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https://www.readbyqxmd.com/read/28231454/zinc-complexes-of-diflunisal-synthesis-characterization-structure-antioxidant-activity-and-in-vitro-and-in-silico-study-of-the-interaction-with-dna-and-albumins
#1
Alketa Tarushi, Chrisoula Kakoulidou, Catherine P Raptopoulou, Vassilis Psycharis, Dimitris P Kessissoglou, Ioanna Zoi, Athanasios N Papadopoulos, George Psomas
From the reaction of ZnCl2 with the non-steroidal anti-inflammatory drug diflunisal (Hdifl), complex [Zn(difl-O)2(MeOH)4], 1 was formed, while in the presence of a N,N'-donor heterocyclic ligand 2,2'-bipyridylamine (bipyam), 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) and 2,2'-dipyridylketone oxime (Hpko), the complexes [Zn(difl-O,O')2(bipyam)], 2, [Zn(difl-O,O')2(bipy)], 3, [Zn(difl-O,O')2(phen)], 4 and [Zn(difl-O)2(Hpko)2], 5 were isolated, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 2, 3 and 5 were determined by X-ray crystallography...
February 12, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28231439/the-rights-of-drug-treatment-patients-experience-of-addiction-treatment-in-poland-from-a-human-rights-perspective
#2
Justyna Klingemann
BACKGROUND: Drug dependence is a recognized medical condition and therefore, right to health applies in the same way to drug dependence as it does to any other health condition. The human rights in patient care framework - which refers to the application of basic human rights principles in the delivery of health care services - was used to explore the experiences of equality in the dignity and rights protected by Polish law within four different specialist drug treatment settings in Poland...
February 20, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28231414/mir-135a-3p-as-a-promising-biomarker-and-nucleic-acid-therapeutic-agent-for-ovarian-cancer
#3
Satoshi Fukagawa, Kohei Miyata, Fusanori Yotsumoto, Chihiro Kiyoshima, Sung Ouk Nam, Haruchika Anan, Takahiro Katsuda, Daisuke Miyahara, Masaharu Murata, Hiroshi Yagi, Kyoko Shirota, Shin'ichiro Yasunaga, Kiyoko Kato, Shingo Miyamoto
Ovarian cancer is the most lethal gynecologic malignancy. Recently, several molecularly targeted anticancer agents have been developed for ovarian cancer; however, its prognosis has remained extremely poor. The development of molecularly targeted therapy, as well as companion diagnostics, is required to improve outcomes for patients with ovarian cancer. In this study, to identify microRNAs involved in the progression of ovarian cancer we analyzed serum microRNAs in patients with ovarian cancer using microRNA array and qRT-PCR and examined the anticancer properties of microRNA expression in ovarian cancer cells...
February 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28231291/osteosarcoma-cell-proliferation-and-survival-requires-mglur5-receptor-activity-and-is-blocked-by-riluzole
#4
Sally Liao, Yuleisy Ruiz, Hira Gulzar, Zarina Yelskaya, Lyes Ait Taouit, Murielle Houssou, Trisha Jaikaran, Yuriy Schvarts, Kristina Kozlitina, Upal Basu-Roy, Alka Mansukhani, Shahana S Mahajan
Osteosarcomas are malignant tumors of bone, most commonly seen in children and adolescents. Despite advances in modern medicine, the poor survival rate of metastatic osteosarcoma has not improved in two decades. In the present study we have investigated the effect of Riluzole on a human and mouse metastatic osteosarcoma cells. We show that LM7 cells secrete glutamate in the media and that mGluR5 receptors are required for the proliferation of LM7 cells. Riluzole, which is known to inhibit glutamate release, inhibits proliferation, induces apoptosis and prevents migration of LM7 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28231276/alterations-in-cellular-pharmacokinetics-and-pharmacodynamics-of-elvitegravir-in-response-to-ethanol-exposure-in-hiv-1-infected-monocytic-u1-cells
#5
Narasimha M Midde, Namita Sinha, Pradeep B Lukka, Bernd Meibohm, Santosh Kumar
Ethanol consumption is negatively associated with antiretroviral therapy (ART) adherence and general health in HIV positive individuals. Previously, we demonstrated ethanol-mediated alterations to metabolism of elvitegravir (EVG) in human liver microsomes. In the current study, we investigated ethanol influence on the pharmacokinetic and pharmacodynamic interactions of EVG in HIV infected monocytic (U1) cells. U1 cells were treated with 5 μM EVG, 2 μM Cobicistat (COBI), a booster drug, and 20 mM ethanol for up to 24 hours...
2017: PloS One
https://www.readbyqxmd.com/read/28231062/relationship-between-metabolic-phenotypes-and-genotypes-of-cyp1a2-and-cyp2a6-in-the-nigerian-population
#6
Ayorinde Adehin, Oluseye O Bolaji, Simran Maggo, Martin A Kennedy
BACKGROUND: CYP1A2 and CYP2A6 are polymorphic drug-metabolising enzymes that are also implicated in the activation of procarcinogens in humans. Some of their alleles and haplotypes, often varied in prevalence across populations, are thought to influence activity despite the known contribution of environmental factors. This study assessed the potential influence of some genetic variants of CYP1A2 and CYP2A6 on metabolic phenotypes in Nigerians. METHODS: Genomic DNA was extracted from blood samples of 100 healthy, unrelated subjects for whom CYP1A2 and CYP2A6 phenotypes had previously been determined, alongside an additional 80 other individuals for whom phenotype data were unavailable...
February 23, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28231034/upscaling-of-hips-cell-derived-neurons-for-high-throughput-screening
#7
Stefanie Traub, Heiko Stahl, Holger Rosenbrock, Eric Simon, Ralf Heilker
The advent of human-induced pluripotent stem (hiPS) cell-derived neurons promised to provide better model cells for drug discovery in the context of the central nervous system. This work demonstrates both the upscaling of cellular expansion and the acceleration of neuronal differentiation to accommodate the immense material needs of a high-throughput screening (HTS) approach. Using GRowth factor-driven expansion and INhibition of NotCH (GRINCH) during maturation, the derived cells are here referred to as GRINCH neurons...
March 2017: SLAS Discov
https://www.readbyqxmd.com/read/28230985/discovery-of-competitive-and-non-competitive-ligands-of-the-organic-cation-transporter-1-oct1-slc22a1
#8
Eugene C Chen, Natalia Khuri, Xiaomin Liang, Adrian Stecula, Huan-Chieh Chien, Sook Wah Yee, Yong Huang, Andrej Sali, Kathleen M Giacomini
Organic cation transporter 1 (OCT1) plays a critical role in the hepatocellular uptake of structurally diverse endogenous compounds and xenobiotics. Here, we identified competitive and noncompetitive OCT1 interacting ligands in a library of 1,780 prescription drugs by combining in silico and in vitro methods. Ligands were predicted by docking against a comparative model based a eukaryotic homolog. In parallel, high-throughput screening (HTS) was conducted using the fluorescent probe substrate ASP+ in cells overexpressing human OCT1...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230790/influence-of-chitosan-swelling-behaviour-on-controlled-release-of-tenofovir-from-mucoadhesive-vaginal-systems-for-prevention-of-sexual-transmission-of-hiv
#9
Fernando Notario-Pérez, Araceli Martín-Illana, Raúl Cazorla-Luna, Roberto Ruiz-Caro, Luis-Miguel Bedoya, Aitana Tamayo, Juan Rubio, María-Dolores Veiga
The main challenges facing efforts to prevent the transmission of human immunodeficiency virus (HIV) are the lack of access to sexual education services and sexual violence against young women and girls. Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Vaginal mucoadhesive tablets can be developed by including natural polymers that have good binding capacity with mucosal tissues, such as chitosan or guar gum, semisynthetic polymers such as hydroxypropylmethyl cellulose, or synthetic polymers such as Eudragit(®) RS...
February 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28230778/caffeic-acid-expands-anti-tumor-effect-of-metformin-in-human-metastatic-cervical-carcinoma-htb-34-cells-implications-of-ampk-activation-and-impairment-of-fatty-acids-de-novo-biosynthesis
#10
Malgorzata Tyszka-Czochara, Pawel Konieczny, Marcin Majka
The efficacy of cancer treatments is often limited and associated with substantial toxicity. Appropriate combination of drug targeting specific mechanisms may regulate metabolism of tumor cells to reduce cancer cell growth and to improve survival. Therefore, we investigated the effects of anti-diabetic drug Metformin (Met) and a natural compound caffeic acid (trans-3,4-dihydroxycinnamic acid, CA) alone and in combination to treat an aggressive metastatic human cervical HTB-34 (ATCC CRL-1550) cancer cell line...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230762/the-development-of-ck2-inhibitors-from-traditional-pharmacology-to-in-silico-rational-drug-design
#11
REVIEW
Giorgio Cozza
Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by "trial and error testing". In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range...
February 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28230534/knockdown-of-antiapoptotic-genes-in-breast-cancer-cells-by-sirna-loaded-into-hybrid-nanoparticles
#12
Leônidas Mello Júnior, Gabriela Rosa E Souza, Evelyn Winter, Adny Henrique Silva, Frederico Pittella, Tânia Beatriz Creczynski-Pasa
Tumorigenesis is related to an imbalance in controlling mechanisms of apoptosis. Expression of the genes BCL-2 and BCL-xL results in promotion of cell survival by inhibiting apoptosis. Thus, a novel approach to suppress antiapoptotic genes is the use of small interfering RNA (siRNA) in cancer cells. However, there are some limitations for the application of siRNA such as low bioavailability, requiring vectors as a strategy to achieve the nucleic acid transfection. In this study formulations containing CaP-siRNA-PEG-polyanion hybrid nanoparticles were developed to enhance siRNA delivery to cultured human breast cancer cells (MCF-7) in order to evaluate if the silencing of antiapoptotic genes BCL-2 and BCL-xL by siRNA would succeed in increasing cancer cells death...
February 23, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28230062/triple-combination-therapy-in-the-treatment-of-hypertension-a-review-of-the-evidence
#13
REVIEW
R Düsing, B Waeber, M Destro, C Santos Maia, P Brunel
Hypertension is a serious public health concern with inadequate control of blood pressure (BP) worldwide. Contributing factors include low efficacy of drugs, underuse of combination therapies, irrational combinations, physicians' therapeutic inertia and poor adherence to treatment. Current guidelines recommend the use of initial (dual) combination therapy in high-risk patients for immediate BP response, better short- and long-term BP control, and continued/improved patient adherence. This article aims to review the existing evidence of triple-combination therapies with respect to efficacy, safety and adherence to treatment...
February 23, 2017: Journal of Human Hypertension
https://www.readbyqxmd.com/read/28230059/synergistic-effects-of-dimethyloxallyl-glycine-and-recombinant-human-bone-morphogenetic-protein-2-on-repair-of-critical-sized-bone-defects-in-rats
#14
Xin Qi, Yang Liu, Zhen-Yu Ding, Jia-Qing Cao, Jing-Huan Huang, Jie-Yuan Zhang, Wei-Tao Jia, Jing Wang, Chang-Sheng Liu, Xiao-Lin Li
In bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230005/current-mechanism-of-acquired-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-and-updated-therapy-strategies-in-human-nonsmall-cell-lung-cancer
#15
REVIEW
Kaixian Zhang, Qianqian Yuan
Lung cancer continues to be a major health problem and the most common cancer-related mortality worldwide with about 80%-85% patients suffering from nonsmall cell lung cancer (NSCLC). More than 80% of NSCLC cases are often diagnosed as advanced stage and harbor epidermal growth factor receptor (EGFR) activating mutation. Although great success in initial response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are found in EGFR-mutant NSCLC patients, acquired resistance usually occurs on the continuous treatment...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28229982/circulating-free-dna-mutation-associated-with-response-of-targeted-therapy-in-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer
#16
Qing Ye, Fan Qi, Li Bian, Shao-Hua Zhang, Tao Wang, Ze-Fei Jiang
BACKGROUND: The addition of anti-human epidermal growth factor receptor 2 (HER2)-targeted drugs, such as trastuzumab, lapatinib, and trastuzumab emtansine (T-DM1), to chemotherapy significantly improved prognosis of HER2-positive breast cancer patients. However, it was confused that metastatic patients vary in the response of targeted drug. Therefore, methods of accurately predicting drug response were really needed. To overcome the spatial and temporal limitations of biopsies, we aimed to develop a more sensitive and less invasive method of detecting mutations associated with anti-HER2 therapeutic response through circulating-free DNA (cfDNA)...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28229909/paradoxical-inhibition-of-glycolysis-by-pioglitazone-opposes-the-mitochondriopathy-caused-by-aif-deficiency
#17
Paule Bénit, Alice Pelhaître, Elise Saunier, Sylvie Bortoli, Assetou Coulibaly, Malgorzata Rak, Manuel Schiff, Guido Kroemer, Massimo Zeviani, Pierre Rustin
Mice with the hypomorphic AIF-Harlequin mutation exhibit a highly heterogeneous mitochondriopathy that mostly affects respiratory chain complex I, causing a cerebral pathology that resembles that found in patients with AIF loss-of-function mutations. Here we describe that the antidiabetic drug pioglitazone (PIO) can improve the phenotype of a mouse Harlequin (Hq) subgroup, presumably due to an inhibition of glycolysis that causes an increase in blood glucose levels. This glycolysis-inhibitory PIO effect was observed in cultured astrocytes from Hq mice, as well as in human skin fibroblasts from patients with AIF mutation...
February 16, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28229907/expression-and-functional-evaluation-of-biopharmaceuticals-made-in-plant-chloroplasts
#18
REVIEW
Bei Zhang, Balamurugan Shanmugaraj, Henry Daniell
After approval of the first plant-made biopharmaceutical by FDA for human use, many protein drugs are now in clinical development. Within the last decade, significant advances have been made in expression of heterologous complex/large proteins in chloroplasts of edible plants using codon optimized human or viral genes. Furthermore, advances in quantification enable determination of in-planta drug dosage. Oral delivery of plastid-made biopharmaceuticals (PMB) is affordable because it eliminates prohibitively expensive fermentation, purification processes addressing major challenges of short shelf-life after cold storage...
February 21, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28229586/chlorhexidine-loaded-amorphous-calcium-phosphate-nanoparticles-for-inhibiting-degradation-and-inducing-mineralization-of-type-i-collagen
#19
Xue Cai, Bing Han, Yan Liu, Fucong Tian, Fuxin Liang, Xiaoyan Wang
A major shortcoming of contemporary dentin adhesives is their limited durability. Exposed collagen fibrils within the bonding interface are degraded by matrix metalloproteinases (MMPs), resulting in aging of the resin-dentin bond. In this study, chlorhexidine-loaded amorphous calcium phosphate (ACP) nanoparticles were synthesized to induce the mineralization of collagen fibrils. The nanoparticles sustainably released chlorhexidine, to inhibit MMPs during mineralization. Three types of ACP nanoparticles were prepared: N-ACP containing no chlorhexidine, C-ACP containing chlorhexidine acetate, and G-ACP containing chlorhexidine gluconate, which had a higher drug-loading than C-ACP...
February 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28229517/affinity-capillary-electrophoresis-and-fluorescence-spectroscopy-for-studying-enantioselective-interactions-between-omeprazole-enantiomer-and-human-serum-albumin
#20
Yujing Xu, Tingting Hong, Xueping Chen, Yibing Ji
Baseline separation of omeprazole (OME) enantiomers was achieved by affinity capillary electrophoresis (ACE), using human serum albumin (HSA) as the chiral selector. The influence of several experimental variables such as HSA concentration, the type and content of organic modifiers, applied voltage and running buffer concentration on the separation was evaluated. The binding of esomeprazole (S-omeprazole, S-OME) and its R-enantiomer (R-omeprazole, R-OME) to HSA under simulated physiological conditions was studied by ACE and fluorescence spectroscopy which was considered as a reference method...
February 23, 2017: Electrophoresis
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