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https://www.readbyqxmd.com/read/27913127/co-assembly-of-doxorubicin-and-curcumin-targeted-micelles-for-synergistic-delivery-and-improving-anti-tumor-efficacy
#1
Wenzhuan Ma, Qiang Guo, Ying Li, Xiaohui Wang, Jinling Wang, Pengfei Tu
Chemotherapeutic drugs have a series of limitations in anti-tumor treatment, mainly including multidrug resistance (MDR) and serious adverse reactions. Co-delivery system with two or more synergistic therapeutic drugs is an effective strategy to settle these limitations. In this study, active tumor-targeted co-delivery micelles (DOX+Cur)-PMs, with two synergistic drugs of a therapeutic drug of doxorubicin (DOX) and a chemosensitizer of curcumin (Cur) co-encapsulated into hyaluronic acid-vitamin E succinate (HA-VES) graft copolymer, were prepared and delivered simultaneously into tumor cells for improving therapeutic effects of DOX...
November 29, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27911932/chemical-and-cellular-assays-combined-with-in-vitro-digestion-to-determine-the-antioxidant-activity-of-flavonoids-from-chinese-bayberry-myrica-rubra-sieb-et-zucc-leaves
#2
Yu Zhang, Shiguo Chen, Chaoyang Wei, Hui Gong, Lanqi Li, Xingqian Ye
Oxidative stress is highly associated with the development of cardiovascular diseases and cancer and has drawn great attention. Natural products suggest a potential role in prevention of these disorders. The aim of this study was to investigate the antioxidant and anti-cancer properties of Chinese bayberry leaves (Myrica rubra Sieb. et Zucc.) flavonoids (BLF) comprehensively through the combination of in vitro digestion, chemical and cellular antioxidant assays. Based on the LC/MS data, the major flavonoids of BLF were myricitrin and quercetin 3-rhamnoside...
2016: PloS One
https://www.readbyqxmd.com/read/27911809/unique-attributes-of-cyanobacterial-metabolism-revealed-by-improved-genome-scale-metabolic-modeling-and-essential-gene-analysis
#3
Jared T Broddrick, Benjamin E Rubin, David G Welkie, Niu Du, Nathan Mih, Spencer Diamond, Jenny J Lee, Susan S Golden, Bernhard O Palsson
The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911495/synthesis-and-evaluation-of-caged-sirna-with-terminal-single-vitamin-e-modification
#4
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
#5
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/27907865/biophysical-characterization-and-antineoplastic-activity-of-new-bis-thiosemicarbazonato-cu-ii-complexes
#6
Elisa Palma, Filipa Mendes, Goreti Ribeiro Morais, Inês Rodrigues, Isabel Cordeiro Santos, Maria Paula C Campello, Paula Raposinho, Isabel Correia, Sofia Gama, Dulce Belo, Vítor Alves, Antero J Abrunhosa, Isabel Santos, António Paulo
Aiming to explore alternative mechanisms of cellular uptake and cytotoxicity, we have studied a new family of copper(II) complexes (CuL(1)-CuL(4)) with bis(thiosemicarbazone) (BTSC) ligands containing pendant protonable cyclic amines (morpholine and piperidine). Herein, we report on the synthesis and characterization of these new complexes, as well as on their biological performance (cytotoxic activity, cellular uptake, protein and DNA binding), in comparison with the parental Cu(II)ATSM (ATSM=diacetyl-bis(N4-methylthiosemicarbazonate) complex without pendant cyclic amines...
November 23, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27906617/evaluation-of-cellular-purine-transport-and-metabolism-in-the-caco-2-cell-using-comprehensive-high-performance-liquid-chromatography-method-for-analysis-of-purines
#7
T Fukuuchi, M Kobayashi, N Yamaoka, K Kaneko
Using Caco-2 cells and our previously developed high-performance liquid chromatography method for quantification of purine bases, nucleosides, and nucleotides, we evaluated cellular purine transport and uptake. The analytes were separated using YMC-Triart C18 column with gradient elution. We used Caco-2 cells as intestinal model cells and monitored purine transport across a monolayer for 2 h. The degree of change of purine concentrations in the permeate was very slight; however, it was possible to simultaneously determine these parameters for all purines because of our method's high sensitivity...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906055/mesenchymal-stem-cells-multipotent-stromal-cells-mscs-are-glycolytic-and-thus-glucose-is-a-limiting-factor-of-in-vitro-models-of-msc-starvation
#8
Austin Nuschke, Melanie Rodrigues, Albin W Wells, Kyle Sylakowski, Alan Wells
BACKGROUND: Mesenchymal stem/multipotent stromal cells (MSCs) contribute to tissue repair but are challenged during wound healing when the blood supply is disrupted, thereby limiting nutrient delivery. Survival mechanisms against 'starvation' include autophagy, which we previously found to enhance differentiation efficiency. MSC response to models of in vitro nutrient deprivation are of great interest for improving MSC survival and therapeutic efficacy; however, the rate-limiting nutrients are unknown...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27904971/mutations-in-slc5a6-associated-with-brain-immune-bone-and-intestinal-dysfunction-in-a-young-child
#9
Veedamali S Subramanian, Alexandru R Constantinescu, Paul J Benke, Hamid M Said
The human sodium-dependent multivitamin transporter (hSMVT) is a product of the SLC5A6 gene and mediates biotin, pantothenic acid, and lipoate uptake in a variety of cellular systems. We report here the identification of mutations R94X, a premature termination, and R123L, a dysfunctional amino acid change, both in exon 3 of the SLC5A6 gene in a child using whole genome-scanning. At 15 months of age, the child showed failure to thrive, microcephaly and brain changes on MRI, cerebral palsy and developmental delay, variable immunodeficiency, and severe gastro-esophageal reflux requiring a gastrostomy tube/fundoplication, osteoporosis, and pathologic bone fractures...
November 30, 2016: Human Genetics
https://www.readbyqxmd.com/read/27903581/the-plasma-membrane-metal-ion-transporter-zip14-contributes-to-non-transferrin-bound-iron-uptake-by-human-%C3%AE-cells
#10
Richard Coffey, Mitchell D Knutson
The relationship between iron and β cell dysfunction has long been recognized as individuals with iron overload display an increased incidence of diabetes. This link is usually attributed to the accumulation of excess iron in β cells leading to cellular damage and impaired function. Yet, the molecular mechanism(s) by which human β cells take up iron has not been determined. In the present study, we assessed the contribution of the metal-ion transporters ZIP14, ZIP8, and DMT1 to iron uptake by human β cells...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27903454/effects-of-frequently-used-pharmaceutical-excipients-on-the-organic-cation-transporters-1-3-and-peptide-transporters-1-2-stably-expressed-in-mdckii-cells
#11
Marcus Otter, Stefan Oswald, Werner Siegmund, Markus Keiser
There is ample evidence that pharmaceutical excipients, which are supposed to be pharmacologically inactive, have an impact on drug metabolism and efflux transport. So far, little is known whether they also modulate uptake transporter proteins. We have recently shown that commonly used solubilizing agents exert significant effects on the function of organic anion uptake transporting polypeptides. Therefore, we investigated in this study the influence of frequently used pharmaceutical excipients on the transport activity of organic cation transporters OCT1, OCT2 and OCT3 and the peptide transporters PEPT1 and PEPT2...
November 26, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27902780/co-regulation-of-iron-metabolism-and-virulence-associated-functions-by-iron-and-xibr-a-novel-iron-binding-transcription-factor-in-the-plant-pathogen-xanthomonas
#12
Sheo Shankar Pandey, Pradeep Kumar Patnana, Santosh Kumar Lomada, Archana Tomar, Subhadeep Chatterjee
Abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. Bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the environment. In many bacteria the ferric uptake regulator (Fur) functions as transcription factor that utilize ferrous form of iron as cofactor to regulate transcription of iron metabolism and many cellular functions...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27901157/exploring-the-activity-of-a-polyazine-bridged-ru-ii-pt-ii-supramolecule-in-f98-rat-malignant-glioma-cells
#13
Jie Zhu, José Á Rodríguez-Corrales, Reece Prussin, Zongmin Zhao, Anthony Dominijanni, Samantha L Hopkins, Brenda S J Winkel, John L Robertson, Karen J Brewer
The mixed-metal supramolecular complex, [(Ph2phen)2Ru(dpp)PtCl2](2+), displays significant DNA modification, cell growth inhibition, and toxicity towards F98 malignant glioma cells following visible light irradiation. The design of this complex affords superior cellular uptake and antiproliferative activity compared to the classic chemotherapeutic agent, cisplatin.
November 30, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27900805/effect-of-preorganized-charge-display-on-the-cell-penetrating-properties-of-cationic-peptides
#14
Yvonne A Nagel, Philipp S Raschle, Helma Wennemers
The effect of preorganized versus undefined charge display on the cellular uptake of cationic cell-penetrating peptides (CPPs) was investigated by comparing conformationally well-defined guanidinylated oligoprolines with flexible oligoarginines. Flow cytometry and confocal microscopy studies with different cancer cell lines (HeLa, MCF-7, and HT-29) showed that preorganization of cationic charges in lateral distances of ≈9 Å enhanced the cellular uptake of CPPs. Binding affinity measurements revealed tighter binding of analogues of cell-surface glycans to the guanidinylated octaproline with localized charges compared to flexible octaarginine, a finding that was further correlated to the cellular uptake by studies with CHO cells deficient in glycans on the outer plasma membrane...
November 30, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27899655/visualization-of-self-delivering-hydrophobically-modified-sirna-cellular-internalization
#15
Socheata Ly, Deanna M Navaroli, Marie-Cécile Didiot, James Cardia, Lakshmipathi Pandarinathan, Julia F Alterman, Kevin Fogarty, Clive Standley, Lawrence M Lifshitz, Karl D Bellve, Matthieu Prot, Dimas Echeverria, Silvia Corvera, Anastasia Khvorova
siRNAs are a new class of therapeutic modalities with promising clinical efficacy that requires modification or formulation for delivery to the tissue and cell of interest. Conjugation of siRNAs to lipophilic groups supports efficient cellular uptake by a mechanism that is not well characterized. Here we study the mechanism of internalization of asymmetric, chemically stabilized, cholesterol-modified siRNAs (sd-rxRNAs(®)) that efficiently enter cells and tissues without the need for formulation. We demonstrate that uptake is rapid with significant membrane association within minutes of exposure followed by the formation of vesicular structures and internalization...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899210/comparative-analysis-of-the-internalization-of-the-macrophage-receptor-sialoadhesin-in-human-and-mouse-primary-macrophages-and-cell-lines
#16
Marjorie De Schryver, Annelies Leemans, Isabel Pintelon, Davie Cappoen, Louis Maes, Guy Caljon, Paul Cos, Peter L Delputte
Sialoadhesin (Sn) is a surface receptor expressed on resident macrophages with the ability to bind with sialic acids. During inflammation, an upregulation of Sn is observed. Upon binding of monoclonal antibodies to Sn, the receptor becomes internalized and this has been observed in multiple species. The latter characteristic, combined with the strong upregulation of Sn on inflammatory macrophages and the fact that Sn-positive macrophages contribute to certain inflammatory diseases, makes Sn an interesting entry portal for phenotype-modulating or cytotoxic drugs...
November 21, 2016: Immunobiology
https://www.readbyqxmd.com/read/27897986/gold-nanoparticles-in-single-cell-analysis-for-surface-enhanced-raman-scattering
#17
REVIEW
Mine Altunbek, Gamze Kuku, Mustafa Culha
The need for new therapeutic approaches in the treatment of challenging diseases such as cancer, which often consists of a highly heterogeneous and complex population of cells, brought up the idea of analyzing single cells. The development of novel techniques to analyze single cells has been intensively studied to fully understand specific alternations inducing abnormalities in cellular function. One of the techniques used for single cell analysis is surface-enhanced Raman spectroscopy (SERS) in which a noble metal nanoparticle is used to enhance Raman scattering...
November 25, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27897452/characterization-of-two-recombinant-hvt-ibd-vaccines-by-vp2-insert-detection-and-cell-mediated-immunity-after-vaccination-of-specific-pathogen-free-chickens
#18
Fiona Ingrao, Fabienne Rauw, Thierry van den Berg, Bénédicte Lambrecht
Infectious bursal disease (IBD) is an avian viral disease that causes severe economic losses in the poultry industry worldwide. The live IBD virus (IBDV) has a potential immunosuppressive effect. Currently available IBDV vaccines have shortcomings, prompting the development of safer and more effective vaccination approaches, including the use of the recombinant turkey herpesvirus vaccine expressing the immunogenic structural VP2 protein of IBDV (rHVT-IBD). The objectives of this study were twofold: (i) to develop in vitro assays and molecular tools to detect the VP2 protein and gene, and (ii) to evaluate cell-mediated immunity (CMI) induced by rHVT-IBD vaccination of day-old specific pathogen-free chickens...
November 29, 2016: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/27897109/effect-of-the-modification-of-p24-peptide-antigen-on-dendritic-cell-uptake-and-t-cell-activation
#19
P L Smith, K J Norgate, E Hegarty, N Grageda, E Heelas, M Sommerfelt, T Lange, Arnt-Ove Hovden, B Sørenson, A Dalgleish, M Bodman-Smith
BACKGROUND: Vacc-4x is a candidate therapeutic vaccine consisting of 4 modified peptides based on conserved regions of HIV-1 p24Gag. Vacc4x has been shown to induce long term cellular immunity in immunized infected individuals resulting a reduction in viral load on treatment interruption. OBJECTIVE: Vacc-4x peptides are modified. In this study the effect of modification on uptake of the peptides into PBMC, their subsequent presentation and antigenicity was tested...
November 29, 2016: Current HIV Research
https://www.readbyqxmd.com/read/27896487/natural-compounds-as-occult-ototoxins-ginkgo-biloba-flavonoids-moderately-damage-lateral-line-hair-cells
#20
Sarah Neveux, Nicole K Smith, Anna Roche, Bruce E Blough, Wimal Pathmasiri, Allison B Coffin
Several drugs, including aminoglycosides and platinum-based chemotherapy agents, are well known for their ototoxic properties. However, FDA-approved drugs are not routinely tested for ototoxicity, so their potential to affect hearing often goes unrecognized. This issue is further compounded for natural products, where there is a lack of FDA oversight and the manufacturer is solely responsible for ensuring the safety of their products. Natural products such as herbal supplements are easily accessible and commonly used in the practice of traditional eastern and alternative medicine...
November 28, 2016: Journal of the Association for Research in Otolaryngology: JARO
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