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https://www.readbyqxmd.com/read/29148696/the-epidermal-penetration-of-gold-nanoparticles-and-its-underlying-mechanism-based-on-human-reconstructed-3d-episkin-tm-model
#1
Fang Hao, Xiaoting Jin, Qian S Liu, Qunfang Zhou, Guibin Jiang
Nanomaterials are widely used in diverse aspects and their translocation behavior through the skin would be helpful in understanding the corresponding exposure risks. To reveal how surface functionalization of nanoparticles influence the skin penetration, three kinds of gold nanoparticles (GNPs) with negatively, neutrally and positively charged surfaces, i.e. cetyltrimethyl ammonium bromide-coated GNPs (CTAB@GNP), polyvinyl pyrrolidone-coated GNPs (PVP@GNP), and citrate-coated GNPs (Citrate@GNP), were studied using human reconstructed 3D EpiskinTM model...
November 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29146447/in-the-ovary-of-ciona-intestinalis-type-a-immune-related-galectin-and-phenoloxidase-genes-are-differentially-expressed-by-the-follicle-accessory-cells
#2
Daniela Parrinello, Maria Antonietta Sanfratello, Maria Giovanna Parisi, Aiti Vizzini, Matteo Cammarata
Riboprobes (in situ hybridization) and antibodies (immunohistochemistry), previously used to show the upregulation of Ciona intestinalis (Type A) galectins (CiLgals-a, CiLgals-b) and phenoloxidase (CinPO2) immune-related genes, were tested on histological sections of the ovary. The ovarian follicles are composed of oocytes encased by follicular cells (FCs) and test cells (TCs). Results show the transcription upregulation of both CiLgals and CinPO2 genes in the vitellogenic FCs, conversely distinct cytolocalization of the proteins are shown...
November 13, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29140158/endosomal-trafficking-regulates-receptor-mediated-transcytosis-of-antibodies-across-the-blood-brain-barrier
#3
Arsalan S Haqqani, Christie E Delaney, Eric Brunette, Ewa Baumann, Graham K Farrington, William Sisk, John Eldredge, Wen Ding, Tammy-Lynn Tremblay, Danica B Stanimirovic
Current methods for examining antibody trafficking are either non-quantitative such as immunocytochemistry or require antibody labeling with tracers. We have developed a multiplexed quantitative method for antibody 'tracking' in endosomal compartments of brain endothelial cells. Rat brain endothelial cells were co-incubated with blood-brain barrier (BBB)-crossing FC5, monovalent FC5Fc or bivalent FC5Fc fusion antibodies and control antibodies. Endosomes were separated using sucrose-density gradient ultracentrifugation and analyzed using multiplexed mass spectrometry to simultaneously quantify endosomal markers, receptor-mediated transcytosis (RMT) receptors and the co-incubated antibodies in each fraction...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29134730/role-of-central-versus-peripheral-opioid-system-in-antinociceptive-and-anti-inflammatory-effect-of-botulinum-toxin-type-a-in-trigeminal-region
#4
V Drinovac Vlah, B Filipović, L Bach-Rojecky, Z Lacković
BACKGROUND: Although botulinum toxin type A (BT-A) is approved for chronic migraine treatment, its site and mechanism of action are still elusive. Recently our group discovered that suppression of CGRP release from dural nerve endings might account for antimigraine action of pericranially injected BT-A. We demonstrated that central antinociceptive effect of BT-A in sciatic region involves endogenous opioid system as well. Here we investigated possible interaction of BT-A with endogenous opioid system within the trigeminal region...
November 13, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29133120/enhanced-oral-absorption-and-anticancer-efficacy-of-cabazitaxel-by-overcoming-intestinal-mucus-and-epithelium-barriers-using-surface-polyethylene-oxide-peo-decorated-positively-charged-polymer-lipid-hybrid-nanoparticles
#5
Tianyang Ren, Qian Wang, Ying Xu, Lin Cong, Jingxin Gou, Xiaoguang Tao, Yu Zhang, Haibing He, Tian Yin, Haotian Zhang, Yan Zhang, Xing Tang
Polymer-lipid hybrid nanoparticles, PMONPs, were developed to improve the oral absorption of cabazitaxel (CTX), a semi-synthetic taxane derivative, by overcoming multiple gastrointestinal barriers. The nano-carrier is comprised of a poly(ε-caprolactone) (PCL) and chain triglyceride (MCT) hybrid core for drug loading, and a positively charged surface while slightly concealed with a polyethylene oxide (PEO) shell by insertion of poloxamer 188, with the aim of improving the intestinal mucus permeation and epithelial cell uptake...
November 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29129657/transport-mechanism-of-lipid-covered-saquinavir-pure-drug-nanoparticles-in-intestinal-epithelium
#6
Dengning Xia, Yuan He, Qiuxia Li, Cunde Hu, Wei Huang, Yunhai Zhang, Feng Wan, Chi Wang, Yong Gan
Pure drug nanoparticles (NPs) represent a promising formulation for improved drug solubility and controlled dissolution velocity. However, limited absorption by the intestinal epithelium remains challenge to their clinical application, and little is known about how these NPs within the cells are transported. To improve cellular uptake and transport of pure nanodrug in cells, here, a lipid covered saquinavir (SQV) pure drug NP (Lipo@nanodrug) was designed by modifying a pure SQV NP (nanodrug) with a phospholipid bilayer...
November 9, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29111119/direct-central-nervous-system-effects-of-botulinum-neurotoxin
#7
Matteo Caleo, Laura Restani
Local intramuscular injections of botulinum neurotoxin type A (BoNT/A) are effective in the treatment of focal dystonias, muscle spasms, and spasticity. However, not all clinical effects of BoNT/A may be explained by its action at peripheral nerve terminals. For example, the therapeutic benefit may exceed the duration of the peripheral neuroparalysis induced by the neurotoxin. In cellular and animal models, evidence demonstrates retrograde transport of catalytically active BoNT/A in projection neurons. This process of long-range trafficking is followed by transcytosis and action at second-order synapses...
October 27, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29103910/nanotherapeutics-for-gene-modulation-that-prevents-apoptosis-in-the-brain-and-fatal-neuroinflammation
#8
Sang-Soo Kim, Antonina Rait, Emilio R Garrido-Sanabria, Kathleen F Pirollo, Joe B Harford, Esther H Chang
The failure of therapeutic agents to cross the blood-brain barrier (BBB) has been a major impediment in the treatment of neurological disorders and brain tumors. We have addressed this issue using an immunoliposome nanocomplex (designated scL) that delivers therapeutic nucleic acids across the BBB into the deep brain via transcytosis mediated by transferrin receptors. We validated brain delivery of payloads after systemic administration by monitoring uptake of fluorescently labeled payloads and by confirming up- or down-modulation of specific target gene expression in the brain, mainly in neuronal cells...
October 10, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29098649/molecular-insights-into-the-mechanisms-of-m-cell-differentiation-and-transcytosis-in-the-mucosa-associated-lymphoid-tissues
#9
REVIEW
Shunsuke Kimura
Microfold cells (M cells), which are located in the follicle-associated epithelium (FAE) covering mucosal lymphoid follicles, are specialized epithelial cells that initiate mucosal immune responses. These cells take luminal antigens and transport them via transcytosis across the FAE to the antigen-presenting cells underneath. Several intestinal pathogens exploit M cells as their portal for entry to invade the host and cause disease conditions. Recent studies have revealed that the uptake of antigens by M cells is essential for efficient antigen-specific IgA production and that this process likely maintains the homeostasis of mucosal tissues...
November 2, 2017: Anatomical Science International
https://www.readbyqxmd.com/read/29090274/a-novel-lrp1-binding-peptide-l57-that-crosses-the-blood-brain-barrier
#10
Kotaro Sakamoto, Tokuyuki Shinohara, Yusuke Adachi, Taiji Asami, Tetsuya Ohtaki
The blood-brain barrier (BBB) is a major obstacle to drug delivery into the central nervous system (CNS), in particular for macromolecules such as peptides and proteins. However, certain macromolecules can reach the CNS via a receptor-mediated transcytosis (RMT) pathway, and low-density lipoprotein receptor-related protein 1 (LRP1) is one of the promising receptors for RMT. An LRP1 ligand peptide, Angiopep-2, was reported to pass through the BBB and deliver covalently conjugated drugs into the CNS. While conjugation of LRP1 ligands with drugs would be an effective approach for drug delivery to the CNS, no other reliable LRP1 ligands have been reported to date...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29074396/translocation-and-dissemination-of-botulinum-neurotoxin-from-the-intestinal-tract
#11
Yukako Fujinaga, Michel R Popoff
Botulinum neurotoxins (BoNTs) are potent toxins which induce flaccid paralysis by inhibiting the release of acetylcholine at the neuromuscular junctions. They associate with non-toxic proteins (ANTPs or NAPs) to form complexes of various sizes which are resistant to acidic pH and protease degradation. BoNT trafficking from the digestive tract to the target neurons is still a matter of debate. BoNTs use different strategies to pass through the intestinal barrier including passage of BoNT complexes containing hemagglutinins (HAs) via M cells, HA-dependent perturbation of E-cadherin intercellular junctions between enterocytes and paracellular passage of BoNT complexes, and transcytosis of BoNT free of NAPs through certain intestinal epithelial cells...
October 23, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29058910/n-deoxycholic-acid-n-o-hydroxyethyl-chitosan-with-a-sulfhydryl-modification-to-enhance-the-oral-absorptive-efficiency-of-paclitaxel
#12
Yanfang Yu, Meirong Huo, Ying Fu, Wei Xu, Han Cai, Lingling Yao, Qingyu Chen, Yan Mu, Jianping Zhou, Tingjie Yin
Currently, the most prominent barrier to the success of orally delivered paclitaxel (PTX) is the extremely limited bioavailability of delivered therapeutic. In light of this issue, an amphiphilic sulfhydrylated N-deoxycholic acid-N,O-hydroxyethyl chitosan (TGA-DHC) was synthesized to improve the oral bioavailability of PTX. First, TGA-DHC demonstrated substantial loading of PTX into the inner hydrophobic core. A desirable enhancement in the bioavailability of PTX by TGA-DHC was verified by pharmacokinetic studies on rats against Taxol and non-sulfhydrylated DHC micelles...
November 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29054590/double-fluorescent-labelling-of-a-bipolar-epithelial-cell-in-vitro-the-outer-hair-cell
#13
Csaba Harasztosi, Entcho Klenske, Susanne Badum, Emese Harasztosi, Anthony W Gummer
BACKGROUND: Fluorescence membrane markers are efficient tools for visualizing the dynamics of membrane recycling processes in living cells. The outer hair cell (OHC) - a bipolar epithelial cell in the cochlea - possesses endocytic activity at both its apical and basal poles. The best visual overview of transcytosis in the OHC is achieved when the cell is isolated, so that both the apical and the basal poles are in the same focal plane to allow confocal imaging. Until now, fluorescent markers were applied to the extracellular environment of isolated OHCs without distinguishing the apical and basal poles...
October 17, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29038658/the-peyer-s-patch-mononuclear-phagocyte-system-at-steady-state-and-during-infection
#14
REVIEW
Clément Da Silva, Camille Wagner, Johnny Bonnardel, Jean-Pierre Gorvel, Hugues Lelouard
The gut represents a potential entry site for a wide range of pathogens including protozoa, bacteria, viruses, or fungi. Consequently, it is protected by one of the largest and most diversified population of immune cells of the body. Its surveillance requires the constant sampling of its encounters by dedicated sentinels composed of follicles and their associated epithelium located in specialized area. In the small intestine, Peyer's patches (PPs) are the most important of these mucosal immune response inductive sites...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29016922/morphologic-mechanisms-of-increased-vascular-permeability-of-triolein-emulsion-to-the-blood-brain-barrier
#15
Yuri Sol, Seon Hee Choi, Hak Jin Kim, Yong-Woo Kim, Byung Mann Cho, Hyung Soo Han, Ki J Choi
Triolein emulsion has been known to increase vascular permeability in the brain when it is infused into the carotid artery. The purpose of this study was to identify the morphologic mechanism of increased vascular permeability in brain induced by infusion of emulsified triolein into the carotid artery by transmission electron microscopy (TEM). Triolein emulsion was infused into the carotid artery of rats. TEM using lanthanum tracer was used to evaluate morphologic changes in endothelium with a focus on transcytotic vesicles and tight junction opening...
October 1, 2017: Microscopy
https://www.readbyqxmd.com/read/28993773/targeting-malignant-brain-tumors-with-antibodies
#16
REVIEW
Rok Razpotnik, Neža Novak, Vladka Čurin Šerbec, Uros Rajcevic
Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood-brain barrier (BBB) makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain delivery platforms for antibodies have been studied such as liposomes, nanoparticle-based systems, cell-penetrating peptides (CPPs), and cell-based approaches...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28992081/apical-secretion-of-wnt1-in-polarized-epithelial-cells-is-regulated-by-exocyst-mediated-trafficking
#17
Hideki Yamamoto, Akira Sato, Akira Kikuchi
Wnts are glycosylated proteins secreted from various cell types including mesenchymal, hematopoietic and epithelial cells. Directional secretion of Wnts in polarized epithelial cells is unique; Wnt11 is secreted apically, whereas Wnt5a and Wnt3a are secreted basolaterally. Here, we found that Wnt1 is equivalently secreted both apically and basolaterally in MDCK cells. Wnt1 was modified with a complex- or hybrid-type glycan at Asn29 and Asn359 and the high-mannose- or hybrid-type glycan at Asn316. Although glycosylation of Wnt11 at the N-terminal site was shown to be essential for its apical secretion, glycosylation of Asn29 of Wnt1 was not required...
November 1, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28985008/transcellular-vesicular-transport-in-epithelial-and-endothelial-cells-challenges-and-opportunities
#18
REVIEW
Karen Y Fung, Gregory D Fairn, Warren L Lee
Vesicle-mediated transcellular transport or simply "transcytosis" is a cellular process used to shuttle macromolecules such as lipoproteins, antibodies, and albumin from one surface of a polarized cell to the other. This mechanism is in contrast to the transit of small molecules such as anions, cations and amino acids that occur via uptake, diffusion through the cytosol and release and is also distinct from paracellular leak between cells. Importantly, transcytosis has evolved as a process to selectively move macromolecules between two neighboring yet unique microenvironments within a multicellular organism...
October 6, 2017: Traffic
https://www.readbyqxmd.com/read/28974108/l-carnitine-conjugated-nanoparticles-to-promote-permeation-across-blood-brain-barrier-and-to-target-glioma-cells-for-drug-delivery-via-the-novel-organic-cation-carnitine-transporter-octn2
#19
Longfa Kou, Yanxian Hou, Qing Yao, Weiling Guo, Gang Wang, Menglin Wang, Qiang Fu, Zhonggui He, Vadivel Ganapathy, Jin Sun
Overcoming blood-brain barrier (BBB) and targeting tumor cells are two key steps for glioma chemotherapy. By taking advantage of the specific expression of Na(+)-coupled carnitine transporter 2 (OCTN2) on both brain capillary endothelial cells and glioma cells, l-carnitine conjugated poly(lactic-co-glycolic acid) nanoparticles (LC-PLGA NPs) were prepared to enable enhanced BBB permeation and glioma-cell targeting. Conjugation of l-carnitine significantly enhanced the uptake of PLGA nanoparticles in the BBB endothelial cell line hCMEC/D3 and the glioma cell line T98G...
October 3, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28970916/tailored-theranostic-apolipoprotein-e3-porphyrin-lipid-nanoparticles-target-glioblastoma
#20
M A Rajora, L Ding, M Valic, W Jiang, M Overchuk, J Chen, G Zheng
The development of curative glioblastoma treatments and tumour-specific contrast agents that can overcome the blood-brain barrier (BBB) and infiltrative tumour morphology remains a challenge. Apolipoprotein E3 (apoE3) is a high density lipoprotein apolipoprotein that chaperones the transcytosis of nanoparticles across the BBB, and displays high-affinity binding with the low density lipoprotein receptor (LDLR), a cell-surface receptor overexpressed by glioblastoma cells. This LDLR overexpression and apoE3 binding capacity was exploited for the development of glioblastoma-targeted porphyrin-lipid apoE3 lipid nanoparticles (pyE-LNs) with intrinsic theranostic properties...
August 1, 2017: Chemical Science
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