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https://www.readbyqxmd.com/read/28106996/evaluation-of-jatrophane-esters-from-euphorbia-spp-as-modulators-of-candida-albicans-multidrug-transporters
#1
Mélissa Esposito, Shweta Nim, Louis-Félix Nothias, Jean-François Gallard, Manpreet Kaur Rawal, Jean Costa, Fanny Roussi, Rajendra Prasad, Attilio Di Pietro, Julien Paolini, Marc Litaudon
Twenty-nine jatrophane esters (1-10, 12-30) and one lathyrane (11) diterpenoid ester isolated from Euphorbia species were evaluated for their capacity to inhibit drug-efflux activities of the primary ABC transporter CaCdr1p and the secondary MFS transporter CaMdr1p of Candida albicans, in yeast strains overexpressing the corresponding transporter. These diterpenoid esters were obtained from Euphorbia semiperfoliata (1-10), E. insularis (11), and E. dendroides (12-30) and included five new compounds, euphodendroidins P-T (26-30)...
January 20, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28106284/oxidative-stress-promotes-doxorubicin-induced-pgp-and-bcrp-expression-in-colon-cancer-cells-under-hypoxic-conditions
#2
Martha L Pinzón-Daza, Yenith Cuellar-Saenz, Francisco Nualart, Alejandro Ondo-Mendez, Lilia Del Riesgo, Fabio Castillo-Rivera, Ruth Garzón
P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) are ATP binding cassette (ABC) transporters that are overexpressed in different drug-resistant cancer cell lines. In this study, we investigated whether doxorubicin promotes Pgp and/or BCRP expression to induce drug resistance in colon cancer cells under hypoxic conditions. We analyzed HIF-1α activity via ELISA, Pgp and BCRP expression by qRT-PCR and the relationship between doxorubicin uptake and ABC transporter expression via confocal microscopy in HT-29WT and HT-29 doxorubicin-resistant colon cancer cells (HT-29DxR)...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106223/next-generation-of-network-medicine-interdisciplinary-signaling-approaches
#3
REVIEW
Tamas Korcsmaros, Maria Victoria Schneider, Giulio Superti-Furga
In the last decade, network approaches have transformed our understanding of biological systems. Network analyses and visualizations have allowed us to identify essential molecules and modules in biological systems, and improved our understanding of how changes in cellular processes can lead to complex diseases, such as cancer, infectious and neurodegenerative diseases. "Network medicine" involves unbiased large-scale network-based analyses of diverse data describing interactions between genes, diseases, phenotypes, drug targets, drug transport, drug side-effects, disease trajectories and more...
January 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28105986/canagliflozin-dapagliflozin-and-empagliflozin-monotherapy-for-treating-type-2-diabetes-systematic-review-and-economic-evaluation
#4
Rhona Johnston, Olalekan Uthman, Ewen Cummins, Christine Clar, Pamela Royle, Jill Colquitt, Bee Kang Tan, Andrew Clegg, Saran Shantikumar, Rachel Court, J Paul O'Hare, David McGrane, Tim Holt, Norman Waugh
BACKGROUND: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors...
January 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28105892/molecularly-imprinted-cryogel-membranes-for-mitomycin-c-delivery
#5
Pınar Öncel, Kemal Çetin, Aykut Arif Topçu, Handan Yavuz, Adil Denizli
In this study, cryogel-based implantable molecularly imprinted drug delivery systems were designed for the delivery of antineoplastic agent. Mitomycin C imprinted poly(2-hydroxyethyl methacrylate-N-methacryloyl-l-glutamic acid) cryogel membranes were produced by free-radical bulk polymerization under partially frozen conditions. The membranes were characterized by swelling tests, Fourier transform infrared spectroscopy, scanning electron microscopy, surface area measurements and in vitro hemocompatibility tests...
January 20, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28104361/igfbp-a-novel-target-of-lung-cancer
#6
REVIEW
QiongGe Hu, Yong Zhou, Kejing Ying, Wenjing Ruan
The insulin-like growth factor-1 receptor(IGF-1R) is a central component of lung cancer signal transduction pathways. A phase III study failed for carboplatin, paclitaxel, with or without figitumumab in first-line treating metastatic non-small cell lung cancer (NSCLC). There is an urgent need for a better understanding of signaling in IGF system. Insulin-like growth factor-binding proteins(IGFBPs) function as modulators for IGF signaling through sequestration of IGFs in serum and the extracellular fluid. IGFBPs can also act as transporters or modulators for IGF action and insulin action...
January 16, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28103195/the-enhancement-of-nasal-drug-absorption-from-powder-formulations-by-the-addition-of-sodium-carboxymethyl-cellulose
#7
Akiko Tanaka, Tomoyuki Furubayashi, Hitomi Yamasaki, Katsuko Takano, Mayuko Kawakami, Shunsuke Kimura, Daisuke Inoue, Hidemasa Katsumi, Toshiyasu Sakane, Akira Yamamoto
For nasal drug absorption, powder formulations can be expected to provide many advantages. The first aim of this study was to examine drug absorption following nasal administration of powder formulations in rats. Pharmaceutical excipients are typically added to most powder formulations. The second aim was to investigate the change in nasal drug absorption of powder formulations in the presence of sodium carboxymethyl cellulose (CMC-Na). Model drugs used were norfloxacin (NFX), warfarin (WF), and piroxicam (PXC)...
January 4, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28102869/design-considerations-to-minimize-the-impact-of-drug-absorption-in-polymer-based-organ-on-a-chip-platforms
#8
V S Shirure, S C George
Biocompatible polymers, such as polydimethylsiloxane (PDMS), are the materials of choice for creating organ-on-a-chip microfluidic platforms. Desirable qualities include ease of fabrication, optical clarity, and hydrophobicity, the latter of which facilitates oxygen transport to encased cells. An emerging and important application of organ-on-a-chip technology is drug discovery; however, a potential issue for polymer-based microfluidic devices has been highlighted by recent studies with PDMS, which have demonstrated absorption (and thus loss) of hydrophobic drugs into PDMS under certain experimental conditions...
January 19, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28102715/capsaicin-pretreatment-enhanced-the-bioavailability-of-fexofenadine-in-rats-by-p-glycoprotein-modulation-in-vitro-in-situ-and-in-vivo-evaluation
#9
Satish Kumar Bedada, Ramgopal Appani, Praveen Kumar Boga
BACKGROUND AND OBJECTIVE: Capsaicin is the main pungent principle present in chilli peppers has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro, which may have the potential to modulate bioavailability of P-gp substrates. Therefore, purpose of the present study was to evaluate the effect of capsaicin on intestinal absorption and bioavailability of fexofenadine, a P-gp substrate in rats. METHODS: The mechanistic evaluation was determined by non-everted sac and intestinal perfusion studies to explore the intestinal absorption of fexofenadine...
January 19, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28102676/novel-antitumor-platinum-ii-conjugates-containing-the-nonsteroidal-anti-inflammatory-agent-diclofenac-synthesis-and-dual-mechanisms-of-antiproliferative-effects
#10
Francesco Paolo Intini, Juraj Zajac, Vojtech Novohradsky, Teresa Saltarella, Concetta Pacifico, Viktor Brabec, Giovanni Natile, Jana Kasparkova
One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines...
January 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28102546/ataluren-and-similar-compounds-specific-therapies-for-premature-termination-codon-class-i-mutations-for-cystic-fibrosis
#11
REVIEW
Aisha A Aslam, Colin Higgins, Ian P Sinha, Kevin W Southern
BACKGROUND: Cystic fibrosis is a common life-shortening genetic disorder in the Caucasian population (less common in other ethnic groups) caused by the mutation of a single gene that codes for the production of the cystic fibrosis transmembrane conductance regulator protein. This protein coordinates the transport of salt (and bicarbonate) across cell surfaces and the mutation most notably affects the airways. In the lungs of people with cystic fibrosis, defective protein results in a dehydrated surface liquid and compromised mucociliary clearance...
January 19, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28101792/medical-management-of-diabesity-do-we-have-realistic-targets
#12
REVIEW
Joseph M Pappachan, Ananth K Viswanath
PURPOSE OF REVIEW: The global prevalence of "diabesity"-diabetes related to obesity-is increasing steadily over the past few decades because of the obesity epidemic. Although bariatric surgery is an effective treatment option for patients with diabesity, its limited availability, invasiveness, relatively high costs and the potential for surgical and postsurgical complications restrict its widespread use. Therefore, medical management is the only option for a majority of patients with diabesity...
January 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28101766/crossing-the-blood-brain-barrier-recent-advances-in-drug-delivery-to-the-brain
#13
Mayur M Patel, Bhoomika M Patel
CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting...
January 18, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28101456/overview-of-albumin-and-its-purification-methods
#14
REVIEW
Ramin Raoufinia, Ali Mota, Neda Keyhanvar, Fatemeh Safari, Sara Shamekhi, Jalal Abdolalizadeh
As the most frequent plasma protein, albumin constitutes more than 50% of the serum proteins in healthy individuals. It has a key role in oncotic pressure maintenance and it is known as a versatile protein carrier for transportation of various endogenous and exogenous ligands. Reduced amounts of albumin in the body will lead to different kinds of diseases such as hypovolemia and hypoproteinemia. It also has various indications in shocks, burns, cardiopulmonary bypass, acute liver failure and etc. Further applications in research consist of cell culture supplement, drug delivery carrier and protein/drug stabilizer...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28101198/elevated-expression-of-nrf2-mediates-multidrug-resistance-in-cd133-head-and-neck-squamous-cell-carcinoma-stem-cells
#15
Bao-Cai Lu, Jing Li, Wen-Fa Yu, Guo-Zheng Zhang, Hui-Min Wang, Hui-Min Ma
Enhanced expression of the ATP-binding cassette (ABC) transporter protein ABC sub-family G member 2 (ABCG2) in cancer stem cells (CSCs) plays a major role in chemotherapeutic drug efflux, which results in therapy failure and tumor relapse. In addition to downregulating apoptosis in CSCs, it has been reported that the transcriptional upregulation of the redox sensing factor Nrf2 is involved in the upregulation of ABCG2 expression and consequent chemoresistance. The current study investigated the presence of cancer stem-like side population (SP) cells from head and neck squamous cell carcinoma (HNSCC) samples, and evaluated the Nrf2 expression profile and multidrug resistance properties of HNSCC stem cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101166/hsp70-inducer-17-allylamino-demethoxygeldanamycin-provides-neuroprotection-via-anti-inflammatory-effects-in-a-rat-model-of-traumatic-brain-injury
#16
Youquan Gu, Jun Chen, Tianhong Wang, Chaoning Zhou, Zhaodong Liu, Lanhua Ma
Traumatic brain injury (TBI) is the predominant cause of mortality in young adults and children living in China. TBI induces inflammatory responses; in addition, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 are important pro-inflammatory cytokines. Considering the observation that Hsp-70 overexpression can exert neuroprotection, identifying a drug that is able to induce the upregulation of Hsp70 has the potential to be a promising therapy for the treatment of neurological diseases. Thus, the present study assessed the clinical effectiveness of an anticancer drug and Hsp70 activator, 17-allylamino-demethoxygeldanamycin (17-AAG), to evaluate its potential as a treatment for patients with TBI...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28099869/amitriptyline-down-regulates-coenzyme-q10-biosynthesis-in-lung-cancer-cells
#17
Tamara Ortiz, Marina Villanueva-Paz, Eduardo Díaz-Parrado, Matilde Illanes, Ana Fernández-Rodríguez, José A Sánchez-Alcázar, Manuel de Miguel
Amitriptyline, a tricyclic antidepressant, has been proposed as an antitumoral drug in oxidative therapy. Its pro-apoptotic effects, mediated by high reactive oxygen species generation, have been already described. In this study we analysed the effect of amitriptyline on the biosynthesis of coenzyme Q10 (CoQ), an essential component for electron transport and a potent membrane antioxidant involved in redox signaling. We treated H460 cells, a non-small-cell lung cancer cell line, with amitriptyline and we analyzed CoQ levels by HPLC and CoQ biosynthesis rate, as well as the enzymes involved in CoQ biosynthesis by real-time PCR and Western blot...
January 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28099756/levofloxacin-effect-on-erlotinib-absorption-evaluation-of-the-interaction-in-undernutrition-situations-through-population-pharmacokinetic-analysis-in-rats
#18
Alejandro Pérez Pitarch, Beatriz Guglieri-López, Amparo Nacher, Virginia Merino, Matilde Merino-Sanjuan
The main objective of this study was to develop a pharmacokinetic model in order to describe the intestinal absorption of erlotinib in rat and to quantify the interaction of levofloxacin on this process in well- and undernourished rats. Absorption studies were performed in male Wistar rats. Concentration-time profiles in proximal and distal intestine were analysed through non-linear mixed effect modelling using the NONMEM software version 7.3. Simulations were performed in order to explore the influence of covariates on apparent absorption rate constant...
January 18, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28099443/inhibition-of-human-drug-transporter-activities-by-the-pyrethroid-pesticides-allethrin-and-tetramethrin
#19
Lisa Chedik, Arnaud Bruyere, Marc Le Vee, Bruno Stieger, Claire Denizot, Yannick Parmentier, Sophie Potin, Olivier Fardel
Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells...
2017: PloS One
https://www.readbyqxmd.com/read/28099407/effects-of-functional-cyp2c8-cyp2c9-cyp3a5-and-abcb1-genetic-variants-on-the-pharmacokinetics-of-insulin-sensitizer-pioglitazone-in-chinese-han-individuals
#20
Sheng-Ju Yin, Hui-Min Qi, Xin Wang, Pu Zhang, Yuan Lu, Min-Ji Wei, Pu Li, Guang-Zhao Qi, Ya-Qing Lou, Chuang Lu, Guo-Liang Zhang
BACKGROUND AND OBJECTIVES: Pioglitazone is a thiazolidinedione antihyperglycemic drug with insulin-sensitizing properties. We investigated whether the variant genotypes of cytochrome P450 2C8 (CYP2C8), CYP2C9, CYP3A5 and transporter ABCB1 influence the pharmacokinetic phenotype of the substrate pioglitazone in Chinese individuals. PARTICIPANTS AND METHODS: Single-nucleotide polymorphisms were determined by the PCR-restriction fragment length polymorphism method in 244 (CYP2C8 and CYP2C9) healthy Chinese Han individuals...
January 17, 2017: Pharmacogenetics and Genomics
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