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https://www.readbyqxmd.com/read/27911495/synthesis-and-evaluation-of-caged-sirna-with-terminal-single-vitamin-e-modification
#1
Jiali Yang, Lijia Yu, Liangliang Zhang, Xingsu Long, Yuzhuo Ji, Xinjing Tang
RNA-induced gene silencing has been widely applied as a powerful research tool in drug development due to its sequence-specific degradation of target mRNA. Conditional regulation of gene functions with small interfering RNAs (siRNAs) is highly useful, especially when specific gene expression regulation with spatiotemporal resolution and amplitude is desired. Here, the synthesis of a series of new caged siRNAs with vitamin E (vitE) modification and/or a single photolabile linker at the 5' terminal is described...
December 1, 2016: Current Protocols in Nucleic Acid Chemistry
https://www.readbyqxmd.com/read/27911475/carboplatin-complexed-and-crgd-conjugated-unimolecular-nanoparticles-for-targeted-ovarian-cancer-therapy
#2
Yuyuan Wang, Liwei Wang, Guojun Chen, Shaoqin Gong
Platinum-based chemotherapy has been widely used to treat cancers including ovarian cancer; however, it suffers from dose-limiting toxicity. Judiciously designed drug nanocarriers can enhance the anticancer efficacy of platinum-based chemotherapy while reducing its systemic toxicity. Herein the authors report a stable and water-soluble unimolecular nanoparticle constructed from a hydrophilic multi-arm star block copolymer poly(amidoamine)-b-poly(aspartic acid)-b-poly(ethylene glycol) (PAMAM-PAsp-PEG) conjugated with both cRGD (cyclo(Arg-Gly-Asp-D-Phe-Cys) peptide and cyanine5 (Cy5) fluorescent dye as a platinum-based drug nanocarrier for targeted ovarian cancer therapy...
December 1, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27911362/automated-acoustic-dispensing-for-the-serial-dilution-of-peptide-agonists-in-potency-determination-assays
#3
Jacqueline Naylor, Alessandra Rossi, Christopher Brankin, David C Hornigold
As with small molecule drug discovery, screening for peptide agonists requires the serial dilution of peptides to produce concentration-response curves. Screening peptides affords an additional layer of complexity as conventional tip-based sample handling methods expose peptides to a large surface area of plasticware, providing an increased opportunity for peptide loss via adsorption. Preventing excessive exposure to plasticware reduces peptide loss via adherence to plastics and thus minimizes inaccuracies in potency prediction, and we have previously described the benefits of non-contact acoustic dispensing for in vitro high-throughput screening of peptide agonists(1)...
November 10, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911223/advances-in-capillary-electrophoresis-and-the-implications-for-drug-discovery
#4
Claire M Ouimet, Cara I D'Amico, Robert T Kennedy
Many screening platforms are prone to assay interferences that can be avoided by directly measuring the target or enzymatic product. Capillary electrophoresis (CE) and microchip electrophoresis (MCE) have been applied in a variety of formats to drug discovery. CE provides direct detection of the product allowing for the identification of some forms of assay interference. The high efficiency, rapid separations, and low volume requirements make CE amenable to drug discovery. Areas Covered: This article describes advances in capillary electrophoresis throughput, sample introduction, and target assays as they pertain to drug discovery and screening...
December 2, 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27910990/a-ph-responsive-sequential-disassembly-nanohybrid-for-mitochondrial-targeting
#5
Lijia Li, Wei Sun, Lian Li, Yuanyuan Liu, Lei Wu, Fengling Wang, Zhou Zhou, Zhirong Zhang, Yuan Huang
Cationic materials have been reported as promising tools for targeting to mitochondria which are the "power houses" and "metabolic garbage keepers" of cells. However, their positive nature also restricts their in vivo application due to the quick clearance. Herein, we fabricated a nanohybrid consisting of the pH-responsive N-(2-hydroxypropyl)methacrylamide (HPMA) co-polymer (R-P) shells and positive mesoporous silica nanoparticle cores via electrostatic interaction. The anticancer drug, docetaxel (DTX), was encapsulated in the positive MSN cores (MSN-DTX)...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27910950/human-antibody-3e1-targets-the-ha-stem-region-of-h1n1-and-h5n6-influenza-a-viruses
#6
Wenshuai Wang, Xiaoyu Sun, Yanbing Li, Jinpeng Su, Zhiyang Ling, Tianlong Zhang, Fang Wang, Hong Zhang, Hualan Chen, Jianping Ding, Bing Sun
As influenza A viruses remain a major threat to human health worldwide, the discovery of broadly neutralizing monoclonal antibodies that recognize conserved epitopes would facilitate the development of antibody-based therapeutic strategies. Here we report that a VH4-4-encoded human mAb named 3E1 could neutralize H1 and H5 subtype viruses in vitro and protect mice against the H1N1 and H5N6 viruses by inhibiting the low pH-induced conformational rearrangement of haemagglutinin (HA), hence blocking membrane fusion...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27910899/glial-pannexin1-contributes-to-tactile-hypersensitivity-in-a-mouse-model-of-orofacial-pain
#7
Regina Hanstein, Menachem Hanani, Eliana Scemes, David C Spray
Drug studies in animal models have implicated pannexin1 (Panx1) in various types of pain, including trigeminal hypersensitivity, neuropathic pain and migraine. However, the tested drugs have limited specificity and efficacy so that direct evidence for Panx1 contribution to pain has been lacking. We here show that tactile hypersensitivity is markedly attenuated by deletion of Panx1 in a mouse model of chronic orofacial pain; in this model, trigeminal ganglion Panx1 expression and function are markedly enhanced...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910877/a-comprehensive-map-of-molecular-drug-targets
#8
Rita Santos, Oleg Ursu, Anna Gaulton, A Patrícia Bento, Ramesh S Donadi, Cristian G Bologa, Anneli Karlsson, Bissan Al-Lazikani, Anne Hersey, Tudor I Oprea, John P Overington
The success of mechanism-based drug discovery depends on the definition of the drug target. This definition becomes even more important as we try to link drug response to genetic variation, understand stratified clinical efficacy and safety, rationalize the differences between drugs in the same therapeutic class and predict drug utility in patient subgroups. However, drug targets are often poorly defined in the literature, both for launched drugs and for potential therapeutic agents in discovery and development...
December 2, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27910782/chemoprevention-of-colon-cancer-through-inhibition-of-angiogenesis-and-induction-of-apoptosis-by-nonsteroidal-anti-inflammatory-drugs
#9
Preety Ghanghas, Shelly Jain, Chandan Rana, Sankar Nath Sanyal
Cancer cells require nourishment for the growth of the primary tumor mass and spread of the metastatic colony. These needs are fulfilled by tumor-associated neovasculature known as angiogenesis, which also favors the transition from hyperplasia to neoplasia, that is, from a state of cellular multiplication to uncontrolled proliferation. Therefore, targeting angiogenesis is profitable as a mechanism to inhibit tumor growth. Furthermore, it is important to understand the cross-communication between vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in the neoplastic and proinflammatory milieu...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27910765/gene-therapy-for-rheumatoid-arthritis
#10
Shuang Liu, Kazutaka Maeyama
With the aim of controlling disease relapse and bone deformation of individual joints, the application of gene therapy in rheumatoid arthritis (RA) has slowly progressed on a trial-and-error basis. Several new therapeutic targets have been identified in preclinical studies in animal models, although a limited number of gene-based clinical trials have been conducted. In this article, we summarize the status of gene therapy for RA by addressing issues related to innovating drug development. More disease- and target-specific preclinical tests are required to overcome the insufficient information regarding pharmacokinetics and toxicokinetics, which are related to safety issues in the field of RA gene therapy...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910752/submicron-emulsions-and-their-applications-in-oral-delivery
#11
Veenu Mundada, Mitali Patel, Krutika Sawant
A "submicron emulsion" is an isotropic mixture of drug, lipids, and surfactants, usually with hydrophilic cosolvents and with droplet diameters ranging from 10 to 500 nm. Submicron emulsions are of increasing interest in medicine due to their kinetic stability, high solubilizing capacity, and tiny globule size. Because of these properties, they have been applied in various fields, such as personal care, cosmetics, health care, pharmaceuticals, and agrochemicals. Submicron emulsions are by far the most advanced nanoparticulate systems for the systemic delivery of biologically active agents for controlled drug delivery and targeting...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27910749/role-of-toll-like-receptors-in-hepatitis-c-virus-pathogenesis-and-treatment
#12
Usman Ali Ashfaq, Muhammad Sarfaraz Iqbal, Saba Khaliq
Viral infections are rising every day, and viruses appear to be the most dangerous pathogens in the world. Hepatitis C virus (HCV) is accepted as one of the major destructive factors of promoting severe hepatic disorders by infecting more than 180 million individuals throughout the world. Chronic infection caused by HCV poses a serious global health emergency and appears to be a powerful threat to humanity. Almost 20 years have passed since the disclosure of HCV, but even now, treatment preferences remain limited...
2016: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/27910742/review-article-fabricated-microparticles-an-innovative-method-to-minimize-the-side-effects-of-nsaids-in-arthritis
#13
Shaivad Shabee Hulhasan Abadi, Afrasim Moin, Gangadharappa Hosahalli Veerabhadrappa
Microparticles are polymeric bodies ranging 1-1000 µm that constitute a variety of forms such as microcapsules, microspheres, microcages, microshells, microrods, biosensors microparticles, radiolabeled microparticles, and so forth. This review focuses on general microparticles, mainly microcapsules and microspheres. Nonsteriodal anti-inflammatory drugs (NSAIDs) are one of the mostcommonly prescribed medications in the world. Most of the NSAIDs available have severe side effects. With increased awareness of NSAID-induced gastrointestinal (GI) side effects, safety has become a priority in treatment of arthritis and other inflammatory diseases with NSAIDs...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27910739/overview-on-therapeutic-applications-of-microparticulate-drug-delivery-systems
#14
Swarna Bale, Amit Khurana, A Shiva Shankar Reddy, Mandip Singh, Chandraiah Godugu
Research in novel drug delivery systems is being explored competitively in order to attain maximum therapeutic effect while minimizing the adverse effects. Despite several advancements in pharmaceutical formulations, one of the major challenges still persisting is sustained drug release. Microencapsulation enacts as an intelligent approach with a strong therapeutic impact and is in demand globally in medical technology due to its specific and attractive properties, including biocompatibility, stability, target specificity, uniform encapsulation, better compliance, and controlled and sustained release patterns that are responsible for diminishing the toxicity and dosage frequency...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27910713/sn-38-loading-capacity-of-hydrophobic-polymer-blend-nanoparticles-formulation-optimization-and-efficacy-evaluation
#15
Simona Dimchevska, Nikola Geskovski, Gjorgji Petruševski, Marina Chacorovska, Riste Popeski-Dimovski, Sonja Ugarkovic, Katerina Goracinova
One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to nanoparticles prepared using individual polymers...
December 2, 2016: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/27910243/recent-advances-in-aliphatic-polyesters-for-drug-delivery-applications
#16
REVIEW
Katherine E Washington, Ruvanthi N Kularatne, Vasanthy Karmegam, Michael C Biewer, Mihaela C Stefan
The use of aliphatic polyesters in drug delivery applications has been a field of significant interest spanning decades. Drug delivery strategies have made abundant use of polyesters in their structures owing to their biocompatibility and biodegradability. The properties afforded from these materials provide many avenues for the tunability of drug delivery systems to suit individual needs of diverse applications. Polyesters can be formed in several different ways, but the most prevalent is the ring-opening polymerization of cyclic esters...
December 1, 2016: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/27910223/synthesis-and-preliminary-evaluation-of-a-99m-tc-labeled-folate-pamam-dendrimer-for-fr-imaging
#17
Manli Song, Zhide Guo, Mengna Gao, Changrong Shi, Duo Xu, Linyi You, Xiaowei Wu, Xinhui Su, Rongqiang Zhuang, Weimin Pan, Ting Liu, Xianzhong Zhang
Folate receptor is an ideal target for tumor-specific diagnostic and therapeutic. The aim of this study was to synthesize (99m) Tc-labeled folate-polyamidoamine dendrimer modified with 2-hydrazinonicotinic acid ((99m) Tc-HP3 FA) for FR imaging. The (99m) Tc-HP3 FA conjugate was prepared using N-tris-(hydroxymethyl)-methylglycine and trisodium triphenylphosphine-3,3',3″-trisulfonate as coligands. Physicochemical properties, in vitro cell uptake study, and in vivo micro-single-photon emission computed tomography/CT imaging were performed...
November 7, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27910188/comparing-rewarding-and-reinforcing-properties-between-bath-salt-3-4-methylenedioxypyrovalerone-mdpv-and-cocaine-using-ultrasonic-vocalizations-in-rats
#18
Steven J Simmons, Ryan A Gregg, Fionya H Tran, Lili Mo, Eva von Weltin, David J Barker, Taylor A Gentile, Lucas R Watterson, Scott M Rawls, John W Muschamp
Abuse of synthetic psychostimulants like synthetic cathinones has risen in recent years. 3,4-Methylenedioxypyrovalerone (MDPV) is one such synthetic cathinone that demonstrates a mechanism of action similar to cocaine. Compared to cocaine, MDPV is more potent at blocking dopamine and norepinephrine reuptake and is readily self-administered by rodents. The present study compared the rewarding and reinforcing properties of MDPV and cocaine using systemic injection dose-response and self-administration models...
December 1, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27910185/drug-eluting-balloon-angioplasty-for-below-the-knee-lesions-in-end-stage-renal-disease-patients-with-critical-limb-ischemia-midterm-results
#19
Burak Teymen, Süleyman Aktürk
BACKGROUND: The 1-year restenosis rate after standard balloon angioplasty (BA) of long lesions in below-the-knee arteries may be as high as 70%. Our aim was to investigate the efficacy and safety of paclitaxel drug-eluting balloon (DEB) for treatment of below the knee lesions in end stage renal disease patients (ESRD) with critical limb ischemia (CLI). METHODS: Our study is a retrospective, single-center study. Inclusion criteria were ESRD, critical limb ischemia (Rutherford class 4 or higher) and significant stenosis or occlusion of at least 1 below-the-knee vessel...
December 2, 2016: Journal of Interventional Cardiology
https://www.readbyqxmd.com/read/27910061/inhaled-gene-transfer-for-pulmonary-circulation
#20
Jaume Aguero, Lahouaria Hadri, Nadjib Hammoudi, Lauren Leonardson, Roger J Hajjar, Kiyotake Ishikawa
Chronic pulmonary hypertension (PH) is associated with right ventricular failure and high mortality regardless of the underlying disease. Currently, therapies can improve clinical outcomes in specific subsets of patients, but have little impact on the progression of pulmonary vascular remodeling. Upon new advances in vector development and delivery techniques, gene therapy is a novel strategy in this field with the potential of overcoming the main limitations of approved drug therapies: modulation of novel anti-remodeling targets and selective pulmonary vasculature targeting with minimal systemic effects...
2017: Methods in Molecular Biology
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