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https://www.readbyqxmd.com/read/29771629/brain-uptake-of-multivalent-and-multi-specific-dvd-ig-proteins-after-systemic-administration
#1
Denise Karaoglu Hanzatian, Annette Schwartz, Farid Gizatullin, Jamie Erickson, Kangwen Deng, Ruth Villanueva, Christopher Stedman, Cristina Harris, Tariq Ghayur, Andrew Goodearl
Therapeutic monoclonal antibodies and endogenous IgG antibodies show limited uptake into the central nervous system (CNS) due to the blood-brain barrier (BBB), which regulates and controls the selective and specific transport of both exogenous and endogenous materials to the brain. The use of natural transport mechanisms, such as receptor-mediated transcytosis (RMT), to deliver antibody therapeutics into the brain have been studied in rodents and monkeys. Recent successful examples include monovalent bispecific antibodies and mono- or bivalent fusion proteins; however, these formats do not have the capability to bind to both the CNS target and the BBB transport receptor in a bivalent fashion as a canonical antibody would...
May 17, 2018: MAbs
https://www.readbyqxmd.com/read/29761581/congenital-zika-syndrome-pitfalls-in-the-placental-barrier
#2
REVIEW
Nia Robinson, Evangelina E Mayorquin Galvan, Isidro G Zavala Trujillo, Maria G Zavala-Cerna
Much progress with respect to congenital Zika virus (ZIKV) pathogenesis has been achieved after the 2015 outbreak in Brazil. It is now accepted that ZIKV is vertically transmitted, infects cells of the developing central nervous system and the placenta, yet it is unclear to what extent placental affection contributes to the development of congenital ZIKV. The association between fulminant villitis and severe fetal involvement emerges as a possibility. ZIKV is unique among the Flaviviruses in its ability to be sexually transmitted, possibly responsible for its teratogenicity...
May 15, 2018: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29760588/in-vitro-gentamicin-exposure-alters-caveolae-protein-profile-in-cochlear-spiral-ligament-pericytes
#3
Elisa Ghelfi, Yohann Grondin, Emil J Millet, Adam Bartos, Magda Bortoni, Clara Oliveira Gomes Dos Santos, Humberto J Trevino-Villarreal, Rosalinda Sepulveda, Rick Rogers
Background: The aminoglycoside antibiotic gentamicin is an ototoxic drug and has been used experimentally to investigate cochlear damage induced by noise.We have investigated the changes in the protein profile associated with caveolae in gentamicin treated and untreated spiral ligament (SL) pericytes, specialized cells in the blood labyrinth barrier of the inner ear microvasculature. Pericytes from various microvascular beds express caveolae, protein and cholesterol rich microdomains, which can undergo endocytosis and transcytosis to transport small molecules in and out the cells...
2018: Proteome Science
https://www.readbyqxmd.com/read/29756169/vitellogenin-transcytosis-in-follicular-cells-of-the-honeybee-apis-mellifera-and-the-wasp-polistes-simillimus
#4
Virgínia Teles Dohanik, Wagner Gonzaga Gonçalves, Leandro Licursi Oliveira, José Cola Zanuncio, José Eduardo Serrão
Vitellogenin receptor (VgR) is a low-density lipoprotein receptor responsible for the mediated endocytosis of vitellogenin (Vg) during egg formation in insects. The maturing oocyte is enveloped by a follicular epithelium, which has large intercellular spaces during Vg accumulation (patency). However, Vg has been reported in the cytoplasm of follicular cells, indicating that there may be a transcellular route for its transport. This study verified the presence of VgR in the follicular cells of the ovaries of the honeybee Apis mellifera and the wasp Polistes simillimus in order to evaluate if Vg is transported via transcytosis in these insects...
May 13, 2018: Protoplasma
https://www.readbyqxmd.com/read/29743371/roles-of-fc-domain-and-exudation-in-l2-antibody-mediated-protection-against-human-papillomavirus
#5
Joshua W Wang, Wai Hong Wu, Tsui-Chin Huang, Margaret Wong, Kihyuck Kwak, Keiko Ozato, Chien-Fu Hung, Richard B S Roden
To address how L2-specific antibodies prevent human papillomavirus (HPV) infection of the genital tract we generated neutralizing monoclonal antibodies (MAbs) WW1, a rat IgG2a that binds L2 residues 17-36 (like mouse MAb RG1), and JWW3, a mouse IgG1 derivative of Mab24 specific to L2 residues 58-64. By Western blot, WW1 recognized L2 of 29/34 HPV genotypes tested, compared to only 13/34 for RG1, and 25/34 for JWW3. WW1 IgG and (Fab')2 bound HPV16 pseudovirions similarly, however whole IgG provided better protection against HPV vaginal challenge...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29742434/live-imaging-of-hiv-1-transfer-across-t-cell-virological-synapse-to-epithelial-cells-that-promotes-stromal-macrophage-infection
#6
Fernando Real, Alexis Sennepin, Yonatan Ganor, Alain Schmitt, Morgane Bomsel
During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4+ T cells and the epithelial cell mucosal surface...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29741927/transcellular-transport-of-cobalamin-in-aortic-endothelial-cells
#7
Luciana Hannibal, Keerthana Bolisetty, Armend Axhemi, Patricia M DiBello, Edward V Quadros, Sergey Fedosov, Donald W Jacobsen
Cobalamin [Cbl (or B12 )] deficiency causes megaloblastic anemia and a variety of neuropathies. However, homeostatic mechanisms of cyanocobalamin (CNCbl) and other Cbls by vascular endothelial cells are poorly understood. Herein, we describe our investigation into whether cultured bovine aortic endothelial cells (BAECs) perform transcytosis of B12 , namely, the complex formed between serum transcobalamin and B12 , designated as holo-transcobalamin (holo-TC). We show that cultured BAECs endocytose [57 Co]-CNCbl-TC (source material) via the CD320 receptor...
May 9, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29734145/the-role-of-caveolae-on-albumin-passage-through-glomerular-endothelial-and-epithelial-cells-the-new-etiology-of-urinary-albumin-excretion
#8
Takahito Moriyama, Kazunori Karasawa, Kosaku Nitta
BACKGROUND: In the traditional theory of albuminuria, small amounts of albumin pass through the fenestrae in glomerular endothelial cells, then through the slit membrane in the gaps between foot processes of glomerular epithelial cells. In the novel theory, large amounts of albumin pass through glomerular capillaries and are taken up by megalin and cubilin receptors on tubular epithelial cells. These etiologies of urinary albumin excretion are still controversial, and the details of albumin passage through the three layers of glomerular capillaries (glomerular endothelial cells, basement membrane, and epithelial cells) have never been entirely elucidated...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29717108/the-aff-1-exoplasmic-fusogen-is-required-for-endocytic-scission-and-seamless-tube-elongation
#9
Fabien Soulavie, David H Hall, Meera V Sundaram
Many membranes must merge during cellular trafficking, but fusion and fission events initiating at exoplasmic (non-cytosolic) membrane surfaces are not well understood. Here we show that the C. elegans cell-cell fusogen anchor-cell fusion failure 1 (AFF-1) is required for membrane trafficking events during development of a seamless unicellular tube. EGF-Ras-ERK signaling upregulates AFF-1 expression in the excretory duct tube to promote tube auto-fusion and subsequent lumen elongation. AFF-1 is required for scission of basal endocytic compartments and for apically directed exocytosis to extend the apical membrane...
May 1, 2018: Nature Communications
https://www.readbyqxmd.com/read/29704325/transcytosis-of-junonia-coenia-densovirus-vp4-across-the-gut-epithelium-of-spodoptera-frugiperda-lepidoptera-noctuidae
#10
Mariah Kemmerer, Bryony Bonning
The Junonia coenia densovirus rapidly traverses the gut epithelium of the host lepidopteran without replicating in the gut cells. The ability of this virus to transcytose across the gut epithelium is of interest for the potential use of virus structural proteins as delivery vehicles for insecticidal peptides that act within the insect hemocoel, rather than in the gut. In this study, we used fall armyworm, Spodoptera frugiperda to examine the binding of the virus to brush border membrane vesicle proteins by two-dimensional ligand blot analysis...
April 27, 2018: Insect Science
https://www.readbyqxmd.com/read/29688440/a-subpopulation-of-intracellular-neisseria-gonorrhoeae-escapes-autophagy-mediated-killing-inside-epithelial-cells
#11
Ping Lu, Shuyi Wang, Yan Lu, Dante Neculai, Qiming Sun, Stijn van der Veen
The bacterial pathogen Neisseria gonorrhoeae is able to transmigrate across the mucosal epithelia following the intracellular route and cause disseminated infections. It is currently unknown whether the autophagy pathway is able target intracellular N. gonorrhoeae for destruction in autolysosomes or whether this bacterium is able to escape autophagy-mediated killing. Here we demonstrate that during the early stage of epithelial cell invasion N. gonorrhoeae is targeted by the autophagy pathway and sequestered into double-membrane autophagosomes that subsequently fuse with lysosomes for destruction...
April 24, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29684679/comparing-ex-vivo-and-in-vitro-translocation-of-silver-nanoparticles-and-ions-through-human-nasal-epithelium
#12
Jonathan L Falconer, Jeremiah A Alt, David W Grainger
Silver nanomaterials are widely used in clinically approved devices, consumer goods, and over-the-counter nutraceutical products. Despite the increase in silver nanomaterial research, few investigations have specifically distinguished the biological effects resulting from silver nanoparticles (AgNPs) versus silver ions released from AgNPs. This is in part, due to the complex analytical methods required to characterize silver ion release from AgNPs in biological media. This study sought to analyze silver ion release from AgNPs in biological media, compare silver transport from soluble AgNO3 and AgNPs through ex vivo full thickness sinus human tissue explants and human nasal epithelium and determine fractional AgNP internalization by human nasal epithelial cells...
April 14, 2018: Biomaterials
https://www.readbyqxmd.com/read/29652177/broncho-epithelial-iga-secretion-is-impaired-in-asthma-role-of-il-4-il-13
#13
Maha Zohra Ladjemi, Delphine Gras, Sébastien Dupasquier, Bruno Detry, Marylène Lecocq, Céline Garulli, Chantal Fregimilicka, Caroline Bouzin, Sophie Gohy, Pascal Chanez, Charles Pilette
RATIONALE: Asthma is associated with increased lung IgE production, but whether the secretory (S-)IgA system is affected in this disease remains unknown. OBJECTIVES: We explored mucosal IgA transport in human asthma and its potential regulation by Th2 inflammation. METHODS: Bronchial biopsies from asthma and control subjects were assayed for broncho-epithelial pIgR expression and correlated to Th2 biomarkers. Bronchial epithelium reconstituted in vitro from these subjects, upon culture in air-liquid interface, was assayed for pIgR expression and regulation by IL-4/IL-13...
April 13, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29629621/pdgfr-%C3%AE-restores-blood-brain-barrier-functions-in-a-mouse-model-of-focal-cerebral-ischemia
#14
Jie Shen, Guihua Xu, Runxiu Zhu, Jun Yuan, Yoko Ishii, Takeru Hamashima, Takako Matsushima, Seiji Yamamoto, Yusuke Takatsuru, Junichi Nabekura, Masakiyo Sasahara
Although platelet-derived growth factor receptor beta (PDGFR-β) mediates the recruitment of vascular pericytes into ischemic lesion to restore the blood-brain barrier (BBB) dysfunction, its mechanisms still remain elusive . Compared with control PDGFR-βfloxed / floxed mice (Floxed), postnatally induced systemic PDGFR-β knockout mice (Esr-KO) not only showed severe brain edema, neurologic functional deficits, decreased expression of tight junction (TJ) proteins, abundant endothelial transcytosis, and deformed TJs in the BBB, but also showed reduced expression of transforming growth factor-β (TGF-β) protein after photothrombotic middle cerebral artery occlusion (MCAO)...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29621428/hematopoietic-cells-as-site-of-first-pass-catabolism-after-subcutaneous-dosing-and-contributors-to-systemic-clearance-of-a-monoclonal-antibody-in-mice
#15
Wolfgang F Richter, Gregory J Christianson, Nicolas Frances, Hans Peter Grimm, Gabriele Proetzel, Derry C Roopenian
The neonatal Fc receptor (FcRn) has been demonstrated to contribute to a high bioavailability of monoclonal antibodies (mAbs). In this study, we explored the cellular sites of FcRn-mediated protection after subcutaneous (SC) and intravenous (IV) administration. SC absorption and IV disposition kinetics of a mAb were studied in hFcRn transgenic (Tg) bone marrow chimeric mice in which hFcRn was restricted to radioresistant cells or hematopoietic cells. SC bioavailabilities close to 90% were observed in hFcRn Tg mice and chimeric mice with hFcRn expression in hematopoietic cells, whereas SC bioavailabilities were markedly lower when FcRn was missing in hematopoietic cells...
April 5, 2018: MAbs
https://www.readbyqxmd.com/read/29605467/an-insight-of-in-vitro-transport-of-pegylated-non-ionic-surfactant-vesicles-nsvs-across-the-intestinal-polarized-enterocyte-monolayers
#16
Rosita Primavera, Paola Palumbo, Christian Celia, Benedetta Cinque, Elisabetta Carata, Maria Carafa, Donatella Paolino, Maria Grazia Cifone, Luisa Di Marzio
PEGylated non-ionic surfactant-based vesicles (NSVs) are promising drug delivery systems for the local, oral and systemic administrations of therapeutics. The aim of this study was to test the cellular biocompatibility and transport of Nile Red-loaded NSVs (NR-NSVs) across the Caco-2-cell monolayers, which represent an in vitro model of human intestinal epithelium. The NR-NSVs assumed a spherical shape with a mean size of 140 nm, and a narrow size distribution. The NR-NSVs did not modify Caco-2 cell viability, which remained unaltered in vitro up to a concentration of 1 mM...
March 29, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29593696/transmission-of-turnip-yellows-virus-by-myzus-persicae-is-reduced-by-feeding-aphids-on-double-stranded-rna-targeting-the-ephrin-receptor-protein
#17
Michaël Mulot, Baptiste Monsion, Sylvaine Boissinot, Maryam Rastegar, Sophie Meyer, Nicole Bochet, Véronique Brault
Aphid-transmitted plant viruses are a threat for major crops causing massive economic loss worldwide. Members in the Luteoviridae family are transmitted by aphids in a circulative and non-replicative mode. Virions are acquired by aphids when ingesting sap from infected plants and are transported through the gut and the accessory salivary gland (ASG) cells by a transcytosis mechanism relying on virus-specific receptors largely unknown. Once released into the salivary canal, virions are inoculated to plants, together with saliva, during a subsequent feeding...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29584446/the-insulin-receptor-is-expressed-and-functional-in-cultured-blood-brain-barrier-endothelial-cells-but-does-not-mediate-insulin-entry-from-blood-to-brain
#18
Maria Hersom, Hans C Helms, Christoffer Schmalz, Thomas Å Pedersen, Stephen T Buckley, Birger Brodin
Insulin and its receptor are known to be present and functional in the brain. Insulin cerebrospinal fluid concentrations have been shown to correlate with plasma levels of insulin in a non-linear fashion, indicative of a saturable transport pathway from the blood to the brain interstitial fluid. The aim of the present study was to investigate whether insulin was transported across brain endothelial cells in vitro via an insulin receptor-dependent pathway. The study showed that the insulin receptor was expressed at both mRNA and protein level in bovine brain endothelial cells...
March 27, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29579950/hydrolysis-and-transepithelial-transport-of-two-corn-gluten-derived-bioactive-peptides-in-human-caco-2-cell-monolayers
#19
Long Ding, Liying Wang, Ting Zhang, Zhipeng Yu, Jingbo Liu
The objective of this paper was to investigate the transepithelial transport of two novel corn gluten-derived antioxidant peptides, YFCLT and GLLLPH, using Caco-2 cell monolayers. Results showed that both of YFCLT and GLLLPH could transport in intact form across Caco-2 cell monolayers with apparent permeability coefficient (Papp ) values of (1.10±0.16)×10-7 cm/s and (1.98±0.23)×10-7 cm/s, respectively. However, it was found that the two peptides were susceptible and easily hydrolyzed by brush border membrane peptidases...
April 2018: Food Research International
https://www.readbyqxmd.com/read/29577457/traceable-nanoparticles-with-dual-targeting-and-ros-response-for-rnai-based-immunochemotherapy-of-intracranial-glioblastoma-treatment
#20
Chenmeng Qiao, Jun Yang, Qi Shen, Ruiyuan Liu, Yanhui Li, Yuanjie Shi, Jingli Chen, Yanqin Shen, Zuobing Xiao, Jie Weng, Xin Zhang
The chemotherapy of glioblastoma is severely hindered by the immunosuppressive tumor microenvironment, especially the tumor growth factor β (TGF-β), an immunosuppressive cytokine. In this study, it is proposed to employ RNAi-based immunomodulation to modify the tumor immune microenvironment and improve the effect of chemotherapy. Herein, a nanotheranostic system (Angiopep LipoPCB(Temozolomide+BAP/siTGF-β), ALBTA) with dual targeting and ROS response is established for intracranial glioblastoma treatment...
March 25, 2018: Advanced Materials
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