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https://www.readbyqxmd.com/read/28102683/key-structural-elements-for-cellular-uptake-of-acinetobactin-a-major-siderophore-of-acinetobacter-baumannii
#1
Woon Young Song, Dawa Jeong, Jimin Kim, Min Wook Lee, Man Hwan Oh, Hak Joong Kim
Acinetobactin is a major siderophore utilized by the human pathogen Acinetobacter baumannii. The rapid acquisition of drug resistance by A. baumannii has garnered concern globally. Herein, acinetobactin and systematically generated analogues were prepared and characterized; the binding and cellular delivery of Fe(III) by the analogues were evaluated. This investigation not only led to the clarification of the physiologically relevant acinetobactin structure but also revealed several key structural elements for its functionality as a siderophore...
January 19, 2017: Organic Letters
https://www.readbyqxmd.com/read/28102569/human-%C3%AE-defensin-3-increases-the-tlr9-dependent-response-to-bacterial-dna
#2
Sarah L McGlasson, Fiona Semple, Heather MacPherson, Mohini Gray, Donald J Davidson, Julia R Dorin
Human β-defensin 3 (hBD3) is a cationic antimicrobial peptide with potent bactericidal activity in vitro. HBD3 is produced in response to pathogen challenge and can modulate immune responses. The amplified recognition of self-DNA by human plasmacytoid dendritic cells has been previously reported, but we show here that hBD3 preferentially enhances the response to bacterial DNA in mouse Flt-3 induced dendritic cells (FLDCs) and in human peripheral blood mononuclear cells. We show the effect is mediated through TLR9 and although hBD3 significantly increases the cellular uptake of both E...
January 19, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28099844/acetate-recapturing-by-nuclear-acetyl-coa-synthetase-2-prevents-loss-of-histone-acetylation-during-oxygen-and-serum-limitation
#3
Vinay Bulusu, Sergey Tumanov, Evdokia Michalopoulou, Niels J van den Broek, Gillian MacKay, Colin Nixon, Sandeep Dhayade, Zachary T Schug, Johan Vande Voorde, Karen Blyth, Eyal Gottlieb, Alexei Vazquez, Jurre J Kamphorst
Acetyl-CoA is a key metabolic intermediate with an important role in transcriptional regulation. The nuclear-cytosolic acetyl-CoA synthetase 2 (ACSS2) was found to sustain the growth of hypoxic tumor cells. It generates acetyl-CoA from acetate, but exactly which pathways it supports is not fully understood. Here, quantitative analysis of acetate metabolism reveals that ACSS2 fulfills distinct functions depending on its cellular location. Exogenous acetate uptake is controlled by expression of both ACSS2 and the mitochondrial ACSS1, and ACSS2 supports lipogenesis...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099809/a-gemcitabine-based-peptide-conjugate-with-improved-metabolic-properties-and-dual-mode-of-efficacy
#4
Theodoros Karampelas, Eleni Skavatsou, Orestis Argyros, Demosthenes Fokas, Constantin Tamvakopoulos
Gemcitabine is a clinically established anticancer agent potent in various solid tumors but limited by its rapid metabolic inactivation and off-target toxicity. We have previously generated a metabolically superior to gemcitabine molecule (GSG) by conjugating gemcitabine to a gonadotropin releasing hormone receptor (GnRH-R) ligand peptide, and showed that GSG was efficacious in a castration resistant prostate cancer (CRPC) animal model. The current manuscript provides an in-depth metabolic and mechanistic study of GSG, coupled with toxicity assays that strengthen the potential role of GSG in the clinic...
January 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28097872/a-dual-responsive-bola-type-supra-amphiphile-constructed-from-water-soluble-pillar-5-arene-and-naphthalimide-containing-amphiphile-for-intracellular-drug-delivery
#5
Xin Liu, Keke Jia, Yichen Wang, Wei Shao, Chenhao Yao, Luming Peng, Dongmei Zhang, Xiao-Yu Hu, Leyong Wang
Supramolecular construction of multi-stimuli platform for drug delivery is a challenging task. In this work, a pH and GSH (glutathione) dual-responsive bola-type supramolecular amphiphile was successfully fabricated by the complexation between a water-soluble pillar[5]arene (WP5) and a bolaform naphthalimide guest (G) in water. The resulting bola-type amphiphile further self-assembled into supramolecular binary vesicles, which could be disassembled by low pH and/or high GSH concentration environment. Furthermore, the results of drug loading and releasing tests showed that doxorubicin (DOX), the hydrophobic anticancer drug, could be successfully encapsulated into the Stern region of the obtained supramolecular vesicles and generated the DOX-loaded vesicles with good drug-loading efficiency...
January 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28097276/hydrophobicity-determines-the-fate-of-self-assembled-fluorescent-nanoparticles-in-cells
#6
Arthur H A M van Onzen, Lorenzo Albertazzi, Albertus P H J Schenning, Lech-Gustav Milroy, Luc Brunsveld
The fate of small molecule nanoparticles (SMNPs) composed of self-assembling intrinsically fluorescent π-conjugated oligomers was studied in cells as a function of side-chain hydrophobicity. While the hydrophobic SMNPs remained intact upon cellular uptake, the more hydrophilic SMNPs disassembled and dispersed throughout the cytosol.
January 18, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28096667/hyaluronan-modified-superparamagnetic-iron-oxide-nanoparticles-for-bimodal-breast-cancer-imaging-and-photothermal-therapy
#7
Rui-Meng Yang, Chao-Ping Fu, Jin-Zhi Fang, Xiang-Dong Xu, Xin-Hua Wei, Wen-Jie Tang, Xin-Qing Jiang, Li-Ming Zhang
Theranostic nanoparticles with both imaging and therapeutic abilities are highly promising in successful diagnosis and treatment of the most devastating cancers. In this study, the dual-modal imaging and photothermal effect of hyaluronan (HA)-modified superparamagnetic iron oxide nanoparticles (HA-SPIONs), which was developed in a previous study, were investigated for CD44 HA receptor-overexpressing breast cancer in both in vitro and in vivo experiments. Heat is found to be rapidly generated by near-infrared laser range irradiation of HA-SPIONs...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28096436/angiotensin-ii-induces-differential-insulin-action-in-rat-skeletal-muscle
#8
Juthamard Surapongchai, Mujalin Prasannarong, Tepmanas Bupha-Intr, Vitoon Saengsirisuwan
Angiotensin II (ANGII) is reportedly involved in the development of skeletal muscle insulin resistance. The present investigation evaluated the effects of two ANGII doses on the phenotypic characteristics of insulin resistance syndrome and insulin action and signaling in rat skeletal muscle. Male Sprague-Dawley rats were infused with either saline (SHAM) or ANGII at a commonly used pressor dose (100 ng/kg/min; ANGII-100) or a higher pressor dose (500 ng/kg/min; ANGII-500) via osmotic minipumps for 14 days. We demonstrated that ANGII-100-infused rats exhibited the phenotypic features of non-obese insulin resistance syndrome, including hypertension, impaired glucose tolerance and insulin resistance of glucose uptake in the soleus muscle, whereas ANGII-500-treated rats exhibited diabetes-like symptoms, such as post-prandial hyperglycemia, impaired insulin secretion and hypertriglyceridemia...
January 17, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28096156/bacterial-derived-cell-penetrating-peptides-deliver-gentamicin-to-kill-intracellular-pathogens
#9
Marta Gomarasca, Thaynan F C Martins, Lilo Greune, Philip R Hardwidge, M Alexander Schmidt, Christian Rüter
Commonly used antimicrobials show poor cellular uptake and often have limited access to intracellular targets, resulting in low antimicrobial activity against intracellular pathogens. An efficient delivery system to transport these drugs to the intracellular site of action is needed. Cell-penetrating peptides (CPPs) mediate the internalization of biologically active molecules into the cytoplasm. Here we characterized two CPPs, α1H and α2H, derived from the Y. enterocolitica YopM effector protein. These CPPs, as well as Tat(Trans-activator of transcription) from HIV-1 virus, were used to deliver the antibiotic gentamicin to target intracellular bacteria...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28094285/urinary-exosomes-contain-micrornas-capable-of-paracrine-modulation-of-tubular-transporters-in-kidney
#10
Tannia Gracia, Xiaonan Wang, Ya Su, Elizabeth E Norgett, Timothy L Williams, Pablo Moreno, Gos Micklem, Fiona E Karet Frankl
Exosomes derived from all nephron segments are present in human urine, where their functionality is incompletely understood. Most studies have focused on biomarker discovery rather than exosome function. Through sequencing we identified the miRNA repertoire of urinary exosomes from healthy volunteers; 276 mature miRNAs and 345 pre-miRNAs were identified (43%/7% of reads). Among the most abundant were members of the miR-10, miR-30 and let-7 families. Targets for the identified miRNAs were predicted using five different databases; genes encoding membrane transporters and their regulators were enriched, highlighting the possibility that these miRNAs could modulate key renal tubular functions in a paracrine manner...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28093948/design-and-evaluation-of-a-stearylated-multicomponent-peptide-sirna-nanocomplex-for-efficient-cellular-sirna-delivery
#11
Yu Wan, Peter M Moyle, Pei Z Gn, Istvan Toth
AIM: To develop a new synthetic peptide-based nanoparticulate siRNA delivery system. MATERIALS & METHODS: DEN-K(GALA)-TAT-K(STR) was generated by incorporating stearic acid into a multicomponent peptide (DEN-K(GALA)-TAT), containing a cationic poly-L-lysine dendron, an endosome-disrupting peptide GALA and a cell-penetrating peptide TAT(48-60). Its physicochemical characteristics, size, toxicity, cellular uptake and gene knockdown activity of the peptide/siRNA complexes were studied...
January 17, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28093941/novel-surface-engineered-solid-lipid-nanoparticles-of-rosuvastatin-calcium-for-low-density-lipoprotein-receptor-targeting-a-quality-by-design-driven-perspective
#12
Sarwar Beg, Sanyog Jain, Varun Kushwah, Gurjit Kaur Bhatti, Premjeet Singh Sandhu, O P Katare, Bhupinder Singh
AIM: The present studies describe Quality by Design-oriented development and characterization of surface-engineered solid lipid nanoparticles (SLNs) of rosuvastatin calcium for low density lipoprotein-receptor targeting. MATERIALS & METHODS: SLNs were systematically prepared employing Compritol 888 and Tween-80. Surface modification of SLNs was accomplished with Phospholipon 90G and DSPE-mPEG-2000 as the ligands for specific targeting to the low density lipoprotein-receptors...
January 17, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28093351/in-vitro-uptake-and-transport-studies-of-peg-plga-polymeric-micelles-in-respiratory-epithelial-cells
#13
Xiao Hu, Fei-Fei Yang, Chun-Yu Liu, Carsten Ehrhardt, Yong-Hong Liao
Polymeric micelles are considered promising carriers for pulmonary drug delivery. Their interaction with the respiratory epithelium, however, is mostly unknown. In the present study, methoxypoly (ethylene glycol) (mPEG)-poly (lactic-co-glycolic acid) (PLGA) micelles containing curcumin acetate (CA) or a mixture of CA and Nile Red (NR) were prepared using the solvent evaporation method. Calu-3 and NCI-H441 human respiratory epithelial cell monolayers were used as in vitro models of upper and lower respiratory tract epithelium barrier, respectively, to study the cellular uptake and transport of the vesicles...
January 13, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28092499/nanoparticles-for-sirna-based-gene-silencing-in-tumor-therapy
#14
Anish Babu, Ranganayaki Muralidharan, Narsireddy Amreddy, Meghna Mehta, Anupama Munshi, Rajagopal Ramesh
Gene silencing through RNA interference (RNAi) has emerged as a potential strategy in manipulating cancer causing genes by complementary base-pairing mechanism. Small interfering RNA (siRNA) is an important RNAi tool that has found significant application in cancer therapy. However due to lack of stability, poor cellular uptake and high probability of loss-of-function due to degradation, siRNA therapeutic strategies seek safe and efficient delivery vehicles for in vivo applications. The current review discusses various nanoparticle systems currently used for siRNA delivery for cancer therapy, with emphasis on liposome based gene delivery systems...
December 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28091953/fullerene-c60-penetration-into-leukemic-cells-and-its-photoinduced-cytotoxic-effects
#15
D Franskevych, K Palyvoda, D Petukhov, S Prylutska, I Grynyuk, C Schuetze, L Drobot, O Matyshevska, U Ritter
Fullerene C60 as a representative of carbon nanocompounds is suggested to be promising agent for application in photodynamic therapy due to its unique physicochemical properties. The goal of this study was to estimate the accumulation of fullerene C60 in leukemic cells and to investigate its phototoxic effect on parental and resistant to cisplatin leukemic cells. Stable homogeneous water colloid solution of pristine C60 with average 50-nm diameter of nanoparticles was used in experiments. Fluorescent labeled C60 was synthesized by covalent conjugation of C60 with rhodamine B isothiocyanate...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28091675/a-highly-sensitive-sers-based-platform-for-zn-ii-detection-in-cellular-media
#16
Hongjun Zhuang, Zhenzhen Wang, Xiangchun Zhang, James A Hutchison, Wenfeng Zhu, Zhiyi Yao, Yuliang Zhao, Min Li
We report a highly sensitive and selective surface-enhanced Raman scattering (SERS)-based detection of aqueous Zn(ii) ions (limit of detection 10(-14) M). Spectral changes for a silver nanoparticle-bound Raman reporter upon Zn(ii) chelation constitutes the assay, which is applied to drinking water and to measurements of cellular uptake of Zn(ii).
January 16, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28091567/quantifying-the-relative-contributions-of-different-solute-carriers-to-aggregate-substrate-transport
#17
Mehdi Taslimifar, Lalita Oparija, Francois Verrey, Vartan Kurtcuoglu, Ufuk Olgac, Victoria Makrides
Determining the contributions of different transporter species to overall cellular transport is fundamental for understanding the physiological regulation of solutes. We calculated the relative activities of Solute Carrier (SLC) transporters using the Michaelis-Menten equation and global fitting to estimate the normalized maximum transport rate for each transporter (Vmax). Data input were the normalized measured uptake of the essential neutral amino acid (AA) L-leucine (Leu) from concentration-dependence assays performed using Xenopus laevis oocytes...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089916/stable-curcumin-loaded-polymeric-micellar-formulation-for-enhancing-cellular-uptake-and-cytotoxicity-to-flt3-overexpressing-eol-1-leukemic-cells
#18
Singkome Tima, Songyot Anuchapreeda, Chadarat Ampasavate, Cory Berkland, Siriporn Okonogi
The present study aims to develop a stable polymeric micellar formulation of curcumin (CM) with improved solubility and stability, and that is suitable for clinical applications in leukemia patients. CM-loaded polymeric micelles (CM-micelles) were prepared using poloxamers. The chemical structure of the polymers influenced micellar properties. The best formulation of CM-micelles, namely CM-P407, was obtained from poloxamer 407 at drug to polymer ratio of 1:30 and rehydrated with phosphate buffer solution pH 7...
January 12, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28089705/so-as-we-worry-we-weigh-visible-burrow-system-stress-and-visceral-adiposity
#19
REVIEW
Michelle T Foster
The visible borrow system (VBS) simulates a natural rodent habitat that supports genuine stress provoking social interactions. This model allows investigation of behavioral, neural and endocrine alterations caused by chronic stress. The Sakai lab further used this model to investigate metabolic outcomes of stress in relation to dominance hierarchies formed within the VBS. Communal social conflict occurs among all VBS rats, but only the SUB rats succumb to the redistribution of lipids in the visceral cavity and consequent metabolic dysregulation, such as hyper-insulinemia...
January 12, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28089688/functional-identification-of-plasma-membrane-monoamine-transporter-pmat-slc29a4-as-an-atenolol-transporter-sensitive-to-flavonoids-contained-in-apple-juice
#20
Yoshihisa Mimura, Tomoya Yasujima, Kinya Ohta, Katsuhisa Inoue, Hiroaki Yuasa
The intestinal absorption of atenolol has recently been reported to be reduced by simultaneous ingestion of fruit juices, such as apple juice. This finding implies a possibility that an unidentified carrier-mediated transport system, which could be interfered by some components of those juices, might be involved in atenolol absorption. In an attempt to explore that possibility, we successfully identified plasma membrane monoamine transporter (PMAT/SLC29A4) as a transporter that can operate for cellular atenolol uptake in the intestine, using Madin-Darby canine kidney II cells stably expressing PMAT...
January 12, 2017: Journal of Pharmaceutical Sciences
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