Min-Yen Hsu, Min-Wei Huang, Tsuo-Hung Lan, Ching-Heng Lin
BACKGROUND: Previous studies demonstrated increased risk of cataract development among users of selective serotonin reuptake inhibitors (SSRIs). However, it remains unknown whether this risk also prevails with the use of other types of antidepressants. The aim of this study was to investigate whether use of antidepressants is associated with an increased risk of cataract development. Moreover, the relationship between binding affinities of serotonin transporter (SERT) of antidepressant and the risk of cataracts is examined...
March 18, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28342321/improvement-of-paracellular-transport-in-the-caco-2-drug-screening-model-using-protein-engineered-substrates
#17
Rebecca L DiMarco, Daniel R Hunt, Ruby E Dewi, Sarah C Heilshorn
The Caco-2 assay has achieved wide popularity among pharmaceutical companies in the past two decades as an in vitro method for estimation of in vivo oral bioavailability of pharmaceutical compounds during preclinical characterization. Despite its popularity, this assay suffers from a severe underprediction of the transport of drugs which are absorbed paracellularly, that is, which pass through the cell-cell tight junctions of the absorptive cells of the small intestine. Here, we propose that simply replacing the collagen I matrix employed in the standard Caco-2 assay with an engineered matrix, we can control cell morphology and hence regulate the cell-cell junctions that dictate paracellular transport...
March 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28341944/discriminative-stimulus-effects-of-psychostimulants
#18
Michael D Berquist, William E Fantegrossi
Numerous drugs elicit locomotor stimulant effects at appropriate doses; however, we typically reserve the term psychostimulant to refer to drugs with affinity for monoamine reuptake transporters. This chapter comprises select experiments that have characterized the discriminative stimulus effects of psychostimulants using drug discrimination procedures. The substitution profiles of psychostimulants in laboratory rodents are generally consistent with those observed in human and nonhuman primate drug discrimination experiments...
March 25, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28340987/discovery-of-novel-curcumin-derivatives-targeting-xanthine-oxidase-and-urate-transporter-1-as-anti-hyperuricemic-agents
#19
Gui-Zhen Ao, Meng-Ze Zhou, Yu-Yao Li, Si-Ning Li, Hua-Nian Wang, Qian-Wen Wan, Huan-Qiu Li, Qing-Hua Hu
A series of curcumin derivatives as potent dual inhibitors of xanthine oxidase (XOD) and urate transporter 1 (URAT1) was discovered as anti-hyperuricemic agents. These compounds proved efficient effects on anti-hyperuricemic activity and uricosuric activity in vivo. More importantly, some of them exhibited proved efficient effects on inhibiting XOD activity and suppressing uptake of uric acid via URAT1 in vitro. Especially, the treatment of 4d was demonstrated to improve uric acid over-production and under-excretion in oxonate-induced hyperuricemic mice through regulating XOD activity and URAT1 expression...
January 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28340578/abcb1-and-abcg2-drug-transporters-are-differentially-expressed-in-non-small-cell-lung-cancers-nsclc-and-expression-is-modified-by-cisplatin-treatment-via-altered-wnt-signaling
#20
M Vesel, J Rapp, D Feller, E Kiss, L Jaromi, M Meggyes, G Miskei, B Duga, G Smuk, T Laszlo, I Karner, J E Pongracz
BACKGROUND: Lung cancer (LC) is still the most common cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all LC cases but is not a single entity. It is now accepted that, apart from the characteristic driver mutations, the unique molecular signatures of adeno- (AC) and squamous cell carcinomas (SCC), the two most common NSCLC subtypes should be taken into consideration for their management. Therapeutic interventions, however, frequently lead to chemotherapy resistance highlighting the need for in-depth analysis of regulatory mechanisms of multidrug resistance to increase therapeutic efficiency...
March 24, 2017: Respiratory Research
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