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https://www.readbyqxmd.com/read/28449430/poloxamer-surface-modified-trimethyl-chitosan-nanoparticles-for-the-effective-delivery-of-methotrexate-in-osteosarcoma
#1
Shenglong Li, Yuyuan Xiong, Xiaojing Zhang
The present work is an effort to explore the poloxamer-modified trimethyl chitosan (TMC) encapsulated MTX for osteosarcoma treatment in order to improve the therapeutic efficacy and minimize severe toxicity associated with the clinical usage of MTX. The methotrexate-loaded pluronic-chitosan nanoparticles (MTCN) was nanosized and exhibited a controlled release of drug from the carrier system. The MTCN showed higher accumulation in cell cytoplasm region evident by the high red fluorescence indicating its uptake through energy-dependent endocytosis process...
April 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28447868/doxorubicin-loaded-liposomes-enhancing-the-oral-bioavailability-by-modulation-of-physicochemical-characteristics
#2
Marjan Daeihamed, Azadeh Haeri, Seyed Nasser Ostad, Masoud Faghih Akhlaghi, Simin Dadashzadeh
AIM: In this study, the effects of liposome characteristics on oral absorption of doxorubicin, as a hydrophilic low-permeability drug, were investigated. MATERIALS & METHODS: Different doxorubicin-loaded liposomes were prepared, characterized and orally administered to 18 groups of rats. Plasma concentrations of doxorubicin and its aglycone metabolite were measured, and Caco-2 uptake and transport of optimum liposomes were investigated. RESULTS: After studying different factors, a fourfold increase in oral bioavailability was achieved with the non-PEGylated, 120-nm-sized positively charged rigid liposomes (lipid to drug ratio = 10)...
April 27, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28446613/structural-basis-for-ligand-capture-and-release-by-the-endocytic-receptor-apoer2
#3
Hidenori Hirai, Norihisa Yasui, Keitaro Yamashita, Sanae Tabata, Masaki Yamamoto, Junichi Takagi, Terukazu Nogi
Apolipoprotein E receptor 2 (ApoER2) is a close homologue of low-density lipoprotein receptor (LDLR) that mediates the endocytosis of ligands, including LDL particles. LDLR family members have been presumed to explore a large conformational space to capture ligands in the extended conformation at the cell surface. Ligands are subsequently released through a pH-titrated structural transition to a self-docked, contracted-closed conformation. In addition to lipoprotein uptake, ApoER2 is implicated in signal transduction during brain development through capture of the extracellular protein reelin...
April 26, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28445864/tumor-antigen-glycosaminoglycan-modification-regulates-antibody-drug-conjugate-delivery-and-cytotoxicity
#4
Helena C Christianson, Julien A Menard, Vineesh Indira Chandran, Erika Bourseau-Guilmain, Dmitry Shevela, Jon Lidfeldt, Ann-Sofie Månsson, Silvia Pastorekova, Johannes Messinger, Mattias Belting
Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443330/mechanisms-by-which-salt-concentration-moderates-the-dynamics-of-human-serum-transferrin
#5
Haleh Abdizadeh, Ali Rana Atilgan, Canan Atilgan
The dynamical and thermodynamic behavior of human transferrin (hTf) protein in saline aqueous solution of various concentrations is studied. hTf is an essential transport protein circulating iron in the blood and delivering it to tissues. It displays highly pH dependent cooperativity between the two lobes each carrying an iron, and forms a tight complex with the receptor during endocytosis, eventually recycled to the serum after iron release. Molecular dynamics simulations are used to investigate the effects of the amount of salt on protein conformation and dynamics to analyze the structure-function relationship in free hTf at serum pH...
April 26, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28442903/magnetic-and-ph-dual-responsive-mesoporous-silica-nanocomposites-for-effective-and-low-toxic-photodynamic-therapy
#6
Jieqiong Zhan, Zhiqiang Ma, Dan Wang, Xinfang Li, Xiangui Li, Lijing Le, Anfeng Kang, Pengwei Hu, Lan She, Feng Yang
Nonspecific targeting, large doses and phototoxicity severely hamper the clinical effect of photodynamic therapy (PDT). In this work, superparamagnetic Fe3O4 mesoporous silica nanoparticles grafted by pH-responsive block polymer polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) were fabricated to load the model photosensitizer rose bengal (RB) in the aim of enhancing the efficiency of PDT. Compared to free RB, the nanocomposites (polyethylene glycol-b-polyaspartate-modified rose bengal-loaded magnetic mesoporous silica [RB-MMSNs]) could greatly enhance the cellular uptake due to their effective endocytosis by mouse melanoma B16 cell and exhibited higher induced apoptosis although with little dark toxicity...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28442497/an-in-silico-model-of-retinal-cholesterol-dynamics-rcd-model-insights-into-the-pathophysiology-of-dry-age-related-macular-degeneration
#7
Seyedeh Maryam Zekavat, James Lu, Cyrille Maugeais, Norman A Mazer
We developed an in-silico mathematical model of retinal cholesterol (Ch) dynamics (RCD) to quantify the physiological rate of Ch turnover in the rod outer segment (ROS), the lipoprotein transport mechanisms by which Ch enters and leaves the outer retina, and the rates of drusen growth and macrophage-mediated clearance in dry Age-Related Macular Degeneration (AMD). Based on existing experimental data and mechanistic hypotheses, we estimate the Ch turnover rate in the ROS to be 1-6 pg/mm2/min, dependent on the rate of Ch recycling in the outer retina, and find comparable rates for LDL receptor-mediated endocytosis of Ch by the retinal pigment epithelium (RPE), ABCA1-mediated Ch transport from the RPE to outer retina, ABCA1-mediated Ch efflux from the RPE to choroid, and the secretion of 70 nm ApoB-Ch particles from the RPE...
April 25, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28442379/peripheral-membrane-associations-of-matrix-metalloproteinases
#8
REVIEW
Steven R Van Doren, Tara C Marcink, Rama K Koppisetti, Alexander Jurkevich, Yan G Fulcher
Water soluble matrix metalloproteinases (MMPs) have been regarded as diffusing freely in the extracellular matrix. Yet multiple MMPs are also observed at cell surfaces. Their membrane-proximal activities include sheddase activities, collagenolysis, bacterial killing, and intracellular trafficking reaching as far as the nucleus. The catalytic domains of MMP-7 and MMP-12 bind bilayers peripherally, each in two different orientations, by presenting positive charges and a few hydrophobic groups to the surface. Related peripheral membrane associations are predicted for other soluble MMPs...
April 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28438500/ap2-%C3%AE-modulates-cystic-fibrosis-transmembrane-conductance-regulator-function-in-the-human-intestine
#9
Vandana Kumari, Shruti Desai, Nadia A Ameen
BACKGROUND: AP2 is a clathrin-based endocytic adaptor complex comprising α, β2, μ2 and σ2 subunits. μ2 regulates CFTR endocytosis. The α subunit interacts with CFTR in the intestine but its physiologic significance is unclear. METHODS: CFTR short circuit current was measured in intestinal T84 cells following shRNA knock down of AP2α (AP2αKD). Clathrin-coated structures (CCS) were immunolabeled and quantified in AP2αKD intestinal Caco2BBe (C2BBe) cells. GST tagged human AP2α appendage domain was cloned and its interaction with CFTR determined by GST pull down assay...
April 21, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28437568/insights-into-deep-sea-adaptations-and-host-symbiont-interactions-a-comparative-transcriptome-study-on-bathymodiolus-mussels-and-their-coastal-relatives
#10
Ping Zheng, Minxiao Wang, Chaolun Li, Xiaoqing Sun, Xiaocheng Wang, Yan Sun, Song Sun
Mussels (Bivalve: Mytilidae) have adapted to various habitats, from freshwater to the deep sea. To understand their adaptive characteristics in different habitats, particularly in the bathymodiolin mussels in deep-sea chemosynthetic ecosystems, we conducted a comparative transcriptomic analysis between deep-sea bathymodiolin mussels and their shallow-water relatives. A number of gene families related to stress responses were shared across all mussels, without specific or significantly expanded families in deep-sea species, indicating that all mussels are capable of adapting to diverse harsh environments, but that different members of the same gene family may be preferentially utilized by different species...
April 24, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28437167/the-fgvps39-fgvam7-fgsso1-complex-mediates-vesicle-trafficking-and-is-important-for-the-development-and-virulence-of-fusarium-graminearum
#11
Bing Li, Luping Liu, Ying Li, Xin Dong, Haifeng Zhang, Huaigu Chen, Xiaobo Zheng, Zhengguang Zhang
Vesicle trafficking is an important event in eukaryotic organisms. Many proteins and lipids transported between different organelles or compartments are essential for survival. These processes are mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, Rab-GTPases, and multisubunit tethering complexes such as class C core vacuole or endosome tethering and homotypic fusion or vacuole protein sorting (HOPS). Our previous study has demonstrated that FgVam7, which encodes a SNARE protein involving in vesicle trafficking, plays crucial roles in growth, asexual or sexual development, deoxynivalenol production, and pathogenicity in Fusarium graminearum...
April 24, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28436508/purification-characterization-and-bioactivities-of-polysaccharides-from-pleurotus-ferulae
#12
Jinyu Li, Pengfei Yuan, Xinhui Wang, Adila Aipire, Minjing Li, Jie Yang, Hong Tao, Tianlei Ying, Changshuang Fu, Xianxian Wei, Fuchun Zhang, Jinyao Li
Pleurotus ferulae is an edible mushroom and has been used in Uygur medicine for a long time. In this study, we purified polysaccharides from P. ferulae (PFPS) and investigated its structural characteristics. We obtained a homogeneous PFPS with a molecular weight of around 1600 kDa and prominent characteristic polysaccharide groups, which mainly contained glucose (97%), followed by mannose and galactose (3%). Both (1)H and (13)C NMR spectra indicated that PFPS contained both α- and β-anomeric configurations...
April 24, 2017: Food & Function
https://www.readbyqxmd.com/read/28436498/integrative-meta-modeling-identifies-endocytic-vesicles-late-endosome-and-the-nucleus-as-the-cellular-compartments-primarily-directing-rtk-signaling
#13
Jared C Weddell, Princess I Imoukhuede
Recently, intracellular receptor signaling has been identified as a key component mediating cell responses for various receptor tyrosine kinases (RTKs). However, the extent each endocytic compartment (endocytic vesicle, early endosome, recycling endosome, late endosome, lysosome and nucleus) contributes to receptor signaling has not been quantified. Furthermore, our understanding of endocytosis and receptor signaling is complicated by cell- or receptor-specific endocytosis mechanisms. Therefore, towards understanding the differential endocytic compartment signaling roles, and identifying how to achieve signal transduction control for RTKs, we delineate how endocytosis regulates RTK signaling...
April 24, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28436082/tricellulin-is-a-target-of-the-ubiquitin-ligase-itch
#14
Susanne Jennek, Sonnhild Mittag, Juliane Reiche, Julie K Westphal, Stefanie Seelk, Max J Dörfel, Thorsten Pfirrmann, Karlheinz Friedrich, Anja Schütz, Udo Heinemann, Otmar Huber
Tricellulin, a member of the tight junction-associated MAGUK protein family, preferentially localizes to tricellular junctions in confluent polarized epithelial cell layers and is downregulated during the epithelial-mesenchymal transition. Posttranslational modifications are assumed to play critical roles in the process of downregulation of tricellulin at the protein level. Here, we report that the E3 ubiquitin ligase Itch forms a complex with tricellulin and thereby enhances its ubiquitination. Pull-down assays confirmed a direct interaction between tricellulin and Itch, which is mediated by the Itch WW domain and the N-terminus of tricellulin...
April 24, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28435459/aptamer-internalization-via-endocytosis-inducing-s-phase-arrest-and-priming-maver-1-lymphoma-cells-for-cytarabine-chemotherapy
#15
Huan Li, Shuanghui Yang, Ge Yu, Liangfang Shen, Jia Fan, Ling Xu, Hedong Zhang, Nianxi Zhao, Zihua Zeng, Tony Hu, Jianguo Wen, Youli Zu
The goal of precision therapy is to efficiently treat cancer without side effects. Aptamers are a class of small ligands composed of single-stranded oligonucleotides that bind to their targets with high affinity and specificity. In this study, we identified an ssDNA aptamer specifically targeting Maver-1 lymphoma cells with high binding affinity (Kd = 70±8 pmol/L). Interestingly, cellular cycle studies revealed that exposure of Maver-1 cells to synthetic aptamers triggered S-phase arrest of 40% of the cells (vs...
2017: Theranostics
https://www.readbyqxmd.com/read/28435246/cuprous-oxide-nanoparticle-inhibited-melanoma-progress-by-targeting-melanoma-stem-cells
#16
Bin Yu, Ye Wang, Xinlu Yu, Hongxia Zhang, Ji Zhu, Chen Wang, Fei Chen, Changcheng Liu, Jingqiang Wang, Haiying Zhu
Recent studies have shown that metal and metal oxide have a potential function in antitumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271(+/high) cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28433919/identification-of-differentially-expressed-mirnas-through-high-throughput-sequencing-in-the-chicken-lung-in-response-to-mycoplasma-gallisepticum-hs
#17
Yabo Zhao, Yue Hou, Kang Zhang, Bo Yuan, Xiuli Peng
Mycoplasma gallisepticum (MG) infects chickens, causes chronic respiratory diseases (CRD) and severely damages the poultry industry. It has been suggested that micro-ribonucleic acids (miRNAs) are involved in microbial pathogenesis. Here, we identified miRNAs that are associated with MG infection in chicken lungs at 3 and 10days post-infection by deep sequencing. Thirty-six down-regulated and 9 up-regulated miRNAs belonging to 31 miRNA families were detected at 3days post-infection, whereas 50 down-regulated and 18 up-regulated miRNAs belonging to 41 miRNA families were found at 10days post-infection...
April 12, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28433812/the-perlecan-interacting-growth-factor-progranulin-regulates-ubiquitination-sorting-and-lysosomal-degradation-of-sortilin
#18
Ryuta Tanimoto, Chiara Palladino, Shi-Qiong Xu, Simone Buraschi, Thomas Neill, Leonard G Gomella, Stephen C Peiper, Antonino Belfiore, Renato V Iozzo, Andrea Morrione
Despite extensive clinical and experimental studies over the past decades, the pathogenesis and progression to the castration-resistant stage of prostate cancer remains largely unknown. Progranulin, a secreted growth factor, strongly binds the heparin-sulfate proteoglycan perlecan, and counteracts its biological activity. We established that progranulin acts as an autocrine growth factor and promotes prostate cancer cell motility, invasion, and anchorage-independent growth. Progranulin was overexpressed in prostate cancer tissues vis-à-vis non-neoplastic tissues supporting the hypothesis that progranulin may play a key role in prostate cancer progression...
April 20, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28433787/facile-encapsulation-of-hydroxycamptothecin-nanocrystals-into-zein-based-nanocomplexes-for-active-targeting-drug-delivery-and-cell-imaging
#19
Hongdi Wang, Wei Zhu, Yunna Huang, Zhixian Li, Yanbin Jiang, Qiuling Xie
Nano-drug delivery systems that integrate inorganic and organic or even bioactive components into a single nanoscale platform are playing a greatly important role in cancer treatment. Here, the fabrication of a versatile nanocarrier based on self-assembled structures of gold nanoparticles (AuNPs)-zein is reported, which displays high drug-loading efficiency for needle-shaped hydroxycamptothecin (HCPT) nanocrystals. The surface modification with folate-conjugated polydopamine (PFA) renders them stable and also facilitates their selective cellular internalization and enhancement of endocytosis...
April 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28433697/rab22a-enhances-cd147-recycling-and-is-required-for-lung-cancer-cell-migration-and-invasion
#20
Yang Zhou, Bo Wu, Jiang-Hua Li, Gang Nan, Jian-Li Jiang, Zhi-Nan Chen
Rab22a is a member of the Ras-related small GTPase family, which plays a key role in regulating the recycling of cargo proteins entering cells through clathrin-independent endocytosis (CIE). Rab22a is overexpressed in different cancer types, including liver cancer, malignant melanoma, ovarian cancer and osteosarcoma. However, its oncogenic role remains unknown. In this study, we found that silencing of Rab22a suppressed the migration and invasion of lung cancer cells. Furthermore, Rab22a interacts with CD147, and knockdown of Rab22a blocks CD147 recycling and promotes CD147 degradation...
April 19, 2017: Experimental Cell Research
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