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https://www.readbyqxmd.com/read/28224999/allograft-inflammatory-factor-1-is-a-regulator-of-transcytosis-in-m-cells
#1
Sari Kishikawa, Shintaro Sato, Satoshi Kaneto, Shigeo Uchino, Shinichi Kohsaka, Seiji Nakamura, Hiroshi Kiyono
M cells in follicle-associated epithelium (FAE) are specialized antigen-sampling cells that take up intestinal luminal antigens. Transcription factor Spi-B regulates M-cell maturation, but the molecules that promote transcytosis within M cells are not fully identified. Here we show that mouse allograft inflammatory factor 1 (Aif1) is expressed by M cells and contributes to M-cell transcytosis. FAE in Aif1(-/-) mice has suppressed uptake of particles and commensal bacteria, compared with wild-type mice. Translocation of Yersinia enterocolitica, but not of Salmonella enterica serovar Typhimurium, leading to the generation of antigen-specific IgA antibodies, is also diminished in Aif1-deficient mice...
February 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28218523/transepithelial-transport-of-ywdhnnpqir-and-its-metabolic-fate%C3%AF-with-cytoprotection-against-oxidative-stress%C3%AF-in-human-intestinal-caco-2-cells
#2
Feiran Xu, Lifeng Wang, Xingrong Ju, Jing Zhang, Shi Yin, Jiayi Shi, Rong He, Qiang Yuan
Studies on the antioxidant peptides extracted from foodstuff sources have included not only experiments to elucidate the chemical characteristics of them but have also investigated their bioavailability and intracellular mechanisms. This study was designed to clarify the absorption and antioxidative activity of YWDHNNPQIR (named RAP) which derived from rapeseed protein using Caco-2 cells transwell model. Results showed that 0.8% RAP (C0=0.2mM, t=90min) could maintain the original structure to across the Caco-2 cell monolayers via the intracellular transcytosis pathway, and the Papp (drug apparent absorption rate) was (6...
February 20, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28215212/dietary-fat-and-physiological-determinants-of-plasma-chylomicron-remnant-homoeostasis-in-normolipidaemic-subjects-insight-into-atherogenic-risk
#3
Deasy Irawati, John C L Mamo, Karin M Slivkoff-Clark, Mario J Soares, Anthony P James
TAG depleted remnants of postprandial chylomicrons are a risk factor for atherosclerosis. Recent studies have demonstrated that in the fasted state, the majority of chylomicrons are small enough for transcytosis to arterial subendothelial space and accelerate atherogenesis. However, the size distribution of chylomicrons in the absorptive state is unclear. This study explored in normolipidaemic subjects the postprandial distribution of the chylomicron marker, apoB-48, in a TAG-rich lipoprotein plasma fraction (Svedberg flotation rate (Sf>400), in partially hydrolysed remnants (Sf 20-400) and in a TAG-deplete fraction (Sf<20), following ingestion of isoenergetic meals with either palm oil (PO), rice bran or coconut oil...
February 20, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28213463/membrane-transport-across-polarized-epithelia
#4
Maria Daniela Garcia-Castillo, Daniel J-F Chinnapen, Wayne I Lencer
Polarized epithelial cells line diverse surfaces throughout the body forming selective barriers between the external environment and the internal milieu. To cross these epithelial barriers, large solutes and other cargoes must undergo transcytosis, an endocytic pathway unique to polarized cell types, and significant for the development of cell polarity, uptake of viral and bacterial pathogens, transepithelial signaling, and immunoglobulin transport. Here, we review recent advances in our knowledge of the transcytotic pathway for proteins and lipids...
February 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28208831/resveratrol-and-grape-extract-loaded-solid-lipid-nanoparticles-for-the-treatment-of-alzheimer-s-disease
#5
Joana A Loureiro, Stephanie Andrade, Ana Duarte, Ana Rute Neves, Joana Fontes Queiroz, Cláudia Nunes, Emmanuel Sevin, Laurence Fenart, Fabien Gosselet, Manuel A N Coelho, Maria Carmo Pereira
The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer's disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aβ aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated...
February 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28207487/antibody-mediated-immune-exclusion-of-hiv
#6
Ruth M Ruprecht, Samir K Lakhashe
PURPOSE OF REVIEW: Although approximately 90% of all HIV transmissions in humans occur through mucosal contact, the induction of mucosal anti-HIV immune responses has remained understudied. Here we summarize data demonstrating the powerful protection that is achievable at mucosal frontlines through virus-specific mucosal IgA alone or combined with IgG. RECENT FINDINGS: Passive immunization with different monoclonal antibody subclasses but identical epitope specificity (the conserved V3-loop crown of HIV gp120) has revealed that the dimeric IgA1 (dIgA1) form with its open hinge can prevent simian-human immunodeficiency virus (SHIV) acquisition in rhesus macaques at a higher rate than dIgA2...
February 15, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28204818/reactive-oxygen-species-mediate-angiotensin-ii-induced-transcytosis-of-low-density-lipoprotein-across-endothelial-cells
#7
Fang Bian, Jun Cui, Tao Zheng, Si Jin
The retention of plasma low-density lipoprotein (LDL) particles to subendothelial spaces through transcytosis across the endothelium is the initial step of atherosclerosis (AS). Angiotensin II (Ang II), as the principal effector molecule of the renin-angiotensin system (RAS), is implicated in several important steps of AS development. However, whether or not Ang II can directly exert a pro‑atherogenic effect by promoting LDL transcytosis across endothelial barriers, has not been defined. In the present study, we found that Ang II upregulated intracellular reactive oxygen species (ROS) levels in endothelial cells (ECs) by measuring fluorescence of 2',7'-dichlorofluorescein (DCF‑DA)...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28193722/targeting-the-mucosal-barrier-how-pathogens-modulate-the-cellular-polarity-network
#8
Travis R Ruch, Joanne N Engel
The mucosal barrier is composed of polarized epithelial cells with distinct apical and basolateral surfaces separated by tight junctions and serves as both a physical and immunological barrier to incoming pathogens. Specialized polarity proteins are critical for establishment and maintenance of polarity. Many human pathogens have evolved virulence mechanisms that target the polarity network to enhance binding, create replication niches, move through the barrier by transcytosis, or bypass the barrier by disrupting cell-cell junctions...
February 13, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28137846/endothelial-wnt-%C3%AE-catenin-signaling-reduces-immune-cell-infiltration-in-multiple-sclerosis
#9
Justin E Lengfeld, Sarah E Lutz, Julian R Smith, Claudiu Diaconu, Cameron Scott, Sigal B Kofman, Claire Choi, Craig M Walsh, Cedric S Raine, Ilir Agalliu, Dritan Agalliu
Disruption of the blood-brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis. Although wingless integrated MMTV (Wnt)/β-catenin signaling plays an essential role in BBB formation and maintenance in healthy CNS, its role in BBB repair in neurologic diseases such as MS remains unclear...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28130864/complex-roles-of-annexin-a2-in-host-blood-brain-barrier-invasion-by-cryptococcus-neoformans
#10
Wei Fang, Zhen-Zong Fa, Qun Xie, Gui-Zhen Wang, Jiu Yi, Chao Zhang, Guang-Xun Meng, Ju-Lin Gu, Wan-Qing Liao
INTRODUCTION: Fungal transversal across the brain microvascular endothelial cells (BMECs) is the essential step for the development of cryptococcal meningoencephalitis. Annexin A2 (AnxA2) is an important signaling protein involved in several intracellular processes such as membrane trafficking, endocytosis, and exocytosis. AIM: To investigate the roles and mechanism of AnxA2 during cryptococcal transversal of BMECs. RESULTS: Cryptococcus neoformans infection initiated upregulation of AnxA2 in mouse BMECs...
January 28, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28119111/cellular-interactions-of-a-lipid-based-nanocarrier-model-with-human-keratinocytes-unravelling-transport-mechanisms
#11
Elisabete Silva, Luísa Barreiros, Marcela A Segundo, Sofia A Costa Lima, Salette Reis
: Knowledge of delivery system transport through epidermal cell monolayer is vital to improve skin permeation and bioavailability. Recently, nanostructured lipid carriers (NLCs) have gained great attention for transdermal delivery due to their biocompatibility, high drug payload, occlusive properties and skin hydration effect. However, the nanocarriers transport related mechanisms in epidermal epithelial cells are not yet understood. In this research, the internalization and transport pathways of the NLCs across the epidermal epithelial cell monolayer (HaCaT cells) were investigated...
January 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28116899/the-transmembrane-pathways-and-mechanisms-of-rod-like-paclitaxel-nanocrystals-through-mdck-polarized-monolayer
#12
Feiyang Deng, Hua Zhang, Xing Wang, Yuan Zhang, Hongxiang Hu, Siyang Song, Wenbing Dai, Bing He, Ying Zheng, Xueqing Wang, Qiang Zhang
Drug nanocrystals (NCs) appear to be favorable to improving oral bioavailability of poorly water-soluble drugs as evidenced by the great success they have had in the market. However, the pathway and mechanism of drug NCs through epithelial membrane are still unclear. In an attempt to clarify their transport features, paclitaxel nanocrystals (PTX-NCs), and paclitaxel hybrid NCs with lipophilic carbocyanine dyes, were prepared and characterized as the models. The endocytosis, intracellular trafficking, paracellular transport and transcytosis of PTX-NCs were carefully investigated with Förster resonance energy transfer (FRET) analysis, as well as a colocalization assay, flow cytometry, gene silencing, western-blot, transepithelial electrical resistance (TEER) study and other approaches on MDCK cells...
January 24, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28112392/intracellular-transcytosis-of-albumin-in-glomerular-endothelial-cells-after-endocytosis-through-caveolae
#13
Takahito Moriyama, Kayo Sasaki, Kazunori Karasawa, Keiko Uchida, Kosaku Nitta
BACKGROUND/AIMS: We previously described albumin endocytosis through caveolae in human renal glomerular endothelial cells (HRGECs). This suggested a new albumin transcytosis pathway, in addition to the fenestral pathway. As a next step, we investigated albumin transcytosis in HRGECs after caveolar endocytosis. METHODS AND RESULTS: HRGECs were incubated with Alexa Fluor 488-labeled bovine serum albumin from 0 to 360 minutes. Next, markers for endosomes, endoplasmic reticulum (ER), golgi apparatus (GA), lysosomes and proteasomes and Fc receptors, microtubules and actin were monitored by immunofluorescence...
January 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28108572/use-of-ldl-receptor-targeting-peptide-vectors-for-in-vitro-and-in-vivo-cargo-transport-across-the-blood-brain-barrier
#14
Yves Molino, Marion David, Karine Varini, Françoise Jabès, Nicolas Gaudin, Aude Fortoul, Karima Bakloul, Maxime Masse, Anne Bernard, Lucile Drobecq, Pascaline Lécorché, Jamal Temsamani, Guillaume Jacquot, Michel Khrestchatisky
The blood-brain barrier (BBB) prevents the entry of many drugs into the brain and, thus, is a major obstacle in the treatment of CNS diseases. There is some evidence that the LDL receptor (LDLR) is expressed at the BBB and may participate in the transport of endogenous ligands from blood to brain, a process referred to as receptor-mediated transcytosis. We previously described a family of peptide vectors that were developed to target the LDLR. In the present study, in vitro BBB models that were derived from either wild-type and LDLR knockout animals (ldlr(-/-)) were used to validate the specific LDLR-dependent transcytosis of LDL via a nondegradative route...
January 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28101766/crossing-the-blood-brain-barrier-recent-advances-in-drug-delivery-to-the-brain
#15
Mayur M Patel, Bhoomika M Patel
CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting...
January 18, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28069747/a-targeted-rnai-screen-identifies-factors-affecting-diverse-stages-of-receptor-mediated-transcytosis
#16
Bradlee Nelms, Natasha Furtado Dalomba, Wayne Lencer
Endosome transport by transcytosis is the primary mechanism by which proteins and other large cargo traverse epithelial barriers in normal tissue. Transcytosis is also essential for establishing and maintaining membrane polarity in epithelia and other polarized cells. To identify novel components of this pathway, we conducted a high-throughput RNA interference screen for factors necessary for the bidirectional transcytosis of IgG by the Fcγ receptor FcRn. This screen identified 23 genes whose suppression resulted in a reproducible decrease in FcRn-mediated transcytosis...
February 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28042336/bivalent-brain-shuttle-increases-antibody-uptake-by-monovalent-binding-to-the-transferrin-receptor
#17
Greta Hultqvist, Stina Syvänen, Xiaotian T Fang, Lars Lannfelt, Dag Sehlin
The blood-brain barrier (BBB) is an obstacle for antibody passage into the brain, impeding the development of immunotherapy and antibody-based diagnostics for brain disorders. In the present study, we have developed a brain shuttle for active transport of antibodies across the BBB by receptor-mediated transcytosis. We have thus recombinantly fused two single-chain variable fragments (scFv) of the transferrin receptor (TfR) antibody 8D3 to the light chains of mAb158, an antibody selectively binding to Aβ protofibrils, which are involved in the pathogenesis of Alzheimer's disease (AD)...
2017: Theranostics
https://www.readbyqxmd.com/read/28040636/protein-engineering-approaches-for-regulating-blood-brain-barrier-transcytosis
#18
REVIEW
Loukas I Goulatis, Eric V Shusta
The blood brain barrier (BBB) presents a challenge for the delivery of brain therapeutics. Trans-BBB delivery methods that use targeting vectors to coopt the vesicle trafficking machinery of BBB endothelial cells have been developed, but these are often hampered by limited flux through the BBB. A solution to this problem lies in the semi-rational engineering of BBB targeting vectors. Leveraging knowledge of intracellular trafficking, researchers have begun to tune selected binding properties of the vector-receptor interaction...
December 29, 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28017890/rigidity-of-polymer-micelles-affects-interactions-with-tumor-cells
#19
Tal Stern, Inon Kaner, Neta Laser Zer, Hila Shoval, Dvir Dror, Zakhariya Manevitch, Liraz Chai, Yifat Brill-Karniely, Ofra Benny
Controlling the interaction of drug delivery systems (DDS) with tissues is critical for the success of therapies. Specifically in cancer, due to the high density of the tumors, tissue penetration of DDS is critical and may be challenging. In previous work we have shown that Solidified Polymer Micelles (SPMs) rapidly internalize into cells and tissues. Using AFM analysis, in the present work we measured differences in rigidity of SPM compared with Wet Polymer Micelles (WPM). We further examined whether the semi-solid form of hydrated SPMs has an effect on the interaction with tumor cells both in mono-layer systems and in multi-layer clusters of cells as spheroids...
December 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27989702/development-of-novel-self-assembled-es-plga-hybrid-nanoparticles-for-improving-oral-absorption-of-doxorubicin-hydrochloride-by-p-gp-inhibition-in-vitro-and-in-vivo-evaluation
#20
Jia Wang, Lin Li, Lei Wu, Bingjun Sun, Yuqian Du, Jin Sun, Yongjun Wang, Qiang Fu, Peng Zhang, Zhonggui He
To increase the encapsulation efficiency and oral absorption of doxorubicin hydrochloride (DOX), a novel drug delivery system of enoxaparin sodium-PLGA hybrid nanoparticles (EPNs) was successfully designed. By introducing the negative polymer of enoxaparin sodium (ES) to form an electrostatic complex with the cationic drug, DOX, the encapsulation efficiency (93.78%) of DOX was significantly improved. The X-ray diffraction (XRD) results revealed that the DOX-ES complex was in an amorphous form. An in vitro release (pH6...
March 1, 2017: European Journal of Pharmaceutical Sciences
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